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Biomedical subjects

B J Davis

Publications and source records attributed to B J Davis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Clonal selection of CD56+ t(8;21) AML blasts: further suggestion of the adverse clinical significance of this biological marker?

Although patients with acute myelogenous leukaemia (AML) and t(8;21)(q22;q22) have a favourable prognosis, a subset die despite receiving appropriate treatment. Recent reports suggest that expression of the CD56 antigen might predict for both extramedullary disease and poor outcome in these patients. We describe a patient who presented with CD56-negative t(8;21) AML who achieved a complete remission and was subsequently treated with three consolidative courses of high-dose cytarabine therapy. She relapsed 9 months later with extramedullary and bone marrow involvement of CD56-positive t(8;21) AML. This case demonstrates clonal evolution and provides further support that blast expression of CD56 might be an unfavourable prognostic factor in t(8;21) AML.

Adult↗
PubMed1999

Hydranencephaly and cerebellar hypoplasia in two kittens attributed to intrauterine parvovirus infection.

Six weeks after vaccination with modified live feline parvovirus vaccine, a cat gave birth to five kittens, three of which died soon afterwards. The remaining two kittens (A and B) survived, but at 8 weeks of age were unable to walk and showed abnormal behaviour, with lack of menace and oculovestibular responses, and severe dysmetria. These signs suggested multifocal disease associated with the cerebrum and cerebellum. Magnetic resonance imaging demonstrated severe bilateral (kitten A) or unilateral (kitten B) hydrocephalus or hydranencephaly, combined with cerebellar agenesis (kitten A) or severe hypoplasia (kitten B). Hydranencephaly was confirmed histopathologically in both kittens. Parvovirus was isolated from the kidney of one kitten. Parvoviral DNA was amplified by the polymerase chain reaction (PCR) from paraffin wax-embedded brain of both kittens. The severe malformations observed in these kittens presumably resulted from an in-utero parvovirus infection, possibly due to vaccination, that occurred late in the first, or early in the second, trimester of pregnancy.

Animals↗
PubMed1999

Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1beta.

Mice carrying a null mutation for either of the two cyclooxygenase (COX) isoenzymes, necessary for prostanoid production, exhibit several isotype-specific reproductive abnormalities. Mice deficient in COX-1 are fertile but have decreased pup viability, whereas mice deficient in COX-2 fail to ovulate and have abnormal implantation and decidualization responses. The present study identifies the specific contribution of each COX isoenzyme in hypothalamic, pituitary, and ovarian function and establishes the pathology and rescue of the anovulatory syndrome in the COX-2-deficient mouse. In both COX-1- and COX-2-deficient mice, pituitary gonadotropins were selectively increased, whereas hypothalamic LHRH and serum gonadotropin levels were similar to those in wild-type animals (+/+). No significant differences in serum estrogen or progesterone were noted among the three genotypes. Exogenous gonadotropin stimulation with PMSG and hCG produced a comparable 4-fold increase in ovarian PGE2 levels in wild-type and COX-1(-/-) mice. COX-2(-/-) mice had no increase in PGE2 over PMSG-stimulated levels. Wild-type and COX-1(-/-) mice ovulated in response to PMSG/hCG; very few COX-2(-/-) animals responded to this regimen. The defect in ovulation in COX-2 mutants was attributed to both an abnormal cumulus oophorum expansion and subsequent stigmata formation. Gonadotropin stimulation and concurrent treatment with PGE2 or interleukin-1beta resulted in ovulation of COX-2(-/-) mice comparable to that in COX-2(+/+), whereas treatment with PGF2alpha was less effective. Collectively, these data demonstrate that COX-2, but not COX-1, is required for the gonadotropin induction of ovarian PG levels; that COX-2-related prostanoids are required for stabilization of the cumulus oophorum during ovulation; and that ovulation can be restored in the COX-2(-/-) animals by simultaneous treatment with gonadotropins and PGE2 or interleukin-1beta.

Animals↗
PubMed1999

Evaluating the effects of endocrine disruptors on endocrine function during development.

The major concerns with endocrine disruptors in the environment are based mostly on effects that have been observed on the developing embryo and fetus. The focus of the present manuscript is on disruption of three hormonal systems: estrogens, androgens, and thyroid hormones. These three hormonal systems have been well characterized with regard to their roles in normal development, and their actions during development are known to be perturbed by endocrine-disrupting chemicals. During development, organs are especially sensitive to low concentrations of the sex steroids and thyroid hormones. Changes induced by exposure to these hormones during development are often irreversible, in contrast with the reversible changes induced by transient hormone exposure in the adult. Although it is known that there are differences in embryonic/fetal/neonatal versus adult endocrine responses, minimal experimental information is available to aid in characterizing the risk of endocrine disruptors with regard to a number of issues. Issues discussed here include the hypothesis of greater sensitivity of embryos/fetuses to endocrine disruptors, irreversible consequences of exposure before maturation of homeostatic systems and during periods of genetic imprinting, and quantitative information related to the shape of the dose-response curve for specific developmental phenomena.

Adult↗
PubMed1999

Extragonadal teratocarcinoma in chimeric mice.

Chimeric mice often are created through the genetic manipulation of the mouse embryo in the process of developing animal models of disease. These mice have variable percentages of their somatic and germ cells derived from the donor embryonic stem cells and host blastocysts. In the development of mouse models deficient in the breast cancer susceptibility gene 2 (Brca2) or the 70-kd heat shock protein (Hsp70-2), 3-4-week-old chimeras developed single or multiple masses composed of both well-differentiated and poorly differentiated tissues derived from all three germ layers. These cases of extragonadal teratocarcinoma, a rarely reported tumor, may be related to the genetic predisposition of the 129/Ola mouse strain used to generate the embryonic stem cells.

Animals↗
PubMed1998

Excitatory and inhibitory modulation of taste responses in the hamster brainstem.

The rostral portion of the nucleus of the solitary tract (NST) contains second-order gustatory neurons, sends projections to the parabrachial complex and brainstem reticular formation, and receives descending projections from several nuclei of the ascending gustatory pathway. Electrophysiological responses of NST neurons can be modulated by several factors, including blood glucose and insulin levels and taste aversion conditioning. We are using extracellular electrophysiological recording in vivo, combined with local microinjection of neurotransmitter agonists and antagonists, to study the mechanisms by which taste responses of cells in the hamster NST can be modulated. Afferent fibers of the chorda tympani (CT) nerve make excitatory synaptic contact with NST neurons; this excitation is probably mediated by the excitatory amino acid glutamate. Microinjection of kynurenic acid, a nonspecific glutamate receptor antagonist, into the NST completely and reversibly blocks afferent input from the CT nerve, produced by either anodal electrical or chemical stimulation of the anterior tongue. The non-NMDA ((RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) also completely blocks gustatory input to these cells, whereas the N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) produces only a small effect. There are many gamma-aminobutyric acid (GABA)-containing neurons within the NST and taste-responsive NST cells are maintained under a tonic GABAergic inhibition. Microinjection of the GABAA receptor antagonist bicuculline methiodide increases the taste responsiveness of NST neurons, whereas application of GABA inhibits taste responses in these cells. Preliminary data show that GABAergic inhibition can be produced by stimulation of the gustatory cortex. There are both intrinsic substance P (SP)-containing neurons and extrinsic SP-immunoreactive fibers in the rostral NST. Microinjection of SP into the NST enhances the responses of many NST cells to gustatory stimulation; NaCl-best neurons are preferentially excited by SP.

Animals↗
PubMed1998

Synaptic relationships between the chorda tympani and tyrosine hydroxylase-immunoreactive dendritic processes in the gustatory zone of the nucleus of the solitary tract in the hamster.

The toxic lectin ricin was applied to the hamster chorda tympani (CT), producing anterograde degeneration of its terminal boutons within the gustatory zone of the nucleus of the solitary tract (NST). Immunocytochemistry was subsequently performed with antiserum against tyrosine hydroxylase (TH), and the synaptic relationships between degenerating CT terminal boutons and either TH-immunoreactive or unlabeled dendritic processes were examined at the electron microscopic level. Degenerating CT terminal boutons formed asymmetric axodendritic synapses and contained small, clear, spherical synaptic vesicles that were densely packed and evenly distributed throughout the ending, with no accumulation at the active synaptic. The degenerating CT terminated on the dendrites of TH-immunoreactive neurons in 36% (35/97) of the cases. The most frequent termination pattern involved the CT and two or three other inputs in synaptic contact with a single immunoreactive dendrite, resulting in a glomerular-like structure that was enclosed by glial processes. In 64% (62/97) of the cases, the degenerating CT was in synaptic contact with unlabeled dendrites, often forming a calyx-like synaptic profile that surrounded much of the perimeter of a single unlabeled dendrite. These results indicate that the TH-immunoreactive neurons of the gustatory NST receive direct input from the CT and taste receptors of the anterior tongue and that the termination patterns of the CT vary with its target neuron in the gustatory NST. The glomerular-like structure that characterizes many of the terminations of the CT provides an opportunity for the convergence of several functionally distinct inputs (both gustatory and somatosensory) onto putative dopaminergic neurons that may shape their responsiveness to the stimulation of the oral cavity.

Animals↗
PubMed1998

Brca1 and Brca2 expression patterns in mitotic and meiotic cells of mice.

The mouse homologues of the breast cancer susceptibility genes, Brca1 and Brca2, are expressed in a cell cycle-dependent fashion in vitro and appear to be regulated by similar or overlapping pathways. Therefore, we compared the non isotopic in situ hybridization expression patterns of Brca1 and Brca2 mRNA in vivo in mitotic and meiotic cells during mouse embryogenesis, mammary gland development, and in adult tissues including testes, ovaries, and hormonally altered ovaries. Brca1 and Brca2 are expressed concordantly in proliferating cells of embryos, and the mammary gland undergoing morphogenesis and in most adult tissues. The expression pattern of Brca1 and Brca2 correlates with the localization of proliferating cell nuclear antigen, an indicator of proliferative activity. In the ovary, Brca1 and Brca2 exhibited a comparable hormone-independent pattern of expression in oocytes, granulosa cells and thecal cells of developing follicles. In the testes, Brca1 and Brca2 were expressed in mitotic spermatogonia and early meiotic prophase spermatocytes. Northern analyses of prepubertal mouse testes revealed that the time course of Brca2 expression was delayed in spermatogonia relative to Brca1. Thus, while Brca1 and Brca2 share concordant cell-specific patterns of expression in most proliferating tissues, these observations suggest that they may have distinct roles during meiosis.

Animals↗
PubMed1998

Influence of carbohydrate status on immune responses before and after endurance exercise.

To determine the effect of carbohydrate (CHO) status on immune responses after long-duration exercise, on two occasions, 10 men completed a glycogen-depleting bout of cycle ergometry followed by 48 h of either a high-CHO diet (HiCHO; 8.0 g CHO/kg) or a low-CHO diet (LoCHO; 0.5 g CHO/kg). After the 48 h, subjects completed a 60-min ride at 75% maximal O2 uptake (EX). Blood samples were taken predepletion, pre-EX, post-EX, and 2 and 24 h post-EX and were assayed for leukocyte number and function, glucose, glutamine, and cortisol. The glucose responses were significantly higher in the HiCHO (4.62 +/- 0.26 mM) vs. the LoCHO (3.19 +/- 0.15 mM) condition post-EX, and glutamine was significantly higher in the HiCHO (0.472 +/- 0.036 mM) vs. the LoCHO (0.410 +/- 0.025 mM) condition throughout. Cortisol levels were significantly greater in the LoCHO (587 +/- 50 nM) vs. the HiCHO (515 +/- 62 nM) condition throughout the trial. Lymphocyte proliferation (phytohemagglutinin) was significantly depressed after exercise. However, there was no difference between conditions, and the depression was not correlated with elevations in cortisol. Circulating numbers of leukocytes, neutrophils, lymphocytes, and lymphocyte subsets were significantly greater in the LoCHO vs. the HiCHO condition at the post-EX and 2 h post-EX time points. These data indicate that the exercise and diet manipulation altered the number of circulating leukocytes but did not affect the decrease in lymphocyte proliferation that occurred after exercise.

Adult↗
PubMed1998

A unique autosomal dominant disorder with indifference to pain: clinicopathologic correlation of indifference to pain and thalamic gliosis.

We present updated information on a previously reported kindred with an autosomal dominant disorder variably expressed as indifference to pain, dementia, and ataxia. Additional clinical and radiological information is presented, as are autopsy results form the index case. In addition to evidence of Alzheimer's disease, the autopsy revealed bilateral thalamic gliosis, which may be a neuroanatomic substrate for the indifference to pain seen in this patient. To our knowledge, this is the first reported association of thalamic gliosis and indifference to pain.

Adult↗
PubMed1998

Radiation therapy for relapsed CNS germinoma after primary chemotherapy.

PURPOSE: To retrospectively evaluate the ability of radiation therapy to salvage patients with CNS germinoma who relapsed after treatment with primary chemotherapy on a multiinstitution trial that included carboplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Eight patients with CNS germinoma received carboplatin, etoposide, and bleomycin as their only nonsurgical treatment following their initial diagnosis. At the time of relapse each patient received high-dose cyclophosphamide (one to three cycles) followed by craniospinal irradiation (25.2 to 36 Gy) and a boost to the site of recurrent disease (45 to 54 Gy). Six of eight patients had disease at relapse that was more extensive than at diagnosis. One patient had magnetic resonance imaging (MRI) evidence of leptomeningeal enhancement in the cauda equina although CSF cytology was negative, and one patient had cytologic evidence of CSF involvement. The median time to relapse following primary chemotherapy was 17 months. RESULTS: Although myelosuppression was prolonged following the administration of preirradiation chemotherapy, all patients completed a continuous course of radiation therapy. With a median follow-up after radiation therapy of 32 months (range, 16 to 47 months), no failures have occurred. CONCLUSION: Radiation therapy has a proven record of efficacy in the treatment of intracranial germinoma and it remains the standard therapy with which others are compared for treatment response, local control, and overall survival. Arguments can be made for alternative approaches when patients face hormonal or neurocognitive dysfunction as a result of radiation therapy; however, any reduction in late effects will have to be weighed against the probability of survival if alternative approaches prove to be inferior.

Adolescent↗
PubMed1997

Substance P modulates taste responses in the nucleus of the solitary tract of the hamster.

The effects of substance (SP) microinjections on the electrophysiological response of gustatory neurons within the nucleus of the solitary tract (NST) were examined in hamsters following either anodal electrical or NaCl stimulation of the anterior tongue. For both types of stimulation, SP produced excitatory and suppressive effects on the activity of gustatory NST neurons, with excitatory effects being more common. In response to repetitive anodal stimulation of the tongue, the modulatory effect of SP lasted 30-400 s. In the presence of SP, the firing rate of 48% of the neurons was increased and that of 9% was decreased following NaCl stimulation. This dual action of SP could be due to direct excitation of teste-responsive neurons and to excitation of inhibitory local circuit neurons which, in turn, decrease the responsiveness of gustatory neurons.

Animals↗
PubMed1997

External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center.

PURPOSE: Approximately 10% of patients with metastatic renal cell carcinoma are diagnosed with brain metastases. Most of these patients receive palliative radiotherapy and die of progressive brain metastatic disease. This retrospective study examines the M. D. Anderson Cancer Center experience with such patients who received only whole brain radiation therapy (WBRT). METHODS AND MATERIALS: Records of 200 patients with brain metastases from renal carcinoma who were treated at M. D. Anderson Cancer Center between 1976 and 1993 were reviewed. Of these patients, 119 received WBRT only and constitute the basis of this study. Different prognostic factors were analyzed. RESULTS: Overall median survival time from diagnosis of the brain metastases was 4.4 months. Multiple brain tumors were treated in 70 patients (58.8%) who had a survival of 3.0 months compared with 4.4 months for patients having a single brain metastasis (p = 0.043). Among 117 patients the causes of death were neurologic in 90 (76%), systemic cancer in 19 (16%), and unknown in 9 (8%). Survival rates at 6 months, 1 year, and 2 years, were 33.6, 16.8, and 5.9%, respectively. Patients in whom brain metastases were diagnosed synchronously with a renal primary (n = 24) had a median survival time of 3.4 months compared with 3.2 months for those 95 who were diagnosed metachronously (p < 0.79, NS). In the Cox multivariate analysis of 13 possible prognostic factors, only a single brain metastasis (p = 0.0329), lack of distant metastases at the time of diagnosis (p = 0.0056), and tumor diameter < or = 2 cm (p < 0.0016) were statistically significant. CONCLUSION: These unsatisfactory results with WBRT suggest that more aggressive approaches, such as surgery or radiosurgery should be applied whenever possible.

Adult↗
PubMed1997

Toxicity of methoxyacetic acid in cultured human luteal cells.

Ethylene glycol monomethyl ether (EGME) and its proximate metabolite, 2-methoxyacetic acid (MAA), increase ovarian luteal cell progesterone production in the female rat in vivo and in cultured rat luteal cells in vitro, respectively. In order to better assess the potential hazard of EGME and MAA to women, these studies were conducted to determine whether the same concentrations of MAA increase progesterone in human luteinized granulosa cells as in rat luteal cells. Human cells were collected from healthy anonymous oocyte donors, washed, plated 25,000 viable cells per well, and treated with 10 IU hCG and 0-5 mM MAA for 6-48 hr. Progesterone in media was significantly elevated after 24 hr incubation at >/=1 mM MAA. MAA had no effect on ATP levels at 6 or 24 hr. Thus, MAA increased progesterone production in cultured human luteal cells at the same concentration as MAA increased progesterone in rat luteal cells. The implication is that EGME has the potential to alter ovarian luteal function in women. These data should be useful for determining the real health hazards and potential risks of EGME exposure.

Acetates↗
PubMed1997

The effects of perinatal/juvenile methoxychlor exposure on adult rat nervous, immune, and reproductive system function.

In order to address data gaps identified by the NAS report Pesticides in the Diets of Infants and Children, a study was performed using methoxychlor (MXC). Female rats were gavaged with MXC at 0, 5, 50, or 150 mg/kg/day for the week before and the week after birth, whereupon the pups were directly dosed with MXC from postnatal day (pnd) 7. Some dams were killed pnd7 and milk and plasma were assayed for MXC and metabolites. For one cohort of juveniles, treatment stopped at pnd21; a modified functional observational battery was used to assess neurobehavioral changes. Other cohorts of juveniles were dosed until pnd42 and evaluated for changes to the immune system and for reproductive toxicity. Dose-dependent amounts of MXC and metabolites were present in milk and plasma of dams and pups. The high dose of MXC reduced litter size by approximately 17%. Ano-genital distance was unchanged, although vaginal opening was accelerated in all treated groups, and male prepuce separation was delayed at the middle and high doses by 8 and 34 days, respectively. In the neurobehavioral evaluation, high-dose males were more excitable, but other changes were inconsistent and insubstantial. A decrease in the antibody plaque-forming cell response was seen in males only. Adult estrous cyclicity was disrupted at 50 and 150 MXC, doses which also showed reduced rates of pregnancy and delivery. Uterine weights (corrected for pregnancy) were reduced in all treated pregnant females. High-dose males impregnated fewer untreated females; epididymal sperm count and testis weight were reduced at the high, or top two, doses, respectively. All groups of treated females showed uterine dysplasias and less mammary alveolar development; estrous levels of follicle stimulating hormone were lower in all treated groups, and estrus progesterone levels were lower at 50 and 150 MXC, attributed to fewer corpora lutea secondary to ovulation defects. These data collectively show that the primary adult effects of early exposure to MXC are reproductive, show that 5 mg/kg/day is not a NO(A)EL in rats with this exposure paradigm (based on changes in day of vaginal opening, pubertal ovary weights, adult uterine and seminal vesicle weights, and female hormone data) and imply that the sites of action are both central and peripheral.

Animals↗
PubMed1997

Ovarian luteal cell toxicity of ethylene glycol monomethyl ether and methoxy acetic acid in vivo and in vitro.

These studies define the site and mechanisms of reproductive toxicity of ethylene glycol monomethyl ether (EGME) in a nongravid female animal model using in vivo and in vitro methods. In vivo studies assessed vaginal cytology and histology, ovarian histology, and serum hormones in 80- to 90-day-old, adult, regularly cycling, female Sprague-Dawley rats treated daily with EGME or vehicle by oral gavage. Dose-response and time-course studies (four to nine rats per group per treatment) determined that 300 mg/kg EGME suppressed cyclicity without systemic toxicity within 3 to 8 days, and doses less than 100 mg/kg had no effect. Pathogenesis studies (six to nine rats per time and treatment) determined that 300 mg/kg EGME elevated serum progesterone within 32 hr after dosing, while serum estradiol, FSH, LH, and prolactin remained at baseline levels. In EGME-treated rats, cyclicity was suppressed, ovulation was inhibited, and corpora lutea were hypertrophied. Thus, EGME appeared to target the ovarian luteal cell. To further examine the toxicity in vitro, luteal cells were recovered from 23-day-old, hCG-primed Sprague-Dawley rats and treated with 0-10 mM methoxy acetic acid (MAA), the proximate toxic metabolite of EGME. MAA (1-10 mM) maintained elevated progesterone levels as production declined in untreated cells at 24 and 48 hr of culture. Progesterone production was maintained independent of LH-stimulated cAMP levels. MAA decreased ATP, but only at 48 hr and at 2.5 mM or greater concentrations. Thus, these studies establish that the ovarian luteal cell is a target of EGME and MAA in vivo and in vitro and that the effect on luteal cell progesterone production is likely independent of LH-stimulated cAMP pathways.

Acetates↗
PubMed1997

AED withdrawal.

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Anticonvulsants↗