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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 613 records · Page 34Linked to original sources
PubMed1992

Characterization of a paired box- and homeobox-containing quail gene (Pax-QNR) expressed in the neuroretina.

The retina is an integral part of the central nervous system, and consists of two layers, the outer pigmented layer and the inner sensory layer or neuroretina (NR). The NR layer contains several strata of cells (glial and neuronal) derived from proliferating neuroectodermal precursors that differentiate after terminal mitosis. In vitro, NR cells can differentiate not only into neuronal and glial types, but also into pigment and lens cells. Quail (Coturnix coturnix japonica) NR cells (QNR) infected with MC29 transforming retrovirus become pigmented after several passages in vitro. In order to characterize the genes expressed in these pigmented MC29 QNR, a cDNA library was prepared from these cells. After differential screening we have isolated a cDNA clone which identifies an RNA expressed in NR but not in the pigmented layer of the retina. This cDNA encodes a protein related to that of Drosophila, mouse and zebrafish paired box- and homeobox-containing segmentation genes and is called Pax-QNR. The expression of Pax-QNR in the NR is confined to the ganglionic cell layer and to the lower part of the inner nuclear layer containing the amacrine or correlation neurones.

Amino Acid Sequence↗
PubMed1992

Animal behavioural studies in the evaluation of antidepressant drugs.

Animal behavioural models of psychiatric disorders cannot exactly simulate human psychopathology, but they can be used to evaluate the behavioural changes induced by drugs and to suggest hypotheses about the functions of the CNS and its involvement in psychiatric disorders. This should lead to a more heuristic classification of psychotropic drugs and to clarification of their therapeutic possibilities. The following animal models simulate aspects of depressive disorders and are sensitive to the antidepressant effects of drugs. (i) The forced swimming test: described as 'behavioural despair' on the assumption that the animal has given up hope of escaping. (ii) The 'restraint stress' test: this may indicate a failure to adapt to stress. (iii) The learned-helplessness model: exposed to uncontrollable events, animals exhibit learning performance deficit and behavioural changes, including decreased locomotor activity and loss of appetite. (iv) Waiting behaviour: improvement in the ability to wait for and/or postpone an active response; this could be related to the reported beneficial effects of antidepressants on impulsive behaviour.

Animals↗
PubMed1992

Listeria monocytogenes peritonitis: case report and literature review.

Listeria monocytogenes is a Gram-positive bacillus that is pathogenic in both the normal and compromised host. We describe Listeria peritonitis and cerebritis in a patient with cirrhosis due to non-A, non-B hepatitis, and review the 11 other cases of Listeria peritonitis reported in the English-language literature. Listeria is a rare cause of peritonitis in debilitated, older patients, with two-thirds of the cases occurring in patients with chronic liver disease. Listeria peritonitis may also occur in patients undergoing peritoneal dialysis, or in those with malignancy. Peritonitis due to Listeria is clinically similar to spontaneous bacterial peritonitis, and is associated with fever, variable abdominal pain, and neutrocytic ascites; bacteremia commonly accompanies Listeria peritonitis. This syndrome can be successfully treated with antimicrobial drugs, although the third-generation cephalosporins commonly used in the therapy of spontaneous bacterial peritonitis are not recommended. Ampicillin may be the drug of choice, with combination therapy with an aminoglycoside reserved for cases that do not respond to ampicillin alone.

Aged↗
PubMed1992

[Serum gastrin levels in colorectal cancers. Evolution after treatment].

Increased basal serum gastrin level has been described in patients presenting with colorectal cancer. The aim of this work was to study the evolution of serum gastrin levels after cancer treatment. We measured basal serum gastrin levels before and 1 to 2 months after treatment in 15 patients (7 men, 8 women; mean age: 61.6 years). There were 3 malignant polyps, 4 Dukes A, 3 Dukes B, 4 Dukes C and 1 Dukes D colonic cancers. Treatment included 3 endoscopic polypectomies, 2 laser photodestructions, and 10 surgical resections, Mean basal gastrin level after treatment (49.07 +/- 12.65 mIU/l) was significantly lower (P less than 0.002) than before treatment (104.47 +/- 26.98 mIU/l). In the 2 patients treated by laser therapy, recurrences were associated with reincreasing serum gastrin levels. These results suggest an "autocrine" secretion of gastrin.

Adenocarcinoma↗
PubMed1992

Liver transplantation for viral hepatitis: current status.

Liver transplantation is now considered definitive therapy for end-stage liver disease and has been playing an increasingly important role in the management of fulminant hepatic failure. With the advent of effective immunosuppression and improved surgical techniques, high survival rates can be expected for most transplanted patients. It has become apparent, however, that transplantation for patients with viral hepatitis is associated with some unique problems because of the propensity for viral reinfection of the grafted liver. Patients with actively replicating hepatitis B viral infection pretransplantation appear to be most likely to experience clinically significant recurrent hepatitis. Recurrent hepatitis D (delta) and hepatitis C appear to be relatively less serious in the transplanted liver. Interventions to prevent or treat graft reinfection have thus far met with limited success. Further studies are needed to define more precisely which patients with viral hepatitis are likely to do poorly after liver transplantation, and to develop strategies for treating recurrent hepatitis in transplant recipients.

Hepatitis, Viral, Human↗
PubMed1992

Heparin rebound phenomenon--much ado about nothing?

Significant postoperative bleeding following open-heart surgery is often ascribed to the so-called heparin 'rebound' phenomenon and as such is treated with additional empiric doses of protamine sulphate. However, inappropriate protamine administration has been reported to be associated with acute pulmonary hypertension. The efficacy of heparin reversal was investigated in 42 patients undergoing open-heart surgery. The standard heparin bolus of 3 mg/kg body weight (4.1 IU/ml blood) administered before cardiopulmonary bypass was countered at the end of bypass using an empirical equivalent (3 mg/kg) of protamine. This regimen resulted in complete heparin neutralization (measured by the Hepcon HMS [Hemotec Inc., Englewood, CO, USA]) 15 min after protamine administration in all 42 patients, but heparin levels (0.4 IU/ml) were transiently detectable (duration less than 1 h) in six (14%) of the 42 cases 2 h later. Twenty-four hour postoperative bleeding in these patients did not differ significantly from that seen in patients who did not exhibit heparin rebound. Similarly, the thrombelastographic profiles (at 15 min and 2 h post-operation) and coagulation screen (prothrombin time, activated partial thromboplastin time, activated clotting time and platelets) did not differ significantly from those of non-rebound patients. The significance, if any, of the phenomenon of heparin rebound following cardiac surgery remains to be elucidated, and, until such time, conservative administration of protamine in response to 'rebound' is recommended.

Adolescent↗
PubMed1991

Heterogeneous amino acids in Ras and Rap1A specifying sensitivity to GAP proteins.

Guanosine triphosphatase (GTPase) activity of Ras is increased by interaction with Ras-GAP (GTPase-activating protein) or with the GAP-related domain of the type 1 neurofibromatosis protein (NF1-GRD), but Ras is not affected by interaction with cytoplasmic and membrane forms of Rap-GAP; Rap1A, whose effector function can suppress transformation by Ras, is sensitive to both forms of Rap-GAP and resistant to Ras-GAP and NF1-GRD. A series of chimeric proteins composed of portions of Ras and Rap were constructed; some were sensitive to Ras-GAP but resistant to NF1-GRD, and others were sensitive to cytoplasmic Rap-GAP but resistant to membrane Rap-GAP. Sensitivity of chimeras to Ras-GAP and cytoplasmic Rap-GAP was mediated by amino acids that are carboxyl-terminal to the effector region. Residues 61 to 65 of Ras conferred Ras-GAP sensitivity, but a larger number of Rap1A residues were required for sensitivity to cytoplasmic Rap-GAP. Chimeras carrying the Ras effector region that were sensitive only to Ras-GAP or only to cytoplasmic Rap-GAP transformed NIH 3T3 cells poorly. Thus, distinct amino acids of Ras and Rap1A mediate sensitivity to each of the proteins with GAP activity, and transforming potential of Ras and sensitivity of Ras to Ras-GAP are at least partially independent properties.

Cell Membrane↗
PubMed1991

Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene.

The thyroid hormone receptor alpha (THRA or c-erbA-1) gene belongs to a family of genes which encode nuclear receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. These receptors are composed of several domains important for hormone-binding, DNA-binding, dimerization and activation of transcription. We show here that the human THRA gene is organized in 10 exons distributed along 27 kbp of genomic DNA on chromosome 17. The position of the introns in human THRA is highly conserved when compared to the chicken gene despite their differing lengths. The N-terminal A/B domain as well as the 5' untranslated region is encoded by two exons. Interestingly, each of the putative zinc fingers of the receptor DNA-binding domain is encoded by one exon and the hormone-binding domain is assembled from three exons. The two last exons of the gene are alternatively spliced to generate two different messenger RNAs. In addition, we confirm that another gene, belonging to the nuclear receptor superfamily, ear-1, overlaps with the 3' region of THRA in an opposite transcriptional orientation.

Amino Acid Sequence↗
PubMed1991

Is there a relationship between 5-HT1B receptors and the mechanisms of action of antidepressant drugs in the learned helplessness paradigm in rats?

The present study was undertaken to investigate, in the learned helplessness paradigm, (1) the effects of CGS 12066B, a selective 5-HT1B receptor agonist administered alone, and (2) the effects of CGS 12066B co-administered with tricyclics (clomipramine, imipramine) or 5-HT re-uptake blockers (citalopram, fluvoxamine). The results showed that (1) the selective 5-HT1B agonist failed to reverse the escape deficit, and (2) in the drug interaction studies, CGS 12066B did not modify the ability of tricyclics to reverse the escape deficit. The 5-HT1B agonist, however, did significantly reduce the ability of 5-HT re-uptake blockers to reverse the escape deficit. These results suggest that modulation of 5-HT1B sites might modify the enhancement of 5-HT neurotransmission by antidepressants, particularly 5-HT re-uptake blockers.

Animals↗
PubMed1991

Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies.

Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human class II-positive monocytic (I937) and T leukemic (HUT78) tumor cell lines and Epstein-Barr virus (EBV) transformed B-lymphoid cell lines (EBV-LCL). Class II-negative cell lines (U-937 and the EBV-LCL mutant line 616) were not induced to aggregate. An HLA-G-transfected EBV-LCL, 221-AGN, but not the class I-negative parental line, 221, showed homotypic aggregation in response to an HLA-G specific mAb (87G) and a broad reacting class I-specific mAb (IOT2). Both cell lines responded with aggregation to anti-class II mAb (TU35). The anti-class I mAb, W6/32, had no effect on all cell lines tested and two anti-beta 2-microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature-sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase inhibitors (genistein, herbimycin A). Serine/threonine protein kinase inhibitors (staurosporin, H7) partly inhibited the aggregation responses. There was no strict correlation between induction of aggregation and epitope density. FcR were not involved in the aggregation response, since F(ab')2 fragments of anti-DR mAb, L243, were as effective as the whole antibody. The aggregation was not influenced by mAb against accessory molecules previously shown to be involved directly or indirectly in homotypic aggregation [CD11a (LFA-1)/CD18/CD54 (ICAM-1), CD58 (LFA-3)/CD2, BB1/CD28, CD43, and CD44]. In conclusion, these data provide further evidence that HLA molecules are implicated in a novel, cellular aggregation phenomenon involving the cytoskeleton.

Antibodies, Monoclonal↗
PubMed1991

The amino acid sequence of hemoglobin II from the symbiont-harboring clam Lucina pectinata.

The cytoplasmic hemoglobin II from the gill of the clam Lucina pectinata consists of 150 amino acid residues, has a calculated Mm of 17,476, including heme and an acetylated N-terminal residue. It retains the invariant residues Phe 44 at position CD1 and His 65 at the proximal position F8, as well as the highly conserved Trp 15 at position A12 and Pro 38 at position C2. The most likely candidate for the distal residue at position E7, based on the alignment with other globins, is Gln 65. However, optical and EPR spectroscopic studies of the ferri Hb II (Kraus, D. W., Wittenberg, J. B., Lu, J. F., and Peisach, J., J. Biol. Chem. 265, 16054-16059, 1990) have implicated a tyrosinate oxygen as the distal ligand. Modeling of the Lucina Hb II sequence, using the crystal structure of sperm whale aquometmyoglobin, showed that Tyr 30 substituting for the Leu located at position B10 can place its oxygen within 2.8 A of the water molecule occupying the distal ligand position. This structural alteration is facilitated by the coordinate mutation of the residue at position CD4, from Phe 46 in the sperm whale myoglobin sequence to Leu 47 in Lucina Hb II.

Amino Acid Sequence↗
PubMed1991

Monitoring of coagulation status using thrombelastography during paediatric open heart surgery.

Thrombelastography (TEG) has proved useful in identifying coagulopathies (via assessment of clot elasticity properties) during hepatic surgery, but its role in cardiac surgery has as yet not been defined. Twenty-two children [11M, 11F, mean age (range) 4.9 (0.1-16) years] undergoing open heart surgery were investigated [1] preoperatively, [2] 15 min post protamine, [3] 2 h and [4] 24 h postoperatively using TEG. Comparisons were made between pre- and postoperative measurements and haematological indices. The values obtained from the TEG were: R phase (indicative of thrombokinase and thrombin formation disorders), K phase (indicative of fibrinogenesis) and MA phase (providing information on clot stability and platelet function). The patients were divided into two groups based upon 24 h blood loss; Group 1 - blood loss less than 0.7 ml/kg/h and Group 2 - blood loss greater than 0.7 ml/kg/h. In Group 2 there was a highly significant correlation between post-protamine MA phase and platelet number (r = 0.93, p less than 0.001) but there was no correlation in Group 1 (p greater than 0.1). Furthermore, in Group 2 elevated postoperative blood loss was associated with a prolonged K phase (mean [SD] 12.0 [6.0] versus 6.3 [2.1] min, p less than 0.05) and diminished MA phase (37 [12.5] versus 56 [4.9] mm, p less than 0.01) relative to preoperative values. In Group 1, K and MA phase did not alter significantly (p greater than 0.5 and p greater than 0.2, respectively). TEG predicted with 100% (8/8) accuracy increased post-operative bleeding. The specificity of TEG prediction of future bleeding was 73% [8/11]. Alterations in TEG parameters merit further evaluation as markers of postoperative haemorrhage.

Blood Coagulation↗
PubMed1991

1-(2-pyrimidinyl)-piperazine may alter the effects of the 5-HT1A agonist in the learned helplessness paradigm in rats.

The 5-HT1A agonists buspirone, gepirone and ipsapirone have been shown to possess antidepressive-like properties in several animal models of depression as well as in clinical studies. These compounds are metabolized to 1-(2-pyrimidinyl)-piperazine (1-PP) in rats and humans. In the learned helplessness paradigm, buspirone exhibits a biphasic action: at low or moderate doses it shows an antidepressant-like effect but this action progressively disappears as the doses are increased. In order to establish whether 1-PP affects the reversal of helpless behaviour induced by the 5-HT1A agonists at high doses in rats, we have investigated its role in the learned helplessness. Thus, 1-PP has been evaluated alone (0.06-4 mg/kg/day) or in combination with a selective 5-HT1A agonist 8-OH-DPAT (0.25 mg/kg/day) which is not metabolized to 1-PP and buspirone (0.5 mg/kg/day). In addition, buspirone at a higher dose (2 mg/kg/day) has also been examined in the presence of proadifen which inhibits oxidative metabolism. Our results show that i) daily injections of 1-PP did not reverse helpless behaviour, ii) the reversal of helpless behaviour by 8-OH-DPAT or active dose of buspirone was antagonized by daily coadministration of 1-PP, iii) in rats pretreated with proadifen, the highest "inactive" dose of buspirone induces a reversal of helpless behaviour. These results strongly suggest that up to a certain concentration 1-PP can impair the effects of the parent drug in the learned helplessness.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Effects of positive end-expiratory pressure (PEEP) ventilation on the exocrine pancreas in minipigs.

The effect of positive end-expiratory pressure (PEEP) ventilation on the pancreas was studied in 22 anesthetized minipigs. Five pigs were treated with intermittent positive pressure ventilation (IPPV) for 21 h (Group I) and six pigs were treated with a PEEP of 15 cm H2O for 21 h (Group II). We next explored the influence of PEEP ventilation while stimulating the pancreas with Ceruletide, a synthetic cholecystokinin (CCK) analog, at 2.3 micrograms/kg per h.i.v. for 3 h. Ventilation with IPPV for 4 h (n = 5, group III) was compared with PEEP of 15 cm H2O for 4 h (n = 6, group IV). Changes in serum-lipase were observed in all groups. The average lipase level rose from 12.6 U/l to 67 U/l group I and from 15.1 U/l to 129.2 U/l in group II (P = 0.025 for group I vs group II). In group IV (PEEP and Ceruletide), the mean lipase level rose about six times more than in group III (IPPV and Ceruletide). The difference was significant (P less than 0.00005). By three-factor ANOVA analysis, effects due to the drug (P less than 0.000006) and to PEEP (P less than 0.038) as well as a threefold interaction could be demonstrated, i.e., using Ceruletide a greater PEEP effect on lipase than without the drug (P less than 0.023) took place. There were no significant histological changes of the pancreas in groups I and III. In group II (21 h PEEP), vacuolization of acinar cells was evident; on the ultrastructural level, indication was given that these vacuoles derived both from the Golgi apparatus and from fusion of individual zymogen granules. In group IV (PEEP and Ceruletide), the focal appearance of fatty-tissue necrosis and acinar cells as well as hemorrhage of the gland was observed. We conclude that PEEP ventilation impairs the function of the pancreas and produces even more deleterious effects when the gland is stimulated. These effects should be considered when PEEP is used in clinical practice in the treatment of acute pancreatitis.

Amylases↗
PubMed1991

Association of a thyrotropin-secreting pituitary adenoma and a thyroid follicular carcinoma.

The different factors involved as etiological agents in thyroid cancer have in common long term thyroid follicle stimulation. On this base, a patient with a TSH-producing pituitary adenoma could be at high risk for developing thyroid cancer. A patient consulting for a single thyroid nodule was studied in our unit. He was diagnosed as having a TSH-producing pituitary adenoma and the Thyroid nodule was shown to be a follicular carcinoma following removed. We speculate that elevated TSH levels could have contributed to neoplastic transformation of the thyroid in this patient.

Adenocarcinoma↗