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Biomedical subjects

R Goodman

Publications and source records attributed to R Goodman.

At least 127 records · Page 7Linked to original sources

In vitro effects of thymosin and lithium on lymphoproliferative responses of normal donors and HIV seropositive male homosexuals with AIDS-related complex.

The in vitro effects of thymosin fraction 5 (TF5) and lithium chloride (LiCl) on the ability of peripheral blood mononuclear cells (PBMC) obtained from 37 normal male donors and 33 male patients with AIDS-related complex (ARC) to respond to alloantigenic stimulation (mixed leukocyte reaction, MLR) and to produce interleukin 2 (IL-2) in response to mitogens were studied. TF5 significantly increased MLR responses in normal donors (P less than 0.01) and in a group of 33 ARC patients with depressed cellular immunity (P less than 0.05). Similar effects were observed when LiCl was added to the MLR assays in both the normal and the ARC patient groups. Furthermore, TF5 and LiCl exhibited additive immunoenhancing properties. In 10 normal donors TF5 enhanced phytohemaggutinin (PHA)-induced IL-2 production as well as IL-2 production in response to pokeweed mitogen (PWM) (P less than 0.02). TF5-mediated enhancement of IL-2 production by PBMC obtained from ARC patients was observed in response to both mitogens, i.e., PHA and PWM. Additionally, LiCl increased PHA-induced IL-2 production in both normal subjects and ARC patients. LiCl and TF5 together had an additive effect in the enhancement of IL-2 production in both groups of subjects. Our data extend previous observations regarding the immunoregulatory activities of TF5 and LiCl and provide evidence that PBMC obtained from ARC patients have the potential to respond in vitro to these agents. The significance of these findings is discussed.

AIDS-Related Complex↗

Sine waves enhance cellular transcription.

We previously showed that quasirectangular, asymmetrical, pulsed electromagnetic (EM) fields of low frequency can induce increased transcription in Sciara salivary gland cells. A symmetrical sine wave with the same frequency as known biologically effective asymmetric signals was studied in the present investigations. The results demonstrated that signal shape was not a major factor in causing augmented transcription. The pattern of grain density in transcription autoradiograms, as well as the size classes of RNA responsive to EM fields, was the same irrespective of asymmetry or symmetry of the signal. Following short-term exposure of the cells to either type of EM field, S values of new transcripts were consistent with those expected for processed and unprocessed messenger RNA.

Animals↗

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery: final report of an RTOG study.

This randomized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6-7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks (XRT + BCNU). One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks, radiation therapy to 60 Gy and BCNU (MISO + XRT + BCNU). Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics was comparable among the treatment groups. The median survival for XRT + BCNU was 55.0 weeks, and for MISO + XRT + BCNU 46.0 weeks (p = 0.35). With patients on a minimum dose of dexamethasone of 3 mg/d, misonidazole neurotoxicity included 8.8% peripheral neuropathy, 2.7% CNS toxicity, and a 0.68% ototoxicity. BCNU pulmonary toxicity occurred in 9.3% of patients who received 902-2062 mg/m2 of BCNU.

Adult↗

Split-course radiotherapy of carcinoma of the urinary bladder stages C and D1. A Radiation Therapy Oncology Group Study.

One hundred forty-eight patients with advanced carcinoma of the urinary bladder Stages C or D1 were randomized between continuous-course radiotherapy (6,000 cGy in 30 fractions of 200 cGy each, over 6 weeks) and split-course radiotherapy (2,750 cGy in 10 fractions of 275 cGy each, over 2 weeks; a rest period of 3 weeks; 2,750 cGy in 2 weeks); 139 are analyzed in this report. Ninety-four percent of the patients have been followed at least 5 years or until death. The patients ranged in age from 45 to 80 with a median of 69. Seventy-six percent of the patients were males and 58% had Stage C disease. In patients with information on the size of the tumor, in 66% the lesion measured 5 cm or larger; 26% had a diameter of 8 cm or larger. In general, the treatment groups were well balanced with respect to patient characteristics. Both treatment groups tolerated therapy well. Eighty-seven percent of the patients completed therapy, 66% as planned. Fifty-four percent experienced at least one severe reaction, with the most common types being diarrhea (28%), frequency of urination (24%), soreness or burning on urination (25%), and urgency of urination (19%). Late effects of therapy were minimal. Median survival times were 11.5 months and 9.4 months for continuous-course and split-course, respectively. The treatment differences were not significant (p = 0.88; Mantel-Haenszel stratified by stage and sex). Forty percent of the patients became free of all clinically detectable disease following radiotherapy either alone or in combination with additional surgery (40% for continuous-course, 4% cleared by surgery, and 39% for split-course, 3% cleared by surgery). When the tumor measured less than 5 cm, the clearance rate was 61% (20/33) vs. 33% (13/39) for 5-7.9 cm, and 24% (6/25) for 8 cm or larger (p less than 0.01; chi2 test for linear trend). For those who became disease free, median time disease free within the irradiated volume was 72 months for continuous-course and is currently undefined for split-course; median time disease free was 28 months and undefined, respectively. There were no significant treatment differences in tumor control for any of these endpoints. The ultimate long-term tumor control in the pelvis was 28% (19/68) for continuous- and 25% (18/71) for split-course therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Aortic valve endocarditis due to Salmonella enteritidis.

We have reported the fifth case of endocarditis due to Salmonella enteritidis and the first known survivor of native aortic valve endocarditis from this pathogen. Despite appropriate antibiotic therapy, aortic valve replacement was necessary because of heart failure and embolism. The patient also had concurrent viral hepatitis B infection.

Adult↗

Reduced epidermal Langerhans cell densities in patients with pulmonary malignancies do not correlate with anergy or nutritional status.

Epidermal Langerhans cell (ELC) densities are markedly reduced in a number of clinical situations including anergic sarcoidosis patients. To help determine whether this reduction is related to the anergic or nutritional status of the patient, we examined the non-sun-exposed epidermis of 23 hospitalized patients with various malignancies (MP), 10 hospitalized control (HC) patients without malignancy, and 24 biopsies from historical control (HIC) patients. There was no significant difference in the density of HLA-DR+ ELC among HC, HIC, or patients with nonpulmonary malignancy (primary or metastatic). Six patients with pulmonary malignancy had significantly fewer HLA-DR+ and OKT6+ epidermal cells. The reason ELC densities are reduced specifically in pulmonary malignancies remains under study.

Adult↗

Pulsing electromagnetic fields induce cellular transcription.

Weak, pulsing electromagnetic fields can modify biological processes. The hypothesis that responses to such induced currents depend on pulse characteristics was evaluated by using transcription as the target process. Two pulses in clinical use, the repetitive single pulse and the repetitive pulse train, were tested. These pulses produced different results from each other and from controls when transcription in dipteran salivary gland cells was monitored with tritiated uridine in transcription autoradiography, cytological nick translation, and analysis of isolated RNA fractions. The single pulse increased the specific activity of messenger RNA after 15 and 45 minutes of exposure. The pulse train increased specific activity only after 45 minutes of exposure.

Animals↗

Radiation therapy for treatment of intraductal carcinoma of the breast.

From 1979 to 1981, 14 patients with intraductal (noninvasive) carcinoma of the breast were treated with radiation therapy as an alternative to mastectomy. All patients received external irradiation to the entire breast; in addition, four patients were given a local boost with interstitial Iridium 192. Median follow-up is 23.5 months, with a range of 7-45 months. Twelve of 14 patients remain free of disease. The cosmetic results have been excellent.

Aged↗

Growth factor dependence of pheochromocytoma cells in chemically defined medium.

We have previously described the isolation of a clonal pheochromocytoma cell line (PC-G2) which responds to nerve growth factor (NGF) [Goodman and Herschman, 1978] and epidermal growth factor (EGF) [Goodman et al, 1980] with increased specific activity of tyrosine hydroxylase (TH). This cell line thus can be used for studies of induction of a key enzyme in the biosynthesis of catecholamines using a homogeneous cell population under controlled environmental influences. However, the need for serum in the culture medium used to grow these cells still introduced a lack of total environmental control. Several laboratories have circumvented this problem by growing cells in chemically defined medium. In the present report we demonstrate that with a modification PC-G2 cells can survive and grow in the chemically defined N3 medium devised by Bottenstein and Sato [1979]. While another pheochromocytoma cell line, PC-12, was shown to grow in N3 medium without any supplement [Bottenstein et al, 1979], the PC-G2 cells exhibit an absolute requirement for NGF or EGF in order to grow in this chemically defined medium. As was the case in the induction of TH in serum-containing medium [Goodman and Herschman, 1978; Goodman et al. 1980], EGF was found to be 100 times more potent than NGF in the support of growth of the PC-G2 cells. In the present report we demonstrate not only that either of these growth factors will support the growth of the PC-G2 cells, but also that the relative potency of these two factors for support of the cell growth is similar to their relative potencies in the induction of tyrosine hydroxylase in serum-containing medium.

Animals↗

The biology of SAA: identification of the inducer, in vitro synthesis, and heterogeneity demonstrated with monoclonal antibodies.

Continued studies of the macrophage-derived mediator of SAA synthesis (SAA Stimulating Factor) confirm our previous observations that SAASF copurified with leukocytic pyrogen (LP) and lymphocyte activating factor (LAF). Moreover, new data demonstrate three separate isoelectric points for human LP-LAF-SAASF each of which possess the three biological activities. During the purification of 15,000 MW LP from crude stimulated mononuclear cell supernatants, only those fractions with pyrogenic activity in rabbits caused augmented stimulation of lymphocytes (LAF) and induced SAA synthesis in mice. Purified human LP stimulated isolated mouse hepatocytes in vitro to synthesize SAA in a dose-responsive manner. Colchicine treatment of hepatocytes led to decreased secretion of SAA into the medium and to an intracellular accumulation of SAA. Messenger RNA was isolated from the livers of endotoxin-stimulated mice and translated in a wheat-germ cell-free system. A major product was identified at 13-14,000 MW. Immunoprecipitation with anti-mouse AA identified several bands on autoradiography of polyacrylamide gels. These larger SAA precursors may account for the previously noted heterogeneity of human SAA, comprising at least 6 SAA isomers, of similar molecular weight but different solubility and electrophoretic charge characteristics. Two monoclonal antibodies (IgM-K and IgG1-K) have been prepared using standard cell hybridization techniques. They are directed at the variable COOH terminal region of SAA since they detect differences between the 6 human SAAs but do not react with human, monkey, dog or mouse AA proteins, human AP, C-reactive protein, IgG nor albumin. These antibodies will be useful in examining the origin, structure and function of SAA.

Amyloid↗

Biochemical screening for inherited metabolic disorders in the mentally retarded.

A biochemical screening programme for the detection of inherited metabolic disease was carried out on urine and blood samples from inmates of the Alexandra Institute for the mentally retarded, Cape Town. Of the 1087 patients screened, positive results for phenylketonuria were obtained in 3, for cystinuria in 2 and for Hartnup disease in 1. The overall frequency of metabolic disorders was 0,6%. It is evident that genetic metabolic disease as detected by current screening procedures makes only a small contribution to the overall burden of mental retardation.

Adult↗

Premalignant lymphoid hyperplasia preceding and coexisting with malignant lymphoma in the skin.

A primary malignant lymphoma of the skin had concurrent and antecedent lesions showing histologic changes of completely benign lymphoid hyperplasia. The malignant lymphoma itself evolved during a few years, although specimens from repeated biopsies had previously exhibited benign lymphoid hyperplasia. We urge that persistent benign lymphoid hyperplasia in its many clinical forms in the skin be recognized as a long-term premalignant lesion. Awareness of such a continuum of benign to malignant change aids in the interpretation of the histologic findings in these growths and alerts the clinician to the need for years of careful surveillance. Histologic assessment should indicate whether the specimen shows benign, indeterminate, or malignant change.

Female↗