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Biomedical subjects

I Martin

Publications and source records attributed to I Martin.

At least 163 records · Page 9Linked to original sources
PubMed1993

Orientation and structure of the NH2-terminal HIV-1 gp41 peptide in fused and aggregated liposomes.

For several retroviruses, the N-terminal hydrophobic sequence of the viral envelope glycoprotein has been shown to play a crucial role in the interaction between the virus and the host cell membrane. We report here on the interaction of a synthetic 16 residues peptide corresponding to the gp41 NH2-terminal sequence of Human Immunodeficiency Virus with the phospholipid bilayer. Fluorescence energy transfer measurements show that this peptide can induce lipid mixing of large unilamellar vesicles (LUV) of various compositions at pH 7.4 and 37 degrees C. LUV undergo fusion, provided they contained phosphatidylethanolamine (PE) in their lipid composition. To provide insight into the mechanism of the fusion event, the peptide secondary structure and orientation in the lipid bilayer were determined using Fourier Transform Infrared Spectroscopy (FTIR). The peptide adopts mainly a beta-sheet conformation in the absence of lipids. After interaction with LUV the beta-sheet is partly converted into alpha-helix. The orientation of the peptide with respect to the lipid acyl chains depends on the presence of PE in the lipid bilayer. The peptide is inserted into the lipid bilayer with the helix axis oriented parallel to the lipid acyl chains in the fused vesicles, whereas it is adsorbed parallel to the lipid/water interface in the aggregated vesicles. The role of the two kinds of orientation during the fusion event is discussed.

Amino Acid Sequence↗
PubMed1993

Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protein transferase.

Chaetomellic acids A and B, isolated from Chaetomella acutiseta, are specific inhibitors of farnesyl-protein transferase that do not inhibit geranylgeranyl transferase type 1 or squalene synthase. Chaetomellic acids A and B are reversible inhibitors, resemble farnesyl diphosphate and probably inhibit FPTase by substituting for farnesyl diphosphate. Chaetomellic acid production appears to be widespread within the genus Chaetomella.

Alkyl and Aryl Transferases↗
PubMed1993

Secondary structure of gp160 and gp120 envelope glycoproteins of human immunodeficiency virus type 1: a Fourier transform infrared spectroscopic study.

The secondary structure of the precursor (gp160) of the envelope protein of human immunodeficiency virus type 1 (BH10) and its receptor-binding subunit (gp120) was studied by Fourier-transformed attenuated total reflection spectroscopy. A higher alpha-helix/beta-sheet ratio in the gp120 subunit than in the precursor indicates a structural heterogeneity between the two subunits (gp120 and gp41), in agreement with classical secondary-structure predictions. The secondary structure of gp41 was estimated and compared with existing models. The high alpha-helical content in gp41 and the dominant beta-sheet content in gp120 resemble the distribution in influenza virus hemagglutinin subunits.

CD4 Antigens↗
PubMed1993

Discrimination and pharmacological characterization of I2-imidazoline sites with [3H]idazoxan and alpha-2 adrenoceptors with [3H]RX821002 (2-methoxy idazoxan) in the human and rat brains.

The alpha-2 adrenoceptor antagonist idazoxan has been shown to also recognize with high affinity nonadrenoceptor sites (I2-imidazoline sites). In contrast, the 2-methoxy derivative of idazoxan, 2-methoxy idazoxan (RX821002), binds almost exclusively to alpha-2 adrenoceptors. The purpose of this study was to assess and extend the pharmacological characterization of I2-imidazoline sites and alpha-2 adrenoceptors in the human and rat brains. Competition studies with several imidazoli(di)ne/guanidine drugs and other nonrelated structures were performed in cortical membranes against [3H]idazoxan (4 nM in the presence of 10(-6) M I-epinephrine to prevent binding to alpha-2 adrenoceptors) or [3H]RX821002 (1 nM). Drugs such as cirazoline, guanoxan, naphazoline, tolazoline, clonidine, bromoxidine (UK 14,304) and phenylbiguanide displaced [3H]idazoxan from two distinct binding sites, which suggested the existence of two affinity states for I2-imidazoline sites that were not modulated by MgCl2 or the nucleotide analog guanylyl-5'-imido-diphosphate. Binding affinities at the low-affinity site (KiL) were consistently more than 2 orders of magnitude lower than binding affinities at the high-affinity site (KiH), and there was a good correlation between KiH and KiL values for a given drug in the human (r = 0.89) and rat (r = 0.92) brains. For 18 to 22 drugs, the Ki values in the human brain correlated well with the corresponding Ki values in the rat brain both for I2-imidazoline sites (r = 0.94) and alpha-2 adrenoceptors (r = 0.97). However, the Ki values for I2-imidazoline sites did not correlate with the Ki values for alpha-2 adrenoceptors in human and rat brains. The order of drug potency for the I2-imidazoline sites was: guanoxan (1.3 nM) approximately cirazoline > idazoxan approximately naphazoline > clonidine > phentolamine > RX821002 > (8aR, 12aS, 13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a- decahydro-8H-isoquino[2,1-g]-naphthyridine (RS 15385-197) (> 10 microM). In contrast, the potencies at the alpha-2 adrenoceptor were: RS 1538-197 (0.3 nM) > RX821002 > clonidine > phentolamine > idazoxan approximately naphazoline > guanoxan approximately cirazoline (307 nM). The results demonstrate that I2-imidazoline sites (labeled by [3H]idazoxan) and alpha-2 adrenoceptors are different pharmacological entities with similar characteristics in the human and rat brains. In both species, I2-imidazoline sites are markedly heterogeneous in nature.

Adrenergic alpha-Antagonists↗
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↗