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Biomedical subjects

S Weaver

Publications and source records attributed to S Weaver.

At least 19 recordsLinked to original sources
PubMed2005

Transient or occult HIV infections may occur more frequently than progressive infections: changing the paradigm about HIV persistence.

Evidence of transient HIV infections was found in 8 subjects at high-risk for HIV infection among 47 longitudinally studied over 2-5 (average approximately 3.5) years, whereas only two subjects developed progressive infection. All of these subjects developed serum antibodies (Ab) to conformational epitopes of HIV gp41 (termed "early HIV Ab"), but the 8 transiently infected subjects lost this Ab within 4-18 months, and did not seroconvert to positivity in denatured antigen EIA or Western Blot (WB). However, the two progressively infected subjects eventually seroconverted in the EIA and WB tests within one to two months after the appearance of "early HIV Ab". HIV env and nef sequences were directly PCR amplified from the peripheral blood mononuclear cells (PBMCs) of two of the eight transiently infected subjects during the time of "early HIV Ab"-postivity, and these showed significant sequence divergence from the HIV strains in the laboratory, indicating that they were not laboratory contaminants. Genome identity typing ("paternity-typing") of PBMC samples obtained at the time of "early HIV Ab"-positivity, and later when Ab was absent from each of the 8 subjects, showed that blood samples were not mixed-up. This provides further evidence that transient or occult infection with HIV does occur, and perhaps at a greater frequency than do progressive infections.

Gene Products, env↗
PubMed2004

Blockage of glucocorticoid, but not mineralocorticoid receptors prevents the persistent increase in circulating basal corticosterone concentrations following stress in the rat.

Exposure to a single session of intense inescapable stressors results in elevations of plasma corticosterone levels selective to the trough of the circadian rhythm that last for several days after stressor cessation. In the present study, we examined whether this stress-induced alteration in the regulation of the circadian trough is dependent upon glucocorticoid and/or mineralocorticoid receptor activation during stress. Pre-treatment with the mineralocorticoid receptor (MR) antagonist, spironolactone (RU-28318; 50 mg/kg, s.c.), and/or the glucocorticoid receptor (GR) antagonist, mifepristone (RU-38486; 50 mg/kg, s.c.) 1 h before inescapable stress (40, 2.0-mA tail-shocks delivered over a 1 h period) had no effect on the acute plasma corticosterone response to inescapable stress. Treatment with the MR antagonist alone did not affect the appearance of basal corticosterone elevations in stressed rats. However, the elevated trough plasma corticosterone levels were no longer evident in rats treated previously with the GR antagonist either alone or in combination with the MR antagonist. GR activation during stressor exposure appears to be necessary for the development of subsequent basal corticosterone elevations.

Adaptation, Physiological↗
PubMed2001

Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites.

Environmental conditions in early life permanently alter the development of glucocorticoid receptor gene expression in the hippocampus and hypothalamic-pituitary-adrenal responses to acute or chronic stress. In part, these effects can involve an activation of ascending serotonergic pathways and subsequent changes in the expression of transcription factors that might drive glucocorticoid receptor expression in the hippocampus. This paper summarizes the evidence in favor of these pathways as well as recent studies describing regulatory targets on the promoter region of the rat hippocampal glucocorticoid receptor gene.

Animals↗
PubMed2000

Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin.

Postnatal handling increases glucocorticoid receptor expression in the rat hippocampus, thus altering the regulation of hypothalamic synthesis of corticotropin-releasing hormone and the hypothalamic-pituitary-adrenal response to stress. The effect on glucocorticoid receptor gene expression represents one mechanism by which the early environment can exert a long-term effect on neural development. The handling effect on hippocampal glucocorticoid receptor expression is dependent on peripheral thyroid hormone release and the activation of ascending serotonergic pathways. In primary hippocampal cell cultures, serotonin (5-HT) increases glucocorticoid receptor expression, and this effect appears to be mediated by increased cAMP levels. In the current studies we examined the in vivo effects of handling on hippocampal cAMP-protein kinase A (PKA) activity. In 7-d-old rat pups, we found that (1) postnatal handling increased adenylyl cyclase activity and hippocampal cAMP levels, (2) the effect of handling on cAMP levels was completely blocked by treatment with either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or the 5-HT receptor antagonist, ketanserin, and (3) handling also increased hippocampal PKA activity. We then examined the effects of handling on cAMP-inducible transcription factors. Handling rapidly increased levels of the mRNAs for nerve growth factor-inducible factor A (NGFI-A) (zif268, krox24) and activator protein-2 (AP-2) as well as for NGFI-A and AP-2 immunoreactivity throughout the hippocampus. Finally, we found that the effects of handling on NGFI-A and AP-2 expression were significantly reduced by concurrent treatment with either PTU or ketanserin, effects that paralleled those on cAMP formation. NGFI-A and AP-2 have been implicated in the regulation of glucocorticoid receptor expression during development. Thus, these findings suggest that postnatal handling might alter glucocorticoid receptor gene expression via cAMP-PKA pathways involving the activation of NGFI-A and AP-2.

Adenylyl Cyclases↗
PubMed2000

5'-heterogeneity of glucocorticoid receptor messenger RNA is tissue specific: differential regulation of variant transcripts by early-life events.

Glucocorticoid receptor (GR) gene expression is regulated in a complex tissue-specific manner, notably by early-life environmental events that program tissue GR levels. We have identified and characterized several new rat GR mRNAs. All encode a common protein, but differ in their 5'-leader sequences as a consequence of alternate splicing of, potentially, 11 different exon 1 sequences. Most are located in a 3-kb CpG island, upstream of exon 2, that exhibits substantial promoter activity in transfected cells. Ribonuclease (RNase) protection analysis demonstrated significant levels of six alternate exons 1 in vivo in rat, with differences between liver, hippocampus, and thymus reflecting tissue-specific differences in promoter activity. Two of the alternate exons 1 (exons 1(6) and 1(10)) were expressed in all tissues examined, together present in 77-87% of total GR mRNA. The remaining GR transcripts contained tissue-specific alternate first exons. Importantly, tissue-specific first exon usage was altered by perinatal environmental manipulations. Postnatal handling, which permanently increases GR in the hippocampus, causing attenuation of stress responses, selectively elevated GR mRNA containing the hippocampus-specific exon 1(7). Prenatal glucocorticoid exposure, which increases hepatic GR expression and produces adult hyperglycemia, decreased the proportion of hepatic GR mRNA containing the predominant exon 1(10), suggesting an increase in a minor exon 1 variant. Such tissue specificity of promoter usage allows differential GR regulation and programming.

Alternative Splicing↗
PubMed2000

Topical use of papaya in chronic skin ulcer therapy in Jamaica.

The objective of the study was to determine the prevalence of the use of the fruit (papaya) of Carica papaya as topical ulcer dressings by registered nurses in the Spanish Town Hospital (STH), Kingston Public Hospital (KPH) and the University Hospital of the West Indies (UHWI), Jamaica. A ten-item pretested self-administered questionnaire was distributed to 285 randomly selected registered nurses at the UHWI, KPH and STH. There was a 72% response rate. The prevalence of topical papaya use among the respondents was 75%. Comments from the users of papaya suggested that topical application of the unripe fruit promoted desloughing, granulation and healing and reduced odour in chronic skin ulcers. It was cost effective. Papaya was considered to be more effective than other topical applications in the treatment of chronic ulcers. There was some difficulty in preparation of the fruit and occasionally a sensation of burning was reported by the patients. There was concern about the use of a non-sterile, non-standardised procedure but there were no reports of wound infection from its use. Papaya is widely used by nurses as a form of dressing for chronic ulcers and there is need for standardisation of its preparation and application.

Administration, Topical↗
PubMed1999

Herpes varicella zoster encephalitis in immunocompromised patients.

The authors describe specific MRI features that suggest the diagnosis of varicella zoster encephalitis. MRI initially revealed discrete, subcortical, nonenhancing lesions that coalesced and developed enhancement. Gray matter involvement was seen later. Autopsy revealed spherical lesions of demyelination and hemorrhagic cavitation confirmed as varicella zoster encephalitis. Characteristic MR features may suggest the diagnosis of varicella zoster encephalitis, enabling definitive diagnostic testing and early institution of antiviral treatment.

Adult↗
PubMed1998

The effect of implicit and explicit motivation on recall among old and young adults.

Seventy-six elderly subjects aged sixty-five to eighty-seven and seventy-seven young adults aged twenty-five to forty were compared on implicit and explicit motive levels and on recall of introductions and working memory. Significantly fewer of the elderly than the young participants scored high in the implicit motives, n Affiliation and n Power, confirming results from U.S. national surveys. The surveys also demonstrated a significant decline with age in high levels of n Achievement, a decline not found here. The elderly participants showed major recall deficits on both tasks, but all three of the implicit motives studied were shown to enhance recall for the elderly, but not for the young adults. Eight elderly women scoring high on at least two of the three motives showed no recall deficits compared to the young women on two memory tasks. In old age implicit motive deficits contribute to poor memory but explicit commitments to have a good memory had no effect on recall.

Adult↗
PubMed1996

Sensory processing during early and late nocturnal sleep.

The present experiments in 10 healthy men compared auditory evoked potentials (AEPs) and heart rate (HR) indicators of stimulus processing during early and late phases of nocturnal stage 2 sleep. Definition of early and late sleep relied on endocrine pituitary-adrenal secretory activity which is known to be inhibited during early nocturnal sleep but sharply increases during late sleep. AEPs and HR responses were recorded to trains of 10 tone pips (1000 Hz; interstimulus interval 15 s; intertrain interval > 3 min). On one night, tone pips were presented in the first part of sleep, on the other night tone presentation took place in the second part, with the order of conditions balanced across subjects. Amplitudes of N150 and N550 components of the AEP, and of acceleratory and deceleratory HR responses, were higher during the first than second part of nocturnal sleep (P < 0.05). Moreover, habituation of P240 and N550 amplitudes was slower during the first than second part of sleep (P < 0.05). In supplementary experiments, AEP and HR responses to the same stimuli did not differ between the first and second part of the night when subjects were waking during stimulation. Results indicate a reduced inhibitory control over cortical stimulus processing during early nocturnal sleep. This diminished inhibition of cortical processing together with other concomitant changes during early sleep (such as the enhanced inhibition of pituitary-adrenal secretion) may reflect a coordinated regulatory function of sleep possibly mediated by hippocampal mechanisms.

Acoustic Stimulation↗
PubMed1995

Effects of adrenalectomy and corticosterone replacement on glucocorticoid receptor levels in rat brain tissue: a comparison between western blotting and receptor binding assays.

A sensitive Western blotting technique, using a commercially available antibody, was developed herein to study glucocorticoid receptor (GR) autoregulation in brain tissue. A prominent immunoreactive band at approximately 94 kDa, representing the GR, was observed in soluble fractions prepared from rat hippocampus whereas two bands (approximately 97 and 94 kDa) were detected in frontal cortex preparations. Four-day adrenalectomy significantly increased immunoreactive GR levels in both brain regions. In contrast, adrenalectomized animals implanted with corticosterone pellets of varying concentrations displayed dose-dependent decreases in immunodetectable GR levels. Radioligand binding assays ([3H]dexamethasone +/- RU 28362), performed on these same tissue preparations, revealed a similar pattern of GR response to that measured by Western blotting. However, changes in GR binding capacity were generally greater in magnitude than corresponding changes in immunoreactive GR levels. This discrepancy was most pronounced in adrenalectomized animals administered a bolus of corticosterone 1 h prior to sacrifice where a 60-70% reduction in receptor binding sites occurred, in sharp contrast to the 25-30% decrease in immunoreactive GR levels. Taken together, our findings suggest that Western blotting can be used to study GR regulation in brain tissue and that changes in steroid-binding capacity may not necessarily reflect changes in receptor protein levels.

Adrenalectomy↗
PubMed1994

Delirium as a contributing factor to "crescendo" pain: three case reports.

Cancer patients occasionally experience periods of rapidly escalating pain--"crescendo" pain--that may present a challenge in assessment and management. Although these episodes are often associated with progressive neoplasm, any of a variety of other processes may be involved. Delirium is a potentially treatable and frequently unrecognized factor. We present three patients who illustrate this relationship between delirium and a crescendo pattern of cancer pain.

Adenocarcinoma↗
PubMed1994

Longitudinal pulmonary function losses in Vermont granite workers. A reevaluation.

Previous studies have suggested that excessive losses of FVC and FEV1 were occurring in Vermont granite workers despite the fact that mean quartz levels existing in the industry were below the current OSHA standard of 100 micrograms/m3. We reexamined these losses in granite workers over an 8-year period, testing the workforce biennially from 1979 to 1987. All workers, including stone shed, quarry, and office, were offered forced spirometry using a 10-L water-sealed spirometer (Collins). In the peak year of participation (1983), 887 workers out of a total of approximately 1,400 were tested. Estimates of longitudinal loss were based on 711 workers who participated in at least three of the surveys. The mean age of this group was 42.9 years, and the mean years employed was 19.3 years; 21.4 percent were non-smokers (NS), 34.2 percent were ex-smokers (ES), and 44.4 percent were current smokers (CS). Average annual losses of FVC were 0.018 (SD = 0.056) L (CS, 0.025 L; NS, 0.006 L: and ES, 0.016 L). Average annual losses of FEV1 were 0.030 (SD = 0.041) L (CS, 0.038 L; NS, 0.020 L; and ES, 0.027 L). Analysis of covariance indicated that losses were related to the initial values for FVC or FEV1, height, age, and smoking status. After adjusting for these variables, the losses of both FVC and FEV1 were not correlated with years employed in the granite industry. No significant differences existed in the loss of FVC or FEV1 in categories of workers exposed to different levels of granite dust, eg, office, quarry, and stone shed workers. The annual losses of pulmonary function were significantly smaller than those estimated previously, which were 0.070 to .080 L in FVC, and 0.050-0.070 L in FEV1. We conclude that dust levels in the Vermont granite industry, which have been in conformance with OSHA permissible exposure limits, do not accelerate pulmonary function loss.

Adult↗
PubMed1992

Influence of a menhaden oil diet on cercarial penetration of Schistosoma mansoni.

The ability of a menhaden oil (MO) diet to influence cercarial penetration into mouse tail skin was evaluated. Male CD-1 mice 4-6 wk old (15.2 g average weight) were fed a 0, 10%, or 20% MO-supplemented diet for 2 wk. After this time mice were infected with either 65 +/- 3 or 145 +/- 3 [35S]methionine/cysteine-labeled cercariae for 1 hr by tail immersion. Twenty-four hours and 7 days later groups of mice were killed and their tail skin removed and autoradiographed. At 24 hr postinfection, mice fed a 20% MO diet had significantly higher cercarial penetration than controls and 10% MO diets (56% +/- 5.2 vs. 44% +/- 2.9, P = 0.02, 1-tailed t-test). After 7 days mice fed a 20% MO diet retained more radioactive foci than controls or 10% MO diets (21% +/- 2.0 vs. 15% +/- 1.3, P = 0.01, 1-tailed t-test).

Animals↗
PubMed1991

Isolation and characterization of a cytosolic aldehyde dehydrogenase-encoding cDNA from mouse liver.

A series of overlapping cDNA clones encoding AHD-2, the constitutive liver cytosolic aldehyde dehydrogenase of the mouse, were isolated from lambda gt11 libraries by screening with antibody and hybridization probes. Together, these clones span 2036 bp, virtually the entire Ahd-2 transcript. The protein corresponding to the cDNA contains 501 amino acids (aa) with a predicted Mr of 54467. The aa sequence is 87% and 84% identical to liver cytosolic AHDs of human and horse, respectively. Major and minor transcription start points (tsp), located 43 and 44 bp upstream from the ATG codon, respectively, were identified by primer extension analysis. The sequence of a 700-bp genomic fragment containing the first exon and 546 bp of 5'-flanking DNA was determined. TATA and CCAAT motifs are located 31 and 73 bp, respectively, from the major tsp.

Aldehyde Dehydrogenase↗