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Biomedical subjects

R Goodman

Publications and source records attributed to R Goodman.

At least 55 records · Page 3Linked to original sources

Exposure of salivary gland cells to low-frequency electromagnetic fields alters polypeptide synthesis.

This study demonstrates that exposure of cells to extremely low-frequency electromagnetic fields can cause measurable changes in protein synthesis. Sciara coprophila salivary gland cells were exposed to five low-frequency (1.5-72 Hz) electromagnetic signals: three signals (1.5, 15, and 72 Hz) produced pulsed asymmetric electromagnetic fields and two signals (60 and 72 Hz) were sinusoidal. Subsequent analyses of two-dimensional gels showed that cell exposure to either type of low-frequency electromagnetic field resulted in both qualitative and quantitative changes in patterns of protein synthesis. Thus, signals producing diverse waveform characteristics induced previously undetectable polypeptides, some of which were signal specific and augmented or suppressed other polypeptides as compared with nonexposed cells. The pattern of polypeptide synthesis differed from that seen with heat shock: only five polypeptides in cells exposed to electromagnetic signals overlap those polypeptides exposed to heat shock, and the suppression of protein synthesis characteristic of heat shock does not occur.

Animals

Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.

The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity. All 24 putative gating charges of the vertebrate protein are in identical positions in the Drosophila gene. Ten introns interrupt the coding regions of the four homology units; introns with positions conserved among homology units bracket a region hypothesized to be the selectivity filter for the channel. The Drosophila gene maps to the right arm of the second chromosome in region 60D-E. This position does not coincide with any known mutations that confer behavioral phenotypes, but is close to the seizure locus (60A-B), which has been hypothesized to code for a voltage-sensitive sodium channel.

Amino Acid Sequence

Transcriptional patterns in the X chromosome of Sciara coprophila following exposure to magnetic fields.

We previously demonstrated that exposure of salivary gland cells of the dipteran, Sciara coprophila, to either asymmetrical or symmetrical changing magnetic fields results in an increase in the incorporation of radioactive uridine into RNA. The present report is an analysis of the grain count distribution over the X chromosome of Sciara in transcription autoradiograms following exposure of the salivary gland cells to two pulsed magnetic signals and a 72-Hz sine wave signal. The results show augmented uptake of 3H-uridine into nascent RNA chains following short exposures of the cells to magnetic fields. Transcription is augmented in previously active loci, as well as at chromosome regions that are not detectable as active in control cells. The quantitative pattern of RNA synthesis in transcription autoradiograms is hypothesized to be signal specific on the basis of differences in grain counts over significantly labelled chromosome sites.

Animals

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