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Biomedical subjects

S Harvey

Publications and source records attributed to S Harvey.

At least 19 recordsLinked to original sources

The effects of continuous exposure to 20-kHz sawtooth magnetic fields on the litters of CD-1 mice.

Mated CD-1 mice were exposed to 20-kHz sawtooth magnetic fields similar to those associated with video display terminals (VDT). Four groups of animals were continuously exposed from day 1 to day 18 of pregnancy to field strengths of 0, 3.6, 17, or 200 microT. There were no less than 185 mated dams in each exposure group. On day 18, the dams were sacrificed and assessed for weight gain and pregnancy. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral and skeletal malformations, and fetal weights. There were no less than 140 pregnant females in each group, and there were no significant differences between any of the exposure groups and the sham group (0 microT) for any of the end points. The results of this study do not support the hypothesis that the 20-kHz VLF magnetic fields associated with video display terminals are teratogenic in mammals.

Abnormalities, Radiation-Induced

Thyroid and adrenal function in the ring dove (Streptopelia risoria) during food deprivation and a breeding cycle.

The concentration of plasma triiodothyronine (T3), thyroxine (T4), corticosterone, and glucose as well as body weight and food intake were measured in pairs of ring doves throughout a breeding cycle and during food deprivation. During courtship and incubation the levels of plasma T4 were significantly higher in males than in females. A transitory decrease in food intake in both sexes was measured at the onset of incubation but was not associated with a change in body weight or in levels of plasma thyroid hormones. After the eggs had hatched, food intake increased but was associated with a reduction in body weight and concentrations of plasma T3 and T4, although plasma corticosterone and glucose both increased. Food deprivation for 48 hr resulted in a significant fall in the concentration of plasma T3 and an increase in plasma corticosterone. These changes suggest that all the food was not being digested by the adult birds during brooding but was almost exclusively regurgitated to feed the squabs.

Adrenal Glands

Androgens are necessary for the establishment of secretory protein expression in the guinea pig seminal vesicle epithelium.

The guinea pig seminal vesicle epithelium (GPSVE) synthesizes and secretes milligram quantities of four related secretory proteins in an androgen-dependent manner. To investigate the role of androgens in the establishment of secretory protein synthesis during the development of the GPSVE, animals were castrated at Day 5, approximately 10 days before secretory protein accumulation begins in intact animals. Castration did not eliminate secretory protein mRNA from the SVE, but it did indefinitely postpone the developmentally programmed increase in secretory protein mRNA. Injection of neonatally castrated guinea pigs with either estradiol or dexamethasone did not alter levels of secretory protein mRNAs. However, treatment of castrated neonates with either testosterone propionate or dihydrotestosterone (DHT) led to specific increases in secretory protein mRNAs within 4 days. Although neonatally castrated animals accumulated and translated significant amounts of secretory protein mRNA, the newly synthesized secretory proteins failed to accumulate until exogenous androgens were provided. This observation suggests that androgens regulate both the accumulation of secretory protein mRNA and the accumulation of secretory proteins in the GPSVE.

Androgens

Relationship between serum and saliva theophylline levels in patients with cystic fibrosis.

Theophylline levels in stimulated and unstimulated mixed saliva were compared with total and free (unbound) serum theophylline levels in 11 outpatients with cystic fibrosis (CF) who were using theophylline regularly. Stimulated saliva from CF patients predicted both total and unbound serum theophylline concentrations to within +/- 1 microgram/ml in 53.3 and 80.0%, respectively, of the samples examined. In addition, the total serum levels from CF patients could be used to predict unbound serum concentrations to within +/- 1 micrograms/ml in 100% of the cases examined. Furthermore, it was observed that prediction equations derived in a previous study with asthmatics employing identical methodology would allow both unbound and total serum theophylline levels to be predicted from saliva levels in CF patients with a degree of accuracy and precision that was approximately equal to or slightly better than the results obtained using prediction equations derived in other CF patients. These results indicate that saliva levels allow predictions of the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable noninvasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 micrograms/ml, is approximately 5.55-11.3 micrograms/ml.

Adolescent

Patterns of alcohol consumption in white collar-workers--a cross-sectional and longitudinal study.

A 6-year follow-up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to data on sickness absence, promotion and labour turnover, revealed that even moderate alcohol and consumption in this population was associated with social costs for the employer and the employee, particularly in terms of sickness absence. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on promotion prospects and labour turnover.

Adult

Variability of the serum protein binding of theophylline in patients with asthma and cystic fibrosis.

1. The serum protein binding of theophylline was studied in 28 asthmatics and 11 patients with cystic fibrosis (CF) who were receiving the drug regularly. Peak theophylline samples were collected at 2 week intervals on four occasions in each asthmatic and on three occasions in each CF patient. The binding was measured using ultrafiltration at 37 degrees C and pH 7.4. The total and free (unbound) theophylline concentrations were measured using high-performance liquid chromatography. 2. The mean free-fractions (+/- s.d.) in asthmatics (0.50 +/- 0.03) and in CF patients (0.51 +/- 0.04) were not significantly different. The intra- and inter-subject variability in the free-fraction (fu) was relatively small in both patient groups. The binding was found to be concentration-independent at serum theophylline concentrations up to 30.9 micrograms ml-1. The effects of age, gender, serum albumin and total serum protein on the free fraction were evaluated. 3. The results indicate that the binding of theophylline is similar in the two disease states. The low degree of variability in serum theophylline binding indicates that measurements of total serum theophylline concentrations will reflect unbound serum concentrations with acceptable accuracy in both patient groups studied.

Adolescent

A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol.

Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover.

Absenteeism

Ubiquitous distribution of growth hormone receptors and/or binding proteins in adenohypophyseal tissue.

Liver GH receptor (GHR)-like mRNA has been shown to be widely distributed throughout rat and rabbit pituitary glands. In the present study RNA extracted from rabbit anterior pituitary glands was reverse transcribed, and the cDNA amplified by the polymerase chain reaction (PCR) in the presence of 3'- and 5'-flanking oligonucleotide primers for the extracellular and transmembrane domains of the rabbit GHR. A 499-basepair (bp) fragment was generated, identical in size to that in rabbit liver, kidney, and adipose tissue. Digestion of this fragment with a restriction endonuclease (SalI) produced moieties of 280 and 219 bp, as observed for the amplified cDNA fragments from liver, kidney, and adipose tissue. In situ hybridization of a cRNA probe for the rabbit GHR with cryostat sections of the anterior pituitary gland was demonstrated. Specific hybridization occurred throughout the adenohypophysis and was present in somatotroph and nonsomatotroph cells, identified by hybridization of the same tissue sections with a complementary riboprobe for rat GH mRNA. Electron microscopy and immunogold staining, using monoclonal antibodies against the extracellular domain of the rat (MAb 263) or rabbit (MAb 7) GHR, demonstrated the presence of the receptor or binding protein throughout rat and rabbit anterior pituitary gland. Immunostaining occurred in somatotroph and nonsomatotroph cells and was widely distributed throughout the intracellular and nuclear compartments. In GH-secreting cells gold particles were specifically accumulated in the secretory granules and heterochromatin, but were also present in mitochondria, Golgi, endoplasmic reticulum, cytoplasm, nucleoplasm, and cellular and nuclear membranes. A similar distribution of GHR immunoreactivity was observed within rat and rabbit hepatocytes. Specific binding sites for radiolabeled ovine GH to cytosolic fractions and to crude solubilized preparations of plasma and nuclear membranes of the rat anterior pituitary gland were also demonstrated. The binding of the tracer to these sites was inhibited by prior exposure to MAb 263, which binds to epitopes in the ligand-binding domain of the rat GHR. These results provide evidence of 1) the expression and translation of the GHR gene in rat and rabbit adenohypophysis in 2) GH and non-GH-secreting cells, and 3) the presence of GH receptors/binding proteins throughout the intracellular and nuclear compartments of these cells.

Animals

Expression and translation of the growth hormone-receptor gene in the guinea-pig.

The refractoriness of guinea-pigs to the growth-promoting actions of exogenous GH has been suggested to be due to a deficiency or defect in tissue GH receptors or in GH-receptor gene expression. GH-receptor mRNA was, however, demonstrated by Northern blot analysis and by the polymerase chain reaction in extracts of guinea-pig liver, adipose tissue, brain, hypothalamus and pituitary gland. High-affinity, low-capacity binding sites for radio-labelled ovine GH were also demonstrated on the plasma membranes of guinea-pig liver and were similar to those in rat liver. These results demonstrate that the unresponsiveness of guinea-pigs to exogenous GH is not due to the absence of GH receptors.

Adipose Tissue

Expression of the growth hormone receptor gene in chicken pituitary glands.

Although GH has no direct effect on GH release from chicken pituitary glands, GH receptor mRNA similar to that in the rabbit liver was identified by Northern blot analysis in extracts of adult chicken pituitaries. Complementary (c) DNA, reverse transcribed from chicken pituitary RNA, was amplified by the polymerase chain reaction (PCR) in the presence of 3'- and 5'-oligonucleotide primers coding for the extracellular domain of the chicken liver GH receptor and was found to contain an electrophoretically separable fragment of 500 bp, identical in size to that in chicken liver. Digestion of this pituitary cDNA with NcoI produced expected moities of 350 and 150 bp. Amplification of chicken pituitary cDNA in the presence of oligonucleotide primers for the intracellular sequence of the chicken liver GH receptor produced an electrophoretically separable fragment of approximately 800 bp, similar to that in chicken liver. This fragment was cut into expected moieties of 530 and 275 bp after digestion with EcoRI. These PCR fragments were identified in extracts of the pituitary caudal lobe, in which somatotrophs are confined and account for the majority of endocrine cell types, and in the cephalic lobe, in which somatotrophs are lacking. Translation of the GH receptor mRNA in the pituitary gland was indicated by the qualitative demonstration of radiolabelled GH-binding sites in plasma membrane preparations, in pituitary cytosol and in nuclear membranes. These results provide evidence for the expression and translation of the GH receptor gene in pituitary tissue, in which GH receptors appear to be widely distributed within cells and in different cell types. GH may therefore have paracrine, autocrine or intracrine effects on pituitary function.

Animals

Risk of human infections with Crimean-Congo hemorrhagic fever virus in a South African rural community.

Crimean-Congo hemorrhagic fever (CCHF) virus is widely distributed in wild and domestic mammals, birds, and ticks throughout many regions of Africa, Europe, and Asia. Interviews were conducted with 484 individuals from nine farms in the Republic of South Africa from which recent human CCHF cases had originated and with individuals from 27 farms without recognized cases. Serum samples were obtained from all consenting individuals. Blood was also drawn from 2,212 farm animals. Human infection with CCHF virus was uncommon (point prevalence 12.6/1,000). Antibody prevalence in humans on farms increased with age (P less than 0.001), and was correlated with handling lambs. Overall, a greater number of older animals were antibody positive than animals less than one year of age (P less than 0.001), but 12.7% of young animals on farms with human were antibody positive compared with 5.8% on those farms without human infection (P less than 0.05). Physical contact with ticks or tick bite was also found to be a risk factor, but contact with animal blood or fresh meat was not. The risk of CCHF virus infection in the community increased seven-fold following contact with a recognized CCHF case, even when other risk factors were taken into account (point prevalence rate 4.7%). In contrast, antibody prevalence was less than 1% (1 of 128) in the local hospital staff who had cared for patients with CCHF. Prevention is best achieved by education of the farming community and establishing and maintaining awareness in the hospital staff.

Adult

Serum/saliva correlations for theophylline in asthmatics.

Theophylline levels in mixed saliva (both stimulated and unstimulated) were compared with total and free (unbound) serum theophylline levels in 28 asthmatic outpatients using theophylline regularly. Stimulated saliva predicted both total and unbound serum theophylline concentrations within +/- 1 microgram/mL in 62.5% and 92.9%, respectively, of the samples examined. In addition, the total serum levels could be used to predict unbound serum concentrations to within +/- 1 mg/L in 100% of the cases that were examined. These results indicate that saliva levels predict the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable non-invasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 mg/L, is approximately 5.6-11.3 mg/L.

Administration, Oral

Central somatostatinergic regulation of growth hormone secretion in dwarf chickens.

1. Basal circulating growth hormone (GH) concentrations in sex-linked-dwarf (SLD) chickens were unaffected by the intracerebroventricular (icv) injection of 10, 50 or 100 micrograms somatostatin (SRIF). 2. The GH response to systemic thyrotropin-releasing hormone (TRH; 10 micrograms/kg, iv) was, however, 'paradoxically' enhanced 20 min after icv SRIF administration. 3. A lower dose (1.0 micrograms) of SRIF had no effect on basal or TRH-induced GH release. 4. High-titre SRIF antisera (4 microliters) also had no acute effect on basal plasma GH concentrations, but augmented the GH response to TRH challenge. 5. SRIF would appear to act at central sites to modulate stimulated GH secretion in SLD chickens.

Animals

Differential effects of T4 and T3 on TRH- and GRF-induced GH secretion in the domestic fowl.

The in vivo growth hormone (GH) response of immature domestic fowl to thyrotrophin-releasing hormone (TRH) and GH-releasing factor (GRF) was suppressed in birds fed diets supplemented (1 ppm) with triiodothyronine (T3) or given bolus intraperitoneal (ip) injections (100 micrograms/kg for 10 d) of T3. Supplementation (ppm) of the diet with T4 had no effect on secretagogue- induced GH release. Exogenous T3 or T4 suppressed basal, TRH- and GRF-induced GH release 2 h after daily ip administration (100 micrograms/kg for 10 d). 24 h after the last injection, only T3 was effective in inhibiting basal and stimulated GH secretion in vivo. The systemic administration of T3 was followed 2 h and 24 h later by a downregulation of pituitary TRH binding sites. T4 administration had no effect on pituitary TRH binding. When chicken pituitary glands were incubated in vitro, basal GH release was unaffected by the addition of 10(-9)-10(-5) M T3 or T4 to the incubation media. The in vitro GH response to TRH (10(-6) M) or GRF (10(-6) M) challenge was, however, suppressed in a dose-related manner by T3 but was unaffected by the coincubation of T4. These results demonstrate inhibitory effects of T3 and T4 on basal and secretagogue-induced GH secretion in fowl. T4 is less active than T3 and probably exerts some of its effects via T3-independent mechanisms.

Administration, Oral

Post-transcriptional regulation of secretory protein production during the development of the guinea pig seminal vesicle.

To investigate the influence of androgens on secretory protein expression during the development of the guinea pig seminal vesicle epithelium, we examined the patterns of mRNA and protein accumulation during the first 2 wk after birth. Hybridization of total seminal vesicle RNA to cDNA probes revealed that the secretory protein genes were active as early as 5 days after birth. However, the accumulation of secretory proteins was barely detectable between Days 5 and 10, and could not be enhanced by treatment of neonatal animals with exogenous androgens. Secretory protein mRNA and protein levels both increased rapidly between Days 10 and 15. However, the 800-fold rise in protein levels between Days 5 and 15 greatly exceeded the magnitude of the increase in secretory protein mRNA that occurred during this interval. These data indicate that the rate of secretory protein accumulation in the guinea pig seminal vesicle is not determined strictly by the availability of secretory protein mRNA, and suggest that post-transcriptional mechanisms may contribute to the regulation of secretory protein accumulation in neonatal guinea pigs.

Aging

Hemolytic and sphingomyelinase activities of Clostridium perfringens alpha-toxin are dependent on a domain homologous to that of an enzyme from the human arachidonic acid pathway.

The N-terminal domain of Clostridium perfringens alpha-toxin, homologous with the nontoxic phospholipase C of Bacillus cereus, was expressed in Escherichia coli and shown to retain all of the phosphatidylcholine hydrolyzing activity of the alpha-toxin, but not the sphingomyelinase, hemolytic, or lethal activities. The C-terminal domain of alpha-toxin showed sequence and predicted structural homologies with the N-terminal region of arachidonate 5-lipoxygenase, an enzyme from the human arachidonic acid pathway which plays a role in inflammatory and cardiovascular diseases in humans.

Amino Acid Sequence

Hypo- and hypercalcemic peptides in fish pituitary glands.

Immunoreactive parathyroid hormone (irPTH), PTH-related peptide (PTHrp), and stanniocalcin-like peptides were detected in Coho salmon pituitary glands. The PTH, PTHrp, and stanniocalcin immunoreactivity of the salmon pituitary was separated by high-performance liquid chromatography purification into distinct peptide fractions that coeluted with pure preparations of these hormones. Stanniocalcin was localized by immunocytochemistry in the neurohypophysis and preoptic area of the platyfish brain, in areas in which irPTH has previously been detected in other teleosts. Although it is well established that the fish pituitary exerts hypercalcemic control over calcium metabolism, these results demonstrate the presence of hyper- and hypocalcemic peptides in teleost pituitary glands. The detection of PTHrp in the fish pituitary is the first report of its presence outside of mammalian species and suggests an early evolutionary divergence of PTH and PTHrp from an ancestral gene.

Animals