Biomedical subjects

H E Kaiser

Publications and source records attributed to H E Kaiser.

At least 127 records · Page 7Linked to original sources

PubMedDate not supplied

Microbial induced hemocytic immune reactions in chilopods.

Hemocytic immune reactions were investigated in the chilopod myriapods Scolopendra cingulata and Lithobius forficatus. Hemocytes were taken into cell culture medium and challenged with latex beads, pre-fixed rat erythrocytes, or bacteria. After 1 to 4 hours in vitro hemocyte preparations were processed for electron microscopy. All tested particles were phagocytosed by the hemocytes and where possible degrated. In both animals the phagocytic cells inside the nodules were found to be tightly encircled by neighboring hemocytes. Aggregation of hemocytes and nodule formation significantly varied with the nature of the particles added. Bacteria stimulated nodules were larger, more compact and more regular in shape than aggregations formed in the presence of latex beads or fixed erythrocytes. The results are discussed with respect to investigations on cytokines, attraction factors and gap junctions in other invertebrates.

Animals↗

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Curative effect of split low dosage total-body irradiation on murine AIDS induced by Friend virus: the results and the possible mechanism.

Mice infected with Friend Leukemia Virus (FLV) rapidly develop erythroleukemia and severe immune deficiency which resembles human AIDS. We have reported that mice infected with a lethal dose of FLV can be 100% cured by 150 cGy total body irradiation (TBI). This curative effect was associated with restoration of cellular immunity which was compromised by the virus. This restoration may result from activation of the IFN-gamma system and IL-2 production. Our research work further demonstrated that no spleen focus-forming virus (SFFV) specific mRNAs, no 6.0kb SFFV fragments and SFFV envelope glycoproteins were detectable in FLV-infected mice treated with low dose TBI. Predicated on our report, del Regato has initiated clinical trials to treat AIDS patients with low dose TBI. The preliminary results are encouraging and the study is continuing. We have also studied the effects of low dose TBI on the expression of the P53 gene. The results show loss or inactivation of P53 tumor suppressor genes in FLV-infected mice, but P53 expression was restored in FLV-infected mice treated by low dose TBI. It is intriguing to speculate that in the curative effect of low dose TBI on mice infected with retrovirus, the P53 tumor suppressor gene may play an important role. It would be of interest to see if this type of treatment, which was well tolerated by mice, would be beneficial in other types of virally induced disease, including AIDS.

Animals↗

PubMedDate not supplied

Naturin: a potent bio-immunomodifier in experimental studies and clinical trials.

A number of traditional Chinese medicinal herbs have become extremely interesting in the search for potential BRMs in the international medical community, especially in the United States and Japan. Naturin, a new Chinese medical herb produced by XingYa Pharmaceutical Co., Ltd., has enhanced immune response, inhibited tumor metastases and retroviral infection in animal models as well as in clinical studies. The results demonstrated that the inhibition of Natural Killer (NK) and Lymphokine-activated Killer (LAK) cell activity and lymphocyte proliferation was compromised by tumor metastases and retrovirus infection (Murine AIDS), even immunosuppression induced by surgical amputation can be restored by Naturin. It is also shown that Naturin can protect the mice from lethal total body irradiation. These studies indicated that Naturin possesses immunomodulatory effects in vivo for a broad range of stresses. The results of the clinical studies on Naturin have demonstrated: (a) significantly improved symptoms of patients, including MDS, acute and chronic leukemia, aplastic anemia, lung cancer, and association with the increased number and percentage of CD4 (Helper T-cell) which have been reduced in some patients, (b) Lymphocyte proliferation and NK cell activity which were suppressed in cancer patients can be significantly restored by Naturin treatment, (c) the addition of Naturin treatment to patients receiving radiotherapy and chemotherapy augments immune response and reduces radiation and chemotherapy injury, and (d) no cytotoxic side effects were found in patients given Naturin treatment for up to eight months.

Animals↗

PubMedDate not supplied

The retinoblastoma gene: its role in cell cycle and cancer.

The retinoblastoma gene is the prototype of the tumor suppressor genes, which play critical roles in the genesis of cancer in humans. Although the precise function of the retinoblastoma gene product remains unknown, recent data suggests that it plays dual roles in gating cell cycle progression and promoting cellular differentiation. The molecular mechanisms involved in these roles are becoming clear in some biological systems: pRb binds and sequester several transcription factors to regulate entry of cell cycle and to initiate terminal cellular differentiation. However, it is difficult to rationalize the expression of pRb in a wide range of tissues with the fact that only limited cell types are susceptible to tumor formation when Rb expression is lost. Recent characterizations of Rb-associated proteins may provide some clues as to how Rb function may be differentially modulated in a cell type-specific manner.

Cell Cycle↗

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Crowding.

Crowding is the situation in which case a large number of animals, including man, are restricted in environmental space. Such an occurrence may start with just a few animals. In plants, including bacteria in culture, agriculture may be considered as an artificial example of this process. We see the ontogenic forms of crowding developing from stress into superorganisms (such as certain social insects) and from stress into pathological crowding in animals, plants and man. Crowding is shown by environmental changes such as in the introduction of new species of certain rodents and lagomorphs into the Australian environment. Aspects of crowding play a role during the housing of zoos, domestic or laboratory animals. Space limitations and overpopulation initiates stress and infections such as tuberculosis and tumours. This is found in man himself in the development of slums through to urbanisation as seen in Asia particularly, in prisons, in the workplace, in the school or home.

Animals↗

PubMedDate not supplied

Cell culture observations of human postnatal thymic epithelium: an in vitro model for growth and humoral influence on intrathymic T lymphocyte maturation.

Sixteen postnatal human thymuses were obtained at the time of corrective cardiovascular surgery and maintained in vitro as separate cultures of thymocytes and reticulo-epithelial (RE) cells. The stages of differentiation of the thymocytes were investigated in situ with a library of 10 monoclonal antibodies (MoABs) directed against human lymphocyte differentiation antigens. Employing immunofluorescence staining and flow cytometric (FACS) analysis, in vitro immunophenotype (IP) changes were demonstrated, which appeared after use of a combination of mitogen (PHA), recombinant interleukin-2 (rIL-2) and autologous thymic RE cell culture supernatants. RE cell supernatant participated in increasing the expression of the IL-2 receptor (IL-2R) during combined stimulation with phytohaemagglutinin (PHA) and rIL-2. Thymocyte proliferation was measured in 4 hour tritiated-thymidine (3H-TdR) incorporation (proliferation) assay. We were able to isolate the thymic nurse cells (TNC) with and without enzymatic tissue digestion. TNCs were separated from accompanying thymocytes and cultured. They grew as large, sometimes connected cells, but did not display the epithelial type of tissue organization. After in vitro culturing, the cytoskeleton of TNCs expressed high molecular weight cytokeratin and vimentin and intracytoplasmic tonofilaments, characteristic of epithelium. Whole thymic tissue pieces were cultured with and without previous trypsinization. The initial outgrowth of the cuboidal epithelial tissue layer occurred within 24-48 hours, and the RE cells remained functionally active for at least 15 days. RE cell supernatants were collected daily for two weeks and used in thymocyte differentiation experiments. The results indicated that thymic humoral factors contribute to a select, not fully understood differentiation pathway of thymocytes: a) more mature immunophenotype (IP) characterized by CD3 expression; b) de novo synthesis of interleukin-2 receptor (IL-2R); and; c) differentiation of the CD8+ subpopulation, identifying regulatory cells within the two major CD8+ and CD4+ subsets. Use of mitogenic (PHA) stimulation, after 5 days in vitro, resulted in a T helper (CD4+) oriented differentiation pathway of cortical thymocytes. At the same time, the cultured thymocytes expressed CD11 de novo, an early thymocyte differentiation antigen, and CD7, a marker not present on mature peripheral lymphocyte subsets (the IP changes demonstrated a dedifferentiation). Our overall impression, following the studies with the proliferation assays, was that in our experimental in vitro model, thymic hormones did not contribute to the induction of generalized thymocyte proliferation.

Antigens, CD1↗

PubMedDate not supplied

Immunophenotypic characterization of human primary and metastatic melanoma infiltrating leukocytes.

During a systematic screening of melanoma infiltrating mononuclear and polynuclear immunological effector cells we employed 10 well characterized monoclonal antibodies, directed against leukocyte differentiation antigens, and the alkaline phosphatase conjugated, indirect, streptavidinbiotin immunocytochemical antigen detection technique and when necessary, the recently developed antigen retrieval method to enhance the intensity of the immunoreactivity to characterize the heterogeneous infiltrate of human primary (n = 30) and metastatic (n = 10) melanomas. Our study is the first to employ formalin fixed, paraffin embedded tissue sections in seeking to determine the ex vivo presence of tumor infiltrating leukocytes, including T lymphocytes, in human melanomas. We established the presence of some type of melanoma infiltrating host's immunological effector cells in all 40 observed melanoma cases'. More specifically, we found NK cells, macrophages and granulocytes in 30 out of 30 PMs and 10 out of 10 MMs. These effector cells represented the vast majority (> 80%) of the melanoma infiltrating immunocompetent cells. T lymphocytes were observed in 20 out of 30 PMs and 6 out of 10 MMs, but their numbers represented only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cells were found in 22 out of 30 PMs and 8 out 10 MMs, their numbers representing less than 5%. Presence of cells of the dendritic reticulum, involved in antigen presentation was not determined in any of the observed PMs and MMs. There were more than enough macrophages and neutrophils, cells which are deeply involved in antigen presentation and, as previously mentioned, we found these cells within the melanomas. Thus defective antigen presentation cannot be the reason for the small proportion of T lymphocytes. What is to blame is probably the increased dedifferentiation of the melanoma immunophenotype (IP) to a degree that MHC class I molecules and the antigens complexed with them are lost and therefore there is nothing to be recognized by the T lymphocytes. In view of these results it is our-opinion that following the initial non-specific immune reaction, which may not be tumor specific, the specific immune response of effector T cells takes over. After significant IP changes by the majority of melanoma cells, including the internalization or shedding of MHC class I antigens, these highly specialized cells are no longer effective and the immune system responds by causing the reappearance of NK cells, macrophages and granulocytes. Thus, the relationship between melanoma and the host's immune system is evolutionarily dynamic: changes are readily made by either side when necessitated.

Antibodies, Monoclonal↗

PubMedDate not supplied

Clinical and prognostic significance of Ki-67 and proliferating cell nuclear antigen expression in childhood primitive neuroectodermal brain tumors.

The cell proliferation activity of sixteen childhood primitive neuroectodermal tumors (PNETs) was observed immunocytochemically, to determine the cell kinetics and cell proliferation activity of these relatively undifferentiated, malignant brain tumors. Two mouse anti-human monoclonal antibodies (MoABs) were employed for the detection of the nuclear antigen (Ki-67) present during proliferation in frozen sections and proliferating cell nuclear antigen (PCNA) expression in formalin fixed, paraffin embedded tissue sections. A sensitive four step, indirect, streptavidin-biotin, alkaline phosphatase (AP) conjugated, immunocytochemical experimental technique, was used. The anti-Ki-67 MoAB which binds to a special nuclear antigen, identified its expression only in proliferating cells. This nuclear antigen was detectable during the whole mitotic cycle of all malignant and fast proliferating cells, only absent between and during phases G0 (resting phase) and the first gap phase (G1). The mean labeling index (MLI) was defined as the percentage of Ki-67 and PCNA antigen positive cells of the total number counted. The MLI for the PNETs ranged between 1.4% and 11.6%, with a mean MLI of 6.2% for Ki-67; and between 3.2% and 16.8%, with a mean of 9.74% for PCNA. All observed PNETs demonstrated heterogeneous nuclear stainings, but the highest MLIs were found among the poorly differentiated classic medulloblastomas (over 30% for the Ki-67 antigen and 46% for PCNA). MLIs were low in 5/13 PNETs (under 4% for antigen Ki-67 and 9.4% for PCNA) and in this group we defined our lowest (1.4%) MLI, suggesting the presence of in vivo neuritogenesis of these undifferentiated, embryonal tumors. MLIs in 6/13 PNETs were intermediate in magnitude. The MLIs were higher in two PNETs with clear cellular differentiation towards an ependymal (10.4%) and melanocytic (8.8%) direction. Formation of astrocytes within the tumor mass did not affect the intermediate character of the MLI (7.8%). The prognosis of every intracranial tumor is obviously correlated with its proliferation activity and cell kinetics. The clinical significance of these parameters is great since they provide direct information concerning the growth characteristics of an intracranial tumor.

Adolescent↗

PubMedDate not supplied

Immunohistochemical detection of p53 protein overexpression in primary human osteosarcomas.

Detection of p53 expression has been reported to be associated with poor prognosis in a variety of human malignancies. The aim of the current study was to utilize immunocytochemical antigen detection techniques to search for evidence of altered p53 protein overexpression in 43 primary osteosarcomas (OS). The study was carried out on formalin fixed, paraffin-wax embedded 3 to 4 microns, previously decalcified OS tissue sections. A four step biotin-streptavidin based method was employed with peroxidase conjugation as the enzymatic label. Presence of a frequent level of p53 protein expression was detected in all 43 primary osteosarcomas, suggesting a frequent p53 gene mutation. p53 protein alterations were also associated with all grades of cell microenvironment heterogeneity in the observed OSs. Overexpression of the p53 protein was detected in 31/43 (72%) primary OS cases. Formalin fixed and paraffin-wax embedded human breast carcinoma tissue sections were employed as positive control tissue. p53 protein absence was demonstrated in normal postnatal thymus, serving as the negative control tissue. Our results lead us to the following conclusions: a) the altered p53 gene product is detectable employing the chosen mouse anti-human MoAB in decalcified, formalin fixed, paraffin-wax embedded, routine tissue sections of OSs and breast carcinomas which provides an opportunity for numerous retrospective studies and comparison with additional immunodiagnostic indicators; b) primary OSs with similar cell differentiation may be genetically heterogeneous; c) p53 gene or protein alterations represent early, immunodiagnostic markers of a malignant immunophenotype (IP) in various human neoplasms, including OSs; and d) immunomorphological techniques and in situ hybridization should be employed as methods to collect data for computerized, quantitative image analysis (IA) of the cellular accumulation and localization of the altered p53 protein.

Animals↗

PubMedDate not supplied

Nm23/nucleoside diphosphate (NDP) kinase expression in human malignant melanomas: significance and implications in tumor biology.

The nm23/NDP kinase gene located on chromosome 17q has been proposed as metastasis suppressor gene in a variety of tumor types. Nm23 was initially isolated from the highly metastatic murine K-1735 melanoma cell line and levels of nm23 have been found to correlate inversely with metastatic potential in some tumors, but not in others. In the present immunocytochemical study, we investigated nm23 protein expression in 30 primary cutaneous malignant melanomas (CMs) and 10 metastases of malignant cutaneous melanomas (MMCMs) which had already metastasized to a distant site. We employed a sensitive, indirect, four to six step alkaline phosphatase conjugated biotin-streptavidin based immunocytochemical technique using the anti-nm23 affinity purified rabbit anti-human polyclonal antibody on formalin fixed paraffin embedded tissue sections of the malignant melanomas. We found nm23 expression in 24 out of 30 CMs with between 10% and 50% of the melanoma cells exhibiting immunoreactivity with the employed antibody. None of the ten MCMMs expressed nm23. As we described in a previous article (48), malignant melanoma is characterized by a high degree of cellular immunophenotype heterogeneity. In further support of this observation, we observed a diverse level of nm23, staining intensity in the cell subpopulations which comprises the tumor microenvironment. Nm23/NDP kinase has a diverse array of biological functions including roles in signal transduction and microtubule assembly. In our opinion, the many roles of nm23/NDP kinase are mainly involved in cell division and this may be the underlying reason that levels of this protein do not truly correlate with metastatic potential. Therefore, nm23 protein levels may correlate well with proliferative rate and degree of tumor specific dedifferentiation which are important parameters to be established in the early diagnosis, monitoring of neoplasma progression and efficacy of employed clinical trials, and the determination of prognosis of every neoplastic disease.

Animals↗

PubMedDate not supplied

Development of Hassall's bodies of the thymus in humans and other vertebrates (especially mammals) under physiological and pathological conditions: immunocytochemical, electronmicroscopic and in vitro observations.

The histogenesis and cell structure progression of Hassall's bodies (HB) was observed employing light and electronmicroscopic histochemical methods in 212 human and 100 dog fetuses at various stages of ontogenesis. Several human pre- and postnatal thymuses were investigated immunohistochemically, employing a library of over 50 poly- and monoclonal antibodies, seeking to determine the cell origin of HBs. The organization of optimal microenvironmental conditions in the thymus requires the added participation of the neural crest. Spontaneous or experimental ablation of the neural crest during early ontogenesis results in abnormal thymic organogenesis. The reticulo-epithelial (RE) cells of 25 postnatal thymuses were also observed under various tissue culture conditions. The development of the first HB was detected on the 38th day of gestation in dogs and during the second part of the third intrauterine lunar month in human fetuses. The greatest developmental progression and main cell-tissue organization of the HBs was observed between 45 and 54 days of gestation in dogs and between 6 and 10 lunar months in humans. During thymic ontogenesis, the HBs appear when lymphopoiesis is already established and the cortex, medulla and the cortico-medullary junction are capable of conducting the positive and negative selection of T lymphocytes undergoing progressive maturation. The HBs are structurally organized from medullary RE cells, which usually undergo hypertrophy prior to their inclusion in the outer cell layer of the corpuscles. The cellular microenvironment of the thymic medulla is composed of networks of cell types, of a variety of origins, and all of them may participate in the construction of growing, progressive HBs. Histochemically, we detected a rich content of basic non-histone proteins, PAS positive substance (glycogen and acid mucopolysaccharides within the bodies. Employing the histological stain of Pasini and immunocytochemical methods with monoclonal antidodies (MoABs) AE2 and AE3, high molecular weight (56.5 to 67 kD) basic keratins were defined in human HBs. Employing a panel of MoABs developed against epithelial cell surface antigens (provided kindly by Dr. Haynes), we observed immunoreactivity localized to the outer cell layer of the HBs with MoABs TE8, TE16 and TE19, while the centrally located cells reacted positively with TE15 and TE19. Immunoreactivity employing the TE8, TE16 and TE19 MoABs was also observed in the epidermal granulosa cell layer, while TE15 reacted with cells of the stratum corneum. The presence of endocrine, peptide secreting RE cells within the HBs was defined with the use of MoAB A2B5, which binds to the GQ ganglioside. The hypertrophied, physiologically active RE cells of the peripheral cell layer of the HBs reacted positively with medium to strong intensity when stained with MoABs UJ127.11, J1153, A2B5, 215.D11, and 275.G7. These results further suggest that HBs are not exclusively degenerative structures. Our transmission electronmicroscopical (TEM) studies on HBs determined the existence of groups of RE cells connected to one another by desmosomes. We also observed long cytoplasmic processes originating from medullary RE cells and directly contacting thymic T lymphocytes and accessory antigen presenting cells (macrophages, dendritic cells, interdigitating cells, Langerhans cells, etc.) by the use of scanning electronmicroscopy (SEM). During our observations on human thymic organ and tissue cultures, no development of HBs could be registered. It is possible that additional cell to cell interactions with cells of different derivations may be necessary for the development of HBs. Thus, our results indicate that the HBs are unique, antigenically distinct, functionally active, multicellular components of the nonlymphocytic, cellular microenvironment of the thymic medulla, and participate in the physiological activities of the prenatal and adult thymus.(ABSTRACT TRUNCATED)

Animals↗

PubMedDate not supplied

Immunohistochemical detection of p53 protein expression in various childhood astrocytoma subtypes: significance in tumor progression.

Detection of p53 protein expression and overexpression has been reported to be associated with poor prognosis in a number of human malignancies. The aim of this study was to utilize immunocytochemical antigen detection techniques to search for evidence of abnormal p53 protein accumulation in ten human childhood astrocytoma (ASTR) subtypes (five pilocytic, two pure anaplastic, one anaplastic ASTR with primitive neuroectodermal tumor elements, one ASTR containing a majority of oligodendrocytes and one glioblastoma multiforme). The immunocytochemistry was carried out on routine, formalin fixed, paraffin-wax embedded 3 to 4 microns thick ASTR tissue sections. A four step, indirect, biotin-streptavidin based method was employed with peroxidase enzyme conjugation. Surprisingly, p53 protein expression was demonstrated in all ten ASTRs. The immunoreactivity pattern was mostly heterogeneous, with cells groups of similar intensity clustered within the ASTRs. The number of cells stained and the intensity of the immunoreactivity correlated directly with the known degree of malignancy of the various subtypes of ASTRs: lowest in the pilocytic ASTR cases and highest in the glioblastoma multiforme. Low-grade human ASTRs possess an intrinsic tendency for cell dedifferentiation toward the embryonic cell immunophenotype (IP). Loss of p53 function is associated with most, if not all, human malignancies. Mutation of p53 has yet to be demonstrated in pilocytic ASTRs. The accumulation of p53 in some pilocytic ASTR cells, as demonstrated in our study, suggests that the mere dysfunction of the p53 protein may be involved in the ealry stages of ASTR progression from the grade I pilocytic subtype to the more "malignant" pure ASTR, which is characterized by p53 gene mutations. The loss of p53 provides the necessary genetic instability needed for further IP changes and further progression towards more malignant IPs, e.g. anaplastic ASTR and glioblastoma multiforme. Such facts make the use of p53 in the assessment of ASTRs indispensible. p53 levels may be used in identifying cell clones within pilocytic ASTR microenvironments, which have a clear tendency for progression toward more malignant IPs and the establishment of the alteration of the p53 gene in more advanced ASTR subtypes (grades II to IV).

Animals↗

PubMedDate not supplied

Immunocytochemical detection of the p170 multidrug resistance (MDR) and the p53 tumor suppressor gene proteins in human breast cancer cells: clinical and therapeutical significance.

The phenomenon of multidrug resistance (MDR) is characterized by resistance to several unrelated cytotoxic agents, such as anthracyclines, vinca alkaloids and epipodophylline derivatives. MDR has been described frequently in human breast carcinoma (BC), as has the alteration of the p53 gene, responsible for ensuring the integrity of the genome. The most well known type of MDR is associated with the overexpression of a 170kD glycoprotein (p170). This mechanism of MDR is the result of increased transcription of the mdr 1 gene. The p170 glycoprotein in normal cells with excretory functions is a permanent component of a membrane transport system and an increase in its expression, such as that which occurs in neoplastically transformed cells, results in increased drug efflux and decreased intracellular drug concentration. The present immunocytochemical study was carried out on routine, formalin fixed, paraffin-wax embedded, 3-4 microns thick tissue sections of 15 breast carcinomas, treated at the University of Southern California. The immunoperoxidase antigen detection protocol, developed by Hsu et al (1981) was employed using three anti-p170 monoclonal antibodies (MoABs), JSB-1, C-219 and C-494 (Signet Laboratories, Dedham, MA, USA), and the anti-p53 MoAB PAb1801 (NeaMarkers, Inc., Fremont, CA, USA). 14/15 BCs contained large proportions of cells which displayed the characteristic transmembrane localized expression of p170. All 15 BCs were comprised of distinct groups of cells which accumulated p53 in their nucleus and occasionally in their cytoplasm. A distinct, heterogeneous immunophenotype (IP) of the cells comprising the tumor microenvironment and different grades of neoplastic differentiation was also observed. In 5/15 BC cases intense immunoreactivity, correlating with p170 overexpression, was detected. The 15 BCs exhibited different staining patterns typical for each anti-p170 MoAB. MoAB JSB-1 reacted strongly with the transmembranic antigen epitope, as did MoAB C-494, the long incubation time employed with MoAB C-219, on the other hand, resulted in inhomogeneous cytoplasmic staining. Previous reports suggest a direct correlation between the presence of the p170 glycoprotein in human cancer cells and the poor response to chemotherapy. Furthermore, the genetic instability, which is the consequence of the loss of wild-type p53 function, may be the underlying property which allows highly malignant cells to amplify the mdr 1 gene and thus become resistant to a wide spectrum of cytotoxic drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Clinical and prognostic significance of the expression of the c-erbB-2 and c-erbB-3 oncoproteins in primary and metastatic malignant melanomas and breast carcinomas.

Several growth factors and proto-oncogenes play a leading regulatory role during human carcinogenesis. In this systematic immunocytochemical study we observed the expression (overexpression) of the c-erbB-2 and c-erbB-3 oncoproteins in 30 primary cutaneous malignant melanomas (CMMs), 10 already metastasized malignant melanomas (MMMs) and 15 lymph-node negative breast carcinomas (BCs). Both oncoproteins were expressed as a result of either oncogene amplification or post-translational stabilization c-erbB-2 alone is unable to bind neuregulins, but it is able to act as a pan c-erbB receptor subunit. Heterodimerization between cerbB-2 and c-erbB-3 is required to initiate neuregulin directed signal transduction. We employed an indirect, four step streptavidinbiotin conjugated immunocytochemical technique for antigen detection. The visualization of the primary antigen-antibody reaction was carried out with alkaline phosphatase or immunoperoxidase labeling and the use of the appropriate enzymatic substrates. The presence of c-erbB-2 oncoprotein was detected in 12/30 CMMs, 8/10 MMMs and 6/15 BCs, while c-erbB-3 was identified in 14/30 CMMs, 7/10 MMMs and 6/15 BCs. The intensity of the cell membrane localized immunoreactivity was observed to be greater when the c-erbB-2 oncoprotein was targeted (A, AB and B). The c-erbB-3 oncoprotein was also detected in the cytoplasm with medium intensity (B, BC and C). Unfortunately, little is known concerning the range of oncoprotein overexpression after formalin fixation and paraffin embedding. We demonstrated overexpression localized to several cell clones within the oncoprotein positive population of malignant cells. The immunocytochemically defined extent of expression of both oncoproteins was between 10-40% (+ to +2) of the total cell population in the malignant melanomas and 20-35% (+2) of the total cell population in the BCs. In conclusion a) the results of the present study demonstrate the presence of c-erbB-2 and c-erbB-3 oncoprotein expression (overexpression) in melanoma and breast carcinoma, and b) oncogene receptor directed immunotherapy, as part of a more individualized anti-cancer treatment, represents a potentially valuable targeted treatment for the future.

Breast Neoplasms↗

PubMedDate not supplied

Antibacterial immune response in Astacus leptodactylus (Crustacea, Decapoda).

Antibacterial substances (ABS) in the hemolymph of Astacus leptodactylus were studied by agar-plate lysis and inhibition tests. The results demonstrate ABS against Gram-positive and Gram-negative bacteria. ABS against Gram-positive bacteria were identified as a lysozyme with a molecular weight of 14 kDa, heat resistance (< 50 degrees C) and lability to freezing. ABS against Gram-negative bacteria lost 50% of their activity at 50 degrees C and completely at 70 degrees C but were stable to freezing. Both ABS are inducible; they are produced and stored in the granular and semigranular hemocytes. Lysozyme is found in treated and untreated animals, ABS against Gram-negative bacteria only after induction.

Animals↗

PubMedDate not supplied

Immunocytochemical detection of prostate specific antigen expression in human primary and metastatic melanomas.

Prostate-specific antigen (PSA), a 33 kD glycoprotein, was initially reported to be a tissue specific protein, detected in the seminal fluid and produced by normal and abnormal epithelial cells of the prostate gland, as well as other tissues in the human body. The expression of PSA has been described to be elevated during benign and neoplastic cell growth in the prostate, and in a number of other human malignancies. The presence and production of PSA in human primary cutaneous malignant melanomas (CMMs) and metastatic malignant melanomas (MMMs) has not been reported prior to the present study. We examined the expression of PSA employing a biotin-streptavidin based, alkaline phosphatase conjugated antigen detection technique in routine, neutral formalin fixed, paraffin-wax embedded, 3-4 microns thick tissue sections of 30 CMMs and 10 MMMs. Human postnatal thymic tissue, among others, was used as a negative tissue control, while normal prostate and prostate carcinomas (PCs) were included in the collection of antigen positive tissues. We observed the presence of PSA in 16/30 CMMs and 6/10 MMMs. The intensity of the staining was moderate (C to B) and localized to between 20% and 30% of the total tumor cell population in both CMMs and MMMs, with cells of similar immunoreactivity being clustered in groups within the tumor microenvironment. This result directly contradicts the previous opinion concerning the prostate epithelium specificity of PSA expression and production. The immunophenotype (IP) heterogeneity of malignant melanoma cells in further substantiated by the pattern of their PSA immunoreactivity. The establishment of the clinical significance of these findings necessitates further in vivo and in vitro research in malignant melanomas. PSA related, novel antineoplastic immunotherapy may also be recommended in the treatment of both CMMs and MMMs.

Adult↗

PubMedDate not supplied

Advances in the understanding of lung cancer.

Lung cancers still represent an incurable group of malignancies, where we have to admit that therapy, be it surgery, chemotherapy or radiation, still fails. The emphasis in research has centered on exogenous factors causing the initiation and progression of the different types of lung cancer, especially exposure to tobacco smoke. But so far we have learned that endogenous factors play an equal, if not a more important role, in the onset of this group of diseases. Cancer arising spontaneously never appears to be due to one specific factor, but experimental cancers have been shown to do so. In this light, recent advances in molecular biology have pointed out the relevance of the role of oncogenes and tumor suppressor genes in the pathogenesis of lung cancers. It is the purpose of this paper to review these latest findings, especially from a genetic point of view.

Chromosome Mapping↗

PubMedDate not supplied

Immunocytochemical detection of prostate specific antigen expression in human breast carcinoma cells.

To date, no true tissue specific antigen has been discovered. Prostate-specific antigen (PSA) was initially reported to be a tissue specific protein, detected in the seminal fluid and produced by normal and abnormal epithelial cells of the prostate gland. PSA is a 33 kD glycoprotein, with serine protease activity, and it is produced by several different tissues in the human body. Its expression levels may be elevated during benign and neoplastic cell growth in the prostate, and in a number of other human malignancies. The detection of PSA is also useful in monitoring the efficacy of anticancer treatment in malignant prostatic adenocarcinoma. In the present immunocytochemical study, PSA expression was examined employing a biotin-streptavidin based, alkaline phosphatase conjugated antigen detection technique in 16 routine, neutral formalin fixed, paraffin-wax embedded, primary BC tissue sections. Human postnatal thymic tissue, among others, was used as a negative tissue control, while normal prostate and prostate carcinomas (PCs) were included in the collection of antigen positive tissues. We observed the presence of PSA in all 16 BC cases, and this expression was independent of estrogen receptor status. The intensity of the staining was moderate to high (B to A) and localized to 20% to 40% of the total BC cell population, with cells of similar immunoreactivity being clustered in groups within the tumor microenvironment. This result directly contradicts the previous opinion concerning the prostate epithelium specificity of PSA expression and production. The immunophenotype (IP) heterogeneity of BC cells is further substantiated by their PSA positivity and its association with the presence of steroid hormone receptors. The establishment of the clinical significance of these findings necessitates further in vivo and in vitro research in BCs. The prognostic significance of PSA in BCs may lie in the identification of a subset of estrogen receptor negative BC patients who have malignancies associated with a good prognosis. PSA related, novel antineoplastic immunotherapy may also be recommended.

Antibodies, Monoclonal↗