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Biomedical subjects

J Halpern

Publications and source records attributed to J Halpern.

At least 109 records · Page 6Linked to original sources

Effect of second tumors and of prostaglandin-leukotriene inhibitors on radiation therapy of transplanted rodent tumors.

The prostaglandin and leukotriene inhibitor sodium meclofenamate (SM) failed to influence radiation therapy induced regression of 6C3HED Gardner lymphosarcoma in C3H mice. Recurrence after radiation therapy, however, was reduced by treatment with SM. During these experiments, we observed that if a tumor was "cured" by radiation therapy, it required inoculation of a larger number of cells to establish a second tumor. Presumably, a certain degree of immunity has developed. On the other hand, if a second tumor was already established, less tumor cells were needed to establish a third tumor. This may be related to immuno-suppressor products of the second tumor. This effect could be partly inhibited by SM, suggesting that prostaglandins and leukotrienes may be involved in this phenomenon.

Animals↗

Radiation induced brain edema in primates, studied with sequential brain cat scanning and histopathology. Protective effect of sodium meclofenamate. A preliminary report.

Four Cynomologous monkeys (Mecaca fascicularis) received 2000 Rad whole brain irradiation. One remained untreated and exhibited loss of hair, facial edema, brain edema and hydrocephalus. There was loss of alertness and motor activity. One was scheduled to be treated with phenobarbital, but died in 24 hours after irradiation. One animal received 2 mg/kg dexamethasone I.M. daily. It died two weeks after irradiation apparently due to treatment related infection. One animal received 20 mg/kg sodium meclofenamate (Meclomen) orally daily. This animal showed no brain edema and only minimal hydrocephalus, delayed and incomplete hair loss and no facial edema. Further studies of this treatment appear to be justified.

Animals↗

Human peripheral blood mononuclear cells cultured in serum-free medium: a functional and morphological study using light and scanning electron microscopy.

Mononuclear cells of the human peripheral blood (PBMs), separated by the gradient-centrifugation technique, were cultured in serum-free medium. After separation into adherent cells (A-PBMs) and non-adherent cells (NA-PBMs), morphological differences between the two cell populations were observed. A-PBMs grew in serum-free culture for up to 70 days and the NA-PBMs for 30 days, without loss of viability. Cells were examined for phagocytosis of latex particles and prostaglandin secretion (PGE2 and thromboxane), in particular. Of all cells studied, the young adherent cells (3-7 days in culture) were the most efficient in performing these functions. In mixed cultures, containing A-PBMs and NA-PBMs, attachments between both cell types via elongated cytoplasmic extensions were seen. Toward the end of the culture period, a dense cellular network developed on the substrate of the culture chamber. This phenomenon has not been reported for PBMs culture using conventional serum-enriched media.

Blood↗

Oral estramustine phosphate (Estracyt): a broad phase II study.

Thirty-five patients with advanced cancers were treated with estramustine phosphate tablets (Estracyt). Doses ranged between 420 mg and 700 mg daily. One partial response was documented in a hormone resistant prostatic cancer patient. Four minor responses (less than 50% responses, or less than one month more than 50% response) were obtained; one in a hormone resistant prostatic cancer, two in metastatic colorectal cancers; and another in a malignant melanoma. Toxicity phenomena included nausea (9/35 - 25%), water retention (4/35 - 11.5%) and mild elevation of alkaline phosphatase (2/35 - 6%). Other toxicity effects were vaginal bleeding in two women, acne in one woman and mild pruritus in another patient. Myelosuppression and immune suppression were not significantly detected.

Adult↗

Early precursors of pancreatic cancer in college men.

From college data on 50,000 male former students, the records of 126 men who died of pancreatic cancer in a 16-50 yr follow-up period were compared with those of 504 surviving classmates with respect to physical and social characteristics. Return mail questionnaires received from 30,000 surviving alumni in 1962 or 1966 also were reviewed for characteristics that might predict altered risk of pancreatic cancer. Strong positive associations were found for cigarette smoking as reported both during college (p less than 0.001) and at time of questionnaire return (p = 0.03). Smoking 10 or more cigarettes per day during college corresponded to a relative risk of 2.6 with 95% confidence limits 1.5 to 4.6, and a positive smoking history at questionnaire return yielded a relative risk of 2.4 (1.1-5.1). No association was found for collegiate coffee drinking, either before or after adjustment for cigarette smoking. The relative risk for coffee drinking adjusted for smoking was 1.1 (0.7-1.8). In contrast, collegiate tea consumption was associated with a reduction in pancreatic cancer risk. The relative risk for tea drinking adjusted for smoking was 0.5 (0.3-0.9). Men who at college physical examination complained of occasional abdominal pain or discomfort had increased relative risk of pancreatic cancer (3.1 : 1.1-9.0) in the follow-up period.

Adolescent↗

Binding and internalization of epidermal growth factor by rat pituitary tumor cells.

Epidermal growth factor (EGF) regulates hormone synthesis and decreases the growth rate of clonal lines of rat pituitary tumor cells. [125I]iodo-EGF bound to specific receptors on GH4C1 rat pituitary cells with an apparent Kd of 0.34 nM. At 0 degrees C, 84% of specifically bound [125I]iodo-EGF appeared to be on the cell surface, while at 37 degrees C, 84% of bound [125I]iodo-EGF appeared to be internalized and could not be removed by treatment with an acidic high-salt buffer. Internalization of surface-bound [125I]iodo-EGF required 10 min to reach completion and was markedly temperature-dependent. Monodansylcadaverine, bacitracin, ammonium chloride, chloroquine, quinacrine and vinblastin did not inhibit internalization of [125I]iodo-EGF, suggesting that transglutaminase is not involved; but these drugs did cause an increased accumulation of radioactivity, probably by inhibiting degradation. In 2 h at 37 degrees C, approx. 35% of cell-associated [125I]iodo-EGF was degraded as analyzed by gel filtration, and 72% of the material that dissociated from the cells migrated as low molecular weight material or iodo-Tyr. Incubation of GH4C1 cells with unlabeled EGF caused a prolonged and dose-related decrease in the ability of the cells to bind [125I]iodo-EGF in a subsequent incubation, i.e. down-regulation. The pathway for internalization and degradation of the EGF-receptor complex in GH4C1 cells resembles that described for fibroblasts, in which the cellular response is different, but differs from the behavior of other hormone-receptor complexes in GH4C1 pituitary cells.

Animals↗

Treatment of febrile granuloycytopenic cancer patients receiving antineoplastic therapy with a combination of carbenicillin, cefazolin and gentamicin.

A three drug regimen of carbenicillin, cefazolin and gentamicin was used for the treatment of patients with solid tumors, who developed fever while granulocytopenic following chemotherapy. Thirty-five (8%) of 426 cancer patients receiving various combinations of antineoplastic chemotherapy qualified for the antibiotic treatment. Nine patients (26%) had bacteriologically confirmed infections, all with gram negative microorganisms. Twenty-four patients (69%) recovered and eleven (31%) died. All deaths occurred within five days of antibiotic therapy; in patients who recovered, the fever subsided within six days. Mortality was not influenced by the presence of a positive bacterial culture, age, or the cytotoxic agents used. It was, however, strongly related to metastatic spread: nine out of 14 patients with liver metastases (64%) died from the infection, while only two of 11 patients (18%) with other metastatic sites failed to respond to the antibacterial therapy. No death occurred in 10 patients who had local disease or received adjuvant therapy. This combined antibiotic therapy was as effective as reported for other combinations, with no serious side effects.

Adolescent↗

Evidence for an active step in thyroid hormone transport to nuclei: drug inhibition of L-125I-triiodothyronine binding to nuclear receptors in rat pituitary tumor cells.

When added to intact GH4Cl or GH3 cells, cytochalasin b, dansylcadaverine, and chloroquine inhibited the binding of L-125I-triiodothyronine (T3) to nuclear receptors within 30 min. These drugs also reduced the amount of 125I-T3 in the post-nuclear supernatant fraction of cells lysed with Triton X-100. If 125I-T3 was added before the drugs, 125I-T3 that was already bound did not dissociate, but further binding was blocked. Inhibition due to 10 microM cytochalasin b or 150 microM dansylcadaverine was reversible within 2 h of drug removal, and inhibition due to 150 microM chloroquine was partially reversible. Drug inhibition was overcome as the T3 concentration was raised. These drugs did not significantly inhibit 125I-T3 binding to isolated nuclei, and nuclei isolated from drug-treated cultures bound as much 125I-T3 as control nuclei. The results suggest that thyroid hormones reach their nuclear binding sites by an active transport process which is inhibited by the drugs studied.

Animals↗

Direct visualization of receptors for thyrotropin-releasing hormone with a fluorescein-labeled analog.

Thyrotropin-releasing hormone (TRH) binds to specific receptors on GH4C1 pituitary tumor cells. A fluorescently labeled analog of TRH was synthesized by coupling pGlu-His-ProNH(CH2)6NH2 to fluorescein isothiocyanate. The fluorescein-labeled peptide (FL-TRH) stimulated prolactin synthesis and release by GH4C1 cultures and bound to TRH receptors with an apparent Kd of 400 nM. Binding of FL-TRH to unfixed, viable GH4C1 cells was followed by fluorescence microscopy. After incubation with 1.4 microM FL-TRH for 1 hr at 37 degrees C, the surface of all cells was fluorescent and patches of intense fluorescence were evident. Control cultures incubated with FL-TRH and excess TRH were not fluorescent, and a line of pituitary tumor cells which lacks TRH receptors displayed little fluorescence after incubation with FL-TRH. When GH4C1 cells were incubated with FL-TRH for 1 hr at 37 degrees C and then with excess TRH for an additional 1 hr, the fluorescence associated with the cells was diminished to control levels. The results demonstrate that the fluorescein-labeled peptide labels specific TRH receptors.

Animals↗

Spasmus nutans.

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Child↗

Effect of sex of therapist and client on therapists' attitudes toward assertiveness problems.

Four hypothetical cases that contained descriptions of various assertiveness problems of male and female pseudo clients were presented to 57 male and 88 female mental health professionals. In two out of the four cases presented, female therapists found the client more in need of counseling than did male therapists, independent of the sex of the client. All therapists perceived a female client with a conflict between sexual assertiveness and negative judgments from peers to be more in need of counseling than a male client. All therapist preferred working with a female client in one of the cases. Thus, the effect of sex of therapist and client was not consistent across cases.

Adult↗

A two-compartment model for digoxin disposition in dogs.

The disappearance of digoxin from heart and skeletal muscle was studied in dogs using a sequential biopsy technique. The animals were injected with digoxin for five days and subsequently with 3H-digoxin for an additional three days. 12, 24, and 48 h after discontinuation of digoxin, tissue samples of left ventricle, left atrial appendage, and skeletal muscle were taken. In addition, digoxin serum levels were measured. With the help of a computer program, a mathematical model was developed for the description of the disposition and elimination of digoxin from tissue. Disappearance from plasma and tissue was consistent with a two-compartment open model.

Animals↗

The diagnosis of Briquet's syndrome in a male population: the Veterans Administration revisited.

Fifty psychiatric inpatients at a VA Hospital felt to be at high risk for the development of somatic complaints were surveyed for Briquet's syndrome. When criteria for the syndrome were strictly applied, no men were found with the disorder. If the criteria were minimally relaxed, two patients did have a sufficient number of symptoms in multiple areas to qualify for the diagnosis. However, they had alternative clinical and research diagnoses and none of the personality characteristics noted in previous populations of women surveyed for Briquet's syndrome.

Adult↗

A comparison of age-specific burn injury rates in five Massachusetts communities.

We measured burn incidence rates for residents of five Massachusetts cities. The data set included all non-occupational burn injuries and cases of smoke inhalation requiring treatment on an inpatient or an outpatient basis in a hospital, occurring between October 1, 1973 and September 30, 1976. Rates of burn injuries by age, and by burn type were calculated for each city. Examination of the data revealed large differences in the magnitude of the age-specific incidence rates among cities but remarkably similar patterns of rates for each city. Differences in the economic status among the cities and among census tracts within the cities appeared to explain a large proportion of the variation in the crude burn rates. A similar specificity of certain types of burn injury by age and sex was common to each city. These findings can be used by health education specialists to design and implement burn prevention programs in these communities appropriate for those individuals at highest risk.

Adolescent↗

Exclusion of bacteriophage T1 by bacteriophage lambda. I. Early exclusion requires lambda N gene product and host factors involved in N gene expression.

Two modes of exclusion of T1 by lambda are distinguished. "Early" exclusion depends on gene N, but not on gene Q. It is at least partially ineffective against T1am23. "Late" exclusion depends on gene Q and effects T1am23 as well as T1+. Early exclusion is a direct effect of N gene product, rather than N gene being required for the expression of some other lambda gene. Three host mutations, groN, nusA, and nusB, known to interfere with lambda replication by affecting N gene expression, also interfere with the ability of lambda to exclude T1.

Coliphages↗

Effects of type of target, cognitive ability, and age on projection.

It was hypothesized that older and more cognitively developed children would be less likely to use both attributive and contrast projection. Real and ambiguous target figures were used to assess the effect of the type of target on projection. 30 boys and 31 girls between the ages of 7 yr., 10 mo. and 14 yr., 10 mo. predicted a favored classmate's preferences in each of several categories. They also predicted the preferences of an unfavored classmate and of favored and unfavored ambiguous targets. These predictions were compared with the subjects' own preferences to measure attributive and contrast projection. Type of target affected the amount of projection. There was significantly more contrast projection onto ambiguous targets (dolls) than onto real targets (classmates). There was significantly more attributive than contrast projection for the real targets only. A significant negative correlation of -.26 (df = 59) was obtained between age and contrast projection onto the real targets. There were no significant correlations between the other measures of projection and the indices of cognitive ability, including age.

Achievement↗