The late J.A. Bogan.
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Biomedical subjects
Publications and source records attributed to R Evans.
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Adoptive immunotherapy, consisting of cyclophosphamide injection and the i.v. transfer of tumor-sensitized T cells, resulted in rejection of the immunogenic fibrosarcoma, MCA/76-9, by syngeneic C57BL/6J (B6) mice. The same treatment of tumor-bearing congenic immunodeficient mice, homozygous for the deleterious mutations nude (nu) and rhino (hrrh), did not result in tumor rejection. Paradoxically, the intratumor and intrasplenic changes taking place in each of the three strains after therapy were indistinguishable. There was an increase in Thy-1+, Ly-2+, or L3T4+ cells at the tumor site 8 days after adoptive immunotherapy and a similar increase in Thy-1+ cells in the spleen. Moreover, the T cells isolated from the tumors or spleens from each genotype were shown to be specifically cytotoxic in vitro as well as in an in vivo Winn assay. Further evidence that immune amplification had occurred in the immunological mutant mice was provided by experiments showing (a) the ability of spleen cells from tumor-bearers and those tested after therapy to produce IL-2 in response to Con A stimulation and (b) an increase in class II-MHC antigen expression by tumor-associated macrophages. The data suggest that, although amplification of antitumor immune responses occurred in the immunological mutants, the absence of a critical host factor limited the potency of the antitumor response.
Between 1982 and July 1987, more than 1200 patients attending St Stephen's Hospital were found to be HIV antibody positive. Four hundred were inpatients and most of the outpatients attended the sexually transmitted disease clinic. Two hundred and twenty-one patients had AIDS, 480 HIV-related disorders and 500 were asymptomatic. Most inpatients had invasive procedures within the operating theatres and there were 25 postmortems. Four hundred and five antibody tests from 220 health care workers from the STD clinic, operating theatres, isolation ward, intensive care unit and clinical laboratories were voluntarily tested for HIV antibody by an ELISA screening method. All were negative, except one male nurse who had other risk factors. Twenty-nine staff suffered needlestick injury with blood of HIV antibody positive patients; none has developed serological evidence of HIV infection.
The Federal Special Supplemental Food Program for Women, Infants and Children provides nutritious foods and dietary counselling to low income women and children with a medically certified nutritional risk. The Public Health Foundation, a large WIC agency in Los Angeles, observed declining breastfeeding rates among Indochinese participants. We interviewed 110 Cambodian, ethnic Chinese and Vietnamese WIC participants about their infant feeding decisions and experience. These women believed that formula was superior to breastmilk for a number of reasons, some related to the Asian humoral medical system. The women described 'excessive cooling' during childbirth that they hoped to counter-balance by consuming humorally hot foods for 100 days post partum. A hot maternal diet was thought to produce unhealthy breastmilk after 1 month, so the women preferred using infant formula, perceived to be stable and more nourishing than breastmilk. The WIC Program is using these and other findings to make breastfeeding more attractive to Southeast Asians.
Human genes homologous to the v-erbA oncogene of avian erythroblastosis virus have been mapped to at least two human chromosomes. Recently, the ERBA2 gene was shown to encode a thyroid hormone receptor and localized to chromosome 3 by using flow-sorted chromosomes. We now demonstrate that this gene is located at 3p22----3p24.1, using both somatic cell hybrids and in situ hybridization studies. Since this localization is close to the distal border of the small cell lung cancer (SCLC) 3p14----3p23 deletion, we undertook additional studies to examine the ERBA2 gene in SCLC. Using somatic cell hybrids constructed from the SCLC line NCI-H182 as well as matched patient tumor and control tissue samples, we found that ERBA2 is variably deleted. Therefore, ERBA2 defines at the molecular level the distal border of the SCLC deletion and further implies that the putative suppressor gene is located centromeric of this locus. We also determined that, at least in NCI-H182, the 3p14 breakpoint is proximal to the constitutive 3p14.2 fragile site. These studies would indicate that the mechanism or initiation site of chromosomal rearrangement in SCLC is different from that which occurs during induction of the 3p14 fragile site by aphidicolin.
Thirteen premenopausal women who each received 400 micrograms three times daily of intranasal buserelin for 6 months as treatment for endometriosis participated in this study. Cortical bone mineral content (BMC) in the mid-shaft of the right femur measured by dual photon densitometry, and trabecular bone density (TBD) in the lumbar vertebrae (L2-4) measured by quantitative computed tomography, were evaluated prior to, at the end of 6 months' buserelin treatment and after 6 months off treatment. Significant hypo-oestrogenism (P less than 0.001) was sustained during the period on treatment. The significant reduction in the mean lumbar vertebral TBD of 5.9% (P less than 0.02) observed at the end of treatment with buserelin was regained within 6 months following resumption of ovarian activity. There was a marginally significant (P = 0.07) reduction of only 0.9% in the mean femoral cortical BMC at the end of treatment. Six months after the end of treatment cortical BMC values were not significantly different from the pretreatment values. There was no significant correlation between the degree of hypo-oestrogenism and the corresponding change in vertebral TBD, (r = 0.20; P less than 0.10).
The incidence of lower second molar impaction was investigated, comparing the records of two samples of 200 orthodontic patients referred consecutively, in 1976 and 1986. A further study compared 50 cases showing both bilateral and unilateral impactions, with a non-impacted control group. This allowed possible causes of the impactions to be examined, particularly concerning the effect of premature loss of deciduous teeth on the distribution of crowding.
The trend in the prevalence of reported asthma was determined from data collected by the National Center for Health Statistics. The reported prevalence of ever having asthma increased among 6- to 11-year-old children between the first (1971 to 1974) and second (1976 to 1980) National Health and Nutrition Examination Surveys (4.8% to 7.6%, P less than .01). The epidemiology of asthma among children and adolescents 3 to 17 years of age in the United States was examined using data collected in the second National Health and Nutrition Examination Survey. In this paper, asthma is defined as current disease diagnosed by a physician and/or frequent trouble with wheezing during the past 12 months, not counting colds or the flu. Asthma was reported for 6.7% of youths overall and was higher in black than white children (9.4% v 6.2%, P less than .01), boys than girls (7.8% v 5.5%, P less than .01), and urban than rural areas (7.1% v 5.7%, P less than .05). Asthmatic children had a higher prevalence of other allergies (42.6% v 13.2%, P less than .01) and of allergen skin test reactivity (44.5% v 20.7%, P less than .01) than nonasthmatic children. Most asthmatics had their first asthmatic episode before their third birthday. No effect of socioeconomic status on the prevalence of asthma was noted.
Malignant gastric leiomyoblastoma (epithelioid leiomyosarcoma) is an uncommon smooth muscle neoplasm which is generally slow growing but capable of attaining large size. When these tumors project extrinsically from their site of origin in the gastric wall, they present diagnostic difficulty to the clinician and radiologist. This case report documents a highly unusual example of such a tumor which presented as an infected pancreatic pseudocyst and produced symptoms related to inferior vena caval compression.
Prolactin stimulates a hepatotrophic response similar to that caused by phorbol esters or partial hepatectomy in rats. Since phorbol esters, which activate protein kinase C, mimic prolactin action in liver, the relationship between prolactin administration and subsequent hepatic protein kinase C translocation was assessed. Prolactin administration rapidly stimulated a 4-fold elevation of membrane protein kinase C activity. The effect of prolactin on hepatic protein kinase C was specific for lactogenic hormones but could be duplicated by phorbol esters. Further, an increase in serum prolactin was demonstrated subsequent to partial hepatectomy and preceding hepatic protein kinase C translocation. Therefore, translocation of hepatic protein kinase C appears important for hepatic proliferation in response to prolactin administration and to partial hepatectomy.
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Tumors were eradicated following adoptive immunotherapy of (C57BL/6J X DBA/2J) F1 (B6D2F1) hybrid mice bearing the C57B1/6J (B6) sarcoma, MCA/76-9, by treatment with cyclophosphamide (CY) and adoptively transferred tumor-sensitized B6D2F1 T cells. Identical treatment of B6----B6D2F1 or DBA----B6D2F1 chimeric tumor-bearing mice resulted in temporary tumor regression only. Immunotherapy in both systems resulted in the appearance at the tumor site of large numbers of T lymphocytes and macrophages, which were shown to be derived from the adoptively transferred donor immune B6D2F1 cells or from the original reconstituting bone marrow respectively. The TAC and TAL isolated from either B6D2F1 or chimeric mice expressed potent toxicity in vitro towards tumor target cells. In addition, TAC from both systems inhibited tumor growth in a Winn assay in an immunologically specific manner. Suppressor cells detected in spleens 8 days after CY injection of normal B6, DBA, B6D2F1 hybrid and chimeric mice and also after adoptive immunotherapy of tumor-bearing B6, B6D2F1 and chimeric mice and were shown to persist in the spleens of chimeric mice for at least 31 days after adoptive immunotherapy. In contrast, spleen cells taken 31 days after therapy of B6D2F1 mice did not contain detectable suppressor cells and were able to induce tumor eradication when adoptively transferred to CY-treated tumor-bearing B6D2F1 mice. The possibility is discussed that two forms of suppressor mechanisms are induced after adoptive immunotherapy of chimeric mice and that they may down-regulate donor T cell responses at the tumor site.
Previous work identified certain components of the immunological network that had been activated following the adoptive immunotherapy of tumor-bearing mice. The present report shows that part of the activation process involves the IL-1 pathway. Tumor-associated macrophages (TAM) from C57BL/6J mice bearing the immunogenic sarcoma, MCA/76-9, and tumor-bearers injected with cyclophosphamide (CY) or CY plus the intravenous transfer of tumor-sensitized lymphocytes showed relatively high levels of intracellular (IC) IL-1, as demonstrated in the mitogenic and comitogenic assays. Gel chromatography of IC IL-1 and extracellular (EC) IL-1 from TAM induced to secrete IL-1 by stimulation with lipopolysaccharide indicated a single peak of activity of similar molecular size. The active fractions of the EC IL-1 were found to increase in activity as they were diluted to a maximum of 1/64, beyond which IL-1 activity declined. Fractions of the IC IL-1 showed no increased activity on dilution. Filtrates (less than 10 kDa) obtained on concentration of the IC and EC IL-1 samples prior to fractionation were shown to contain an activity (3-5 kDa) that inhibited the uptake of [3H]TdR by thymocytes in the mitogenic and comitogenic assays. Membrane-bound IL-1 activity also was expressed by TAM and this coincided with the previously reported peak Ia expression by these cells. TAM were also shown to induce strong proliferative responses by allogeneic lymphocyte. Systemic amplification of antitumor responses was detected in mice bearing progressing tumors and in those that had received combination therapy as measured both by increases in free IL-1 in the peritoneal cavity and IL-1 within the peritoneal macrophages. These observations indicate that in addition to enhancement of Ia expression, the IL-1 pathway also is activated and amplified systemically in this model system of tumor progression and rejection.
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The linear nevus sebaceous syndrome is a rare disorder first described in 1962 in two cases by Feuerstein and Mims. As originally described, it consisted of the triad of the characteristic midline facial linear nevus sebaceous of Jadassohn, seizures, and mental retardation. The authors have followed a patient with this syndrome from birth to age 8 and although he does demonstrate several neurologic and ocular abnormalities, he enjoys normal intelligence and has never suffered seizures. The features of this syndrome and several new ocular findings demonstrated in this case are described. Based on our long-term follow-up of this patient and our review of the reported cases to date, the authors suggest that the triad for this disorder should be changed to include the midline facial linear nevus sebaceous of Jadassohn, neurologic abnormalities which may, but not necessarily, include seizures and mental retardation, and ophthalmologic abnormalities.
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