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Biomedical subjects

T Klein

Publications and source records attributed to T Klein.

At least 145 records · Page 8Linked to original sources
PubMed1995

Assessment of the nucleolar organizer regions by automated image analysis in benign and malignant colonic tumours and adjacent tissues in rats.

An automated computer image analysis technique was used to study the morphological parameters of argyrophilic nucleolar organizer regions (AgNORs) in chemically induced rat colonic tumours of different grades. Different nuclear parameters were of different diagnostic value. For distinguishing tumorous tissue from normal tissue all the parameters studied were capable of serving as diagnostic markers. Malignant processes could, however, be more reliably detected by means of the area of the nucleus, nuclear shape factor, area of AgNOR and ratio of AgNOR area to nuclear area. In macroscopically normal tissue adjacent to a tumour, the values of all the AgNOR parameters studied were similar to those in tumorous tissues. It can be concluded that the initial stages in tumorigenesis are accompanied by changes in all of the nucleus and AgNOR parameters, but as malignancy develops, only some of these parameters continue to change. Close correlations between nuclear parameters in malignant tissue suggest that for diagnostic purposes only nuclear and AgNOR areas should be used.

Adenocarcinoma↗
PubMed1995

Allogeneic human liposomal melanoma vaccine with or without IL-2 in metastatic melanoma patients: clinical and immunobiological effects.

The aim of this pilot study was to assess the clinical and immunological effects of human allogeneic liposomal melanoma vaccine alone or combined with Interleukin-2 (IL-2) in patients with metastatic melanoma. Four concurrent treatment arms were included: vaccine alone (A); vaccine combined with systemic IL-2 (B); vaccine combined with low-dose liposomal regional IL-2 (C); and low-dose regional IL-2 as in group C but without vaccine (D). Vaccine was prepared from semisynthetic phospholipids (dimyristol phosphatidylcholine and dimyristol phosphatidylglycerol) and membranes of six human melanoma cell lines. The latter were chosen as expressing MHC class I and II antigens and a "mosaic" of melanoma-associated antigens (MAAs) as detected by MoAbs R24, p97, CF21 and TA99. Nine of the 24 patients had objective clinical responses: of the ten patients treated with liposomal vaccine and low dose regional IL-2 (arm C), three had complete responses (CR) and three had partial responses (PR); of the five patients treated with liposomal, low-dose regional liposomal IL-2 only (arm D), three had PRs. No clinical responses were seen in patients treated by vaccine alone (A) nor in patients treated by vaccine and systemic IL-2 (B). Patients' in vivo and in vitro cellular immune responses were closely monitored. Conversion to positive cutaneous delayed type hypersensitivity (DTH) to membrane vaccine (without liposomes) was induced only in the six clinical responders of arm C. Positive DTH correlated with augmented in vitro proliferative lymphocyte responses stimulated by melanoma cell lines and membrane preparation and with the augmented cytolytic activity against melanoma cell lines.

Adult↗
PubMed1995

Depletion of total salivary gland protein in blood-fed Anopheles mosquitoes.

Reduction in total salivary gland protein from four anopheline vectors of human malaria, Anopheles stephensi Liston, An. albimanus Wiedmann, An. gambiae Giles, and An. freeborni Aitken, was quantified after mosquitoes blood-fed to repletion on human volunteers, hamsters or through a Baudruche artificial membrane. Total salivary gland protein from pools of six unfed mosquitoes ranged from 4.33 to 7.91 micrograms/ml. The difference between the total protein of glands from unfed and blood-fed mosquitoes for all species ranged from 1.77 to 3.12 (micrograms/ml for six pooled salivary glands. Total salivary gland protein for mosquitoes blood-fed to repletion was significantly less than that of unfed controls from the same cohort. Reduction in total salivary gland protein for An. freeborni and An stephensi blood fed to repletion on human volunteers, hamsters, and a Baudruche membrane ranged from 24 to 46%, from 43 to 56%, and from 24 to 51%, respectively. An. stephensi mosquitoes were allowed to blood feed on humans for 0 (unfed), 0.5-, 1.0-, 2.0-min time periods or to repletion (> 2-5 min). As feeding time increased, there was a significant decrease in total amount of protein in the salivary glands. This decrease was proportional over time, indicating that salivation occurred continuously from the beginning (probing) of blood feeding to withdrawal of the mosquito mouthparts at repletion. These data indicate that during blood feeding there difference between species in the salivary gland output measured as amount of protein depleted from the salivary glands and that depletion of salivary protein from the glands occurred continuously as mosquitoes fed to repletion.

Animals↗
PubMed1995

The significance of soluble interleukin-2, soluble interleukin-2 receptors, soluble ICAM-1 and beta 2-microglobulin in breast cancer patients.

The serum levels of soluble interleukin-2 (sIL-2), sIL-2 receptors (sIL-2R), beta 2-microglobulin (beta 2M) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by the ELISA technique in 129 breast cancer patients and 40 controls. The median serum levels of sIL2-R, beta 2M and sICAM-1 were significantly higher and sIL-2 significantly lower than controls. sIL-2R, sICAM-1 and beta 2M levels were significantly higher in patients with metastatic disease compared to patients on long-term follow-up with no active disease. Initial study measurements of these markers could not identify patients at high risk for relapse. These findings suggest that the sIL-2R level is indicative of metastatic disease and together with other parameters of immune activation may be of help in monitoring disease activity in breast cancer patients.

Adult↗
PubMed1994

Selective inhibition of cyclooxygenase 2.

Cyclooxygenase (COX), a key enzyme in the formation of prostanoids, is known to exist in two isoforms: an inducible enzyme (COX 2) and a constitutive from (COX 1). Both enzymes are inhibited by non-steroidal anti-inflammatory drugs (NSAID), but only marginal selectivity has thus far been reported. In this study, we report on a novel selective inhibitor of COX 2, CGP 28238 (6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanon e). Human washed platelets were used as a source of COX 1. For IL-1 stimulated rat mesangial cells we demonstrated the almost exclusive presence of COX 2 in western blot and mRNA analysis. Therefore these two model systems were chosen for selectivity testing. With an IC50 value of 15 nM, CGP 28238 blocked COX 2 activity in a similar concentration range to that of other potent NSAID such as indomethacin and diclofenac (IC50 = 1.17-8.9 nM). However, in contrast to these reference NSAIDs, CGP 28238 was at least 1000-fold less potent in inhibiting COX 1. Using other cell systems reported to express COX 1 or COX 2, we obtained a similar selectivity for COX 2. Thus, on the basis of our findings, CGP 28238 is a novel, highly potent and selective inhibitor of COX 2 and may be a lead compound for a new generation of potent anti-inflammatory drugs with an improved side-effect profile.

Animals↗
PubMed1994

Natural killer cell activity in early human pregnancy.

Natural killer (NK) cell activity was determined in 41 women during the first trimester of pregnancy. NK cytotoxicity was similar between the study subjects and nonpregnant controls and was not a reflection of a change in the circulating number of cells or density in culture. Although NK cells may play a role in maternal immune status in advanced pregnancy, NK cells do not appear to be crucially involved in the first trimester, when reproductive wastage usually occurs.

Cytotoxicity, Immunologic↗
PubMed1994

The effect of irradiation on expression of HLA class I antigens in human brain tumors in culture.

The immunosuppressive effects of irradiation are well known; however, under certain circumstances irradiation also augments the local immune response by as yet undefined mechanisms. Because of the importance of HLA class I antigen in immune regulation and the fact that killing of tumor cells by cytotoxic T cells is HLA antigen-restricted, the authors studied HLA class I antigen expression in eight glioblastomas multiforme, four meningiomas, and four medulloblastomas. Twenty fragments of each tumor specimen were placed in short-term cultures immediately after resection. For each tumor, control Sample 1 was not irradiated. Sample 2 was irradiated on Day 1, and two groups of the remaining pieces of each tumor (specimens 3 to 10) were irradiated on two consecutive days. Escalating radiation doses were given, starting at 200 cGy/day for Sample 2 up to 1000 cGy/day for Sample 10. The total dose range was 200 to 2000 cGy. Corresponding nonirradiated tumor fragments served as controls. Four hours after irradiation, each sample was processed and stained for HLA class I antigen using the immunoperoxidase technique. The tumor cells were intensely stained in nonirradiated glioblastomas and meningiomas, whereas no staining was observed in medulloblastomas. In four of the eight glioblastomas and in all four meningiomas, irradiation augmented HLA class I antigen expression compared to controls. This effect was dose-dependent and was maximum in the 1200 cGy-treated specimens. No change was observed in the other four glioblastomas or in the medulloblastomas. The data suggest that irradiation does not decrease and may even induce HLA class I antigen expression in some brain tumors. This may be one of the mechanisms by which immunotherapy operates after irradiation. Further studies are required to elucidate optimum radiation doses and fractionation as well as optimum timing of immunotherapy.

Brain Neoplasms↗
PubMed1994

The expression of HLA class I antigen in prostate cancer in relation to tumor differentiation and patient survival.

The expression of HLA class I antigens was studied using the immunoperoxidase technique on 30 patients with prostate cancer and 29 patients with benign prostatic hypertrophy (BPH). Forty-three percent of the tumors stained positive, in contrast to 21% of the BPH. An inverse relationship was noted between class I expression and degree of tumor differentiation: 88% of the well-differentiated tumors (8/9) expressed class I antigen, compared with 33% (3/9) of the moderately differentiated and 16% (2/12) of the poorly differentiated tumors. No significant survival difference was found between those with class I-positive and -negative tumors. However, when both class I expression and degree of differentiation were considered, those with positive tumors at each level of differentiation had better survival than those with negative tumors. These data suggest that HLA class I expression may serve as a finite prognostic factor and may have relevance in future immunotherapy.

Adenocarcinoma↗
PubMed1994

[The relevance of health status for nursing home admission of elderly patients].

The article is based on a longitudinal study examining the risk of institutionalization in old age, especially with reference to the health status. According to the results, chronic disease only in interaction with old age has a significant impact on institutionalization. Other interactions for example between health status and housing conditions or between health status and marital status were not found. However, the age impact on institutionalization is not fully explained by other factors such as health condition. Altogether, healthy elderly people become institutionalized less often and later than elderly people who are either chronically ill or physically disabled or handicapped.

Aged↗
PubMed1994

Management of acyclovir-resistant herpes simplex and varicella-zoster virus infections.

Persons with AIDS who have CD4+ counts < or = 100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7-10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Increase in cytoplasmic free calcium in murine splenocytes following stimulation with anti-CD3 antibody in the presence of delta-9-tetrahydrocannabinol.

It has been previously shown that when mitogens such as concanavalin A (Con A) or phytohemagglutinin (PHA), are used to stimulate lymphoid cells which are treated with varying doses of delta-9-tetrahydrocannabinol (THC), the proliferation of splenocytes from mice of different ages is suppressed. In contrast, when these cells were stimulated with anti-CD3 antibody in combination with THC, lower doses of THC stimulated proliferation of the splenocytes. This stimulation occurred only if the spleens were obtained from adult (2 month) mice as opposed to cells from young (2 week) or aged (24 month) mice. In order to more completely understand this age related differential effect, mobilization of cytosolic free Ca2+ was studied in this system, using fluorescent Ca2+ probes and spectrofluorometry. It was found that adult splenocytes pretreated with anti-CD3 antibody responded to cross-linking by anti-IgG antibody with a further rise in intracellular free Ca2+. Such an increase in Ca2+ was not seen with cells derived from either young or old mice. A similar phenomenon occurred when 5 micrograms/ml THC was used in place of the anti-IgG antibody. Thus, adult spleen cells exposed to both delta-9-THC and anti-CD3 antibody displayed an increase in intracellular free calcium whereas spleen cells from very young mice failed to respond in this manner. Interestingly, when 11-hydroxy-THC, another metabolite of marijuana, was used instead of the delta-9-THC, no rise in intracellular Ca2+ influx was seen in any age group of mice tested. These results emphasize the differential effect of THC on splenocytes from individuals of different ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Distortion in the parental transmission of HLA-A2 haplotypes (locus A,B).

The parental transmission of HLA-2 antigen in association with the epitopes BW4 and BW6 (class I HLA haplotypes locus A,B) was analyzed in sons and daughters from 42 families in which one of the parents carried the HLA-A2 antigen. When the parental transmission of A2 BW4 and A2 BW6 was compared, it was observed that a significantly higher number of siblings inherited the haplotype A2 BW4 from the paternal than from the maternal haplotype. Although the number of cases is small, the mode of inheritance of haplotype A2 BW6 was completely different. The genetic distortion in the transmission of HLA-2 BW4 and HLA-2 BW6 was observed in children of both sexes.

Cytotoxicity, Immunologic↗
PubMed1993

A Minute encoding a ribosomal protein enhances wing morphogenesis mutants.

E(Dl)KP135 has been isolated previously as a recessive lethal Drosophila P element insertion line with a dominant enhancing effect on the phenotype of Delta, a gene encoding a surface membrane protein. We show here that this P insertion also enhances the wing phenotype of nd1, an allele of Notch encoding another transmembrane protein, the putative receptor of Delta, as well as that of if3, an allele of the integrin gene PS2 alpha. Moreover, we noticed that this P insertion causes a severe Minute phenotype. Molecular characterisation revealed that the P element disrupts the putative mRNA leader sequence of the ribosomal protein L19 gene. We tested further Minute genes and found that two of them, similarly to E(Dl)KP135, strongly enhance the nd1 wing phenotype. Our results suggest that the pleiotropic Minute syndrome can affect, probably indirectly, one or more steps of wing morphogenesis that involve surface adhesion of epithelial cells.

Amino Acid Sequence↗