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Biomedical subjects

B J Davis

Publications and source records attributed to B J Davis.

At least 73 records · Page 4Linked to original sources
PubMed1997

Brca1 is expressed independently of hormonal stimulation in the mouse ovary.

BRCA1 mutations lead to cancer susceptibility in hormonally dependent tissues such as the ovary and breast. To test the hypothesis that Brca1 expression in the ovary is hormonally regulated and specifically regulated by a functional estrogen receptor, we examined its expression by in situ hybridization in ovaries from virgin, pregnant, and lactating mice, in hypophysectomized mice treated with hormones, and in estrogen-receptor-deficient mice. To determine the relationship between Brca1 expression and cell cycle, serial and adjacent sections of ovary were evaluated for proliferating cell nuclear antigen by immunohistochemistry. Regardless of the model, Brca1 was consistently expressed in granulosa and thecal cells of follicle populations that proliferate independently of hormonal stimulation. Expression was similar in these same follicle populations in the ovaries of estrogen-receptor-deficient mice, in which the lack of this estrogen receptor results in abnormal and incomplete follicular development. Brca1 expression was diminished in the granulosa and thecal cells of hormonally dependent antral follicles. Brca1 expression was also localized to luteal cells of recently formed corpora lutea and corpora lutea associated with pregnancy, but it was greatly diminished in regressing corpora lutea in cycling mice. In all cases, Brca1 expression correlated to S-phase proliferating cell nuclear antigen nuclear staining. Thus, Brca1 expression in the mouse ovary occurs independently of hormonal status and in the absence of a major estrogen receptor-mediated pathway; it is, however, closely correlated with cell cycle in mouse ovarian granulosa, thecal, and luteal cell.

Animals↗
PubMed1997

Disruption of the mouse cyclooxygenase 1 gene. Characteristics of the mutant and areas of future study.

Surprisingly, disruption of the COX-1 gene resulted in generally healthy mice. This is in spite of the fact that prostaglandin levels in the tissues examined were reduced by greater than 99%. The results obtained to date with the COX-1 deficient mice indicate that some of the physiological roles previously attributed to COX-1 may not be entirely correct. Ongoing studies with the COX deficient mice are aimed at better defining the physiological roles of the cyclooxygenases and concomitantly the mechanisms by which NSAIDs cause their biological effects.

Animals↗
PubMed1996

Cystic hygroma of the arm: a case report and review of the literature.

Cystic hygromas arising outside of the cervicofacial, thoracic, and abdominal areas are extremely rare. Detailed descriptions of this lesions along with its MRI findings, in the extremities are lacking in the literature. The following case report describes such a lesion occurring in the arm.

Adult↗
PubMed1996

Hemolytic-uremic syndrome without evidence of microangiopathic hemolytic anemia on peripheral blood smear.

We report the case of an 18-year old man with hemolytic-uremic syndrome (HUS) having a classic clinical presentation and diagnostic renal pathology without evidence of microangiopathic hemolytic anemia (MAHA) by peripheral blood smear. Indirect evidence of hemolysis was suggested by mild anemia, elevation of serum lactate dehydrogenase, and examination of the patient's bone marrow. We postulate that in this case the inability to detect schistocytes in the peripheral smear reflected a low degree of hemolysis. Review of the literature revealed that evidence of fragmented erythrocytes by peripheral smear is not always present in HUS, yet this observation has received little attention. Thus, the diagnosis of HUS need not include overt evidence of MAHA as is traditionally taught.

Adolescent↗
PubMed1995

Dextromethorphan analogs are neuroprotective in vitro and block glutamate-induced excitotoxic calcium signals in neurons.

Consistent with the neuroprotective effects of the non-opioid antitussive dextromethorphan (DM) described in several models of CNS injury, micromolar concentrations of three novel analogs of DM markedly attenuated the injury produced by glutamate in cultured rat cortical neurons. Furthermore, the neuroprotective actions of the DM analogs correlated with their effects to block glutamate-induced excitotoxic calcium signals and were unrelated to metabolism to the phencyclidine (PCP)-like drug dextrorphan (DX). These observations establish a new class of compounds related to DM which, by virtue of their efficacy to protect neurons against a severe glutamate insult, may possess therapeutic potential as treatment modalities for a number of neurodegenerative diseases.

Animals↗
PubMed1995

Tuberculosis in health care workers at a hospital with an outbreak of multidrug-resistant Mycobacterium tuberculosis.

OBJECTIVE: Investigate reports of tuberculosis in health care workers employed at a hospital with an outbreak of multidrug-resistant Mycobacterium tuberculosis. DESIGN: Case series of tuberculosis in health care workers, January 1, 1989, through May 31, 1992. Antimicrobial susceptibility testing and restriction fragment length polymorphism analysis of M tuberculosis isolates. Longitudinal analysis of cumulative tuberculin skin test surveillance data. Assessment of infection control. The patients consisted of 361 health care workers who had either serial tuberculin skin tests or tuberculosis. RESULTS: Six health care workers, the largest number linked to one multidrug-resistant tuberculosis outbreak, had disease due to M tuberculosis that matched the outbreak strain from hospitalized patients. The two who were seropositive for human immunodeficiency virus died, one of tuberculous meningitis and the other of multiple causes including tuberculosis. The estimated risk of a skin test conversion was positively associated with time and increased by a factor of 8.3 (1979 to 1992). In 1992 the annual risk for workers in the lowest exposure occupational group was 2.4%. In comparison, nurses and housekeepers had relative risks of 8.0 (95% confidence interval, 3.2 to 20.3) and 9.4 (95% confidence interval, 2.7 to 32.3), respectively. Laboratory workers had a relative risk of 4.2 (95% confidence interval, 1.1 to 15.5). Tuberculosis admissions increased, but the hospital had inadequate ventilation to isolate tuberculosis patients effectively. There were lapses in infection control practices. CONCLUSIONS: Health care workers who were exposed during a hospital outbreak of multidrug-resistant tuberculosis had occupationally acquired active disease. The human immunodeficiency virus-infected health care workers with tuberculosis had severe disease and died. The risk of skin test conversion increased during the study period, and higher exposure occupations had elevated risk. Effective infection control is essential to prevent the transmission of tuberculosis to health care workers.

AIDS-Related Opportunistic Infections↗
PubMed1995

The reproductive and developmental toxicity of indium in the Swiss mouse.

Indium is increasingly used in a variety of industries, and while there are few studies of its developmental toxicity, ther are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to determine the relative vulnerability of males and females. We used, initially, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl3 ( < or = 250 mg/kg) were without effect on the male reproductive system or liver. A kidney effect was demonstrated in males by a decrease in urinary N-acetyl glucosaminidase. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intrauterine deaths in the presence of reduced maternal weight gain. A developmental toxicity study identified no increase in fetal malformations, but verified the increased fetal deaths, in the absence of effects on adjusted maternal body weight. In vitro toxicity studies showed that the embryolethality was at least in part a result of direct toxicity to the conceptus, with effective doses in the low micromolar range. A limited disposition study showed that fetuses contained low micromolar concentrations of indium, more indium than maternal liver, and comparable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicate that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low micromolar levels in vivo and at exposures that may or may not affect body weight.

Abnormalities, Drug-Induced↗
PubMed1995

Early changes in sex hormones are not evident in mice exposed to the uterine carcinogens chloroethane or bromoethane.

Chloroethane and bromoethane have been shown to cause a marked uterine tumor response in B6C3F1 mice exposed for 2 years. These chemicals are nearly unique in this regard among the nearly 400 chemicals studied by the National Toxicology Program, and the reasons for this carcinogenic activity are unclear. The possible relationship of changes in blood concentrations of sex hormones to this response was evaluated by examining the estrous cycle of mice prior to and during a 21-day exposure to concentrations of the haloethanes which resulted in the tumorigenic response in the 2-year studies. Serum concentrations of estradiol and progesterone were determined at the termination of the exposures and compared to exposure group and stage of the estrous cycle. No consistent patterns of change were found in estrous cyclicity or in blood concentrations of sex hormones. Thus, the findings suggest that early changes in circulating sex hormones are not important contributing factors in the uterine neoplasia caused by these chemicals.

Animals↗
PubMed1994

Di-(2-ethylhexyl) phthalate suppresses estradiol and ovulation in cycling rats.

Di-(2-ethylhexyl) phthalate (DEHP) is a known reproductive toxicant and a carcinogen in rodent animal models. DEHP may also be a reproductive toxicant in women. Its action in female animal models is undetermined, although its potential to target the ovary has recently been shown. We have identified the ovarian toxicity and target cells of DEHP in the female rat. Adult, regularly cycling Sprague-Dawley rats were dosed daily with 2 g/kg DEHP in corn oil by gavage for 1 to 12 days. Ovarian morphology and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone levels were analyzed. DEHP exposure resulted in prolonged estrous cycles. Specifically, 35 of 42 DEHP-treated rats had 5- or 6-day cycles and only 7 of 42 had a 4-day cycle compared to 44 of 45 control rats with 4-day cycle lengths. DEHP treatment also suppressed or delayed ovulations by the first proestrus/estrus after metestrus-initiated dosing. Microscopic evaluation of the ovaries determined that 7 of 10 DEHP-exposed rats had not ovulated by vaginal estrus, whereas 13 of 13 control rats had ovulated by vaginal estrus. Thus, DEHP treatment significantly altered natural ovulation times. Preovulatory follicles were also quantitatively smaller in DEHP-exposed rats than in controls because the granulosa cells were smaller. The mean control rat preovulatory follicle granulosa cell area was 16 +/- 3 x 10(3) microns, whereas the mean DEHP-treated rat preovulatory follicle granulosa cell area was 12 +/- 4 x 10(3) microns. DEHP exposure significantly suppressed preovulatory follicle granulosa cell estradiol production over 8 days of exposure. Suppressed serum estradiol levels caused secondary increases in FSH levels and did not stimulate the LH surge necessary for ovulation. Consequently, ovulation did not occur in DEHP-treated rats, although DEHP-treated rats ovulated after treatment with human chorionic hormone. Vaginal lavage cytology from rats treated with DEHP did not detect the ovarian toxicity as shown by histology and hormone analysis. In summary, exposure to DEHP resulted in hypoestrogenic anovulatory cycles and polycystic ovaries in adult female rats.

Analysis of Variance↗
PubMed1994

Mono-(2-ethylhexyl) phthalate suppresses estradiol production independent of FSH-cAMP stimulation in rat granulosa cells.

Di-(2-ethylhexyl) phthalate (DEHP) exposure suppressed preovulatory granulosa cell estradiol production in adult cycling rats. The active metabolite of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), suppressed follicle-stimulating hormone (FSH)-stimulated cAMP and progesterone production in cultured rat granulosa cells. To examine how DEHP altered granulosa cell estradiol production, the effects of MEHP were studied in cultures of rat granulosa cells. Granulosa cells were obtained from DES-implanted 25-day-old female Fisher 344 rats and exposed in culture to various concentrations of MEHP (0 to 400 microM) in DMSO. Granulosa cells were stimulated with FSH, 8-bromo cyclic adenosine monophosphate (8br-cAMP), a stable cAMP analog, and various concentrations of testosterone. Estradiol production was measured by standard radioimmunoassays and normalized to cell protein. MEHP suppressed estradiol in a concentration-dependent manner whether granulosa cells were stimulated by FSH or 8-br cAMP. Therefore, MEHP suppressed estradiol independent of its suppression of the FSH-cAMP pathway and, thus, suppressed aromatase conversion of testosterone to estradiol. MEHP (100 microns) decreased the maximum velocity of aromatase in cells supplied with increasing concentrations of testosterone. However, MEHP did not alter the velocity or affinity of microsomal aromatase isolated from adult virgin Sprague-Dawley rat ovaries. Therefore, MEHP altered the absolute amount or availability of aromatase in granulosa cells. Decreased aromatase in granulosa cells would explain decreased estradiol concentrations from DEHP exposure in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Ranitidine-induced cranial dystonia.

We report a case of cranial dystonia related to the administration of ranitidine. The symptoms started shortly after institution of treatment, resolved after discontinuation, and recurred upon repeat administration of the drug. Although there have been a few reports of abnormal involuntary movements related to other histamine2 antagonists, this is only the second reported instance due to ranitidine and the first reported instance of dystonia related to the drug. The pathophysiology of this effect is unclear, but a central cholinergic effect of this agent may be a contributing factor.

Aged↗
PubMed1993

Distribution of tachykinin- and opioid-expressing neurons in the hamster solitary nucleus: an immuno- and in situ hybridization histochemical study.

In several sensory systems, tachykinin- and opioid-expressing neurons functionally interact and influence the processing of afferent information. To determine whether a similar relationship exists for the processing of general and special (gustatory) visceral afferent information, the present study mapped the distributions of these two neuronal phenotypes within the nucleus of the solitary tract (NST) of the hamster by employing a combination of immuno- and in situ hybridization histochemistry (ISHH). The hamster was chosen because it is frequently used as a model in taste studies, yet there is a relative dearth of data about peptide expression or the classical neurotransmitters in the brainstem of this animal. The immunohistochemical analyses employed 2 highly selective antisera directed towards the prototypical tachykinin and opioid peptides, i.e. substance P (SP) and methionine enkephalin (ENK), respectively. Intense staining of fibers and preterminal/terminal puncta was concentrated in the rostral pole or gustatory zone of the NST. SP-, but not ENK-like immunoreactivity was also observed in long courses of axon bundles traversing the brainstem enroute to the NST. Local application of colchicine engendered the appearance of a moderate number of SP-positive somata that were mostly clustered in the medial, central and intermediate subnuclei, as well as being scattered throughout the remainder of the NST, including the gustatory zone. A low number of isolated ENK-positive somata were also observed throughout the NST. The somal areas of the SP- and ENK-positive somata averaged 86.3 and 81.8 microns 2, respectively. The ISHH studies were performed using 2 selective oligodeoxynucleotide probes with complementary sequences to mRNAs encoding gamma-preprotachykinin (PPT) and preproenkephalin (PPE) molecules. Overall, the cellular expression of PPT mRNA within the NST corresponded both in distribution and in number to those identified by immunohistochemical analyses using anti-SP serum. In contrast, ISHH analyses monitored a significantly greater number of PPE-expressing somata in the medial, central, intermediate and ventrolateral nuclei than were ENK immunoreactive. These findings indicate that tachykinin and opioid peptide phenotypes are represented in neurons throughout the hamster NST and suggest a functional role for PPT- and PPE-related peptide forms in the modulation of afferent general visceral and gustatory information.

Animals↗
PubMed1993

GABA-like immunoreactivity in the gustatory zone of the nucleus of the solitary tract in the hamster: light and electron microscopic studies.

The distribution of GABA-like immunoreactive (GABA-LI) somata was studied in the gustatory zone of the nucleus of the solitary tract (NST) in the hamster in order to identify putative inhibitory circuitry in gustatory processing. Immunoreactive somata were located throughout the gustatory NST, in accordance to the distribution of large and small types of neurons as determined in previous morphometric studies. Consequently, GABA-LI somata were mostly found in the dorsal two-thirds of the gustatory zone. Such somata were mostly ovoid in shape and possessed somal areas that averaged 85.5 +/- 2.8 microns 2 (12.7 x 8.4 microns). A narrow range of somal areas (50-125 microns 2) suggested a single functional group. At the electron microscopic level, 18% of the neurons encountered were immunoreactive and their nuclei always possessed deeply invaginated boundaries. This morphological feature indicated that GABA-LI neurons are smaller members of the most common class of neurons within the gustatory NST. Because GABA is often implicated as the neurotransmitter of small inhibitory local circuit neurons, these findings indicate a possible inhibitory aspect to the processing of taste information at the level of the first relay in the brainstem.

Animals↗
PubMed1993

Transmission of multidrug-resistant Mycobacterium tuberculosis among persons with human immunodeficiency virus infection in an urban hospital: epidemiologic and restriction fragment length polymorphism analysis.

From January 1990 to December 1991, 16 patients with multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis resistant to isoniazid, rifampin, and streptomycin were diagnosed at Elmhurst Hospital. Compared with other TB patients, MDR-TB patients were more likely to have human immunodeficiency virus (HIV) infection (14/16 vs. 21/204, P < .001) and a prior admission (10/16 vs. 3/204, P < .001). HIV-infected patients hospitalized for > 10 days within three rooms of an infectious MDR-TB patient had higher risk of acquiring MDR-TB than did HIV-infected patients with shorter hospitalizations or locations further from the MDR-TB patient(s) (6/28 vs. 2/90, P < .001). Isolates of 6 of 8 MDR-TB patients in a chain of transmission were identical by restriction fragment length polymorphism DNA typing. Ambulation on the wards of inadequately masked TB patients and lack of negative pressure in isolation rooms probably facilitated transmission. This report documents nosocomial transmission of MDR-TB and underscores the need for effective isolation practices and facilities in health care institutions.

AIDS-Related Opportunistic Infections↗