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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 199 records · Page 11Linked to original sources

Low-dose irradiation as a measure to improve microbial quality of ice cream.

The present study was undertaken to investigate the efficacy of low-dose irradiation to improve the microbial safety of ice cream. Initially three different flavors (vanilla, strawberry and chocolate) of ice cream were exposed, at -72 degrees C, to doses of 1, 2, 5, 10 and 30 kGy to gamma-radiation. Irradiation at 1 kGy resulted in reduction of microbial population by one log cycle, thus meeting the requirement limits prescribed by Bureau of Indian Standards. Pathogens such as Listeria monocytogenes 036, Yersinia enterocoliticta 5692 and Escherichia coli O157:H19, respectively, showed the D10 values 0.38, 0.15 and 0.2 kGy in ice cream at -72 degrees C suggesting the efficacy of low doses (1 kGy) in eliminating them. Sensory evaluation studies of ice cream irradiated at 1, 2, 3 and 5 kGy by a 15 member panel demonstrated that doses higher than 2 kGy irradiation induced off-odour and an aftertaste was evident in vanilla ice cream. A radiation dose of 1 kGy was sufficient to eliminate the natural number of pathogens present in the ice cream. No statistically significant differences were observed in the sensory attributes of all the three flavours of ice cream either unirradiated or exposed to 1 kGy (P < 0.05).

Colony Count, Microbial↗

[Epileptic emergencies].

Convulsive status epilepticus is a major epileptic emergency. Prompt and effective treatment is requested to prevent death or neurological sequel. First-line drugs must have a favourable benefit to risk ratio. Refractory status must be treated aggressively by second-line sedative drugs. In this situation, EEG monitoring must diagnose subtle status epilepticus by controlling the disappearance of ictal discharges. Non-convulsive generalized or partial status epilepticus is a diagnostic challenge, best solved by emergency EEG. Immediate discontinuation of antiepileptic drugs is requested to avoid potentially serious idiosyncratic side-effects. Prescriptions habits will be avoided to prevent recurrence of isolated convulsive seizures.

Emergencies↗

Survival in children with perinatal HIV infection and very low CD4 lymphocyte counts.

OBJECTIVES: To evaluate clinical conditions associated with mortality in HIV-infected children with CD4+ counts <100 cells/microl. METHODS: The Pediatric Spectrum of HIV Disease Project is a longitudinal medical record review study with eight study sites in the United States, which have been enrolling children since 1989. Survival time from baseline very low CD4 count (<100 cells/microl) to death was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the effect of clinical variables on mortality. RESULTS: Of 522 children (>/=1 year of age) with serial CD4+ T-lymphocyte measurements, the median age at the first very low CD4 count was 4.8 years. The estimated median survival following the first very low CD4 count was 36 months. The following factors present at the first very low CD4 count were independently associated with a higher risk of death: younger age, weight-for-age >2 standard deviations below the mean, and previously diagnosed AIDS. The subsequent development of cytomegalovirus (CMV)-associated disease, Mycobacterium avium intracellulare (MAI) infection, wasting syndrome, or esophageal candidiasis was also independently associated with a higher risk of death. CONCLUSION: Survival in HIV-infected children with very low CD4 counts before introduction of highly active antiretroviral therapy was highly variable. Poor nutritional status and the development of CMV disease or MAI infection were associated with the shortest survival times.

Age Factors↗

Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy?

BACKGROUND: Juvenile myoclonic epilepsy is a frequent form of idiopathic generalized epilepsy that is usually and easily controlled by valproate monotherapy. However, juvenile myoclonic epilepsy is often misdiagnosed, and some drugs, especially carbamazepine and phenytoin, may have an aggravating effect. OBJECTIVES: To determine the risk of aggravation of juvenile myoclonic epilepsy in patients treated with carbamazepine and phenytoin. METHODS: Among 170 consecutive patients with juvenile myoclonic epilepsy (104 female, 66 male) referred between 1981 and 1998, the authors retrospectively found 40 patients (23%) who had received carbamazepine or phenytoin (duration of epilepsy at referral, 1 to 34 years; mean +/- SD, 13.8 +/- 8.5 years; follow-up, 3 to 50 years; mean +/- SD, 16.4 +/- 11 years). RESULTS: Twenty-three patients (57.5%) experienced aggravation of seizures, whereas 6 (15%) apparently benefited from these drugs. There was no effect in the remaining 11 cases (27.5%). Carbamazepine was prescribed to 28 patients: 19 (68%) had aggravated symptoms, including myoclonic status in two; 4 (14%) were improved, one in association with valproate and one in association with valproate and phenobarbital. Phenytoin was prescribed in 16 cases: 6 (38%) had aggravation and 2 (12%) were improved, including one in association with phenobarbital. Vigabatrin was given in only one case, in association with carbamazepine, and provoked a mixed absence and myoclonic status. CONCLUSIONS: Among commonly prescribed anticonvulsants, carbamazepine appears to have the strongest aggravating potential in patients with juvenile myoclonic epilepsy, whereas the aggravating effect of phenytoin is less prominent. Aggravation was mostly in the form of increased myoclonic jerks.

Adolescent↗

Real-time studies of zymogen granule exocytosis in intact rat pancreatic acinar cells.

An adequate understanding of secretion requires the measurement of exocytosis on the same time scale as that used for second messenger dynamics. To investigate the kinetics of ACh-evoked secretion in pancreatic acinar cells, exocytosis of zymogen granules was quantified by continuous, time-differential analysis of digital images. The validity of this method was confirmed by simultaneous fluorescence imaging of quinacrine-loaded zymogen granules. Basal rates of exocytosis were low (0.2 events min(-1)). ACh stimulated a biphasic increase in secretory activity, maximal rates exceeding 20 events min(-1) after 10 s of ACh application (10 microM). Over the next 15 s the rate of exocytosis fell to less than 4 events min(-1); then began a second phase of secretion that peaked 15 s later at approximately 11 events min(-1), but subsequently declined in the continued presence of agonist. Measurements of fura-2 fluorescence demonstrated a biphasic increase in intracellular [Ca2+] ([Ca2+]i). Comparison of the [Ca2+]i records and time-differential analysis revealed that the fall in exocytotic rate following the initial burst occurred despite the fact that [Ca2+]i remained high. The second phase of secretion depended on both [Ca2+]i and [ACh]. At 10 microM ACh there was a decrease in the steepness of the relationship between [Ca2+]i and exocytosis that led to an enhancement of the slow secretory phase. We propose that acinar cells contain two pools of secretory vesicles: a small pool of granules that is exocytosed rapidly, but is quickly depleted; and a reserve pool of granules that can be recruited by ACh in a process that is modulated by second messengers other than calcium.

Acetylcholine↗

Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts.

This paper describes three distinct estrogen receptor (ER) subtypes: ERalpha, ERbeta, and a unique type, ERgamma, cloned from a teleost fish, the Atlantic croaker Micropogonias undulatus; the first identification of a third type of classical ER in vertebrate species. Phylogenetic analysis shows that ERgamma arose through gene duplication from ERbeta early in the teleost lineage and indicates that ERgamma is present in other teleosts, although it has not been recognized as such. The Atlantic croaker ERgamma shows amino acid differences in regions important for ligand binding and receptor activation that are conserved in all other ERgammas. The three ER subtypes are genetically distinct and have different distribution patterns in Atlantic croaker tissues. In addition, ERbeta and ERgamma fusion proteins can each bind estradiol-17beta with high affinity. The presence of three functional ERs in one species expands the role of ER multiplicity in estrogen signaling systems and provides a unique opportunity to investigate the dynamics and mechanisms of ER evolution.

Amino Acid Sequence↗

NEAR at eros: imaging and spectral results

Eros is a very elongated (34 kilometers by 11 kilometers by 11 kilometers) asteroid, most of the surface of which is saturated with craters smaller than 1 kilometer in diameter. The largest crater is 5.5 kilometers across, but there is a 10-kilometer saddle-like depression with attributes of a large degraded crater. Surface lineations, both grooves and ridges, are prominent on Eros; some probably exploit planes of weakness produced by collisions on Eros and/or its parent body. Ejecta blocks (30 to 100 meters across) are abundant but not uniformly distributed over the surface. Albedo variations are restricted to the inner walls of certain craters and may be related to downslope movement of regolith. On scales of 200 meters to 1 kilometer, Eros is more bland in terms of color variations than Gaspra or Ida. Spectra (800 to 2500 nanometers) are consistent with an ordinary chondrite composition for which the measured mean density of 2.67 +/- 0.1 grams per cubic centimeter implies internal porosities ranging from about 10 to 30 percent.

Journal Article↗

Identification of the cystic fibrosis transmembrane conductance regulator domains that are important for interactions with ROMK2.

In addition to functioning as a cAMP-activated chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in conferring regulatory properties on other ion channels. It is known, with respect to CFTR regulation of ROMK2 (renally derived K(ATP) channel), that the first transmembrane domain and the first nucleotide binding fold domain (NBF1) of CFTR are necessary for this interaction to occur. It has been shown that under conditions that promote phosphorylation, the ROMK2-CFTR interaction is attenuated. To elucidate the complex nature of this interaction, CFTR constructs were co-expressed with ROMK2 in Xenopus oocytes, and two microelectrode voltage clamp experiments were performed. Although the second half of CFTR can act as a functional chloride channel, our results suggest that it does not confer glibenclamide sensitivity on ROMK2, as does the first half of CFTR. The attenuation of the ROMK2-CFTR interaction under conditions that promote phosphorylation is dependent on at least the presence of the R domain of CFTR. We conclude that transmembrane domain 1, NBF1, and the R domain are the CFTR domains involved in the ROMK2-CFTR interaction and that NBF2 and transmembrane domain 2 are not essential. Lastly, the R domain of CFTR is necessary for the attenuation of the ROMK2-CFTR interaction under conditions that promote phosphorylation.

Animals↗

Influenza vaccination coverage in old people's home in Carmarthenshire, UK, during the winter of 1998/99.

A mailed questionnaire survey was undertaken in old people's (nursing and residential) homes in Carmarthenshire, UK to determine the influenza vaccine uptake during the 1998/99 season. Out of the total 60 questionnaires circulated, response was received from 47 homes giving an overall response rate of 78%. Amongst the 1399 residents, 1132 (81%) received influenza vaccine in the winter of 1998/99. Uptake was higher in nursing homes (89%) than in residential homes (79%) or dual registered homes (81%). The most common reason for not receiving influenza vaccination was refusal by the residents themselves, although the vaccine was offered to 99% of residents. This study suggests that strategies to improve communication and provision of educational materials outlining the benefits of influenza vaccine to elderly residents and health professionals may help increase the likelihood of vaccine uptake.

Aged↗

MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1.

The bone-specific transcription factor, Cbfa1, regulates expression of the osteocalcin (OCN) gene and is essential for bone formation. However, little is known about the mechanisms regulating Cbfa1 activity. This work examines the role of the MAPK pathway in regulating Cbfa1-dependent transcription. Stimulation of MAPK by transfecting a constitutively active form of MEK1, MEK(SP), into MC3T3-E1 preosteoblast cells increased endogenous OCN mRNA, while a dominant negative mutant, MEK(DN), was inhibitory. MEK(SP) also stimulated activity of a 147-base pair minimal OCN promoter, and this stimulation required an intact copy of OSE2, the DNA binding site for Cbfa1. Effects of MEK(SP) were specific to Cbfa1-positive osteoblast-like cells. A purified His-tagged Cbfa1 fusion protein was directly phosphorylated by activated recombinant MAPK in vitro. Furthermore, (32)P metabolic labeling studies demonstrated that MEK(SP) clearly enhanced phosphorylation of Cbfa1 in intact cells, while MEK(DN) decreased phosphorylation. The specific MEK1/MEK2 inhibitor, PD98059, inhibited extracellular matrix-dependent up-regulation of the OCN promoter, indicating that the MAPK pathway and, presumably, Cbfa1 phosphorylation are also required for responsiveness of osteoblasts to extracellular matrix signals. This study is the first demonstration that Cbfa1 is controlled by MAPKs and suggests that this pathway has an important role in the control of osteoblast-specific gene expression.

Animals↗

Bilateral focal polymicrogyria in Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a heterogeneous group of generalized connective tissue disorders that has been described in association with epilepsy and cerebral cortical dysplasia, mostly gray matter heterotopias, in 3 reports. However, to our knowledge, association of EDS with another type of cortical cerebral dysplasia, bilateral focal polymicrogyria, has never previously been described. SETTING: Two research-oriented hospitals. PATIENTS: We describe 2 patients with EDS and bilateral polymicrogyria. The first, a 29-year-old black man, presented with EDS of unspecified type, seizures, and bilateral frontocentral and frontoposterior polymicrogyria with hypoplasia of the inferior part of the cerebellar vermis. The second, a 20-year-old woman, had type III EDS, seizures and congenital bilateral perisylvian syndrome with polymicrogyria. CONCLUSIONS: The association of bilateral focal polymicrogyria and EDS in these 2 patients suggests that extracellular matrix proteins implicated in the pathogenesis of EDS, such as collagen and tenascin, may play an important role in cerebral cortical formation and organization. In a clinical setting, the association of EDS with these cortical structural lesions has implications for diagnosis and management.

Adult↗

Differential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer.

In a comprehensive immunohistochemical study of the expression of ten metalloproteinases (MMPs) and their four inhibitors (TIMPs) in 115 non-small cell lung carcinomas (NSCLCs), the findings have been correlated with the histological and clinical features of the tumours. All MMPs and TIMPs were expressed in tumours, with frequencies ranging from 41% for MMP-2 to 68% for MMP-13. Stromal immunoreactivity ranged from 6% for TIMP-4 to 87% for MMP-13. In some tumours, an overexpression of these proteins, as revealed by stronger staining in cancer cells than in adjacent normal bronchial epithelium, was also observed. The frequency ranged from 1% for MMP-3 to 28% for MMP-13. Compared with squamous cell carcinoma (SqCC), adenocarcinoma (AdC) more frequently overexpressed MMP-1, -11, -13, -14, and TIMP-2, and TIMP-1 and/or TIMP-2 overexpression positively correlated with more advanced stage disease. None of the MMP or TIMP expression correlated with the ras genotype of the tumours. The higher frequency of MMP overexpression in AdC than in SqCC may relate to the greater tendency of the former for systemic metastasis. The association of TIMP-1 overexpression with more advanced disease may suggest a role in prognosis.

Adult↗

Fecal progesterone, estrogen, and androgen metabolites for noninvasive monitoring of reproductive function in the female Indian rhinoceros, Rhinoceros unicornis.

This investigation aimed to establish noninvasive methods for endocrine monitoring of estrous cycles and pregnancy in the Indian rhinoceros. Fecal samples were collected 1-3 times per week from nonpregnant and pregnant captive females (n = 7). Enzyme immunoassays for fecal progesterone, androgen, and estrogen metabolites, respectively, were tested for their ability to determine follicular and luteal phases and to characterize endocrine profiles during pregnancy. Antibodies used were raised against pregnanediol (20 alpha-OH-pregnanes), 20-oxo-pregnanes, epiandrosterone (17-oxo-androstanes), and total estrogens. Androgens and estrogens were found to be reliable indicators of the follicular phase, whereas 20 alpha-OH- and 20-oxo-pregnanes were reliable indicators of luteal function. Progesterone metabolites were also reliable indicators of pregnancy, whereas 17-oxo-androstanes and estrogens were basal throughout gestation. Estrous cycles were regular throughout the year, with an average cycle length of 43.4 +/- 1.5 (n = 27) days; the length of the follicular phase, as indicated by elevated estrogen levels, was 15.9 +/- 1.0 days, whereas the luteal phase, as indicated by elevated 20-oxo-pregnane levels, was 19.1 +/- 0.4 days. Fecal pregnane values were already increasing while follicular estrogen values were still decreasing. The length of the diestrus, indicated by basal steroid levels between declining 20-oxo-pregnanes and subsequently increasing estrogens, was 11.4 +/- 1.2 days. Pregnane levels increased from the 3rd month of gestation onward and levels exceeded luteal phase concentrations approximately 10 times by the 7th month of gestation onward. HPLC separation of immunoreactive fecal metabolites indicated the presence of estrone, estradiol-17beta, and several 17-oxo-androstanes, 20 alpha-OH-pregnanes, and 20-oxo-pregnanes. Concentrations of a peak with an elution profile similar to that of pregnanediol increased as pregnancy progressed. Postpartum fecal estrogen and 17-oxo-androstane concentrations in one animal indicated follicular development comparable to the follicular phase of the estrous cycle, but this was not followed by a subsequent luteal phase. In conclusion, estrous cycle and pregnancy in Indian rhinoceroses can be monitored using fecal steroid analysis. Pregnane metabolites were reliable indicators of the corpus luteum and pregnancy, whereas fecal 17-oxo-androstanes and estrogens were indicators of the follicular phase.

Androgens↗

Hormonal regulation and cellular distribution of connexin 32.2 and connexin 32.7 RNAs in the ovary of Atlantic croaker.

The in vitro effects of human chorionic gonadotropin (hCG) on ovarian connexin (Cx) 32.2 and 32.7 RNA levels and ovarian follicle maturation were assessed, and the cellular distribution of Cx transcripts in the ovary was determined. hCG caused a concentration-dependent induction of Cx32.2 RNA, which peaked coincidentally with the appearance of morphological indices of oocyte maturational competence (OMC). Cx32.2 RNA levels declined thereafter in all treatment groups, although this decline was not accompanied by the onset of germinal vesicle breakdown (GVBD) at the lowest hCG concentration used. The levels of Cx32.7 RNA initially declined and subsequently increased to preincubation values after hCG treatment, but these changes were not dependent on hCG concentration. In a separate experiment, the decline in Cx32.7 RNA occurred in the presence or absence of hCG and was prevented by low (physiological) concentrations of estradiol-17beta (E2) or by protein kinase C (PKC) inhibitor, but was enhanced in the presence of high E2 concentrations or of PKC activator. These changes in Cx32. 7 RNA abundance were not associated with any indices of oocyte maturation. In situ hybridization of tissue sections showed the presence of Cx32.2 and Cx32.7 RNA in somatic cells of the ovarian follicle but not in oocytes. Cx32.2 RNA seemed to be present in granulosa and thecal cells, but the assay resolution was insufficient to reliably determine the distribution of Cx32.7 transcript by somatic cell type. In view of earlier findings that Cx32.2-based (but not Cx32.7-based) connexons can form functional homotypic channels, these results indicate that Cx32.2 gene expression in granulosa cells is sufficient for the formation of homologous gap junctions (GJ). Northern blot of RNA extracts from ovulated eggs, which are free of follicle cells, showed the presence of relatively low levels of both Cx RNAs. Thus, it is possible that Cx32.2 is present in oocytes and that it participates in heterologous (homotypic) GJ formation between the oocyte and the granulosa cells. In conclusion, Cx32.2 RNA levels in somatic cells of the ovarian follicle correlated positively with morphological indices of OMC acquisition, but subsequently declined during GVBD. These changes in Cx32.2 RNA may function in the regulation of GJ contacts during follicular maturation.

Animals↗

Sex steroids relative to alternative mating behaviors in the simultaneous hermaphrodite Serranus subligarius (Perciformes: Serranidae).

This study is the first investigation of reproductive endocrinology in a simultaneously hermaphroditic teleost, the belted sandfish (Serranus subligarius). We address two questions: (1) Do steroid hormone levels vary during the spawning season or during the daily spawning cycle of sandfish? (2) Do hormone levels vary relative to an individual's phenotype-size, frequency of spawning and aggressive behaviors, and proportion of testis in the gonad? We analyzed circulating estradiol-17beta (E2), testosterone (T), 11-ketotestosterone (11KT), 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20betaS), and 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) concentrations in a field population. Only E2 levels were significantly higher at the new and full moon, suggesting peak periods of vitellogenesis at these times. Naturally spawning sandfish were sampled every 2 h during the photophase of a 25-h period (12 pm to 1 pm the following day) and gonadosomatic index, degree of oocyte hydration and ovulation, and plasma levels of E2, T, DHP, and 20betaS were analyzed. E2 and T levels did not vary during photophase, suggesting continuous recruitment of oocytes into vitellogenesis. The 20betaS levels peaked around the time of final oocyte maturation. Since frequency of spawning behaviors changes with body size, we captured individuals of various sizes throughout the spawning season and analyzed circulating levels of hormones. 11KT and 20betaS levels increased significantly with body size. In 1992, we quantified frequency of spawning and aggressive behaviors, circulating T and 11KT levels and testicular mass relative to ovotestis mass in focal animals. 11KT levels tended to be positively correlated with frequency of courting male behavior, but were unrelated to the frequency of aggressive behavior or testis mass. Because hormone levels increased with size and frequency of each spawning behavior changes with size, we propose that sex steroids influence growth-related changes in spawning tactics of individuals.

Aggression↗

Androgen correlates of socially induced changes in the electric organ discharge waveform of a mormyrid fish.

Weakly electric fish from the family Mormyridae produce pulsatile electric organ discharges (EODs) for use in communication. For many species, male EODs are seasonally longer in duration than those of females, and among males, there are also individual differences in EOD duration. While EOD elongation can be induced by the administration of exogenous androgens, androgen levels have never before been assessed under natural or seminatural conditions. By simulating the conditions occurring during the breeding season in the laboratory, we provide evidence of a sex difference in EOD duration as well as document levels of circulating androgens in males. In this study, we analyzed the nature of social influences on male EOD duration and plasma androgen levels in Brienomyrus brachyistius. Individual males, first housed with a single female and then placed into social groups consisting of three males and three females, showed status-dependent changes in EOD duration. Top-ranking males experienced a relatively large increase in EOD duration. Second-ranking males experienced a more modest increase, and low-ranking males experienced a decrease in EOD duration. These changes were paralleled by differences in circulating levels of plasma 11-ketotestosterone (11-KT), but not testosterone, suggesting that the changes in EOD duration may have been mediated by changes in plasma 11-KT levels. Thus, it appears that EOD duration is an accurate indicator of male status, which is under social and hormonal control.

Androgens↗