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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 307 records · Page 17Linked to original sources
PubMed1999

Expression patterns of neurturin and its receptor components in developing and degenerative mouse retina.

PURPOSE: Neurturin (NTN) and its receptor components (GFRalpha2 and Ret) play an important role in the survival of different populations of neurons in the central and peripheral nervous systems. To gain insight into their possible functions throughout normal retinal development and during retinal neuronal apoptosis, the retinal distribution of expression of NTN and GFRalpha2 mRNAs and Ret protein were compared in control and retinal degeneration (rd) mice. METHODS: Eyes from control and rd animals were fixed in paraformaldehyde before sectioning. For in situ hybridization, retinal sections were hybridized with 35S-radiolabeled sense and antisense riboprobes for murine NTN and GFRalpha2 and were autoradiographed. Ret localization was detected by immunofluorescence. RESULTS: Neurturin mRNA expression was modulated through normal postnatal retinal development and was localized primarily to the inner retina and photoreceptor outer segments. GFRalpha2 mRNA displayed a diffuse developmental pattern of expression, but in the mature normal retina, NTN and GFRalpha2 mRNAs were more closely colocalized. Ret protein was localized particularly at the outer segments of photoreceptors, inner retina, and ganglion cell layers, but there were no prominent differences among genotypes. Increased NTN mRNA expression was detected in the retinal pigment epithelium and neural retina in concert with photoreceptor degeneration in rd mouse. In contrast, the level of GFRalpha2 mRNA was lower in rd compared with that in normal retina. CONCLUSIONS: These results suggest that NTN and its receptor are involved in retinal postnatal development and maintenance and that alterations in their transcription patterns are associated with inherited retinal degeneration.

Animals↗
PubMed1999

Lymph node tuberculosis in the suburbs of Paris: 59 cases in adults not infected by the human immunodeficiency virus.

We report 59 cases of lymph node tuberculosis in adults not infected by the human immunodeficiency virus (HIV), observed over a period of 5 years in the North Eastern suburbs of Paris. There were 31 women and 28 men; 84.7% were aged under 44 years; 69.5% were not French, and 78% had exclusive lymph node tuberculosis. A superficial distribution was found in 52 cases and a deep pattern in 17 cases. Cervical and supraclavicular lymphadenopathies were the most common (64.4%). General symptoms were present in 63% of cases. The diagnosis was established by fine needle aspiration in 10 cases and by biopsy in 36 cases. Three cases of primary resistance to anti-tuberculosis therapy were described. Lymph node tuberculosis is still present in the Paris region, independently of HIV infection, probably due to poor social conditions.

Adolescent↗
PubMed1999

Middle cerebral artery blood flow velocity, end-tidal pCO2 and blood pressure in patients with obstructive sleep apnea and in healthy subjects during continuous positive airway pressure breathing.

There is conflicting evidence in the literature as to the potential effect of continuous positive airway pressure (CPAP) on cerebral perfusion. Compromising cerebral perfusion could possibly outweigh the benefit of improved oxygenation. Patients with the obstructive sleep apnea syndrome (OSAS) have been claimed to have a higher cerebrovascular reactivity to changes in end-tidal pCO2. In this study, we investigated 23 patients with OSAS and 16 healthy young adults in the waking state. Both groups performed a series of 10 min of normal breathing, 20 min with 9 cmH2O nasal CPAP, and then 10 min of normal breathing while wearing a nasal CPAP mask. The following parameters were assessed: bilateral transcranial Doppler signal of the middle cerebral artery, systolic and diastolic blood pressure assessed manually, and cerebrovascular reactivity to changes in pCO2 during hyperventilation and rebreathing into an airbag. Continuous end-tidal pCO2 measurements were performed in 14 subjects. As compared with normal breathing middle cerebral artery blood flow velocity and pCO2 remained unchanged during CPAP. Systolic and diastolic blood pressure increased slightly by 1.2 mmHg (p = 0.015) and 1.1 mmHg (p = 0.007), respectively. Cerebrovascular reactivity did not differ in the two groups. Nasal CPAP of 9 cmH2O is a safe treatment with respect to the maintenance of cerebral blood flow. Our study gives further evidence for the autoregulation's capacity to maintain cerebral blood flow velocity constant during different levels of intrathoracic pressure and different cerebral perfusion pressures. We could not demonstrate any difference in cerebrovascular reactivity between patients with OSAS and healthy persons.

Adult↗
PubMed1999

Enhanced cardiovascular reactivity to desmopressin in water-restricted rats: facilitatory role of immunosuppression.

There is considerable evidence suggesting that vasopressin may play an important role in regulating cardiovascular homeostasis. In the present study the effects of immunosuppressant drugs, ciclosporin and tacrolimus on arterial blood pressure (BP) and heart rate (HR) responses to desmopressin (DDAVP) were compared in anesthetized normally hydrated and 24-h water-restricted rats. When injected intravenously, single bolus doses of DDAVP (0.5-8.0 micrograms/kg) elicited dose-dependent decreases in BP and also attenuated the HR. The enhancement of the vasodepressor response to DDAVP (4 micrograms/kg) was produced 15 min after the intravenous injection of either ciclosporin (3 mg/kg) or tacrolimus (25 micrograms/kg) accompanied by reduction in HR in water-restricted animals, but the response in euhydrated animals remained less modified after the bolus injections of immunosuppressants and DDAVP. To elucidate the possible contribution of the renal vascular system in water-restricted rats, ciclosporin was administered intravenously, followed 15 min later by 4 micrograms/kg injections of arginine vasopressin (AVP) or DDAVP into the renal artery, but there was no significant change in both the cardiovascular parameters as compared with the responses obtained with agonists alone. The present results indicate that the augmentation of the cardiovascular response to DDAVP by ciclosporin and tacrolimus in water-restricted anesthetized rats appears to be mediated by the release of endogenous vasodilatory mediators.

Animals↗
PubMed1999

Chronic lymphatic leukemia presenting as hemolytic anaemia.

In CLL autoimmune phenomena manifest most commonly as autoimmune hemolytic anemia followed by thrombocytopenic purpura and pure red cell aplasia. Here an elderly lady presenting with AIHA as the presenting manifestation of CLL is described.

Aged↗
PubMed1998

Inhibition of Bak-induced apoptosis by HPV-18 E6.

Human papillomavirus (HPV) E6 proteins inhibit apoptosis in both p53-dependent and p53-independent manners. A key point in apoptosis is the regulation provided by the Bcl-2 family; and in differentiating keratinocytes, in which HPV replicates, the Bak protein is highly expressed. We show that HPV-18 E6 will inhibit Bak-induced apoptosis and this is mediated by an interaction between the E6 and Bak proteins resulting in degradation of the Bak protein in vivo. We also show that Bak protein interacts with the ubiquitin ligase, E6AP, and that a mutant of Bak defective in E6AP binding is overexpressed in comparison with wild type. These studies suggest that Bak is probably the first naturally occurring target of E6AP to be identified.

Animals↗
PubMed1998

Upstream elements involved in vivo in activation of the brain-specific rat aldolase C gene. Role of binding sites for POU and winged helix proteins.

The rat aldolase C gene encodes a glycolytic enzyme strongly expressed in adult brain. We previously reported that a 115-base pair (bp) promoter fragment was able to ensure the brain-specific expression of the chloramphenicol acetyltransferase (CAT) reporter gene in transgenic mice, but only at a low level (Thomas, M., Makeh, I., Briand, P., Kahn, A., and Skala, H. (1993) Eur. J. Biochem. 218, 143-151). Here we show that in vivo activation of this promoter at a high level requires cooperation between an upstream 0.6-kilobase pair (kb) fragment and far upstream sequences. In the 0.6-kb region, a 28-bp DNA element is shown to include overlapping in vitro binding sites for POU domain regulatory proteins and for the Winged Helix hepatocyte nuclear factor-3beta factor. An hepatocyte nuclear factor-3beta-binding site previously described in the short proximal promoter fragment is also shown to interact in vitro with POU proteins, although with a lower affinity than the 28-bp motif. Additional binding sites for POU factors were detected in the upstream 0.6-kb sequences. Progressive deletion in this region resulted in decreased expression levels of the transgenes in mice, suggesting synergistic interactions between these multiple POU-binding sites. We propose that DNA elements characterized by a dual binding specificity for both POU domain and Winged Helix transcription factors could play an essential role in the brain-specific expression of the aldolase C gene and other neuronal genes.

Animals↗
PubMed1998

Differences in sexual risk behaviour between young men and women travelling abroad from the UK.

BACKGROUND: Identification of people who most frequently engage in sexual risk behaviour while travelling abroad would be useful for the design and targeting of health education and promotion campaigns. METHODS: Eligible participants were people living in the UK aged 18-34 years who had travelled abroad without a partner in the previous 2 years. Respondents were first screened for eligibility as part of representative face-to-face and telephone surveys by a market research company. Eligible individuals who agreed to take part then underwent a computer-assisted telephone interview. Reinterviewing continued until 400 eligible people had been contacted. We also interviewed a control group of 568 young people who had travelled abroad without a partner in the previous 2 years but who did not report a new sexual relationship during their travels. FINDINGS: One in ten of the eligible participants reported sexual intercourse with a new partner. Travellers who reported a new sexual relationship abroad were also likely to report large numbers of sexual partners at home. Of the 400 people who had a new sexual partner abroad, 300 (75%) used condoms on all occasions with the new partner. Logistic regression modelling showed differences between men and women in those factors linked to the practice of unsafe or safer sex while travelling. For men, patterns of condom use abroad with casual partners (p<.0001) reflected patterns of use at home (p<0.001), whereas for women, patterns of condom use varied according to their partners' backgrounds (p<.0001). INTERPRETATION: Condoms are widely used among young travellers, but patterns of use vary by sex. Campaigns about sexual health targeted at international travellers should continue, not least because young people who meet new sexual partners abroad may be a convenient proxy group for that minority of the population who report most sexual partners at home. Such campaigns should be designed differently for men and women.

Adolescent↗
PubMed1998

Chemoprophylaxis of Theileria annulata and Theileria parva infections of calves with buparvaquone.

A clinical trial testing the prophylactic effect of a 5 mg kg-1 dose of buparvaquone on either Theileria annulata or Theileria parva experimental infections of calves demonstrated its efficacy for periods of at least seven days. The drug given 1 h or seven days before 50% lethal T. annulata sporozoite infection protected all eight calves, but prophylaxis was insufficient after 14 days to protect two out of four calves from severe reaction. When immunity was challenged by a lethal second parasite dose a month after the first, all these calves were immune. In the T. parva trial, calves given drug 1 h or seven days before a 25% lethal infection underwent minimal reaction, but some were over-protected and were susceptible to a similar challenge sporozoite dose. Although drug levels remaining 14 days after prophylaxis protected these calves from the mild challenge, some parameters measured were within the range of the 'no drug' control group. These results indicated the effectiveness of a single 5 mg kg-1 dose of buparvaquone for more than seven days but also the potential risk of its use in the infection and treatment method of immunisation. It is suggested that there may be circumstances where simple field prophylactic treatment with buparvaquone may be beneficial.

Animals↗
PubMed1998

Kinetic analysis of an inhibitor-resistant variant of the OHIO-1 beta-lactamase, an SHV-family class A enzyme.

The Met69-->Ile mutant of the OHIO-1 beta-lactamase, an SHV-family enzyme, is resistant to inactivation by beta-lactamase inhibitors. Analysis of purified Met69-->Ile enzyme reveals that its isoelectric point (pI 7.0) and CD spectrum are identical with those of the OHIO-1 enzyme. Levels of beta-lactamase expression in Escherichia coli as determined by immunoblotting are similar for OHIO-1 and Met69-->Ile beta-lactamase. The kinetic constants of the Met69-->Ile enzyme compared with OHIO-1 are smaller for benzylpenicillin (Km = 6 microM compared with 17 microM; kcat = 234 s-1 compared with 345 s-1 respectively) and carbenicillin (Km = 3 microM compared with 17 microM; kcat = 131 s-1 compared with 320 s-1 respectively). For the cephalosporins cephaloridine and 7-(thienyl- 2-acetamido)-3-[2-(4-N,N- dimethylaminophenylazo)pyridinium-methyl]-3-cephem-4-carboxylic acid (PADAC), a similar pattern is also seen (Km=38 microM compared with 96 microM and 6 microM compared with 75 microM respectively; kcat = 235 s-1 compared with 1023 s-1 and 9 s-1 compared with 50 s-1 respectively). Consistent with minimum inhibitory concentrations that show resistance to beta-lactam beta-lactamase inhibitors, the apparent Ki values, turnover numbers and partition ratios (kcat/kinact) for the mechanism-based inactivators clavulanate, sulbactam and tazobactam are increased. The inactivation rate constants (kinact) are decreased. The difference in activation energy, a measurement of altered affinity for the wild-type and mutant enzymes leading to acylation of the active site, reveals small energy differences of less than 8.4 kJ/mol. In total, these results suggest that the Met-->Ile substitution at position 69 in the OHIO-1 beta-lactamase alters the active site, primarily affecting the interactions with beta-lactamase inhibitors.

Anti-Bacterial Agents↗
PubMed1998

Theileria lestoquardi and T. annulata in cattle, sheep, and goats. In vitro and in vivo studies.

Theileria annulata, causing bovine tropical theileriosis, and T. lestoquardi (syn T. hirci), the agent of malignant ovine theileriosis, are both transmitted by ticks of the genus Hyalomma. Their distribution is thus very similar and, should these parasites infect more than one ruminant species, the difficulty in interpreting epidemiological studies is magnified considerably. A pilot series of experiments was thus conducted in which cattle, sheep and goats were infected with sporozoites of a single stock of each of T. annulata and T. lestoquardi from a laboratory colony of H.a.anatolicum. Reciprocal cross-immunity and serological studies and in vitro culture isolations in mononuclear cells of each ruminant species illustrated both the similarity of these organisms and their differences. The importance of these findings in discriminating parasites in epidemiological studies and the control of these diseases with cell culture vaccines is emphasized.

Animals↗
PubMed1998

Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.

The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.

Alleles↗