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Biomedical subjects

M J Martin

Publications and source records attributed to M J Martin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Case manager attitudes toward client-directed care.

Advocates for individuals with severe and long-term physical disabilities have lobbied aggressively in the U.S. and Canada for the implementation of Independent Provider Care (IPC). In this model of home support service delivery, the client assumes sole responsibility for the management and scheduling of his or her personal care and home support. This article reports on the findings of a Canadian survey that assessed case managers' beliefs regarding the efficacy, benefits, and risks to clients of an IPC program. Survey results indicated that case managers generally believed that IPC would not significantly improve their clients' well-being and quality of care, would pose risks of abuse to both the client and support attendant, and would result in greater job demands for case managers. Possible sources of their apprehension are identified, and measures that may help to alleviate their concerns are discussed.

Attitude of Health Personnel↗
PubMed1994

Influence of the chemical nature of side chain at beta 108 of hemoglobin A on the modulation of the oxygen affinity by chloride ions. Low oxygen affinity variants of human hemoglobin expressed in transgenic pigs: hemoglobins Presbyterian and Yoshizuka.

Hemoglobin A (HbA) and two low oxygen affinity variants of HbA, HbPresbyterian and HbYoshizuka, were produced in transgenic pigs and purified to homogeneity by ion-exchange chromatography. These two variants contain either lysine (HbPresbyterian) or aspartic acid (HbYoshizuka) instead of the normal asparagine residue at position beta 108 in HbA. Transgenic pigs expressed these variants at a level up to 11% and were healthy. Both HbPresbyterian and HbYoshizuka exhibited low O2 affinity (P50 of 21.2 and 18.9, respectively, compared with control HbA value of 11.8 in 0.1 M NaCl, pH 7.5) and retained normal cooperativity with Hill coefficients of 2.9 and 2.5, respectively. HbPresbyterian exhibited Bohr effect comparable with HbA. In contrast, HbYoshizuka had a diminished response to changes in pH. Thus the structural basis of reduced O2 affinity of these variants appears to be distinct: the consequence of mutation at beta 108 is a function of the chemical nature of the side chain. This is further confirmed by the sensitivity of the O2 affinity of the variants to the presence of Cl-. The O2 affinity of HbYoshizuka is insensitive to changes in Cl- concentration, whereas the O2 affinity of HbPresbyterian exhibited a pronounced and dramatic chloride effect. In fact, P50 of HbPresbyterian was identical to that of HbA at very low Cl- concentrations, and the P50 increased to >40 at 0.5 M Cl-. The chloride effect was completely abolished when HbPresbyterian was stabilized at the 2,3-diphosphoglycerate pocket by interdimeric cross-linking. Molecular modeling studies demonstrate that in HbPresbyterian, Cl- can bridge the epsilon-amino group of Lys beta 108 with either the guanidino group of Arg beta 104 or the epsilon-amino group of Lys alpha 99, resulting in the stabilization of the "T" structure. The utility of these low O2 affinity hemoglobins as cell-free oxygen carriers is discussed.

Allosteric Regulation↗
PubMed1994

Molecular epidemiology of HIV-1 in Madrid.

Thirteen HIV-1 isolates from patients of different risk groups in Madrid (Spain) have been analyzed at the genetic level. Two distinct lineages of subtype B have been detected among the HIV-1 circulating in this area: one was related to SF-2/RF strains, whereas the other consists of a more heterogeneous group related to reference strain III-B. Variants of each lineage appeared to circulate preferentially within a risk group: III-B among intravenous drug users, and RF/SF-2 among male homosexuals.

Adult↗
PubMed1994

An isologous porcine promoter permits high level expression of human hemoglobin in transgenic swine.

We describe isologous promoter replacement as an approach to permit high level expression of human hemoglobin in transgenic swine. We linked the human beta globin genomic coding region to the porcine beta globin promoter and used this fusion gene in an expression construct containing the human beta locus control region and the human alpha and epsilon genes to produce transgenic pigs. The highest level of expression was 24% human (32g/liter) and 30% human alpha/pig beta hybrid (40g/liter) hemoglobin in one transgenic pig. This pig was bred to a non-transgenic animal resulting in the transmission of high level human hemoglobin expression to 5 of 12 progeny.

Animals↗
PubMed1993

Acyclovir diphosphate dimyristoylglycerol: a phospholipid prodrug with activity against acyclovir-resistant herpes simplex virus.

Infection with herpes simplex viruses (HSVs) resistant to treatment with acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine, Zovirax) is a growing clinical problem in patients with AIDS and other immunosuppressed states. Most virus isolates resistant to acyclovir are deficient or defective in virally coded thymidine kinase (TK), which converts acyclovir to acyclovir monophosphate in virus-infected cells. To restore acyclovir efficacy, we synthesized acyclovir diphosphate dimyristoylglycerol, an analog of a naturally occurring phospholipid, CDP-diacylglycerol. Its biological activity was tested in WI38 human lung fibroblasts infected with the acyclovir-resistant DM21 strain of HSV, which is TK negative due to an 816-base-pair deletion in the TK coding region. Acyclovir diphosphate dimyristoylglycerol has substantial activity in DM21-infected cells (IC50 = 0.25 microM), whereas acyclovir and acyclovir monophosphate were ineffective (IC50 > 100 microM). Similar results were obtained in TK-altered and TK-deficient strains of HSV-1 and in acyclovir-resistant isolates of HSV-2 obtained from two AIDS patients. The phospholipid prodrug is active by means of TK-independent metabolic pathways that liberate acyclovir monophosphate inside the host cell. Acyclovir phosphates were 56 times greater in WI38 human lung fibroblasts incubated for 24 hr with [8-3H]acyclovir diphosphate dimyristoylglycerol relative to acyclovir. Acyclovir monophosphate added to the culture medium (outside the cell) did not circumvent the acyclovir resistance of the TK-negative DM21 mutant, presumably due to its conversion to acyclovir by phosphatases. Acyclovir diphosphate diacylglycerol prodrugs may be useful in treating TK-deficient mutant and wild-type strains of HSV.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A comparison of 1- and 2-cell ova production by F2 50% Meishan versus F1 White line gilts.

The objective of this study was to compare recovery of pronuclear and 2-cell ova from F2 50% Meishan (MX) gilts versus F1 White line (L42) gilts. Sexually mature MX and L42 gilts were allocated across 2 treatments: Super (MX:n=9; L42:n=10) and Control (MX:n=6; L42:n=5) in a 2 x 2 factorial experiment. Allyl trenbolone (AT) was used to synchronize estrus in all gilts. Super gilts were given pregnant mare serum gonadotropin (PMSG: 1250 IU) at 24 h after AT withdrawal. Eighty-five hours after PMSG administration, all Super gilts received 750 IU of human chorionic gonadotropin (hCG). Super gilts which exhibited estrus within 24 h of hCG administration (MX-Super: n=6; L42-Super: n=5) and all Control gilts were bred naturally to Line 3 boars at 12 and 24 hours after the onset of estrus. Ova were recovered from Super gilts between 60 and 64 h after hCG and Control gilts at 48 h after the onset of estrus. All 1- and 2-cell ova were centrifuged at 15000 x g and observed using differential interference contrast microscopy. The mean ovulation rate was greater (P<0.05) for both MX-Super and L42-Super gilts in comparison to their respective Control groups. No differences were detected in the mean ovulation rate (P>0.38) or the mean number of 1- and 2-cell ova recovered (P>0.50) between MX-Super and L42-Super gilts. The proportion of 1- and 2-cell ova which exhibited visible pronuclei or nuclei was also similar among MX-SUPER and L42-SUPER gilts. This study demonstrates that MX gilts respond/perform comparably to L42 gilts with respect to estrus synchronization, superovulation, ova yield, and the ease of visibility of pronuclei or nuclei in the ova.

Journal Article↗
PubMed1993

Production of human hemoglobin in transgenic swine: an approach to a blood substitute.

Many significant challenges have to be met before a clinically useful hemoglobin-based blood substitute can be developed. A major issue is the choice of a production system. Transgenic swine have several features that appear to be suited to the abundant production of human hemoglobin. Here we show that authentic human hemoglobin can be made in transgenic pigs and purified by simple ion-exchange chromatography. The purified hemoglobin can be modified for testing and use as a blood substitute.

Animals↗
PubMed1992

Predictive binding of beta-carboline inverse agonists and antagonists via the CoMFA/GOLPE approach.

The synthesis and affinities of six new 3-substituted beta-carbolines (6-10, 12) for the benzodiazepine receptor (BzR) are described. These analogs were used both to probe the dimensions of the hydrophobic pocket in the benzodiazepine receptor and to test the predictive ability of a previously reported 3D-QSAR regression model. Of the new analogs synthesized, the gamma-branched derivatives (isobutoxy, 7, IC50 = 93 nM; isopentoxy, 9, IC50 = 104 nM) display significantly higher affinity for the BzR than either the beta-branched (sec-butoxy, 6, IC50 = 471 nM; tert-butyl ketone, 12, IC50 = 358 nM) or delta-branched (isopentoxy, 8, IC50 = 535 nM) analogs. An exception to this rule is the gamma-branched 3-benzyloxy derivative 10 (IC50 > 1000 nM) which appears to have a chain length that is too long to be accommodated by the BzR. The standard error of prediction for these six new beta-carbolines using the original regression model is significantly lower than the standard error estimate of the cross validation runs on the training set, hence the predictions made using this model are much better than expected. In order to obtain more credible predictions, a new procedure called GOLPE (generating optimal linear PLS estimates) was used to eliminate irrelevant electrostatic and steric descriptors from the regression equation. A substantial reduction in the standard error estimate resulted. The predictions from this new regression equation were somewhat less accurate than the ones obtained with the original regression equation; however the standard error of prediction and the standard error estimate are in much closer agreement. Finally, to probe the effect that the quality of the steric and electrostatic potentials has on 3D-QSAR analyses, the semiempirical MNDO parallel PRDDOE geometries and Mulliken charges used in the original analyses were replaced with ab initio 3-21G parallel 6-31G* geometries and electrostatic potential fit charges. A modest decrease in the standard error estimate and increase in cross validated R2 resulted.

Animals↗
PubMed1992

Molecular yardsticks. Rigid probes to define the spatial dimensions of the benzodiazepine receptor binding site.

A series of rigid planar azadiindoles (8a, 8b, and 8d), benzannelated pyridodiindoles (11a, 11b, and 11d), and indolopyridoimidazoles (11c, 20, and 24) were synthesized from 4-oxo-1,2,3,4-tetrahydro-beta-carboline 5 via the Fischer indole cyclization with the appropriate arylhydrazines. These analogues were employed as probes ("molecular yardsticks") to define the spatial dimensions of the lipophilic regions of the benzodiazepine receptor (BzR) binding cleft. Benzannelated indoles 11a-d and indolopyridoimidazoles 20 and 24 were important in establishing an area of negative interaction (S1, see Figure 6, part b) in the binding cleft common to the interactions of both inverse agonists and agonists. Data from this chemical and computer-assisted analysis of the pharmacophore (see Figure 6) indicates that inverse agonists and agonists bind to the same binding region, but the pharmacophoric descriptors required for the two activities are different, in keeping with previous studies with these planar ligands. However, the hydrogen bond donating site H1 and the lipophilic region L1 in the receptor binding site are common interactions experienced by both series of ligands. The low affinities of both indolo[3,2-c]carbazole (3a) and indolo[3,2-b]isoquinoline (3b) for the BzR are consonant with the requirements of a hydrogen bond acceptor interaction at donor site H1 and a hydrogen bond donor interaction at acceptor site A2 for potent inverse agonist activity in the beta-carboline series. The hydrochloride salts of 1-aza- 8a (IC50 10.6 nM), 2-aza- 8b (IC50 51.5 nM), and 4-azadiindole 8d (IC50 11.2 nM) were found to be much more soluble in water than the corresponding salt of the parent diindole 2. Moreover, aza analogues 8a and 8b were shown to be partial inverse agonists with proconvulsant potencies comparable to that of the parent diindole 2.

Animals↗
PubMed1992

Production of functional human hemoglobin in transgenic swine.

A construct containing the locus control region (LCR) from the human beta globin locus together with two copies of the human alpha 1 gene and a single copy of the human beta A gene was used to obtain three transgenic pigs. The transgenic pigs are healthy, not anemic, and grow at a rate comparable to non-transgenic littermates. All animals expressed the human genes. However, alpha globin was consistently expressed at higher levels than beta globin. Isolation of the human hemoglobin from both porcine hemoglobin and other non-hemoglobin proteins was accomplished by ion exchange chromatography. The purified porcine derived human hemoglobin exhibited an oxygen affinity similar to that of human derived human hemoglobin.

Animals↗
PubMed1992

Gastric anti-ulcer activity of silymarin, a lipoxygenase inhibitor, in rats.

Oral treatment with silymarin was found to be effective in the prevention of gastric ulceration induced by cold-restraint stress, in rats. Statistically significant ulcer index values with respect to the control group, were observed. In 6 h pyloric-ligated animals silymarin showed a significant reduction in the number and severity of the ulcers; however, it did not alter the gastric secretion volume or acidity although histamine concentration was significantly decreased. In absolute ethanol-induced ulcers, treatment with silymarin 1 or 2 h before the anti-ulcerogenic agent, did not prevent the formation of gastric lesions. Furthermore, the hexosamine content was decreased significantly, but the total protein output was enhanced, showing similar values to those with the standard drug, carbenoxolone. These results suggest that the anti-ulcerogenic effect of silymarin could be related to its inhibitory mechanism of enzymatic peroxidation by the lipoxygenase pathway, avoiding leukotriene synthesis.

Animals↗
PubMed1991

Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction.

This study was designed to investigate whether auditory P300 event-related potential and smooth pursuit eye-movement abnormalities in schizophrenia are associated with brain structural changes measured using magnetic resonance imaging (MRI). Serial coronal MRI scans obtained from 31 schizophrenic subjects and 33 volunteer controls were analysed by a rater who had no knowledge of the subjects' diagnoses. The brain areas measured bilaterally were the temporal lobe, hippocampus, amygdala, parahippocampal gyrus, head of caudate, cingulate cortex, frontal cortex, and the lateral ventricles. The area of the third ventricle, the thickness of the corpus callosum, and the intracranial area were also measured. Auditory P300 and eye tracking performance were recorded on all subjects. There was a significant increase in the latency and a reduction in amplitude of the P300 in the schizophrenic group. Only in the schizophrenic group was P300 latency correlated negatively with the area of the right and left cingulate cortex and positively with the difference in size between the right and left amygdala. In the subgroup of schizophrenic subjects whose P300 latency was greater than 2 standard deviations above the control mean, the area of the left cingulate cortex was significantly smaller than in controls, and the absolute right-left difference in the area of the amygdala was significantly increased. Eye tracking dysfunction in schizophrenia was not related to changes in the amygdala or cingulate cortex but was significantly correlated with enlargement of the lateral ventricles. Schizophrenic subjects with poor eye tracking had significantly larger lateral ventricles than controls. Eye tracking dysfunction, but not P300 abnormality, was correlated with the severity of both positive and negative symptom of schizophrenia. These findings demonstrate that psychophysiological abnormalities are associated with altered brain structure in schizophrenia.

Arousal↗
PubMed1991

Effect of cell-free synchronous uterine flushings and microsurgery on the development of porcine embryos in vitro.

Experiment I was designed to determine if cell-free synchronous uterine flushings contain an embryotoxic substance that is normally screened by the intact zona pellucida. Sixty 4-cell embryos were allocated to three treatment groups: 1) control embryos (n = 20) were cultured in Modified Kreb's Ringer Bicarbonate medium + 10% bovine calf serum (mKRB-BCS), 2) UF embryos (n = 20) were cultured in 80% mKRB-BCS + 20% sterile dialyzed uterine flushings (UF), 3) MicroUF embryos (n = 20) received a microsurgical incision in the zona pellucida and were cultured in 80% mKRB-BCS + 20% UF. Following 72 h in culture at 37 degrees C under a 90% N2, 5% CO2, and 5% O2 atmosphere, the number of nuclei/embryo and the incidence of protrusion of the trophoblast through the zona pellucida (PTZ) were recorded. Addition of UF had no effect on embryo development. A greater (P less than .005) proportion of MicroUF embryos exhibited PTZ as compared to UF and control embryos. Experiment II was devised to further characterize the occurrence of PTZ in Micro porcine embryos. Thirty-three 4- to 10-cell embryos and 14 morulae were distributed across two treatments: 1) control embryos (n = 16 and 6, respectively) were cultured as described in Experiment I; and 2) micro embryos were treated similarly to MicroUF embryos in Experiment I but were cultured in mKRB-BCS only. At the onset of PTZ, embryos were immediately fixed and examined. The proportion of embryos exhibiting PTZ was greater (P less than .007) for Micro versus control embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Esculine, ranitidine and carbenoxolone: different modes of action on gastric mucosa.

1. This study was designed to determine the antiulcerogenicity of esculine in various types of experimentally induced gastric ulcers in which the appearance of lesions is due to an ischemic process: cold-restraint stress and pylorus-ligated induced ulcers. 2. In the first experimental model, esculine (50 mg/kg) produced a significant diminution not only in the number of haemorrhagic stomachs (21.5% by 37.5% of the controls) but also in the ulcer index, U.I. (1.00 +/- 0.63, P less than 0.05). 3. When the mucosal damage was induced as a consequence of the pylorus-ligated gastric secretion, pretreatment of esculine (25 and 50 mg/kg) prevented the formation of gastric lesions (12.4 +/- 2.8, P less than 0.05 and 12.2 +/- 1.20, P less than 0.005), although it was less effective than ranitidine (2.8 +/- 1.8, P less than 0.025). However a significant reduction on the acidity with a dose of 25 mg/kg was observed (31.69 +/- 6.42, P less than 0.025). For the rest of the studied parameters: pepsin, histamine and Na and K electrolytes no differences with regard to the control groups were produced. 4. The effects of esculine on mucosal lesions produced by intragastric instillation of 1 ml of absolute ethanol, were also studied. In this model esculine did not show any protective effect and high U.I. values were obtained.

Animals↗
PubMed1991

A magnetic resonance imaging study of schizophrenia: brain structure and clinical symptoms.

Thirty-one patients with schizophrenia and 33 normal control subjects underwent MRI. The BPRS was used to rate clinical symptoms and the NART to estimate pre-morbid IQ. All were right handed. The temporal lobe was significantly smaller on the left than the right in both the control and schizophrenic groups. The amygdala was smaller on the left than the right in controls but not in schizophrenics. The parahippocampal gyrus was smaller on the left side in the schizophrenic group but not in controls. In the schizophrenic group, ventricular enlargement and cerebral atrophy were significantly related to severity of symptoms. Patients with marked negative symptoms had a bilateral reduction in the size of the head of caudate and the two measures were significantly correlated. Patients with marked positive symptoms had larger VBRs and again the clinical and morphometric changes were significantly correlated. There were no morphometric differences between patients with short duration (two years or less) and chronic symptoms.

Adult↗