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Biomedical subjects

M Gerber

Publications and source records attributed to M Gerber.

At least 127 records · Page 7Linked to original sources

Radiosensitivity of murine T-lymphocyte cytotoxicity.

A biphasic curve was observed when surviving allogeneic lytic activity was plotted as a function of irradiation delivered before sensitization. Flow cytometry analysis demonstrated that the number of cells was reduced in response to increasing dose and that subset precursors Lyt 1+2+ were proportionally more radiosensitive than the other subsets. Paradoxically, the presence of exogenous T-cell growth factor (TCGF) in limiting dilution analysis changed the shape of the survival curve, and the mere addition of TCGF or Lyt 2- TCGF-producing cells abrogated the irradiation effect even though they were not shown to be the target of low dose irradiation in flow cytometry analysis. It is proposed that TCGF acted by enhancing the proliferation of surviving cells. This effect may be responsible for the relative radioresistance at higher doses due to enhanced availability of TCGF for the remaining cells.

Animals↗

Characterization of RNA transcripts and virally coded proteins synthesized in mouse fibroblasts transfected with hepatitis B DNA: HBeAg synthesis in HBcAg-negative cells with active core-antigen genes.

A line of mouse cells expressing hepatitis B virus (HBV) surface and 'e' antigens identical in their physico-chemical properties to antigens from patients infected with HBV was isolated after transfection of 3T3 cells with cloned HBV DNA. The studies reported here indicate that the cells contain uninterrupted copies of the entire HBV genome which are unmethylated on CCGG sites and have no gross deletions or rearrangements. The entire core region is transcribed into polyadenylated RNAs large enough to serve as messengers for production of viral core antigen (HBcAg) yet no HBcAg can be detected. This suggests that the cells produce a primary translation product copied from the HBcAg messenger which either cannot assume the proper configuration for display of HBcAg determinants or is rapidly converted to HBeAg by proteolysis.

Animals↗

Amplification of expression of hepatitis B surface antigen in 3T3 cells cotransfected with a dominant-acting gene and cloned viral DNA.

3T3 cells containing hepatitis B virus DNA sequences can be efficiently selected by exposure to methotrexate after cotransfection with cloned viral DNA and DNA coding for a methotrexate-resistant dihydrofolate reductase. More than 75% of methotrexate-resistant cells isolated after cotransfection with a head-to-tail tandem of the hepatitis B virus genome synthesized viral surface antigen. The antigen was released into the culture medium in the form of 22-nm particles with buoyant density of 1.20 g/ml. No other virally coded proteins were detected in the cells or the culture medium. Application of selective pressure by increasing the concentration of methotrexate resulted in an amplification of viral DNA sequences and a concomitant increase in the rate of synthesis and release of hepatitis B surface antigen. The ability to produce large amounts of surface antigen appears to be a stable trait and has been maintained in these cultures through more than 30 passages.

Animals↗

A clinical approach to brief dynamic psychotherapies in child psychiatry.

This paper reviews the position of brief psychotherapies in child psychiatry. Brief psychotherapy with children and families has received less attention than similar work with individual adults. After reviewing literature on brief dynamic psychotherapy with children and their families, the authors describe an approach which developed in an outpatient child psychiatry team. After a brief assessment, a focal hypothesis and plan of treatment are concluded. A decision is made as to which unit (the family group, an individual, or a combination of individuals) would be most strategic to treat. The authors coin the phrase "focal treatment unit" to express this concept.

Child↗

Cell-mediated immune response to syngeneic tumour growth and its inhibition by low doses of radiation in mice.

A T-cytotoxic response was demonstrated in a non-productive, viral-induced syngeneic tumoural system in vitro, but it did not result in tumour rejection: When tumour cell inoculum was removed surgically early after transplantation and processed, a specific T-cell-mediated cytotoxic response was observed in vitro and in the Winn assay; however, a tumour-cell challenge was rejected, showing that under certain conditions, the immune response can modify tumour evolution. Localized irradiation was administered according to one of two protocols (7 Gy X 3 over a week and 4 Gy X 3 over 3 weeks). The cumulative dose of the latter regimen was nearly 20% greater than that of the former; however, the outcomes of the two therapies were dramatically different: 50% survival in group 2, and a short delay in tumour growth in group 1. The scattered dose (of around 0.15 Gy) delivered to the spleen in the first group decreased the T-cytotoxic response, but that in the second group (scattering inferior to 0.07 Gy) did not. The similarity in therapeutic results in the two groups when the irradiation regimens were preceded by immunosuppression suggests that this failure of the immune response could influence the outcome of radiotherapy. The effect of low doses of irradiation on tumour rejection was also studied in an allogeneic system.

Animals↗

Significance of cytotoxic lymphocytes after various immunizing procedures in a virus-induced non-producer syngeneic system: correlation between in vitro and in vivo lytic activity.

An originally virus-induced, non-producer tumour system has been studied in relation to humoral and cellular cytotoxic responses to transplantation and other immunization techniques. In all experimental groups cytotoxic lymphocytes (CTL) were observed either directly or after mixed culture of lymphocytes and tumour cells (MLTC). Except for C'-dependent cytotoxic antibodies in mice immunized by irradiated cells, no antibody-mediated cytotoxicity was observed. In 2 protocols (transplantation and immunization by mitomycin-treated cells) CTL in vitro were not protective. In a third protocol (immunization by irradiated cells) CTL afforded partial protection and other factors appeared to be involved. The best in vivo protection was induced by immunization consequent on early surgical removal of a small number of transplanted tumour cells. This study provides lines of evidence for the effectiveness of protection supplied by CTL in well-defined conditions. Comparison with other modes of immunization indicated that these conditions were related to the quantity and to the characteristics of antigen involved.

Animals↗

[Effect on macrophages of acute stress induced in mice by local irradiation].

In examining the role of radiation in inducing immunosuppression in tumor-bearing Mice it has been shown that the experimental acute stress inadvertently generated by the procedure is profoundly immunosuppressive. It would appear that monocytes under the influence of glucocorticoïds are sequestered in the spleen. This monocyte immobilisation leads to rapid suppression of local inflammatory reactions including delayed hypersensitivity. The increased number of marcrophages in the spleen is co-incident with non-specific non T cell splenocyte anti-tumour activity. Stress induced suppression of inflammation is prevented by previous adrenalectomy and restored by hydrocortisone.

Adrenalectomy↗

Differential activation of hepatitis B DNA polymerase by detergent and salt.

Three patterns of activity were evident when the differential activation of the DNA polymerase associated with serum Dane particles by nonionic detergent and salt was investigated. The patterns were obtained by plotting the increase in enzyme activity mediated by the detergent Nonidet P-40 (NP-40) in increasing concentrations of KCl compared to the activity observed in the absence of detergent. The pattern of differential activity of hepatitis B (HB) DNA polymerase in detergent and salt was altered by subjecting the HBAg preparations to shearing forces. Hepatitis B DNA polymerase activity was stable even in NP-40 concentrations as high as 10%. In addition to hepatitis B DNA polymerase, DNA polymerase activated by calf thymus DNA was found in pellets containing Dane particles. The latter DNA polymerase activity was also activated by NP-40 and was not decreased by DNAse; this DNA polymerase coprecipitated with hepatitis B antigen (HBAg) upon addition of anti-HBs. However, the DNA polymerase activated by calf thymus DNA was inhibited by 0.4 M KCl. Electron microscopic observations of serum Dane particles in 0.4 M KCl showed no alterations of morphology of these particles when compared to particles in low-salt buffer. The data indicated that KCl activated HB DNA polymerase by a different mechanism from that of shear or NP-40, which removed the surface antigen coat from the Dane particles.

DNA-Directed DNA Polymerase↗

Peripheral photocoagulation in the treatment of disc neovascularization.

Forty-two eyes in 30 patients with disc neovascularization were treated by the method of extensive photocoagulation of the retinal periphery (ablation). Total obliteration of disc neovascularization was accomplished in 76% of eyes treated. Partial regression was noted in 21% of eyes treated. There were only 2 major complications--traction retinal detachment and one major hemorrhage--in this series. Feeder-frond treatment was necessary to obliterate recurrent disc neovascularization in 2 eyes. It is concluded that therapy is efficacious in the treatment of papillary neovascularization.

Adult↗

Growth stimulating activity in bovine pituitary extract specific for a rat mammary carcinoma cell line.

We report the isolation of a bovine pituitary growth factor (MGF) for a rat mammary carcinoma cell line, 64-24, which was isolated from a highly hormone-dependent mammary tumor. The MGF has been partially purified by a series of Diaflo ultrafiltration membrane sievings, isoelectric focusing and Sephadex columns. The MGF has a molecular weight of approximately 1,000 to 2,000 daltons and has a U.V. absorption spectrum typical for a polypeptide. Its isoelectric point is approximately pH 3.8-4.0. The factor is heat stable. The growth stimulating activity of the MGF does not stimulate other rat cell lines (22-1, RMG or HTC lines) but is specific for the 64-24 mammary tumor cell line. The MGF is not among previously reported pituitary hormones or growth factors.

Animals↗

Retinal vascular lesions in two patients with prolapsed mitral valve leaflets.

Two patients with retinal vascular lesions had mid-late systolic clicks on cardiac auscultation, suggesting the diagnosis of prolapsed mitral valve. The first patient demonstrated an inferonasal arteriolar branch occlusion secondary to embolization; the second patient had a central vein occlusion with multiple hemorrhages, glial proliferative tissue, and retinal neovascularization. This report describes the association between the prolapsed mitral valve syndrome and retinal vascular lesions.

Arterial Occlusive Diseases↗