International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986.
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Biomedical subjects
Publications and source records attributed to R Goodman.
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From 1977 to 1986, 63 patients at high risk for isolated local-regional recurrence following mastectomy and adjuvant chemotherapy received post-operative radiotherapy. All patients had operable primary tumors (T1-3a). For entire group the mean and median number of positive nodes were 10 and 8, respectively. Radiotherapy consisted of 4500 to 5000 rad to the chest wall and regional nodes. Chemotherapy consisted of CMF +/- prednisone (45 patients), CAF (16 patients), and other variable regimens (2 patients). Relapse occurred in 23 patients with only two patients experiencing an isolated local-regional recurrence. In 3 patients local-regional recurrence appeared simultaneously with or following distant metastases and in 18 patients the pattern of failure was distant metastases alone. With a median follow-up of 28 months (range 9-87 mo.), 40 patients are alive without disease, 9 are alive with disease, and 14 have died with disease. The 4-year actuarial overall survival is 67% and the 4-year actuarial disease-free survival is 47%. The 4-year actuarial probability of an isolated local-regional recurrence is 5%. Complications related to the radiation included a 9% incidence of moderate to severe arm edema. This study demonstrates the ability of radiation to reduce the incidence of local-regional recurrence in a previously identified high risk group of patients and has produced encouraging survival results with minimal morbidity.
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.
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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.
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.
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.
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.
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.
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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)
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.
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.
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.
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.