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Biomedical subjects

M Lazarus

Publications and source records attributed to M Lazarus.

At least 19 recordsLinked to original sources
PubMed2004

Species-specific expression of microsomal prostaglandin E synthase-1 and cyclooxygenases in male monkey reproductive organs.

We investigated the tissue distribution and cellular localization of microsomal PGE synthase-1 (mPGES-1) and cyclooxygenase (COX)-1 and -2 in male monkey reproductive organs. Western blotting revealed that monkey mPGES-1 was expressed most intensely in the seminal vesicles, moderately in the testis, and weakly in the epididymis and vas deferens. The tissue distribution profile was quite different from those profiles for rats, rabbits, and pigs, e.g., rat mPGES-1 was the most abundant in the vas deferens, and the rabbit and pig enzymes, in the testis. Immunohistochemical staining with mouse monoclonal anti-human mPGES-1 antibody revealed that monkey mPGES-1 was localized in spermatogonia, Sertoli cells, and primary spermatocytes of testis and in epithelial cells of the epididymis, vas deferens, and seminal vesicles. In monkeys, COX-1 was localized in epithelial cells of the epididymis and vas deferens, whereas COX-2 was dominantly found in epithelial cells of the seminal vesicles.

Animals↗
PubMed2001

Dominant localization of prostaglandin D receptors on arachnoid trabecular cells in mouse basal forebrain and their involvement in the regulation of non-rapid eye movement sleep.

Infusion of prostaglandin (PG) D(2) into the lateral ventricle of the brain induced an increase in the amount of non-rapid eye movement sleep in wild-type (WT) mice but not in mice deficient in the PGD receptor (DP). Immunofluorescence staining of WT mouse brain revealed that DP immunoreactivity was dominantly localized in the leptomeninges (LM) of the basal forebrain but that PGD synthase immunoreactivity was widely distributed in the LM of the entire brain. Electron microscopic observation indicated that DP-immunoreactive particles were predominantly located on the plasma membranes of arachnoid trabecular cells of the LM. The region with the highest DP immunoreactivity was clearly defined as bilateral wings in the LM of the basal forebrain located lateral to the optic chiasm in the proximity of the ventrolateral preoptic area, one of the putative sleep centers, and the tuberomammillary nucleus, one of the putative wake centers. The LM of this region contained DP mRNA 70-fold higher than that in the cortex as judged from the results of quantitative reverse transcription-PCR. PGD(2) infusion into the subarachnoid space of this region increased the extracellular adenosine level more than 2-fold in WT mice but not in the DP-deficient mice. These results indicate that DPs in the arachnoid trabecular cells of the basal forebrain mediate an increase in the extracellular adenosine level and sleep induction by PGD(2).

Adenosine↗
PubMed2000

Cellular localization of lipocalin-type prostaglandin D synthase (beta-trace) in the central nervous system of the adult rat.

We applied high-resolution laser-scanning microscopy, electron microscopy, and non-radioactive in situ hybridization histochemistry to determine the cellular and intracellular localization of lipocalin-type prostaglandin D synthase, the major brain-derived protein component of cerebrospinal fluid, and its mRNA in leptomeninges, choroid plexus, and parenchyma of the adult rat brain. Both immunoreactivity and mRNA for prostaglandin D synthase were located in arachnoid barrier cells, arachnoid trabecular cells, and arachnoid pia mater cells. Furthermore, meningeal macrophages and perivascular microglial cells, identified by use of ED2 antibody, were immunopositive for prostaglandin D synthase. In the arachnoid trabecular cells, the immunoreactivity for prostaglandin D synthase was located in the nuclear envelope, Golgi apparatus, and secretory vesicles, indicating the active production and secretion of prostaglandin D synthase. In the meningeal macrophages, prostaglandin D synthase was not found around the nucleus but in lysosomes in the cytoplasm, pointing to an uptake of the protein from the cerebrospinal fluid. Furthermore, the existence of meningeal cyclooxygenase (COX) -1 and COX-2 was investigated by Western blot, Northern blot, and reverse transcriptase-polymerase chain reaction (RT-PCR), and the colocalization of COX-2 and prostaglandin D synthase was demonstrated in virtually all cells of the leptomeninges, choroid plexus epithelial cells, and perivascular microglial cells, suggesting that these cells synthesize prostaglandin D(2) actively. Alternatively, oligodendrocytes showed prostaglandin D synthase immunoreactivity without detectable COX-2. The localization of lipocalin-type prostaglandin D synthase in meningeal cells and its colocalization with COX-2 provide evidence for its function as a prostaglandin D(2)-producing enzyme.

Animals↗
PubMed1999

Biotransformations with peroxidases.

Enzymes are chiral catalysts and are able to produce optically active molecules from prochiral or racemic substrates by catalytic asymmetric induction. One of the major challenges in organic synthesis is the development of environmentally acceptable chemical processes for the preparation of enantiomerically pure compounds, which are of increasing importance as pharmaceuticals and agrochemicals. Enzymes meet this challenge! For example, a variety of peroxidases effectively catalyze numerous selective oxidations of electron-rich substrates, which include the hydroxylation of arenes, the oxyfunctionalizations of phenols and aromatic amines, the epoxidation and halogenation of olefins, the oxygenation of heteroatoms and the enantioselective reduction of racemic hydroperoxides. In this review, we summarize the important advances achieved in the last few years on peroxidase-catalyzed transformations, with major emphasis on preparative applications.

Biotransformation↗
PubMed1998

IL-10 gene promoter polymorphisms in rheumatoid arthritis.

IL-10 is an anti-inflammatory cytokine which may modulate disease expression in RA. Three dimorphic polymorphisms within the IL-10 gene promoter have recently been identified and appear to influence regulation of its expression. The 1082*A allele has been associated with low and the 1082*G allele with high in vitro IL-10 production. We have analysed 117 unrelated Caucasoid RA patients and 119 ethnically matched controls. No significant differences in the allele frequencies of the three polymorphisms were found between controls and RA patients. In contrast, a significant association between the 1082*A allele and the (-1082*A/-819*C/-592*C) haplotype and IgA RF+ve/IgG RF-ve patients was observed. The association of genotypes encoding low IL-10 production with IgA RF in RA is incompatible with its suggested role in antibody isotype switching. IgA RF has been associated with severe RA and may thus be indirectly correlated with a genotype encoding low IL-10 production.

Alleles↗
PubMed1997

An investigation of polymorphism in the interleukin-10 gene promoter.

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and B-cell proliferation factor and has been implicated in autoimmunity, tumorigenesis and transplantation tolerance. We have identified three single base pair substitutions in the IL-10 gene promoter and have investigated whether this polymorphism correlates with IL-10 protein production in vitro.

Cells, Cultured↗
PubMed1997

Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus.

OBJECTIVE: To investigate interleukin 10 (IL-10) gene promoter polymorphisms in systemic lupus erythematosus (SLE) and its clinical subsets. METHODS: DNA from 76 Caucasian patients with SLE and 119 controls as genotyped for 3 defined dimorphic polymorphisms (G or A at position -1082, C or T at position -819, C or A at position -592) in the promoter region of the IL-10 gene, using the polymerase chain reaction to amplify the IL-10 gene promoter and oligonucleotide probes specific for each allelic sequence. The frequency of genotypes was compared between patients with SLE and controls, and between clinical subsets of patients with the disease. RESULTS: There was no significant change in the allele frequency of the three IL-10 gene promoter dimorphic polymorphisms in the SLE group compared with controls. However, when subgrouped according to autoantibody status and clinical features, IL-10 -1082*G, -819*C, and -592*C alleles were increased in patients possessing Ro autoantibodies and those with renal involvement. These alleles are in preferential allelic association, namely GCC, ACC, and ATA haplotypes, and the GCC haplotype was increased in these patient subgroups. CONCLUSION: Polymorphisms within the IL-10 gene promoter that are associated with high IL-10 levels may be important in the development of certain clinical features in SLE.

Adolescent↗
PubMed1996

Reversal of sodium pump inhibitor induced vascular smooth muscle contraction with digibind. Stoichiometry and its implications.

The possibility that a circulating sodium pump inhibitor contributes to the pathogenesis of volume-dependent hypertension via an action on vascular smooth muscle (VSM) is supported by multiple lines of investigation, but remains controversial. We had two goals in this study. The first was to compare the pattern of contractile response of rabbit aorta induced by two candidates, ouabain and a labile sodium pump inhibitor that we have identified in the peritoneal dialysate of volume-expanded hypertensive patients with chronic renal failure. Our second goal was to examine the ability of Digibind, a Fab fragment of antisera directed against digoxin, to reverse VSM contraction induced by both agents. Ouabain induced a concentration-dependent contraction, which was delayed in onset, was gradual, and reached a stable plateau after many hours. The labile sodium pump inhibitor induced a qualitatively similar series of responses. Digibind rapidly reversed the contractile responses to both sodium pump inhibitors, with a rate of relaxation that matched that induced by physical removal of the pump inhibitor from the bath. For ouabain, the Digibind:ouabain stoichiometry was highly predictable. When Digibind was present in a molar concentration equivalent to that of ouabain, or less, it had no effect. When the Digibind concentration was twice that of ouabain, complete relaxation occurred. Although the concentration:VSM response relationship for ouabain was steep, the concentration:effect interaction with Digibind was even more steep. The molar concentration of Digibind required to reverse the effects of the labile endogenous inhibitor from peritoneal dialysate was consistently lower than that for ouabain, which is compatible with either greater potency of the labile factor in VSM or greater affinity for Digibind. These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume-sensitive hypertension of renal disease.

Animals↗
PubMed1992

Family therapy in general practice: views of referrers and clients.

Family therapy is being used in a variety of settings, including general practice. To assess the views as to the effectiveness and acceptability of a family therapy clinic in a north London surgery, questionnaires were given to general practitioners referring patients, and to clients. Replies were received from seven doctors and 20 clients, representing 11 families. There was a high level of satisfaction among general practitioners referring patients. The clinic proved to be highly acceptable for clients, with 90% agreeing that it was easier to attend a clinic at the practice than at a hospital; and only one patient thought that knowing the general practitioner worked in the practice made it harder to talk openly. Eighty per cent of patients felt the problem had improved at the time of follow up. Where the problem had not improved, 60% felt that they were dealing with it better. Almost all of the patients felt that the family therapy clinic should become a permanent part of local services. The family therapy clinic in general practice has been shown to be effective and popular with users of the service.

Adolescent↗
PubMed1991

Variation in apparent serum digitalis-like factor levels with different digoxin antibodies. The "immunochemical fingerprint".

Increased levels of a circulating digoxin-like factor (DLF) occur in a number of physiologic states in which sodium homeostasis is altered, and may contribute to the pathogenesis of hypertension. We exploited the different affinities for DLF of seven antisera directed at digoxin to develop an immunochemical profile, and then employed this index to address two questions: does the same DLF species exist in several conditions associated with increased DLF levels, including pregnancy, renal failure, hepatic failure, and neonatal cord blood? Will this approach prove useful in assessing candidates proposed to be DLF? An identical profile was identified in serum from pregnant women and patients with renal or hepatic failure, and a highly significant correlation existed between DLF levels measured with antisera of high and intermediate affinity in 42 subjects with increased levels (r = 0.93; P less than .001). In patients with renal failure, when endogenous DLF levels were too low to assess the profile, concentration of the serum resulted in measurable DLF levels that had an identical profile. The profile was somewhat altered in umbilical cord blood, perhaps reflecting an influence of increased steroid hormone levels. Among agents suggested as candidates for DLF, neither lysophosphatidylcholine nor ouabain showed a profile resembling DLF. Progesterone, 17-OH-progesterone, and bufalin, on the other hand, did show substantial similarity, perhaps providing a clue to the structure of DLF. The normal plasma levels of progesterone and 17-OH-progesterone are 100- to 1000-fold too low to be candidates for DLF and bufalin was sufficiently dissimilar not to be a candidate. DLF in at least three different patient populations probably represents identical chemical species.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1988

Evaluation of age, gender, heart rate and blood pressure changes and exercise conditioning on Doppler measured aortic blood flow acceleration and velocity during upright treadmill testing.

To evaluate the effect of upright exercise on aortic peak flow acceleration and velocity, 60 normal subjects between 15 and 74 years of age were evaluated by continuous wave Doppler during treadmill stress testing using the Bruce protocol. Subjects were divided into 3 age groups, each with 20 subjects: group 1, 21 +/- 4 years of age (mean +/- standard deviation), group 2, 36 +/- 5 years and group 3, 58 +/- 7 years. Periodic measurements of heart rate, blood pressure and Doppler blood flow velocity and acceleration were made before, during and after exercise. Continuous wave Doppler measurements were recorded from the suprasternal notch. The relation between Doppler aortic measurements and age, gender, normal heart rate and blood pressure responses during exercise, and exercise preconditioning, was evaluated. Age alone was significantly related (inversely) to immediate postexercise Doppler aortic peak blood flow peak acceleration (group 1, 55 +/- 15, group 2, 46 +/- 11 and group 3, 36 +/- 9 m/s2, p less than 0.05) and peak velocity (1.1 +/- 0.2, 1.0 +/- 0.2 and 0.8 +/- 0.2 m/s, respectively, p less than 0.01). Gender, heart rate and blood pressure changes during exercise, as well as preconditioning, had no significant effect on these flow characteristics. Consequently, the effects of normal aging must be considered when using Doppler measurements of peak aortic acceleration and velocity in the evaluation of left ventricular function, e.g., to detect or exclude the presence of coronary artery disease.

Adolescent↗
PubMed1988

Failure of ambulatory electrocardiographic monitoring to predict results of programmed electrical stimulation. Studies in patients with clinical ventricular tachyarrhythmias.

To test for an association between the results of ambulatory electrocardiographic monitoring (AEM) and programmed electrical stimulation (PES), or whether other factors better predict the results of PES, 57 patients (36 male and 21 female patients) presenting with either ventricular fibrillation (49 percent; 28/57) or sustained ventricular tachycardia (51 percent; 29/57) were studied. Each patient underwent AEM and PES using up to three ventricular extrastimuli. Sixty-three percent (36/57) had coronary disease; and of these, ventricular tachycardia was present during AEM in 64 percent (23/36) and induced by PES in 78 percent (28/36). With the addition of patients with other cardiac diagnoses, the results were 58 percent (33/57) and 60 percent (34/57), respectively. No AEM variable was positively associated with inducible ventricular tachycardia, including frequency of ventricular premature depolarizations, multiformity, couplets, or ventricular tachycardia. Clinical variables positively associated with inducible ventricular tachycardia were coronary disease, previous myocardial infarction, left ventricular dysfunction, male sex, and a history of recurrent arrhythmia. Therefore, clinical characteristics are more useful for predicting the results of PES than information derived from AEM.

Cardiac Pacing, Artificial↗
PubMed1985

Production of lymphokines affecting tumor cells by T-T hybridomas.

T-Cell hybridomas were constructed by fusing BW5147, an AKR lymphoma, with concanavalin A-stimulated murine splenic lymphocytes. The hybrids which were formed were studied for their ability to produce a lymphokine which inhibits tumor cell migration (TMIF) as well as macrophage migration (MIF) using in vitro assays. Clones were identified which affected tumor cell motility without exerting similar effects on murine macrophages, although the opposite effect was not observed. Although noncoordinate production of these factors cannot be unequivocally established, these results demonstrate that clones can be constructed that preferentially secrete TMIF. In these experiments, we also tested the supernatants for another lymphokine effect on tumor cells; namely, the ability to inhibit tumor cell binding to endothelial monolayers. A number of clones were identified that lacked TMIF activity, but could inhibit the tumor cell-endothelial interaction, suggesting the possibility that these effects may be due to separate mediators.

Animals↗