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Biomedical subjects

E M Smith

Publications and source records attributed to E M Smith.

At least 199 records · Page 11Linked to original sources

Health care attitudes and experiences during gynecologic care among lesbians and bisexuals.

Bisexuals (N = 424) and lesbians (N = 1,921) were surveyed regarding their sources of gynecologic care, utilization patterns, openness with physicians, and assessment of quality of care. About 40 per cent of each group believed that physician knowledge about their sexual preference would hinder the quality of medical care and about as many believed that it would have no effect. About one-third in each group had not disclosed their sexual behavior although they desired to do so. Physicians rarely requested this information. A lesbian physician was overwhelmingly preferred for gynecologic care (96 per cent), particularly for problems with sexual functioning. Previous satisfaction with gynecologic care was most often described as "adequate," but almost as often as "variable" and "poor." Data suggest that quality, utilization, and medical outcomes of gynecologic care to this group would be improved if physicians would communicate greater awareness of sexual orientation in a nonprejudicial manner and ensure confidentiality.

Adult↗

A complete regulatory loop between the immune and neuroendocrine systems.

Infection of lymphocytes with Newcastle disease virus induces the cells to synthesize immunoreactive (ir) adrenocorticotropin (ACTH) and endorphins. The irACTH is synthesized de novo, and common properties of lymphocyte and pituitary ACTH include: antigenicity, bioactivity, molecular weight, and retention time on reverse phase high-pressure liquid chromatography. The irACTH appears to be active in vivo because a rise in serum corticosterone levels in hypophysectomized mice corresponds with spleen cell production of irACTH. Furthermore, preliminary experiments showed that B cell depletion blocked the normal rise in serum corticosterone levels after herpes simplex virus infection of intact mice. It seems that a similar system operates in vivo in humans. Typhoid vaccine, which induces lymphocyte-derived irACTH production in vitro, caused a time-dependent increase in the number of irACTH-positive lymphocytes in both hypopituitarism and normal short children. A rise in serum cortisol levels was seen in one patient with hypopituitarism and all normal patients. The above regulatory circuit also seems able to act in the reverse direction. Pituitary ACTH and alpha-endorphin can behave like lymphokines by being immunosuppressive at 0.5 microM in an in vitro antibody synthesis system. Further, lymphocytes were shown to have high-affinity receptors for both of these hormones. Thus, it appears that the immune and neuroendocrine systems have the ability to signal each other through common or related peptide hormones and receptors.

Adrenocorticotropic Hormone↗

Lymphocyte production of endorphins and endorphin-mediated immunoregulatory activity.

The immune and neuroendocrine systems appear able to communicate with each other by virtue of signal molecules (hormones) and receptors common to both systems. This review summarizes our data concerning the production of one type of neuroendocrine hormone, endorphins (END), by stimulated lymphocytes. The induction by various agents and structural characterization are described, as well as the lymphocyte-derived END's potential role as a mediator of endotoxic shock. Also discussed is the ability of pituitary-derived END and the related enkephalins to inhibit a primary in vitro antibody response. These activities are discussed in the context of a complete regulatory circuit between the immune and neuroendocrine systems.

Adrenocorticotropic Hormone↗

Peptide hormones shared by the neuroendocrine and immunologic systems.

While numerous studies have demonstrated that the neuroendocrine system can control immune functions, it is only now becoming apparent that the control is reciprocal in that the immune system can control neuroendocrine functions. In this paper, recent studies which seem to provide a molecular basis for this bidirectional communication are reviewed. These studies suggest that the immune and neuroendocrine systems represent a totally integrated circuit by virtue of sharing a common set of hormones, such as corticotropin, thyrotropin, and endorphins, and their receptors. Possible hypothalamic and immunologic controls of this circuitry are discussed.

Adrenocorticotropic Hormone↗

Opiate receptor mediated effects of IFN-alpha and lymphocyte derived endorphin-like peptides.

Viral infection of lymphocytes induces the synthesis of interferon (IFN)-alpha and immunoreactive corticotropin (irACTH). We have previously shown the irACTH to be antigenically, structurally, and functionally related (if not identical) to pituitary ACTH. Virus infected lymphocytes also synthesize in endorphin as measured by immunofluorescence. The endorphin-like activity was found to be associated directly with IFN-alpha as well as other, lower molecular weight peptide(s) having no antiviral activity. Crude IFN-alpha at 1000 U/ml exhibited opiate receptor binding activity by inhibiting 47.2% of 3H dihydromorphine (4 X 10(-9) M) binding to mouse brain tissue. Homogeneous HuIFN-alpha (10(8.3) U/mg) also bound to opiate receptors but required 10 times the antiviral activity than crude IFN-alpha for a 50% inhibition of dihydromorphine binding. When injected intracerebrally both crude and homogeneous IFN-alpha induced transient analgesia in mice that was reversible and preventable by the opiate antagonist naloxone. The low molecular weight (less than 10 Kd) ir endorphins purified from the IFN-alpha had no antiviral activity, but may represent the majority of the opiate receptor binding material in the infected lymphocyte culture fluid. These data seem to indicate that the opiate-like side effects of exogenous IFN administration may be due to the IFN-alpha molecule binding to opiate receptors and also may be due to the associated low molecular weight endorphin-like moieties synthesized by lymphocytes.

Amnion↗

Enhancement of the in vitro antibody response by thyrotropin.

The pituitary hormone thyrotropin (TSH) has been shown to enhance in a dose dependent manner the in vitro antibody response. Highly purified preparations of bovine and human TSH enhanced up to 375% the number of cells producing antibody to sheep erythrocytes. TSH had to be present prior to 24-48h of the initiation of culture for enhancement of the antibody response. An analogy is discussed between TSH and B lymphocyte growth and differentiation factors.

Animals↗

The regulation of phosphate-activated glutaminase activity and glutamine metabolism in the streptozotocin-diabetic rat.

The activity of phosphate-activated glutaminase was increased in the kidney, liver and small intestine of rats made diabetic for 6 days with injection of streptozotocin (75 mg/kg body wt.). Insulin prevented this increase in all three tissues. Treatment with NaHCO3, to correct the acidosis that accompanies diabetes, prevented the increase in renal glutaminase activity, but not that in liver or small intestine. Chemically induced acidosis (NH4Cl solution as drinking water) or alkalosis (NaHCO3 solution as drinking water) increased and decreased, respectively, glutaminase activity in the kidney, but were without significant effect on the activity in liver and small intestine. The increase in glutaminase activity in the small intestine during diabetes was due to an overall increase in the size of this organ, and was only detectable when activity was expressed in terms of whole organ, not mucosal scrapings or isolated enterocytes. Prolonged diabetes (40 days) resulted in an even greater increase in the size and glutaminase activity of the small intestine. Despite this marked increase in capacity for glutamine catabolism, arteriovenous-difference measurements showed a complete suppression of plasma glutamine utilization by the small intestine during diabetes, confirming the report by Brosnan, Man, Hall, Colbourne & Brosnan [(1983) Am. J. Physiol. 235, E261-E265].

Animals↗

Hydropathic anti-complementarity of amino acids based on the genetic code.

An interesting pattern in the genetic code has been discovered. Codons for hydrophilic and hydrophobic amino acids on one strand of DNA are complemented by codons for hydrophobic and hydrophilic amino acids on the other DNA strand, respectively. The average tendency of codons for "uncharged" (slightly hydrophilic) amino acids is to be complemented by codons for "uncharged" amino acids.

Amino Acids↗

Japanese cohort mortality from cancers of the upper digestive and respiratory tracts.

Cohort mortality between 1875 and 1975 in Japan from cancers of the oesophagus, tongue, and larynx were examined. Death rates were compared with per capita alcohol and tobacco use which are major aetiological agents for these tumours in Westernized countries. Cohort mortality from cancer of the oesophagus remains high for both sexes in a country with historically low alcohol consumption. More consistent with this low drinking pattern are the rates for cancers of the tongue which remain among the lowest in the world. Cancers of the larynx, which have been associated with tobacco and alcohol, declined among successive cohorts, which was in contrast to the sharp cohort increases for lung cancers and tobacco use in Japan during the same period.

Adult↗

Effects of smoking on the development of female reproductive cancers.

The effect of smoking on the development of breast, endometrial, and ovarian cancers is evaluated among cases identified between November 1980 and July 1982 in the Iowa Surveillance, Epidemiology, and End Results Cancer Registry. Population-based, age-frequency matched controls were also evaluated, adjusting for potential confounders: Age, age of menarche, age of menopause, duration of menses, female family reproductive cancer history, obesity, parity, infertility, and lifetime steroid hormone use. Logistic regression analyses of total pack-years of cigarette exposure indicate that smoking is not significantly related to the development of breast cancer [relative risk (RR) = .99; confidence interval (CI) = .97, 1.02] or ovarian cancer (RR = 1.00; CI = 1.00, 1.00). Among women with endometrial cancer, the risk for those who smoke is increased among premenopausal women (RR = 1.27; CI = .65, 2.59) and decreased among postmenopausal women (RR = .41; CI = .16, 1.04).

Adipose Tissue↗

Seasonal occurrence of rotavirus in sewage.

A seasonal distribution was observed for rotaviruses in sewage by using indirect immunofluorescence. Levels were low from May through September and generally higher during winter and spring. In contrast, no seasonal pattern was observed for total enteroviruses. Limitations of the indirect immunofluorescence assay and enzyme immunoassay for environmental samples are discussed.

Enterovirus↗

Regulation of lymphokine (gamma-interferon) production by corticotropin.

We have shown that corticotropin (ACTH), alpha-endorphin, and enkephalins can regulate antibody responses, which suggested a role for neuropeptides in a regulatory circuit between the immune and neuroendocrine systems. ACTH and structurally related peptides were examined here for regulation of mitogen induction of the lymphokine gamma-interferon (IFN gamma) in C57BL/6 mouse spleen cell cultures. Synthetic ACTH1-39 and a porcine pituitary extract containing ACTH activity were potent suppressors of the IFN gamma response. Synthetic ACTH1-39 suppressed the response by approximately 62% at 1 to 3 microM, whereas the porcine extract suppressed by greater than 90% at 1 to 3 microM ACTH. The greater potency of the pituitary extract was shown to be due to the presence of an additional peptide of Mr 2100 that was reactive with antibodies to the N-terminal region of ACTH (ACTH1-13), possessed potent anti-cellular activity against L cells and various transformed cells, but lacked ACTH biologic activity. The anti-cellular peptide suppressed the IFN gamma response by greater than 99% at 0.05 microM. The ACTH1-39 cleavage products, alpha-melanocyte stimulating hormone (alpha MSH; acetylated and amidated ACTH1-13), and corticotropin-like intermediate lobe peptide (CLIP; ACTH18-39) had no effect on IFN gamma production. ACTH1-24, like ACTH1-39, has full steroidogenesis activity but also had no effect on IFN gamma production, which suggests a dissociation of the immunoregulatory and steroidogenic properties of ACTH1-39. ACTH1-39, and possibly also the anti-cellular 2100 Mr peptide, is initially synthesized as the precursor polyprotein pro-opiomelanocortin (POMC). Enzymatic processing of POMC, first to the active ACTH1-39 or the anti-cellular peptide and then to the inactive smaller peptides, probably plays an important role in regulation of lymphokine and antibody production by ACTH and ACTH-related neuropeptides. This is consistent with the recent demonstration of the production of ACTH-like peptides by lymphocytes.

Adrenocorticotropic Hormone↗

A corticotropin (ACTH) related peptide with cytotoxic activity.

A commercially available preparation of corticotropin was found to have potent cytotoxic activity for several established cell lines. Neither synthetic corticotropin nor alpha melanocyte stimulating hormone demonstrated this cytotoxic activity. Gel filtration allowed separation of a 2100 dalton cytotoxic peptide from the actual corticotropin present in the commercially prepared material. The structural relatedness of the cytotoxic peptide to corticotropin was demonstrated by neutralization with antisera to alpha melanocyte stimulating hormone. These studies indicate the existence of a newly identified ACTH related peptide with cytotoxic activity.

Adrenocorticotropic Hormone↗

Human lymphocyte production of immunoreactive thyrotropin.

Interferon-alpha inducers were previously shown to cause human lymphocyte production of a corticotropin (ACTH)-like peptide. Thyrotropin (TSH) was not produced under these conditions. In contrast, this report shows that a T-cell mitogen (staphylococcal enterotoxin A), which does not induce the ACTH-like peptide, caused human lymphocyte production of an immunoreactive (ir) TSH. Lymphocyte synthesis of the ir TSH was first detectable at 24 hr, peaked at 48 hr, and thereafter declined. NaDodSO4/polyacrylamide gel electrophoresis of intrinsically radiolabeled lymphocyte-derived ir TSH showed radiolabeled peaks at 80, 50, and 26 kilodaltons. These peaks presumably correspond to trimeric, dimeric, and monomeric TSH-like proteins, respectively. Acid treatment and reduction caused the ir TSH to migrate as a 14-kilodalton peak with a 12-kilodalton shoulder in a gel filtration column run in 6 M guanidine . HCl. Thus, the ir TSH seemed to be composed of subunits with molecular masses corresponding to those of the beta and alpha chains of human TSH, respectively. The ir TSH appeared to be glycoprotein because it bound to a concanavalin A affinity column. Taken together these data suggest that in addition to ACTH, human lymphocytes can also produce a TSH-like substance.

Concanavalin A↗