Biomedical subjects
Publications and source records attributed to N Cohen.
Two to 3-month old tadpoles (Rana pipiens), thymectomized 2-3 weeks postfertilization, exhibited: sharply reduced numbers of splenic and blood lymphocytes; no in vitro lymphocyte responsiveness to PHA; and normal in vitro lymphocyte reactivity to LPS. These results reveal lymphocyte heterogeneity in this anuran species.
Explants from lactating bovine mammary gland were cultured in vitro in serum-free medium though 1-9 d. casein synthesis was determined by [32P] incorporation into newly synthesized Ca rennin precipitable fraction. High correlation (r = 0.98) was found between incorporation of [32P] and [3H]amino acids in explants cultured under different hormonal regimes, thus indicating that post-translational phosphorylation is not a rate-limiting step in casein synthesis. Hormonal effects on casein synthesis were studied by supplementing the incubating medium with insulin (I), prolactin (PRL), cortisol (F), thyroxine (T4) and triiodothyronine (T3). It was found that both PRL and I were required absolutely for maximal synthesis and almost maximal effect was achieved with 50 ng/ml. The effect of F was less clear, but some increase was achieved at the 200-1000 ng/ml range. T4 and T3 did not affect casein synthesis at a range of 10(-11)-10(-7) M while a significant inhibition was observed at 2 X 10(-5) M. A time-course study of casein synthesis further substantiated the dominant role of PRL in maintenance or even elevation of the initial rate of casein synthesis in the explants, through the first 4 d of incubation.
Rats were conditioned by pairing consumption of a novel sodium saccharin drinking solution with the effects of an ip injection of 75 mg/kg cyclophosphamide, an immunosuppressive drug. Five and ten days after conditioning, an experimental group of conditioned animals (Group CS) was reexposed to the saccharin drinking solution. Control animals (Group CSo) were conditioned but were not reexposed to saccharin. On Day 10, 15, or 25 after conditioning, animals were injected ip with sheep erythrocytes (SRBC), and independent subgroups were sampled for hemagglutinating antibody titer 4, 6, or 8 days later. There was a significant effect of sample time (antibody titers 4 days after immunization were lower than values observed 6 and 8 days after immunization) and a significant effect of treatment; conditioned animals reexposed to the CS had an attenuated antibody response. There were no significant differences between Group CSo and a group of placebo-treated animals, but conditioned animals reexposed to the CS had lower antibody titers than placebo-treated animals 4, 6, and 8 days after antigenic stimulation. These differences are more pervasive than those previously reported and suggest that reexposure to a CS may have long-lasting effects. More generally, these data provide further documentation of conditioned immunopharmacologic effects and the impact of behavioral factors in modifying immunologic reactivity.
Cyclophosphamide (CY), previously used to condition suppression of humoral immune responses, was used to condition suppression of a graft-versus-host response (GvHR). Female (Lewis x Brown Norway) F1 rats were conditioned by pairing consumption of a saccharin solution with an intraperitoneal injection of CY at 50 mg/kg of body weight 48 days before immunization. On day 0, all animals were injected with a suspension of splenic leukocytes (2 x 10(7) cells per footpad) obtained from female Lewis donors. The regional GvHR was assessed on day 5 by weighing popliteal nodes. Conditioned animals given a single low-dose injection of CY and reexposed to conditioned stimuli had lymph node weights significantly lower than control groups and did not differ from animals given three injections of CY during the ongoing GvHR. The results suggest that conditioned immunosuppression, previously demonstrated in thymus-dependent and thymus-independent humoral immune responses, also affects the popliteal GvHR, a cellular immune response.
Fourteen homozygous typing cells identified in Israel are described. Of these typing cells two were of Ashkenazi and 11 of non-Ashkenazi origin, while the remaining HTC was from an Arab donor. Ten of the 14 HTC's characterized in this manner were offspring of consanguineous marriages; all of them were non-Ashkenari. Nine HTC's express specificities previously recognized in Caucasians, 4 HTC's represent new specificities (J1-J4), and one typing cell was found to be analogous to the Japanese Dw12 (DHO) specificity. The distribution of HLA-D specificities in 120 randomly selected Israelis representing the two main Jewish subpopulations, Ashkenazim and non-Ashkenazim, was studied with the locally defined HTC's. HLA-Dw5 and Dw10 were found to be significantly increased while Dw2 and Dw6 were significantly decreased in Israelis as compared to Caucasians.
The association of A3, B7, Dw2 and DR2 histocompatibility (HLA) markers with multiple sclerosis (MS) is well established among Northern Europeans and Caucasoids in the United States. We showed previously that A3 and B7 were not increased among Israelis with MS, and in a preliminary study Dw2 as well. An association of A3 and B7 is also lacking in Italians, Jordanian and Japanese MS patients. In Black American MS patients, the B7 frequency is slightly increased but Dw2 is still significantly associated with MS. For the HLA-DR antigen series DR2 is shown to have a stronger association to MS than A3 and B7. Conceivably, this antigen could be associated with MS even in populations where an association with A3 or B7 is lacking. Therefore, a study of HLA-A, B, C, DR and D antigens was carried out in Israel. No significant excess or deficiency of HLA antigens was found in MS. Possible explanations for these results are as follows: (1) the relevant HLA-D alleles in the Jewish population were not detected by the homozygous typing cells (HTCs) used, since they were derived primarily from European sources; (2) in contrast to the Caucasoid populations the genetic factor predisposing for MS is not associated with HLA alleles in the Israeli population; (3) MS is an heterogeneous disease and in Israelis, an environmental factor is sufficient to cause the disease.
Experience with 81 gas computed tomography (CT) cisternography procedures in 79 patients in searching for acoustic neuroma is reported. Twenty-one tumors, four exclusively intracanalicular, were demonstrated after standard contrast-enhanced CT was negative. Fifty-five examinations were negative; four were inconclusive. The high resolution scanner with digital localization and reconstruction zoom capability greatly improved image detail. In nine of the 12 normal patients examined with it, the intracanalicular bundle was demonstrated. Substitution of carbon dioxide for air greatly reduced the morbidity of acute post-spinal tap headache. The procedure takes 30--45 min and can be performed on an outpatient basis. It is recommended as the procedure of choice when standard CT is negative in subjects clinically suspected of having acoustic neuroma.
Thymectomy of very young leopard frog (Rana pipiens) larvae dramatically reduced in vitro lymphocyte responses to the nitrogen phytohemagglutinin-P and prolonged survival of Lucké tumor alloimplants. However, tumor incidence in premetamorphic or metamorphosing frogs that had received injections as embryos of Lucké tumor herpesvirus (LTHV) was the same in thymectomized and normal immunocompetent animals. This result suggests that T-cell-mediated cytotoxicity does not prevent development of Lucké tumors in immunocompetent larvae and that if tumor-specific transplantation antigens appear, they may induce tolerance rather than destructive immunity in normal LTHV-injected larvae.
Pre- and perimetamorphic larval and post-metamorphic juvenile frogs (Xenopus laevis) from a single family were grafted with skin from either of their patents (who differed from the hosts by one major histocompatibility complex (MHC) haplotype and multiple minor H loci) or from an unrelated adult (to provide a greater immunogenetic disparity). The fate of such skin grafts transplanted to hosts of various developmental stages indicated that a net destructive alloimmunity in this amphibian species develops gradually during ontogeny. In contrast to the uniform rejection of grafts on animals transplanted as postmetamorphic froglets, many recipients of grafts transplanted during larval life became tolerant. The incidence of tolerance depended on the recipients' developmental stage at the time of grafting and on the particular MHC haplotype barriers involved. In general, larvae grafted at an early developmental stage became tolerant, whereas recipients transplanted at older larval stages rejected grafts from the same donor. Even when larvae rejected their grafts, the reaction was often more chronic than that mounted by postmetamorphic froglet controls.
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Smoking is an increasingly prevalent habit in Bangladesh, particularly among men. In the past 10-15 years cigarette consumption has more than doubled. Over 100000 acres (405 Km2) of land that could produce food are planted with tobacco, and cereal imports making up for these production losses generally do not reach the below-subsistence cultivator and landless. Cancer of the lung is already the third commonest cancer among males, and annual deaths from this cause can be expected to increase by 12000 within 15 years. At present respiratory disease is the best-recognised direct health consequence of smoking. However, a more important health risk may be the reduction in nutritional status of young children which results from expenditure on smoking in households whose income for food purchase is already marginal. Smoking of only 5 cigarettes a day in poor household in Bangladesh might lead to a monthly dietary deficit of 8000 calories (33.5 MJ). The existence of young children in Bangladesh is already precarious owing to poor nutrition. If, as seems likely, expenditure on smoking means that they get even less food, then the survival of a large number of children is being seriously endangered.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
One-way mixed leukocyte reactions (MLRs) of responder spleen cells from frogs (Xenopus laevis) that had rejected skin grafts were examined. Maximum and median stimulation indices (SIs) of cultures that contained responder cells from the graft recipient and stimulator cells from the graft donor were significantly greater than the peak and median SIs of cultures in which the responder splenocytes were from control, nonimmune animals. Significant stimulation was also recorded earlier (day 2 of culture) in more cultures involving immune responder cells than in control cultures. This earlier and greater proliferation in MLR was antigen specific.
At The Hospital for Sick Children in Toronto, an attempt was made to bypass long pre-assessment waiting lists by referring an increasing number of patients to local community resources at the point of the initial intake call. During the pilot study, we contacted 40 families who had been redirected along these lines between January and June 1979. We found that 31 (78%) families had followed our recommendation and most were satisfied with the treatment they were receiving. This suggests that "re-referral" upon intake can often be a highly effective and useful service when provided by a central resource and consultation centre. A further systematic follow-up of all applications to children's mental health clinics, including a careful appraisal of no-show cases (families who are accepted so that we can tailor our services to the specific child psychiatry needs of our varied clientel.
Urinary and serum activities of leucine aminopeptidase (LAP), N-acetyl-beta-glucosaminidase (ABG) and gamma-glutamyl transpeptidase (GGTP) were determined in four groups: 1) control subjects with normal oral glucose tolerance test and normal renal function; 2) latent diabetics with elevated oral glucose tolerance test and diabetic parents; 3) overt diabetics; 4) diabetics with slight nephropathy, exemplified by elevated serum creatinine levels and decreased creatinine clearance. No clear differences were found in the urinary GGTP and serum enzyme activities. Urinary LAP activity was significantly increased in Groups 2, 3 and 4, and urinary ABG activity in Groups 3 and 4. However, since the rise in urinary LAP activity was less consistent than that in ABG, it seems that the appearance of the latter enzyme in urine most likely results from tubular damage and may serve as a sensitive indicator of early diabetic kidney disease.
The role of SIgM+ lymphocytes in frog mitogen responses and mixed lymphocyte reactions was examined. A murine monoclonal antibody with specificity for Xenopus laevis IgM was produced. The anti-IgM activity was not inhibited by glycoproteins other than Xenopus IgM, but could be inhibited with periodate-treated frog IgM. Fluorescent microsphere-coupled anti-IgM was used to show that adult and larval thymocytes had few sIgM+ lymphocytes, whereas spleens contained 19 to 34% sIgM+ lymphocytes. The spleens of larvally thymectomized adults were greatly enriched for sIgM+ cells. Lymphocyte suspensions were depleted of sIgM+ cells by incubation of spleen cells on plastic Petri dishes coated with anti-IgM monoclonal antibody. Compared with unseparated controls, the nonadherent cells cultured in serum-free medium were enriched for Con A and PHA mitogen responses and mixed lymphocyte culture (MLC) reactivity. Nonadherent cells were partially depleted of LPS mitogen responsiveness. Depletion or enrichment of the mitogen response was not a result of changes in kinetics or dose-response characteristics of the cells. In 1% FCS-supplemented cultures, the LPS response was not depleted, whereas the PHA response was still enriched. Thus, thymus-dependent and thymus-independent mitogen and MLC responses can be separated by the criterion of sIgM positivity in this anuran species.