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G R Krueger

Publications and source records attributed to G R Krueger.

At least 19 recordsLinked to original sources
PubMed1995

[Apoptosis and cell proliferation in HHV-6 infections. Regulatory mechanisms of p53/bcl-2/ras interactions].

HHV-6 infected immature T (HSB2) and Hodgkin (HDLM2) cells and biopsy tissues from lymph nodes of patients with Hodgkin's disease (HD) and Kikuchi lymphadenitis (KL) were studied immunohistologically for virus antigen expression and for the oncogene/anti-oncogene products ras, bcl-2 and p53. Cell proliferation and cell death were tentatively monitored in tissue culture by PCNA staining, by viability testing and in situ end labeling of fragmented DNA. PCNA was also used in biopsy samples. KL is characterized by high incidences of focal cell death (i.e. histiocytic necrotizing lymphadenitis), while HD is apparently more a proliferative disease. The techniques used revealed no significant differences in the cellular expression of viral DNA or antigens among cell lines, HD or KL. The HDLM2 cell line with the superior survival after HHV-6 infection showed a significantly lower expression of p53 and PCNA than HSB2 cells. Biopsy samples from patients with KL did not express p53, and ras and PCNA were observed in fewer cells than in HD. Bcl-2, however, was significantly more frequently seen than in HD. The interpretation of the data is difficult; they suggest that there are additional regulatory influences in control of cell proliferation and cell death, such as cytokines and growth factors, which are altered after viral infection. Also, virus-induced cell death probably includes other mechanisms besides apoptosis, such as cell damage caused by oxygen radicals.

Apoptosis↗
PubMed1995

[Initial studies of the prevalence of human Herpesvirus 7 (HHV-7) in Mexican blood donors].

Human herpesvirus 7 (HHV-7) has been recently isolated from CD4-positive peripheral blood lymphocytes of a healthy person. The present study was performed to find the antibody prevalence of this virus in the healthy Mexican population. Two hundred blood samples from candidates for blood donation at the General Hospital of Mexico were studied with the indirect immunofluorescence test (IFA) in HHV-7 infected SupT1 cells. 83.5% were male persons and 16.5% female, the mean age for the male group was 28.8 years and for the female group 31.5. The donors came from 12 different states in Mexico, predominantly from the city (60.8%), and had different occupations. Almost all samples (98.5%) were positive to HHV-7. Other studies done revealed 1% positive to brucella, 1% positive to Hepatitis B, 2% positive to syphilis, hepatitis C and HIV test were negative in the whole group studied. There was a high incidence of HHV-7 in the group studied: more than 50% of the subject had high titers. This results should be further studied determine titers indicative of an active infection and to search for any association with illnesses.

Adult↗
PubMed1994

p53 expression in the carcinogenesis in the oral mucosa.

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas. In the clinical treatment of these lesions it would be very important to be able to predict the biological behaviour of an individual lesion. In 64 hyperplastic lesions and 85 squamous cell carcinomas of the oral mucosa, the expression of the mutant tumor suppressor gene p53 was investigated. A positive correlation was seen between the expression of the mutant tumor suppressor gene p53 and the grade of dysplasia of the lesions.

Gene Expression↗
PubMed1994

p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa.

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. The purpose of this study was, therefore, to determine the role of alterations of the tumour suppressor gene p53, and the proliferation status of the lesions determined by PCNA expression. We investigated p53 and PCNA expression in 265 tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oral mucosa by immunohistology. Quantitative analysis showed a gradual increase in PCNA expression from normal mucosa to moderately differentiated SCC. p53 expression was detectable in benign premalignant lesions. The increase in the number of p53-positive biopsies was correlated with the dysplasia and loss of differentiation in the premalignant and malignant lesions.

Carcinoma, Squamous Cell↗
PubMed1993

Hodgkin's lymphoma-derived tissue serially transplanted into severe combined immunodeficient mice.

Hodgkin (H) and Reed-Sternberg (RS) cells are considered to be the malignant cell population in Hodgkin's disease (HD). To date, their analysis has been hampered by their scarcity in primary tumors, poor growth in vitro, and lack of an animal model. To establish an in vivo system for the characterization of the malignant cells in HD, tumor biopsy samples from 13 HD patients were transplanted beneath the renal capsule or into the liver of severe combined immunodeficient (SCID) mice. HD-derived tissue from three patients gave rise to human tumors in SCID mice. Three different histologic patterns were observed: (1) lymphoproliferative disease (LPD), (2) anaplastic large cell lymphoma (ALCL), (3) Hodgkin-like lesions (HDLL). Immunohistochemical analysis showed that the tumors consisted of activated B cells (CD30+, CD20+). Epstein-Barr virus (EBV)-encoded transcripts were found in 80% to 100% of the tumor cells, although H and RS cells in the primary tumors of two patients were EBV-. All tumors examined (3 of 3) and the majority (6 of 10) of cell lines recultured in vitro had an abnormal karyotype. Southern blot analysis of the human Ig heavy chain gene showed that monoclonal or oligoclonal tumors of different B-cell origin grew in the SCID mice from the same germ line-configurated primary biopsy specimen. Our data suggest that the human cells in the SCID mice have either been derived from EBV superinfected H and RS cells or from EBV-infected bystander cells. If the latter is true, then these bystander cells must be genetically abnormal. The genetic defect would be either aneuploidy or instable euploidy. In either case, the cells might proliferate into malignant aneuploid HDLL or ALCL under the influence of EBV and the special environment encountered in the SCID mice.

Adult↗
PubMed1993

Chronic Pneumocystis carinii pneumonia in AIDS.

The clinical and radiologic presentation as well as the macroscopic and histologic characteristics of lung parenchyma in three HIV-infected patients with Pneumocystis carinii pneumonia (PCP) are detailed. The distinguishing clinical feature in these patients was a prolonged stable clinical course of the disease over at least 4 to approximately 24 months. Serial chest radiographs in two patients demonstrated persistent focal radiographic lesions. In one patient blebs in both upper lobes were not recognized until thoracoscopy/thoracotomy was performed. Biopsy specimens of affected areas revealed extensive interstitial fibrosis, occasional giant cell reactions, and honeycombing. In view of the combined clinical, radiologic, macroscopic, and histologic patterns, it is suggested that these patients had a chronic productive form of PCP rather than the well-known acute presentation of the disease. Data from the literature confirm the impression that atypical histologic lesions of PCP, either of a productive or destructive nature, are frequently related to a prolonged clinical course. It is unlikely that prophylactic pentamidine contributes to this entity. Coinfection with other pathogens may have a role. Given the recent evidence on augmented release of tumor necrosis factor a (TNFa) in HIV-associated pulmonary complications, it is speculated that TNFa may be of importance in producing focal fibrosis in Pneumocystis infection of the lung.

AIDS-Related Opportunistic Infections↗
PubMed1993

Expression of interleukin-2R alpha and interleukin-2R beta in Hodgkin's disease.

Hodgkin and Reed-Sternberg cells, the putative malignant cells of Hodgkin's disease (HD), carry regularly the CD25 antigen that forms one chain of the interleukin-2 (IL-2) receptor (IL-2R alpha). To analyze the putative role of IL-2R expression in Hodgkin's disease, we have investigated the expression of both IL-2R alpha and IL-2R beta chains in HD-derived cell lines and in primary specimens from patients with HD. Expression of IL-2R alpha and IL-2R beta was detected in all HD-derived cell lines. In addition, soluble IL-2R alpha molecules were demonstrated in the supernatants of three of these cultured cell lines. In primary tissues, IL-2R alpha and IL-2R beta were seen in some but not all cases. Staining was detected in Hodgkin and Reed-Sternberg and in lymphoid cells. There was a remarkable difference in the pattern of expression, in that IL-2R alpha- but not IL-2R beta-positive cells from HD patients were clustered in frozen sections. We conclude from these data that IL-2R expression might be involved in the biology of HD.

Adolescent↗
PubMed1992

Hodgkin and Reed-Sternberg cells express interleukin 6 and interleukin 6 receptors.

Interleukin 6 (IL-6) is a pleiotropic lymphokine which can stimulate a variety of cells including B and T lymphocytes. It has been suggested that IL-6 plays a crucial role in several diseases such as human plasmacytoma, cardiac myxoma or Castleman's Disease by autocrine or paracrine stimulation. To analyse whether IL-6 is involved in the biology of Hodgkin's Disease (HD), we investigated the expression of IL-6 and IL-6 receptor (IL-6R) in cell lines and primary specimens from patients with HD. IL-6 specific transcripts were detected in three out of six HD derived cell lines by Northern blot analysis and in the culture supernatants of four HD derived cell lines by ELISA. Its biological activity was confirmed by proliferation of an IL-6 dependent cell line. By in-situ hybridization experiments IL-6 specific transcripts were detected in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues in two out of three patients. mRNAs specific for the IL-6 receptor were detected in five HD derived cell lines. Staining of HD derived cell lines revealed expression of the receptor molecules in five cell lines; Western blot experiments confirmed the 80kDa receptor protein in the cells. Immunohistology in primary specimens revealed expression of the receptor molecules on H and RS cells in 8 out of 16 cases with HD. Expression was mostly detected in the mixed cellularity subtype of HD. Elevated levels of IL-6 were detected in the sera of more than 50% of patients with HD. Taken together our data suggest that IL-6 might be involved in the biology of HD.

Adolescent↗
PubMed1991

Immunological dysregulation of lymph nodes in AIDS patients.

Changes in immune competent tissues of the HIV-1-infected person reflect to a certain extent the kind and intensity of immunological dysregulations. The diagnostic approach, however, must include immunophenotyping of cells, immunovirological studies of virus distribution in diseased tissues, and functional tests in addition to classical morphology. The latter technique alone just serves as a crude screening method since structural lesions in lymphoid tissues do not permit discrimination from other HIV-independent immune deficiency and autoimmune disorders. Although the overall appearance of lymph nodes in HIV infection and in chronic autoimmune disorders, such as collagen vascular diseases (e.g., rheumatoid arthritis and systemic lupus erythematosus), is similar, immunophenotyping shows a progressive loss of CD4 cells in HIV infection yet a quantitative increase in this cell population in autoimmune disorders (Krueger 1985a). In addition, there are other persistent active infections by lymphotropic viruses (e.g., EBV or HHV-6) which can cause structural and cellular changes in lymphoid tissues closely resembling HIV-induced lesions (Krueger et al. 1988b; Krueger 1985b). The pathological diagnosis therefore nedds to be supplemented by serological studies and--in selected cases--by in situ hybridization for the demonstration of viral genome. Southern blotting for viral DNA can only detect high numbers of viral genome copies in tissue extracts, not in which cell population the virus resides (e.g., malignant cells vs associated "normal" cells), while the polymerase chain amplification reaction, the most sensitive of all (Buchbinder et al. 1988), cannot yet differentiate between latent and (disease-related) active infection. Taking into consideration the above-described precautions in the evaluation of lymphatic lesions, there are a number of characteristic changes which reflect well the sequelae of HIV infection itself and of the ensuing immune dysregulation. Progressive loss of CD4 cells in the paracortex of lymph nodes and in the peripheral blood leads to inversion of the CD4/CD8 ratio. Loss of demonstrable CD4 cells is probably the consequence not only of cell lysis by HIV-1 infection (note: discrepancy between HIV-1 genome positive cell numbers and depletion of CD4 cells) but also of decreased CD4 marker synthesis in infected cells (Stevenson et al. 1987). In this context it is interesting that Fouchard et al. (1986) were able to show HIV expression in CD8 cells and theorized that these developed from infected CD4 cells which subsequently lost the CD4 epitope and expressed CD8.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

A rare cause of colitis--Brucella melitensis. Report of a case.

Documentation of gastrointestinal lesions in Brucella infections is sparse. A case of Brucella melitensis type 3 infection accompanied by erosive lesions of the colon, observed by endoscopy and histopathologic examination, is reported. Such gastrointestinal lesions have not been described since 1934. Before 1934 only postmortem observations are recorded.

Adult↗
PubMed1991

Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates.

Fifteen human herpesvirus-6 (HHV-6) isolates from normal donors and patients with AIDS, systemic lupus erythematosis, chronic fatigue syndrome, collagen-vascular disease, leukopenia, bone marrow transplants, Exanthem subitum (roseola), and atypical polyclonal lymphoproliferation were studied for their tropism to fresh human cord blood mononuclear cells, growth in continuous T cell lines, reactivity to monoclonal antibodies, and by restriction enzyme banding patterns. All isolates replicated efficiently in human cord blood mononuclear cells, but mitogen stimulation of the cells prior to infection was required. The ability to infect continuous T-cell lines varied with the isolates. Isolates similar to GS prototype infected HSB2 and Sup T1 cells and did not infect Molt-3 cells, whereas isolates similar to Z-29 infected Molt-3 cells but not HSB2 and Sup T1 cells. Some of the monoclonal antibodies directed against the HHV-6 (GS) isolate showed reactivity with all isolates tested, but others only reacted with HHV-6 isolates similar to the GS isolate and not with those similar to Z-29 isolate. Restriction enzyme analysis using EcoRI, BamHI, and HindIII revealed that HHV-6 isolates from roseola, bone marrow transplant, leukopenia, and an HIV-1-positive AIDS patient from Zaire (Z-29) were closely related but distinct from GS type HHV-6 isolates. Based on the above findings, we propose that, like herpes simplex virus types 1 and 2, the 15 HHV-6 isolates analyzed can be divided into group A (GS type) and group B (Z-29 type).

Antibodies, Monoclonal↗
PubMed1991

Increase of lipid fluidity and suppression of proliferation resulting from liposome uptake by human keratinocytes in vitro.

The in vitro effects of liposomes on HaCaT human keratinocytes were studied with regard to their uptake, lipid fluidity and proliferation of the cells. Oligolamellar liposomes, prepared from soya bean phospholipids, had a mean size of 150 mm and consisted predominantly of phosphatidylcholine (83%) and phosphatidylethanolamine (10%) and the fatty acids comprised mainly linoleic acid (66%) or other unsaturated fatty acids. After 6 and 24 h of incubation with 1 and 0.1% w/v of liposomal lipids, phase-contrast microscopy revealed marked cytoplasmic vacuolization of the cells. Keratinocytes treated with the liposomes contained aggregations of multilaminated lipid material without delimiting cell membranes. The cellular lipid fluidity (reciprocal of diphenylhexatriene fluorescence polarization P-value) correlated with liposomal concentration and incubation time. A significant elevation of lipid fluidity (P less than 0.05) was observed with 1 and 0.1% liposomes after 1 h of incubation (81.8 +/- 4.7 and 95.7 +/- 1.2% of control P value) and for 0.01% liposomes after 3 h (96.2 +/- 1.5%). Maximum fluidity occurred after 48 h of exposure to 1% liposomes (42.1 +/- 3.1%). Exposure to liposomal lipids for 24 and 48 h resulted in suppressed cell proliferation with 50% inhibition concentrations (IC50), being 0.06% for incorporation of [3H]-thymidine. 0.08% for [14C]-amino-acid incorporation and greater than 1% for protein content per well after 24 h of exposure. The cells were able to proliferate and lipid fluidity returned to normal within 7 days following discontinuation of incubation with liposomal lipids.

Cell Division↗
PubMed1990

[Acute pneumocystosis during polychemotherapy following the MACOP-B protocol].

Four out of eleven patients--none of them HIV positive--who received treatment for non-Hodgkin lymphoma by the MACOP-B protocol between June 1989 and February 1990 were taken ill during or shortly after the conclusion of the course with fulminant pneumonia necessitating artificial ventilation. In three cases Pneumocystis carinii was identified as the pathogen, and in one patient the diagnosis of pneumocystosis seemed probable. The mean cumulative doses given before the outbreak of pneumonia were as follows: cyclophosphamide 2753 +/- 1161 mg, methotrexate 1590 +/- 667 mg, bleomycin 36 +/- 16.8 mg and prednisone 4378 +/- 1734 mg. The mean haemoglobin concentration was 10.7 +/- 0.5 g/dl, leucocyte count 5250 +/- 2100/microliters, lymphocyte count 1300 +/- 300/microliters and lactate dehydrogenase 227 +/- 34 U/l. The cumulative doses and laboratory findings in the seven patients not affected by pneumocytosis were not significantly different. The patients with pneumonia were supported by mechanical ventilation for 6-26 days and treated with large doses of corticosteroids and co-trimoxazole. One patient died after 17 days' ventilation. Three patients were successfully weaned from the ventilator. Chemotherapy protocols such as MACOP-B predispose to acute Pneumocystis pneumonia. The risk of infection is independent of the cumulative doses of the drugs employed. For this reason, prophylaxis with co-trimoxazole is normally mandatory.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Cellular immunologic parameters in HIV-positive patients with AIDS-related complex and intravenous immunoglobulin therapy.

In a randomized double-blind longitudinal study with 30 HIV-1-positive patients with AIDS-related complex or stage Walter-Reed 5 disease, the effectiveness of intravenous immunoglobulin (IVIG) was tested for correcting eventual immune dysregulation. Although the IVIG-treated patients showed an improvement of their clinical score, no significant changes were observed in lymphocyte phenotypes, activation markers, immunoglobulins and subclasses, lymphocyte turnover or in indicators of acute inflammation. Since severe bacterial infections or autoimmune processes usually leading to IVIG therapy were not prevalent in the patients of the study, such therapy should probably be reserved for later stages of the disease. HIV-1 antigen expression in blood lymphocytes remained uninfluenced by IVIG treatment.

AIDS-Related Complex↗
PubMed1990

Analysis of immunoglobulin, T cell receptor and bcr rearrangements in human malignant lymphoma and Hodgkin's disease.

Rearrangements of immunoglobulin and T cell receptor (TCR) genes have been demonstrated in malignant lymphoid tumors of B and T cell origin. In Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphocytic leukemia cells the bcr and c-abl genes are reorganized and transcripts composed of both genes are expressed. We analyzed the organization of bcr, immunoglobulin and TCR genes in malignant lymphomas. Our data show that in all B cell lymphomas analyzed the JH genes and in some cases also the J kappa genes were rearranged. In a Burkitt lymphoma and in a Kil lymphoma distinct rearranged TCR gamma fragments were detected, in a second Burkitt lymphoma two rearranged TCR beta gene fragments occurred together with a rearranged JH gene fragment. In two T cell lymphomas rearranged TCR beta genes were observed; one of these lymphomas also carried rearranged TCR gamma and JH genes. In Hodgkin's disease in 3 out of 7 cases rearranged immunoglobulin genes were detected. In 1 case, which was diagnosed as a follicular hyperplasia, rearranged JH and TCR gamma fragments appeared. In none of the analyzed lymphomas could bcr rearrangements be observed.

Gene Rearrangement↗