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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 397 records · Page 22Linked to original sources

Behavioural and pharmacological dissociation of chlordiazepoxide effects on discrimination and punished responding.

Effects of chlordiazepoxide (CDP) and ethanolamine-O-sulphate (EOS) alone and in combination were tested on the acquisition and performance of continuous reinforcement - time out (CR-TO) and variable interval reinforcement - time out (VI-TO) operant discriminations in rats. CDP disrupted acquisition of CR-TO discrimination; effects were short lived, and neither CR-TO performance nor its reversal were impaired. Acquisition of VI-TO discrimination was increasingly impaired, and performance disrupted in pre-trained animals. EOS alone was inactive, and with CDP exerted only slight interactive effects. When a conflict component was added to the VI-TO schedule, however, EOS showed substantial additive effects with CDP on punished responding. The results suggest that CDP-induced increases in non-rewarded (TO) responding were related to task difficulty, pointing to a discrimination impairment rather than an anxiolytic effect. In addition, the specificity of EOS potentiation may reflect a pharmacological dissociation between CDP effects on discrimination and on punished responding, and suggest that GABA is selectively involved in resistance to punishment.

Animals↗

Cloning of the human oestrogen receptor cDNA.

Poly A+ RNA isolated from the human breast cancer cell line MCF-7 was fractionated by sucrose gradient centrifugation and those fractions enriched in oestrogen receptor (ER) mRNA were used to prepare randomly primed cDNA libraries in the lambda gt11 vectors. Clones corresponding to the ER were isolated from both libraries after screening with either ER monoclonal antibodies (lambda gt11) or synthetic oligonucleotide probes designed from two peptide sequences of purified ER (lambda gt10). Five cDNA clones were isolated by antibody screening and five after screening with synthetic oligonucleotides. The two largest ER cDNA clones, lambda OR3 (1.3 kbase) and lambda OR8 (2.1 kbase), isolated using antibodies and oligonucleotides, respectively, were able to enrich selectively for ER mRNA by hybrid-selection. Furthermore, lambda OR8 contains DNA sequences which cross-hybridize with each of the other ER cDNA clones. These results demonstrate that the clones isolated correspond to the ER mRNA sequence. Using lambda OR8 as a hybridization probe revealed a single poly A+ RNA band of approx. 6.2 kbase in the ER containing human breast cancer cell lines MCF-7 and T47D. In contrast, no hybridization was seen in the human ER-cell line HeLa. The same probe hybridizes to a chicken gene which is expressed in oviduct tissue as a 7.5 kbase poly A+ RNA.

Animals↗

Reproduction study of caffeine administration to male Osborne-Mendel rats.

The potential for caffeine, administered twice daily by gavage in a total dose of 40 or 80 mg/kg/day, to adversely affect the reproductive performance of male rats was investigated. Treatment was continued through 3 wk of serial mating; mating and dosing were terminated concurrently, after which the sires were autopsied and their testes weighed. Controls were treated similarly with distilled water. Significant dose-related differences were detected for sire body weight, but not for testes weight. The majority of the significant effects on the offspring were for those born to the low-dose sires. Statistically significant differences were sporadically detected for the number of pups born and their body weights and survival; however, these differences were not consistently detected in either a dose- or temporal-related fashion. Thus, caffeine appears to have little potential to produce adverse reproductive effects when administered by gavage to male rats at the levels tested in this study.

Administration, Oral↗

Differential effects of dorsal raphe lesions and intraraphe GABA and benzodiazepines on conflict behavior in rats.

Both reductions in brain serotonin activity and injections of benzodiazepine drugs increase punished responding in rats, but the evidence is conflicting on the role of serotonin pathways in the benzodiazepine effect. Therefore a series of studies were carried out using a Geller-Seifter procedure with three components, to examine drug effects on rewarded, nonrewarded, and punished responding. Using male hooded Lister rats and chronic indwelling cannulae, it was found that neither chlordiazepoxide (1.5 and 5.0 micrograms in 0.5 microliter), midazolam (1.0 and 10.0 micrograms in 0.5 microliter), nor GABA (100, 500, 1000, and 5000 ng in 0.5 microliter), exerted significant anticonflict activity when injected into the dorsal raphe. Lesions of the dorsal raphe produced by injections of 5,6-dihydroxytryptamine significantly increased punished responding, and there were significant correlations between lesion size, extent of forebrain serotonin depletion, and increases in punished responding. Peripheral injections of chlordiazepoxide (5.0 and 10.0 mg/kg) and midazolam (1.25, 2.5, and 5.0 mg/kg) significantly increased punished responding both before and after raphe lesions. The increase in lesioned animals was significantly greater than after drug or lesion alone and represented a powerful additive effect which was specific to punished responding. As intraraphe benzodiazepines did not exert significant anticonflict activity, and raphe lesions did not attenuate the anticonflict activity of peripheral benzodiazepines, it is concluded that increases in punished responding seen after serotonin depletion and after benzodiazepine drugs may be dissociable.

5,6-Dihydroxytryptamine↗

Late-onset hexosaminidase A and hexosaminidase A and B deficiency: family study and review.

Five children from two non-consanguineous Asian families with juvenile-onset hexosaminidase deficiency are presented. Two have juvenile Tay-Sachs disease with hexosaminidase A deficiency and three have juvenile Sandhoff disease with hexosaminidase A and B deficiency. The contributing factors in the spectrum of the hexosaminidase deficiency disease are outlined, and previously reported cases of late-onset Tay-Sachs and Sandhoff disease are reviewed. The heterogeneity of the effects of hexosaminidase deficiency is discussed, with the recommendation that the diagnosis be considered, in its various forms, when there is no other obvious explanation.

Age Factors↗

The inhibition of flexor tendon adhesions.

In a single blind control study using adult rabbits, the effectiveness of locally applied dextran-70 and 1% hyaluronic acid were evaluated in the control of flexor tendon adhesions after laceration of the profundus tendon in Zone II. Dextran-70 proved effective, whereas application of hyaluronic acid did not.

Animals↗

Adjuvant therapy of breast cancer: Southwest Oncology Group studies.

The Southwest Oncology Group has conducted a series of randomized studies of adjuvant therapy in patients with primary breast cancer and positive axillary nodes. The first study, during which combined chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) administered for 1 year was compared with single agent therapy with melphalan (L-PAM) for 2 years, was activated in 1975 and closed in 1978. Of the 366 patients who were eligible, 191 received L-PAM and 175 were given CMFVP. The 2 groups were comparable with regard to known prognostic factors. At a median follow-up of 8 years, CMFVP continues to be superior to L-PAM in disease-free (P = .005) and overall survival (P = .01). Thirty-five percent of patients on CMFVP have died compared with 46% on L-PAM. The greatest survival benefit is apparent in premenopausal women and women with 4 or more positive axillary nodes. Acute toxicity was more frequent with CMFVP than with L-PAM, but it was acceptable and reversible with both regimens. Long-term toxicity was limited to myeloproliferative disease in 2 patients on L-PAM and 1 on CMFVP. The second-generation series of studies, activated in 1979, were designed according to nodal status, estrogen receptor (ER) status, and menopausal status. We randomized ER-negative, node-negative patients to 6 months of combination chemotherapy or to no treatment. Because of slow accrual, the study was closed and patients are now being entered onto a similar intergroup study with the Eastern Cooperative Oncology Group. We randomized ER-negative, node-positive patients to either 1 or 2 years of CMFVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cloning of the human glucocorticoid receptor cDNA.

We show that the human glucocorticoid receptor (GR), isolated from the breast cancer cell line MCF-7, has an apparent molecular weight identical to that of rat liver GR (94 kDa) and reacts with antibodies raised against the latter. These antibodies were used to clone cDNA sequences corresponding to the human GR from a lambda gt11 expression library constructed using MCF-7 poly(A)+ RNA. Three non-homologous cDNA clones with inserts of 125, 220 and 350 bp, which express epitopes recognised by the rat liver GR antibodies, were isolated. Rat liver GR antibodies, immunopurified using the immobilised purified beta-galactosidase fusion proteins, detect partially purified rat liver and human GRs on Western blots. In addition, these antibodies immuno-adsorb rat liver and human GRs affinity-labelled with [3H] triamcinolone acetonide. Northern blot analysis, using all three cDNA probes, reveals the presence of a major MCF-7 poly(A)+ RNA species of approximately 7 kb.

Cloning, Molecular↗

Current status of bioassays in genetic toxicology--the dominant lethal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The term dominant lethal may be defined as death of the heterozygote arising through multiple chromosomal breaks. The assay is generally conducted by treating male animals, usually mice or rats, acutely (1 dose), subacutely (5 doses), or over the entire period of spermatogenesis. Animals treated acutely or subacutely are mated at weekly intervals to females for a sufficient number of weeks to cover the period of spermatogenesis. Those treated for the entire spermatogenic cycle are mated for 1 or 2 successive weeks at the termination of treatment. Females usually are killed at 14 days of pregnancy and examined for the number of total implantations in the uterus, the number of implantations classified as early deaths, and, in some cases, the number of corpora lutea. The category of early death is the most significant index of dominant lethality. A total of 249 papers were reviewed and 140 chemicals were evaluated. Of the 140 chemicals, 65 were positive by the criteria used by the Work Group in evaluating each publication. The category of "positive" includes those responses of a borderline nature. 99 chemicals were declared negative. There is considerable overlap of chemicals in both categories, which accounts for the incongruity in the total number of chemicals tested and the number considered positive and negative. A total of 44 animal carcinogens have been tested in the dominant lethal assay, 26 of which were positive and 18 negative for a correlation of 59%. The role of the assay should be that of confirming positive results from lower tier chromosomal aberration-detecting systems (confirming in the sense of indicating the ability of the chemical to penetrate gonadal tissue and to produce cytogenetic damage). The dominant lethal assay should not be used as a risk assessment method.

Animals↗

Cloning of the human estrogen receptor cDNA.

Poly(A)+ RNA isolated from the human breast cancer cell line MCF-7 was fractionated by sucrose gradient centrifugation and fractions enriched in estrogen receptor (ER) mRNA were used to prepare randomly primed cDNA libraries in the lambda gt10 and lambda gt11 vectors. Clones corresponding to ER sequence were isolated from both libraries after screening with either ER monoclonal antibodies (lambda gt11) or synthetic oligonucleotide probes designed from two peptide sequences of purified ER (lambda gt10). Five cDNA clones were isolated by antibody screening and five were isolated after screening with synthetic oligonucleotides. The two largest ER cDNA clones, lambda OR3 (1.3 kilobase pairs) and lambda OR8 (2.1 kilobase pairs), isolated by using antibodies and oligonucleotides, respectively, were able to enrich selectively for ER mRNA by hybrid-selection. Furthermore, lambda OR8 contains the DNA sequence expected from the two ER peptides and crosshybridizes with each of the other ER cDNA clones. These results demonstrate that the clones isolated correspond to the ER mRNA sequence. Use of lambda OR8 as a hybridization probe revealed a single poly(A)+ RNA band of approximately equal to 6.2 kilobase pairs in the ER-containing human breast cancer cell lines MCF-7 and T47D. In contrast, no hybridization was seen in the human ER-negative cell line HeLa. The same probe hybridizes to a chicken gene that is expressed in oviduct tissue as a 7.5-kilobase-pair poly(A)+ RNA.

Animals↗

Fractures of the hook of hamate: radiographic signs.

Isolated fractures of the hamulus, formerly considered rare, are being seen more frequently. Many of these injuries are sports related, particularly in golf, tennis, racquetball and baseball players. Failure to make an early diagnosis can result in severe pain and sometimes incapacitating disability. We studied the clinical and radiological findings in 12 patients who had fracture of the hook of the hamate. We propose three radiographic signs of fracture that are readily seen on routine PA projections: "absence" of the hook of the hamate; "sclerosis" of the hook; and lack of cortical density, i.e., a barely visible outline, of the hamulus.

Adolescent↗

Effects of murine tumor necrosis factor on Friend erythroleukemic cells.

Tumor necrosis inducing factor (TNF), a 140,000 molecular weight glycoprotein present in the serum of Corynebacterium parvum endotoxin-treated mice, was cytotoxic toward Friend virus-transformed erythroleukemic cells (FELC). These cells grow in culture as undifferentiated pro-erythroblasts but can be induced to differentiate in a limited fashion along the erythroid pathway to orthochromatic normoblasts by various agents such as dimethylsulfoxide (DMSO). Partially and highly purified preparations of TNF were cytotoxic toward logarithmically growing FELC whereas a comparable serum protein fraction from C. parvum treated mice or endotoxin from E. coli had no effect upon FELC viability. DMSO-induced cells were more sensitive to the action of TNF requiring only about half the concentration needed to produce 50% kill in noninduced cells. Inhibition of hemoglobin formation was TNF dose-related and could be decreased by 94%. TNF was also cytotoxic toward DMSO-induced cells in stationary phase and mitomycin C treated noninduced FELC. Neuraminidase modification of the surface of FELC increased the cytotoxicity of TNF by 50%. These results demonstrate that TNF destroys FELC whether they are nondividing, dividing or partially differentiated and suggest that TNF may accomplish this by affecting cell metabolism after internalization.

Animals↗

Antitumor activity of normal human globulin: effects on murine and human erythroleukemic cells.

The effect of the antitumor fraction isolated from the alpha 2-globulin region of normal human serum (NHG-I) upon murine (FELC) and human (K562) erythroleukemic cells in vitro was determined. NHG-I inhibited the growth of both actively growing FELC and K562 cells in a dose-dependent manner. However, it has no effect upon mitomycin C treated FELC which were unable to divide nor upon dimethylsulfoxide-induced FELC in stationary phase. These results indicate that NHG-I has a cytostatic effect upon cell growth and suggests that its action may be dependent upon DNA synthesis. This is in marked contrast to TNF, the alpha 2-globulin factor obtained from murine serum which is also not species-specific but whose action upon these cell lines is cytotoxic.

Alpha-Globulins↗

A cross-cultural look at the relationship between age and innovative behavior.

This study investigates the relationship of age to innovativeness when the effects of opportunity have been controlled. Data were obtained from the Basic Village Education Project. The analysis was conducted on two groups of farmers, the Spanish-speaking Ladino population found in Eastern Guatemala and the Quiche-speaking Mayan population found in the mountains of Western Guatemala. Each group was subdivided into young, middle age and old categories. Innovativeness was defined as the level of agricultural technology utilized by individual farmers at the end of the BVE-project period. A separate analysis was conducted for each culture and findings for both indicate that younger farmers were more likely than their older counterparts to adopt new agricultural practices when economic opportunity is controlled. These findings are of three fold importance: they indicate the importance of economic constraints to innovation; they contain implications for policies concerning target development programs, and they contain a warning about ethnocentric hypotheses in research related to "underdeveloped" countries.

Adolescent↗

Medical psychotherapy.

Medical psychotherapy is often practiced by family physicians unknowingly. It shares certain features with all other forms of psychotherapy, but it also possesses its own unique qualities. Medical psychotherapy represents combinations of techniques, learned largely by experience, that are useful in treating the patient in crisis, as well as the patient with chronic psychiatric or physical illness. It contributes to higher quality medical care.

Adult↗

The clinicopathological spectrum of non-tuberculous mycobacterial osteoarticular infections.

We studied the clinicopathological features of eight patients in whom a non-tuberculous mycobacterium was unexpectedly isolated from osteoarticular material obtained at operation. Three distinct types of infection with non-tuberculous mycobacteria were found: tenosynovitis, synovitis, and osteomyelitis. Tissue specimens from these sites showed a spectrum of pathological findings, including (1) virtually no inflammation, (2) mild to severe non-specific chronic inflammation, (3) granulomas without necrosis, and (4) caseating epithelioid granulomas that were indistinguishable from those of tuberculosis. In six patients the infection responded well to adequate surgical excision alone. In the remaining two the infection responded to surgical intervention and antituberculous therapy.

Adolescent↗