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Biomedical subjects

I Martin

Publications and source records attributed to I Martin.

At least 19 recordsLinked to original sources
PubMed1992

Apolipoprotein A-1 interacts with the N-terminal fusogenic domains of SIV (simian immunodeficiency virus) GP32 and HIV (human immunodeficiency virus) GP41: implications in viral entry.

Previous studies showed that apoA1, the major protein component of HDL (High Density Lipoprotein), inhibited HIV infectivity and virus-induced syncytia formation. The mechanism of inhibition is unknown. We bring here evidence that the amphipathic helices of apoA1 interact with the N-terminal peptides of SIV gp32 and HIV gp41. These peptides have been shown to be associated with the initial steps of the fusion between the host cell and the virus. Binding of apoA1 to these peptides prevents the insertion of the fusogenic domains into the cell membrane and inhibits the fusion and the entry of the virus into the host cell.

Amino Acid Sequence↗
PubMed1992

A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test.

Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Early gastric cancer: 46 cases treated in one surgical department.

Forty six consecutive patients with early gastric cancer were treated between 1970 and 1990. The proportion of cases of early gastric cancer increased significantly (p < 0.01) from 1% of all cases in the first five year period to 15% in the last five year period, because of greater awareness of the condition and more widespread use of endoscopy. There were 33 men and 13 women, of median age 69 years (range 38-86). Most patients (91%) presented with symptoms indistinguishable from those of peptic ulceration. The median duration of symptoms was four months (range 0.1-36 months). All 46 patients were treated surgically. Three patients (6.5%) died after operation and a further 10 (22%) suffered postoperative complications. None of the surviving patients has been lost to follow up and 25 have been followed up for a minimum period of five years. Five year survival by life table analysis was 98%. These findings suggest that in Britain in the 1990s, as in Japan, it may be possible to diagnose an increasing proportion of patients with gastric cancer at a relatively early pathological stage, when most patients can be cured by radical surgical resection with lymphadenectomy.

Adult↗
PubMed1991

Fusogenic activity of SIV (simian immunodeficiency virus) peptides located in the GP32 NH2 terminal domain.

Peptides of 12, 16 and 24 amino acids length corresponding to the NH2 terminal sequence of SIV gp32 were synthesized. Fluorescence energy transfer studies have shown that those peptides can induce lipid mixing of SUV (Small Unilamellar Vesicles) of various compositions at pH 7.4 and 37 degrees C. LUV (Large Unilamellar Vesicles) were shown to undergo fusion, provided they contained PE in their lipid composition. This work is an attempt to determine how the fusogenic activity depends on the structure of the peptide inserted into a lipidic environment. The peptides secondary structure and orientation in the lipid bilayer were determined using Fourier Transform infrared spectroscopy (FTIR). They adopt mainly a beta-sheet conformation in the absence of lipids. After interaction with DOPC SUV, the beta-sheet is partly converted into alpha-helix oriented obliquely with respect to the membrane interface. We bring here evidence that this oblique orientation is a prerequisite to the fusion process.

Amino Acid Sequence↗
PubMed1991

Heart-lung transplantation for cystic fibrosis. 1: Assessment.

Forty five patients with cystic fibrosis (age 5-15 years) were assessed for heart-lung transplantation between September 1987 and March 1990. The two main conditions for acceptance were (i) life expectancy less than 2 years and (ii) a severely impaired quality of life. Patients were accepted onto an active waiting list (n = 26), a provisional waiting list (n = 15), or not accepted (n = 4). Selection was made on clinical grounds with objective measurements used as an aid in assessment. As expected, the mean values for objective measures were significantly different between patients on the active waiting list compared with the provisional waiting list/not accepted group for resting heart rate (118/minute v 101/minute), percentage of ideal weight (83.2% v 93.1%), forced expiratory volume at one second as percent of predicted normal (27.3% v 47.6%), Shwachman-Kulczycki score (33.6 v 52.5), Chrispin-Norman x ray score (25.8 v 22.1), 12 minute walk (540 m v 854 m), and minimal oxygen saturation (81.5% v 92%). Psychological evaluation demonstrated a 55% incidence of individual and a 50% incidence of family morbidity. Of the 26 patients accepted onto the active waiting list, 11 have been transplanted (mean waiting time 3.3 months), 10 have died within a mean of 3.7 months of acceptance, and five remain on the active list (mean 5.6 months).

Adolescent↗
PubMed1991

Heart-lung transplantation for cystic fibrosis. 2: Outcome.

From March 1988 to March 1990, 11 children with cystic fibrosis (age 5-15 years) underwent combined heart-lung transplantation at our institutes. Maintenance immunosuppression consisted of cyclosporin and azathioprine with corticosteroids and antithymocyte globulin used perioperatively and during rejection episodes. Six patients (55%) survive from 1.5-23 months all of whom have improved life quality. Actuarial survival to 1 year was 55%. At six months after transplant, mean forced expiratory volume at one second was 73.5% of predicted normal, compared with 25% before transplant. There was one perioperative death, three later deaths associated with obliterative bronchiolitis at two, eight, and nine months, and one from mediastinitis at four months. Of the 15 children accepted for transplantation but not receiving grafts, 10 have died (eight within four months of being placed onto the transplant list). Early postoperative problems included acute reversible rejection (n = 10), meconium ileus equivalent (n = 3), and pancreatitis (n = 1). There was a high incidence of later pulmonary rejection with a mean of 5.7 episodes per patient in the first six months. Pulmonary infection occurred relatively infrequently, with Pseudomonas aeruginosa being the most common pathogen. Persistent diabetes mellitus requiring insulin occurred in four and systemic hypertension developed in one.

Adolescent↗
PubMed1991

Blocking observed in human eyelid conditioning.

Four eyelid conditioning experiments designed to be comparable to rabbit nictitating membrane (NMR) studies examined the blocking phenomenon in humans. All experiments utilized a within-subjects design, with Stage 1 of discrimination, Stage 2 of compound training, and a final test stage comparing responding to the blocked and non-blocked CSs. In two of the experiments (1 and 4) the comparison was made within subjects over all extinction trials. In Experiment 3 the test phase consisted of further reinforced training of the blocked and non-blocked CSs. These three experiments produced evidence of blocking when all extinction trials were entered into the analysis. Experiment 2, which involved a between-subjects comparison, failed to demonstrate the blocking effect. Wide variability both between and within subjects obscured the experimental effects. Post-experimental questionnaires designed to assess awareness of stimulus relations failed to identify a subjective blocking effect and showed no relationship to conditioned eyelid responding.

Adolescent↗
PubMed1990

Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue. Unaltered iodothyronine 5'-deiodinase activity is necessary for the response to environmental temperature at birth.

We have performed a sequential study on the abundance of the mRNA for uncoupling protein (UCP), subunit II of cytochrome-c oxidase (COII) and lipoprotein lipase in brown adipose tissue during the fetal and postnatal periods. Moreover, we have determined whether these parameters can be modulated by ambient temperature in the early hours after birth, and at which point in development this sensitivity first appears. UCP gene expression in the fetal and neonatal period has particular features when compared with overall mitochondriogenesis (COII mRNA expression) or with the expression of lipoprotein lipase mRNA. There is a specific induction of UCP gene expression between days 18 and 19 of pregnancy followed by a specific increase of UCP gene expression in utero and a further increase after birth. The acquisition of the physiological apparatus capable of the response to UCP and lipoprotein lipase gene expression to the environmental temperature is not achieved until the last day of fetal development. This result suggests that mechanisms of beta-adrenergic modulation of gene expression in brown fat are already established at birth. From an experiment on iopanoic acid treatment of pregnant mothers, it was concluded that iodothyronine 5'-deiodinase activity is not necessary for the expression of the mRNAs for UCP, COII and lipoprotein lipase in the fetus whereas it is necessary for the acquisition of temperature sensitivity to these parameters at birth.

Adipose Tissue, Brown↗
PubMed1990

Lipoprotein lipase mRNA expression in brown adipose tissue: translational and/or posttranslational events are involved in the modulation of enzyme activity.

Lipoprotein lipase mRNA abundance in rat brown adipose tissue increases during the first 24 h of cold exposure. Lipoprotein lipase mRNA levels do not change in brown fat throughout pregnancy and lactation, whereas enzyme activity is significantly lowered. After 5 h of acute cold or noradrenaline administration there is a 2-fold increase in lipoprotein lipase mRNA abundance, whereas lipoprotein lipase activity is stimulated to more than 6-fold the basal values. It is concluded that translational and/or posttranslational mechanisms are involved in the noradrenergic modulation of lipoprotein lipase activity in brown fat.

Acclimatization↗
PubMed1990

Eysenck's incubation of fear hypothesis: an experimental test.

The present experiment was designed to test Eysenck's hypothesis that repeated exposure to an unreinforced CS of brief duration following acquisition of a classical aversive CR may lead to a progressive increase in the strength of that CR, provided that the UCS is intense and the CR has drive-like properties. Using a between-groups design, normal human subjects were given identical classical acquisition trials, followed by extinction trials where CS duration was either 2, 8 or 16 sec. The UCS was of fixed high intensity. Dependent measures were tonic and phasic heart rate and skin conductance. No evidence of incubation was found as a function of CS duration. Nor was there any indication that CS duration differentially affected resistance to extinction. A small number of subjects showed evidence of incubation with heart rate measures during extinction. However, there was no indication that this enhancement was governed by the parameters suggested by Eysenck. UCR amplitude, which showed a positive correspondence with CS-bound activity throughout the trials, did not reliably predict incubation. Problems concerning both the definition and the demonstration of incubation are discussed.

Adolescent↗
PubMed1990

Dihydropyridines on guinea-pig ileum.

1. The effects of three dihydropyridine derivates were studied and compared with those of nifedipine in guinea-pig ileum. 2. Nifedipine, nimodipine, nitrendipine (25-200 nM) and nisoldipine (10-80 nM) produced a dose-dependent inhibition of the contractile responses induced by single pulse stimulation, acetylcholine (1 microM) and high-K (50 mM). 3. From these experiments it is concluded that nimodipine and nitrendipine, like nifedipine, produced a similar and potent inhibitory effect of the contractile responses induced in the guinea-pig ileum. 4. Nisoldipine resulted to be the most active agent.

Acetylcholine↗
PubMed1990

Electrotherapy in mice: dopaminergic and noradrenergic effects in the Tail Suspension Test.

The Tail Suspension Test (TST) is a psychotropic screening test which is used principally to detect antidepressant activity. Electrotherapy (ECT) is used to treat depressions which are resistant to the usual antidepressant drugs and has proved to have a profile in the TST approaching that of antidepressants after treating mice at the rate of 2 shocks per day for 5 days. The results of a single treatment were not statistically different from those of the control group, whereas single daily treatment for 5 days showed a reduction in immobility which did not differ significantly from the control group. The reduction in immobility, induced by 5 days of ECT treatment twice daily, was antagonized by sulpiride and prazosin but not by yohimbine, methysergide, metergoline and DL propranolol. The results suggest that electrotherapy leads to an increase in noradrenergic and dopaminergic activities expressed by a reduction in immobility in the TST.

Animals↗
PubMed1989

Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation.

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation.

Adipose Tissue, Brown↗
PubMed1989

Separation and molecular weight determination of prostaglandin B1 oligomers by size-exclusion chromatography.

An efficient size-exclusion chromatographic method for the simultaneous separation and molecular weight (MW) determination of prostaglandin (PG) oligomers on Sephadex G-50 with borate buffer is described. The prostaglandins 15-keto-PGB1 and 16,16-dimethyl-15-keto-PGB1 were used for the synthesis of oligomers. MW determinations in the monomer to octamer range is based on the linear correlation between the partition coefficient and log (MW) of the oligomers. The essential role of the borate anion between the gel matrix and the oligomers is demonstrated.

Chemical Phenomena↗
PubMed1989

Secondary structure and orientation of a chemically synthesized mitochondrial signal sequence in phospholipid bilayers.

A pre-sequence of 25 amino acids is required for import of yeast cytochrome oxidase subunit IV into mitochondria. Structure and orientation of the 25 amino acids synthesized peptide (p25) in a lipid bilayer were investigated by infrared attenuated total reflection spectroscopy. This method allowed to overcome the difficulties related to the optical turbidity due to the light scattering on membrane fragments which prevents the use of circular dichroism. We demonstrate here that incubation of the peptide with DOPC (dioleoylphosphatidylcholine) and DOPC-CL (dioleoylphosphatidylcholine - cardiolipin) liposomes is accompanied by an increase in alpha-helical content as compared to beta structure. Polarisation measurements indicate that the amphipathic helical segment is inserted parallel to the lipid acyl chains in cardiolipin containing liposomes.

Cardiolipins↗
PubMed1989

Propositional knowledge and mere responding.

This commentary examines views recently offered by Furedy and Riley (1987) on the nature of classical conditioning. Their analysis identifies propositional learning as a component of conditioning separate from response acquisition. They reserve to this component the label cognitive on the epistemological grounds of falsifiability. We suggest that this analysis does not do justice to the concept of cognition in human conditioning. In particular it limits the scope of propositional knowledge to a formal role in the conditioning paradigm and ignores the recent development of propositional models in cognitive science. In seeking to integrate their propositional account with animal conditioning theory they usefully map their two processes on to the conditioned response/instrumental response distinction proposed by Gormezano and Kehoe (1975). However, their propositional contingency interpretation of the Rescorla and Wagner (1972) theory ignores the essentially associative mechanism used in the model to account for interevent relations.

Animals↗
PubMed1989

Time-dependent effects of alcohol on the hypothalamic-hypophyseal-testicular function in the rat.

Adult male rats were followed throughout ethanol administration, in order to examine the time-dependent effects of ethanol on the hypothalamic-pituitary-gonadal axis. The results indicate that there is an increase in plasma prolactin levels together with a reduction in basal plasma luteinizing hormone (LH) levels, which are evident from the beginning of the intoxication period. An exaggerated response of LH to luteinizing hormone-releasing hormone was also evident from 2nd week on, in ethanol-treated rats. Basal and human chorionic gonadotropin-stimulated plasma testosterone levels were decreased in alcohol-treated as compared to control rats, at all time points studied. In addition, plasma estradiol levels were increased in ethanol-fed rats. These data suggest a direct suppressive effect of ethanol on LH release in the beginning of the intoxication period. Subsequent elevations of plasma estradiol and prolactin levels may have contributed to the maintenance of hypogonadism at the end of the intoxication period.

Animals↗