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Biomedical subjects

R Silver

Publications and source records attributed to R Silver.

At least 37 records · Page 2Linked to original sources

Distribution and local differentiation of mast cells in the parenchyma of the forebrain.

Mast cells are found in the brain of many species. Although a considerable body of information is available concerning the development and differentiation of peripheral mast cells, little is known about brain mast cells. In the present study, the ontogeny of mast cells in the dove brain was followed by using three markers: acidic toluidine blue, alcian blue/safranin, and an antiserum to gonadotropin-releasing hormone (GnRH). Mast cells first appear in the pia on embryonic day (E)13-14 in ovo, then along blood vessels extending from the pia into the telencephalon on posthatch day 4-5, and in the medial habenula at week 3. Medial habenular mast cell numbers increase during development, peaking in peripubertal birds, and declining thereafter. Several measures indicate that mast cells mature within the medial habenula: there is an increase in the intensity of metachromasia, a switch from alcian blue granules in young animals to mixed alcian blue and safranin granules in older animals, and an increase in GnRH-like immunoreactivity. These results were extended by using electron microscopy. The architecture of mast cell granules evolved from electron lucent with small electron dense deposits at E15 to more electron dense granules with complex patterns of internal structure by 2 months. Ultrastructural immunocytochemistry for the GnRH-like peptide at 1 month revealed both immunopositive and negative cells, suggesting that the acquisition of this phenotype is not simultaneous across the population. Thus, immature mast cells infiltrate the central nervous system and undergo in situ differentiation within the neuropil.

Animals↗

Gender-specific frequency of background somatic mutations at the hypoxanthine phosphoribosyltransferase locus in cord blood T lymphocytes from preterm newborns.

Limited information is available regarding the frequency, spectrum, and clinical relevance of somatic mutations in the developing fetus. The goal of this study was to determine somatic mutant frequencies (Mfs) at the hypoxanthine phosphoribosyltransferase (HPRT) reporter gene in cord blood T lymphocytes from preterm infants to gain insight into in utero mutational events. Mf determinations were made by using the HPRT T cell cloning assay on cord blood samples from 52 preterm infants. Natural logarithm Mfs (lnMfs) from preterm infants were compared with results from our database for full-term infants. Our analysis revealed higher lnMfs in cord blood T lymphocytes from preterm compared with full-term infants (P = 0.008). In addition, preterm females had significantly higher lnMfs compared with full-term females (P < 0.001), whereas preterm males were found to have significantly lower lnMfs than preterm females (P = 0.005). Regression analyses also demonstrate a significant relationship between lnMf and gestational age for preterm females that does not exist for preterm males. These results demonstrate the gender-specific association between Mf and age in humans.

Female↗

Antiphospholipid antibodies and reproduction: the antiphospholipid antibody syndrome.

In women who have a diagnosis of APS (both clinical and laboratory criteria) the chance for successful pregnancy is reduced. In these cases, treatment appears to be a clear option, particularly in the case of prior thromboembolic events. The current preference of treatment for women with RPL and aPL antibodies is subcutaneous heparin and aspirin. This treatment should begin with a positive pregnancy test and continue postpartum. It is unclear, at this time, what treatment, if any, is required for women who do not meet all the criteria for diagnosis of APS, but who are known to have aPL antibodies. In some cases, these women were tested because of a prior false-positive test for syphilis, with subsequent identification of aPL antibodies. More recently, women undergoing IVF were tested and found to have an increased incidence of aPL antibodies. It was suggested that aPL antibodies are associated with infertility and failure to implant. However, a summary of published reports indicate that positive aPL antibodies in patients undergoing IVF do not influence ongoing pregnancy rates. This subject, however, remains an area of active investigation because aPL antibodies were shown to interact with the syncytiotrophoblast and cytotrophoblast layers and could, theoretically, after implantation.

Antibodies, Antiphospholipid↗

A student emergency: helping school staff cope.

A serious illness, injury, or other medical emergency in a student while in school can be upsetting to school staff not accustomed to such situations. A healthcare emergency in a special health needs child in one school district prompted a nurse and a building principal to develop a protocol which would enable school staff to effectively assist the nurse in the event of a student emergency. The plan involved training school personnel to assist the nurse and the administrator in tasks such as answering and monitoring telephones, serving as a runner, controlling unnecessary traffic into the nurse's office, and passing clean supplies to the nurse.

Adaptation, Psychological↗

Brain mast cells lack the c-kit receptor: immunocytochemical evidence.

Mast cells are reported to differ from other cells of the hematopoietic lineage in that as mature cells, they retain the c-kit receptor, and are thus capable of responding to the stem cell factor (SCF) ligand. SCF is important for development and survival of mast cells. In this study, c-kit expression was examined immunocytochemically in the brains of mice, rats and doves. The results indicate that brain mast cells lack the c-kit receptor; those of the leptomeninges and other connective tissues are a mixed population of c-kit positive and negative cells. The mechanisms whereby brain mast cells might survive in the absence of SCF-c-kit signaling are discussed.

Animals↗

Fiber outgrowth from anterior hypothalamic and cortical xenografts in the third ventricle.

Fetal grafts of the anterior hypothalamus (SCN/AH) containing the suprachiasmatic nucleus (SCN) restore circadian rhythms to SCN-lesioned host hamsters and rats following implantation into the third ventricle. Previous studies suggest that intraventricular SCN/AH grafts are variable in their attachment sites, the extent of their outgrowth, and the precise targets innervated in the host brain. However, the use of different methods to analyze graft outgrowth in this model has previously led to inconsistent results. We have reevaluated the outgrowth of fetal rat SCN/AH grafts implanted in the third ventricle of hamsters by using two methods: the carbocyanine dye, 1,1'dioctadecyl-3,3'-tetramethylindocarbocyanine percholate (DiI), was placed directly onto grafted tissue; and a donor-specific neurofilament marker was used in conjunction with xenografts. We examined the specificity of outgrowth by comparing SCN/AH xenografts with that of control cortical (CTX) xenografts. To evaluate whether SCN/AH graft efferents arise from the donor SCN, we used micropunch grafts that contained minimal extra-SCN tissue. The results show that the use of a donor-specific neurofilament marker reveals more extensive SCN/AH graft outgrowth than DiI. SCN/AH graft efferents project into areas normally innervated by the intact SCN. However, this outgrowth is variable among graft recipients, is not specific to SCN/AH tissue, and does not necessarily derive from the donor SCN. The precise functional role of neural efferents arising from SCN/AH grafts in the restoration of circadian clock function and the extent of SCN-derived efferents remain to be determined.

Animals↗

Thyroid autoantibodies are not associated with recurrent pregnancy loss.

OBJECTIVE: Approximately 1% of all women have recurrent pregnancy loss, defined as >/=3 spontaneous losses of pregnancy; however, a cause is determined in only 50% of cases. Recent studies have associated the presence of thyroid autoantibodies during the first trimester of pregnancy with spontaneous abortion in the current pregnancy among women without a history of recurrent abortion. The objective of this study was to determine whether circulating thyroid autoantibodies were associated with recurrent pregnancy loss. STUDY DESIGN: Sera from 74 nonpregnant women with a history of recurrent pregnancy loss and from 75 healthy, fertile control subjects of similar gravidity were tested for thyroglobulin and thyroid peroxidase antibodies by means of radioimmunoassay kits. All women had a third-generation thyroid-stimulating hormone assay performed. Samples were obtained >/=6 months after a pregnancy. RESULTS: Twenty-two of the women with a history of recurrent pregnancy loss (29.3%) and twenty-eight of the control subjects (37%) had positive results for either one or both of the thyroid autoantibodies (P >. 05). Mean thyroid-stimulating hormone levels and the proportion of women with abnormal thyroid-stimulating hormone values did not differ between the 2 groups. CONCLUSION: Women with a history of recurrent pregnancy loss are no more likely than are fertile control subjects to have circulating thyroid autoantibodies. Testing for antithyroid antibodies is not clinically useful in the evaluation of patients with a history of recurrent pregnancy loss.

Abortion, Habitual↗

Laboratory and diagnostic testing in child and adolescent psychiatry: a review of the past 10 years.

OBJECTIVE: To review in a critical fashion the literature of the past decade covering diagnostic and laboratory testing in the field of child and adolescent psychiatry. METHOD: A computerized search of articles published during the past decade was made, and selected articles are presented. Because of the paucity of articles specifically relating to minors, selected articles from adult psychiatry are cited. RESULTS: With a few notable exceptions, few controlled studies on the specificity and sensitivity of any laboratory test for any specific disorder of behavior presenting in children have been conducted in children and adolescents. A high index of suspicion will remain the clinician's best ally in utilizing laboratory measures in the assessment of psychopathology. Nonetheless, studies have appeared that will guide the clinician as to what tests are not clinically useful. CONCLUSION: Indications and the lack of indications for specific laboratory studies are an integral part of the knowledge base that child psychiatrists must have. Much more empirical data will need to be collected prospectively to inform the field and to move the judicious use of the laboratory from an art to a science.

Adolescent↗

Output signals of the SCN.

The suprachiasmatic nucleus (SCN) of the hypothalamus controls circadian rhythmicity in mammals (for reviews, see Refs. 33 and 59). Responses modulated by the SCN are numerous and include rhythms in sleep/wake cycles, locomotor, gnawing and general activity, temperature, ingestive behavior, and rhythms of hormonal and peptide secretions. Though a great deal is known about the neuroanatomical organization of the SCN, many elements of the structure-function relationships remain to be discovered. For example, it is not known which cellular components of the SCN function as driving pacemakers or which output signal(s) of these pacemakers are important for each of its functions. While some signals from pacemaker cells reach target regions by neural efferents, there is also evidence that rhythmic responses can be controlled by diffusible signals. This article reviews output signals from the SCN. The data available suggest that neural efferents are not necessary for the control of locomotor activity rhythms. Evidence that a diffusible signal is sufficient to restore activity rhythms in SCN-lesioned animals is described. Finally, possible physiological mechanisms for diffusible signals are suggested.

Animals↗

Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome.

OBJECTIVE: To determine whether antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin are associated with recurrent pregnancy loss. METHODS: Sera from three groups of women were studied: 1) 147 women with recurrent pregnancy loss but no clinical signs or symptoms of autoimmune disease who tested negative for lupus anticoagulant and medium-to-high levels of immunoglobulin G anticardiolipin antibodies; 2) 104 healthy, fertile controls of similar age and gravidity; and 3) 43 women with well-characterized antiphospholipid syndrome. Serum antibody binding against six phospholipids (cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol) was determined using enzyme-linked immunoassays, and results were normalized using an anticardiolipin standard. RESULTS: Twenty-six (18%) women with recurrent pregnancy loss and nine (9%) controls tested positive (above the 99th percentile) for antiphospholipid antibodies. Sera from five (3.4%) women with recurrent pregnancy loss and four (3.8%) controls demonstrated binding to phospholipid antigens other than cardiolipin. In contrast, binding to phospholipid antigens was demonstrated in sera from more than 90% of women with antiphospholipid syndrome. Among women testing positive for antiphospholipid antibodies, the median positive value for women in the antiphospholipid syndrome group was significantly higher than for those with recurrent pregnancy loss or normal fertile controls. CONCLUSIONS: Women with recurrent pregnancy loss are no more likely than fertile controls to have elevated levels of antiphospholipid antibodies once lupus anticoagulant, anticardiolipin, and an obvious clinical history of autoimmune disease have been excluded. Testing for antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin is not clinically useful in the evaluation of recurrent pregnancy loss.

Abortion, Habitual↗

Amniotic fluid glycine-valine ratio and neonatal morbidity in fetal growth restriction.

OBJECTIVE: To test the hypothesis that an elevated amniotic fluid glycine-valine ratio predicts neonatal morbidity in growth-restricted newborns. METHODS: Amniotic fluid (AF) was collected from 122 third-trimester pregnancies (range 31-39 weeks), 49 of which were complicated by fetal growth restriction. Amino acid analysis was performed by high-pressure liquid chromatography. Glycine-valine ratios were compared between normal and growth-restricted fetuses. Neonatal morbidity within the group of growth-restricted fetuses was characterized by evaluation of neonatal hypoglycemia, arterial cord blood gas analysis, and birth weight percentile. We also examined the correlation of AF glycine-valine ratio to the umbilical artery resistance index. The median interval between AF sampling and delivery was 1 day (range 0-8 days). Analyses were performed by Student t test, chi 2 with Yates correction, or simple correlation when appropriate. P < .05 was considered significant. RESULTS: Growth-restricted fetuses have a significantly elevated AF glycine-valine ratio compared with control subjects (3.31 +/- 1.06 versus 2.61 +/- 0.77, respectively, P < .001). There was no association of the glycine-valine ratio with gestational age for either group. An elevated glycine-valine ratio was not associated with neonatal hypoglycemia within the growth-restricted group (hypoglycemia: [n = 16] 3.19 +/- 1.07; no hypoglycemia: (n = 30) 3.44 +/- 1.09). There were no significant correlations of glycine-valine ratio with arterial cord blood pH (r = -0.10), oxygen pressure (r = 0.04), or base deficit (r = 0.12). There were no significant correlations of glycine-valine ratio and birth weight percentile (r = -.24) or umbilical artery resistance index (r = -.14). CONCLUSION: Amniotic fluid glycine-valine ratio is elevated in growth-restricted fetuses compared with control fetuses. However, the level of glycine-valine elevation is not associated with neonatal morbidity related to hypoglycemia, arterial cord blood gas abnormalities, or birth weight percentile.

Adult↗

Mast cell number and maturation in the central nervous system: influence of tissue type, location and exposure to steroid hormones.

While it is well established that brain mast cells are usually associated with the cerebral vasculature, in ring doves mast cells lie directly in the neuropil of the medial habenula. During normal development mast cells enter the habenula and complete their differentiation in situ. In the present study, we asked what characteristics of the medial habenula contribute to mast cell entry and differentiation. Grafts of embryonic habenula or control optic tectal grafts were placed in the lateral ventricle or anterior chamber of the eye. Transplantation alters the location of the habenula as well as its neural and vascular connections. Three groups of hosts were used for the ventricular grafts: four-month-old and killed three months after transplantation; four-month-old and killed seven months later, and two- to three-year-old gonadectomized males killed three months later. Hosts for the intraocular grafts were four months of age and killed three months later. Mast cells were present in the habenular grafts but not in the control tissue. Mast cells in three- and seven-month-old grafts were phenotypically immature when compared to those of hosts. They contained fewer metachromatic granules, fewer granules immunoreactive to an antiserum against gonadotropin-releasing hormone, and no highly-sulphated proteoglycans. As previously described, gonadectomized adults had fewer mast cells in their medial habenula than did intact animals, but there was no change in mast cell number in habenular grafts. The current experiments indicate that the occurrence and survival of mast cells can occur within the microenvironment of the medial habenula, but that maturation of these cells requires the normal connections of this nucleus. Furthermore, gonadectomy appears to alter mast cell number in the medial habenula by generating a secondary signal which the transplanted tissue is incapable of receiving or processing.

Aging↗

Antiphospholipid antibodies in healthy pregnant women.

This article discusses the prevalence and clinical significance of antiphospholipid antibodies (aPL) in the normal, healthy pregnant population. Although an increased risk for adverse fetal outcome has been shown in a small subset of this population, most pregnancies in aPL-positive mothers have successful outcomes. We review the variations in aPL levels during pregnancy and consider screening strategies and therapeutic interventions in healthy aPL-positive pregnant women.

Antibodies, Antiphospholipid↗