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Biomedical subjects

E Mayer

Publications and source records attributed to E Mayer.

At least 127 records · Page 7Linked to original sources

Multivariate analysis of the insulin resistance syndrome in women.

The insulin resistance syndrome (IRS) is characterized by a constellation of interrelated coronary heart disease (CHD) risk factors, including dyslipidemia, obesity, central obesity, elevated systolic blood pressure, and hyperinsulinemia. Factor analysis was used to investigate the clustering of these risk factors in individuals by examining the correlational structure among these variables. Data from 281 genetically unrelated nondiabetic women who participated in exam 2 (1979 to 1980) of the Kaiser Permanente Women Twins Study were used. Factor analysis reduced 10 correlated risk factors to 3 uncorrelated factors, each reflecting a different aspect of the IRS: factor 1 (increased body weight, waist circumference, fasting insulin, and glucose), factor 2 (increased postload and fasting glucose and insulin and systolic blood pressure), and factor 3 (larger low-density lipoprotein particles, decreased plasma triglycerides, and increased high-density lipoprotein). Together, the factors explained nearly 66% of the total variance in the data. Thus, factor analysis defined three distinct aspects of the IRS in this sample of nondiabetic women. These factors may reflect separate underlying mechanisms of the syndrome, each of which may also be involved in CHD risk.

Blood Glucose↗

Mitogenic effect of basic fibroblast growth factor on embryonic ventral mesencephalic dopaminergic neurone precursors.

The effects of embryonic age and the presence of basic fibroblast growth factor (bFGF) have been examined on the survival and rate of cell division of dopaminergic neurones of the ventral mesencephalon. Cultures were produced from 7.5 mm and 11 mm rat embryos, pulsed with [3H]thymidine during the first 12 h, and the survival and labelling of cells measured after 3 and 7 days in vitro. bFGF largely prevented the decline in numbers of tyrosine hydroxylase (TH)-positive neurones that occurred in control cultures between 3 days and 1 week. In cultures derived from the younger 7.5 mm embryos there were more TH-positive neurones in the presence of exogenous bFGF than under control conditions after 3 days in vitro. No similar effect was seen in the cultures derived from the older 11 mm embryos. Combined [3H]thymidine labelling and TH immunocytochemistry suggested that this effect was attributable, at least in part, to a bFGF-associated increase in the proliferation of TH-positive neurone progenitors during the first day or so, which was seen in cultures from 7.5 mm but not 11 mm embryos. The effect of bFGF on cultures from older embryos is therefore purely on neuronal survival, while the effect on cultures from younger embryos is a mixture of survival and mitogenic actions.

Animals↗

Extract-specific heterogeneity in high-order complexes containing apolipoprotein B mRNA editing activity and RNA-binding proteins.

The mechanism for tissue-specific differences in apolipoprotein B (apoB) mRNA editing efficiency is not known. Structural data are presented which demonstrate tissue-specific, quantitative differences in the high order complexes containing apoB mRNA editing activity and RNA-binding proteins. The bulk of rat enterocyte extract editing activity sedimented at 11 S with an additional 5-10% at 60 S. Rat liver extract activity was less abundant and only sedimented at 60 S. Ultraviolet light cross-linking revealed two protein activities of approximately 66 and 44 kDa which specifically associated with apoB RNA substrates and cosedimented with editing activity. Extracts differed in the cross-linking yield of p66 and p44 and kinetically, enterocyte RNA-protein complexes reached maximum abundance more rapidly than those in liver extracts. Both 60 and 11 S forms of the editing activity redistributed to 27 S during in vitro editosome assembly. The redistribution of editing activities was accompanied by a corresponding redistribution of p66/p44 to 27 S. The data demonstrate that p66 and p44 are common to liver and enterocyte 27 S editosome assembly processes and suggest that differences in both the pre-editosomal assembly state of editing factors and their abundance may be mechanistically important for tissue-specific differences in editing efficiency.

Animals↗

Improved tracheal allograft viability in immunosuppressed rats.

Airway ischemia has been a common cause of morbidity and mortality in clinical lung transplantation. The present study examined the effects of cyclosporin A (CsA) and methylprednisolone (MP) on the viability of the devascularized trachea after heterotopic transplantation and omentopexy. Thirty-six tracheal segments were harvested from 18 donor Lewis rats, wrapped in omentum, and heterotopically implanted into the abdomen of recipient rats. Tracheal segments were randomly allocated into one of six recipient groups (n = 6): Lewis syngeneic controls, and five groups of Brown Norway recipients, receiving either no treatment, CsA alone (5 mg.kg-1.day-1 or 15 mg.kg-1.day-1), or CsA in combination with MP (5 mg CsA + 1 mg MP per kg/day or 15 mg CsA + 2 mg MP per kg/day, respectively). After 14 days, the tracheal segments were histologically evaluated. Epithelial thickness and the degree of epithelial regeneration were significantly different (p < 0.05) between the syngeneic control group and the untreated Brown Norway group. Without immunosuppression there was virtually no epithelium, whereas low-dose immunosuppression yielded intermediate viability, and with high dose CsA and MP we observed improved tracheal viability. In this high-dose group, the epithelium was thicker than in even the syngeneic control group. These results indicate that, in heterotopic tracheal allografts, viability may be improved with an optimum combination of CsA and MP.

Anastomosis, Surgical↗

Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons--I. Effects in vitro.

We have studied the effects of basic fibroblast growth factor on rat embryonic mesencephalic neurons in vitro. Basic fibroblast growth factor promotes the survival of dopaminergic neurons in vitro, the effect increasing with dose and reaching a maximum at 10 ng/ml. In the absence of basic fibroblast growth factor the number of tyrosine hydroxylase-stained (tyrosine hydroxylase positive) neurons declines to almost zero within 14 days, whereas in the presence of basic fibroblast growth factor numbers remain almost constant from three to 28 days in vitro. This effect of basic fibroblast growth factor is abolished by preventing non-neuronal cells from appearing in the cultures, apart from a basic fibroblast growth factor-mediated increase in the numbers of tyrosine hydroxylase-positive cells during the first two days in vitro. The presence or absence of non-neuronal cells also influences dopaminergic neuronal morphology, the neurons having more, longer, and more varicose processes in the absence of astrocytes. Survival of dopaminergic neurons in vitro in the absence of basic fibroblast growth factor is very dependent on plating cell density, but in the presence of basic fibroblast growth factor this dependency vanishes. It is also possible to make survival independent of plating density by growing the cultures on inverted coverslips, which have the effect of concentrating secreted molecules in the thin layer of medium between coverslip and dish. Our conclusions from these experiments on plating density are that astrocytes probably constitutively secrete a small amount of a trophic factor which promotes survival of dopaminergic neurons, and that the rate of production of this factor is greatly increased by basic fibroblast growth factor. If basic fibroblast growth factor is withdrawn from cultures after two or seven days the dopaminergic neurons soon die. However, if basic fibroblast growth factor is withdrawn after 14 days, after the period of naturally occurring cell death of these neurons, there is no increase in dopaminergic neuronal death compared to controls in which basic fibroblast growth factor treatment is maintained. If basic fibroblast growth factor is used to improve the survival of dopaminergic neurons grafted in vivo, it should therefore be sufficient to treat the grafts for 14 days.

Animals↗

Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons--II. Effects on nigral transplants in vivo.

The clinical potential of transplants of fetal dopaminergic neurons is limited by the fact that the percentage of cells surviving in such grafts is in general quite low. This report investigates the use of basic fibroblast growth factor administration (given either as a pretreatment or by repeated intrastriatal infusions) to promote the survival and behavioural efficacy of embryonic dopamine-rich nigral transplants in rats. Pretreatment of the graft tissue by brief incubation with basic fibroblast growth factor increased the survival of tyrosine hydroxylase-immunoreactive (presumed dopaminergic) neurons in the grafts in comparison to control grafts, and accelerated the recovery in the transplanted animals in tests of drug-induced rotational asymmetry. However, the clear advantage seen in the rotation test conducted three weeks after transplantation had disappeared by nine weeks. The moderate effects of pretreatment were markedly enhanced by repeated intrastriatal infusion of basic fibroblast growth factor into the host animals over 20 days following transplantation. This resulted in > 100% increase in the number of dopaminergic neurons surviving in the grafts, and was accompanied by a significantly greater recovery of the rats' rotational asymmetries which persisted over the full nine weeks of testing. However, the repeated intracerebral infusions induced an inflammatory reaction in the striatum, and the associated trauma both complicates the interpretation of the mechanism of observed recovery and compromises the utility of this route of basic fibroblast growth factor administration for promoting graft survival.

Animals↗

Troponin T--a reliable marker of perioperative myocardial infarction?

Following cardiac surgery, electrocardiography and creatine kinase isoenzyme MB (CK-MB) activities are of limited value in diagnosing a non-transmural infarction. With the recent availability of an assay to detect serial levels of the specific cardiocyte contractile protein troponin T the possibility has been increased of closing a diagnostic gap among cardiosurgical patients. Ninety patients with severe diffuse three-vessel disease undergoing myocardial revascularization were grouped by their postoperative electrocardiographic (ECG) findings (group I--unchanged ECG; group II--new Q-waves representing perioperative myocardial infarction (PMI)). Serial levels of troponin T and the activity of CK-MB were measured 6, 12, 24 and 48 h after aortic unclamping. The course of CK-MB activity was compared to a profile and values derived from patients with unchanged (n = 1312) or new Q-wave ECGS (n = 89). In 72 patients (80.0%) with unchanged postoperative ECG (group I) serial troponin T levels remained constantly low and reached a median peak value of 0.37 microgram/l (quartile 0.13-0.50 microgram/l) after 24 h. Serial CK-MB activities demonstrated the typical non-ischemic course with a monoexponential decline from an initial median peak value of 15.5 U/l (quartile 12.0-21.0 U/l) to 7.0 U/l (quartile 6.0-9.0 U/l). In seven patients (7.8%) with new Q-waves and a pathologic CK-MB profile (group II) troponin T reached median levels of 10.47 micrograms/l (quartile 6.34-12.50 micrograms/l) (P < 0.001 I vs II). Four of five patients with a new right bundle branch block demonstrated low troponin T levels below 1 microgram/l and a normal CK-MB profile. Among six patients with unchanged QRS-configuration and elevated troponin T levels between 0.84 and 4.99 micrograms/l CK-MB activity showed a characteristic PMI pattern in two patients. Troponin T is characterized by a very narrow margin of normal values represented by a maximum third quartile of 0.50 microgram/l. A singular value of troponin after 6 h or 24 h may be sufficient evidence to confirm the diagnosis of a PMI.

Aged↗

The expression of GAP-43 mRNA in developing embryonic striatal tissue grafts.

We have studied by quantitative in situ hybridization histochemistry the mRNA expression of the growth associated phosphoprotein (GAP-43) in grafts of foetal striatal neurones implanted into the ibotenic acid lesioned adult rat neostriatum. Animals were studied at 7, 15, 30 and 90 days after implantation. Using a 35S-labelled specific oligonucleotide probe we observed the highest levels of GAP-43 mRNA in 15-day-old grafts; levels were significantly reduced at 30 days and in 3-month-old grafts GAP-43 mRNA expression was not significantly different from the very low levels in the normal rat striatum. The data indicate that GAP-43 mRNA is highly expressed in developing but not mature neurones and suggest that embryonic striatal grafts may develop a relatively adult phenotype within the host brain by about 4 weeks; by which time most of the synaptic connections are established.

Animals↗

The localization of cholecystokinin mRNA in embryonic striatal tissue grafts: further evidence for the presence of non-striatal cells.

We have studied by in situ hybridization histochemistry the mRNA expression of preprocholecystokinin (CCK) in grafts of foetal striatal tissue neurones implanted into the ibotenic acid lesioned adult rat neostriatum. Animals were studied at 30 and 90 days after implantation. Using a 35S-labelled 'antisense' oligonucleotide (45-mer) probe complementary to the rat CCK cDNA we observed a dense hybridization signal for CCK mRNA in the striatal eminence in developing embryos and in all the striatal grafts examined; no CCK mRNA expressing cells were found in the normal neonatal or adult rat neostriatum. However, CCK mRNA was heavily expressed in other areas of the host brain including the somatosensory cortex, the claustrum, primary olfactory cortex and endopiriform cortex. The germinal cell layer of the striatal eminence is the source of origin for these non-striatal cell groups as well as for cells destined to form the neostriatum. The present results suggest that CCK mRNA expression provides an unambiguous marker for many of the non-striatal cells in 'striatal' grafts.

Animals↗

Chloride channels in myocytes from rabbit colon are regulated by a pertussis toxin-sensitive G protein.

Because of the high intracellular Cl- concentration ([Cl-]i) in gastrointestinal smooth muscle, receptor-mediated opening of Cl- channels at the cell resting potential could represent a plausible mechanism for initial receptor-mediated cell depolarization. To test this hypothesis, we characterized activation of large-conductance Cl- channels by the neurokinin-1 (NK-1) receptor agonist [Sar9,Met(O2)11]-substance P, by specific second messengers, and by direct G protein activation in myocytes isolated from the rabbit colon longitudinal muscle layer. In excised inside-out patches, large-conductance ion channels selective for Cl- over Na+ could be induced by holding the patch at pipette potentials values > 60 mV. The channel showed multiple smaller conductance states (< or = 20) but could open and close via a main gate. When the channel was fully open, its slope conductance was 300 pS, with substates as small as 15 pS, comparable to the predominant conductance observed in cell-attached patches. The voltage-activation profile for full conductance was bell-shaped with maximal open probability (Po) for channel opening of approximately 0 mV. In cell-attached patches, addition of the NK-1 agonist to pipette solution activated a channel that corresponded to a subconductance state of the maxi Cl- channel. The voltage-activation profile for this subconductance state showed a maximal Po value for membrane potentials of approximately 0 mV, with rapid inactivation at more positive and partial inactivation at more negative membrane potentials. In excised inside-out patches, both the full and smaller conductance states of the Cl- channel were activated by the nonhydrolyzable guanosine triphosphate analogue guanosine 5'-O-(3-thiotriphosphate) and inhibited by pertussis toxin (PTX), whereas [Ca2+]i increased channel activity only in concentrations > 1 mM. In cell-attached patches, addition of different Ca2+ ionophores resulted in channel activation in 10% of cells, and activators of protein kinase A or protein kinase C had no effect. These findings are consistent with the hypothesis of a possible role of G protein-coupled Cl- channels in receptor-mediated initial cell depolarization in longitudinal colonic smooth muscle.

Animals↗

Effects of the somatostatin analogue octreotide on rectal afferent nerves in humans.

Somatostatin (Som) administered intrathecally to humans has been shown to exert potent analgesic effects on somatic pain, and anecdotal evidence suggests that Som may also relieve visceral pain. In the current study, we used rectal balloon distension in seven healthy volunteers to evaluate the effect of the Som analogue octreotide (Oct; 1.25 microgram/kg sc) on four pathways mediated by different visceral afferents that originate in the rectum: conscious perception, receptive relaxation, reflex inhibition of internal anal sphincter, and a viscerosomatic reflex. Rectal mechanoreceptors were stimulated either by distending the rectum tonically (volume ramp at 20-40 and 400 ml/min) or phasically (intermittent pressure steps of 60 s duration). Pressure thresholds for nonnoxious and noxious sensations in response to slow tonic distension were increased in the presence of rectal lidocaine (20 ml of 2% solution), whereas those to phasic distension were unaffected. Oct significantly increased pressure and volume thresholds for nonnoxious and noxious sensations in response to slow tonic distension but did not further increase thresholds in the presence of intrarectal lidocaine. In contrast, no effect of Oct on rectal sensations was observed during rapid tonic or phasic distension. Oct had no effect on any of the monitored reflex responses. The effect of Oct on rectal sensation in the concentration used in this study was not associated with changes in the rectal wall pressure-volume relationship during any distension protocol. These findings indicate that the inhibitory effect of Oct on rectal sensation is likely to represent a direct effect on a subset of extrinsic primary afferent neurons, with receptive fields in the mucosa.

Administration, Topical↗

[Preparatory feeding of the dry stage cow in regard to nutritional condition and the status of the rumen mucosa and rumen flora at calving].

Excessive fat deposition prior to calving and a negative energy balance post partum predispose the high producing cow for an intensive postpartal lipolysis and for the health problems resulting thereof. It was postulated that a well proliferated ruminal mucosa at the beginning of lactation could improve the energy supply by stabilizing the pH of the rumen content with energy rich feed and by providing a high absorption capacity for volatile fatty acids. Results of earlier experiments dealing with this problem are reviewed. Furthermore there is described a pilot experiment with 9 dry cows, which was directed to stimulate rumen mucosa growth ante partum by a low energy ration (roughage) during the first half of the dry period and a high energy ration during the last 3 to 4 weeks prior to calving, without inducing a fat cow. The ruminal mucosa reacted to that feeding regimen as expected and desired. The body weight of 3 cows in moderate and 4 cows in medium body condition increased by 7.2% or 3% during 8 to 11 or 7 to 9 weeks respectively. One of two fat cows lost 4.9% of her body weight within 8 to 9 weeks while the condition of the second animal remained unchanged. No problems were observed at calving. A further progress is expected by feeding the dry cows in two groups with different rations according to their body condition at the end of lactation. Results of experiments as well as practical experiences show that no more than 8 to 10 days are necessary to adapt the ruminal flora to a mixed ration (roughage + concentrates).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Epidemiological study on factors influencing fertility indices in Israeli dairy herds.

The objective of this study was to determine feeding factors connected with differences in the fertility of Israeli Kibbutz dairy herds. In an epidemiological case-control survey, data from 30, low-fertility Kibbutz dairy herds having a mean overall conception rate of 35% in multiparous cows were compared with the data from 30, high-fertility Kibbutz dairy herds having a mean overall conception rate of 48% in multiparous cows. Nutritional factors accounted for 67% of the differences between low-fertility and high-fertility herds in the overall conception rate of multiparous cows, while only 4.8% could be related to the body condition during the dry period. Among the factors which occurred more frequently in the low-fertility than in the high-fertility herds were 1) a higher average protein density and lower energy/protein ratio was fed during lactation and 2) a single feeding group was maintained for all lactating cows. 3) There were phytoestrogens in the silage or alfalfa hay, fed during lactation. 4) Faulty dry period was instituted, which was defined as the presence of at least one of the following three practices: a) the daily feed was above 3 kg of high lactation mix; b) more than 15 Mcal of net energy per day was given during the first part of the dry period; c) more than 30% of the cows were obese during the dry period. Three or more risk factors were found in one high-fertility herd and in 20 low-fertility herds. This finding emphasizes the importance of identifying and removing risk factors as a possible means for improving the reproductive performance of herds.

Journal Article↗

Cellular localization of tyrosine hydroxylase mRNA and cholecystokinin mRNA-containing cells in the ventral mesencephalon of the common marmoset: effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

In situ hybridization histochemistry was used to localize tyrosine hydroxylase (TH) mRNA and cholecystokinin (CCK) mRNA-expressing cells in the ventral mesencephalon of the common marmoset (Callithrix jacchus) and to examine the effects of the dopaminergic (DA) neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on these two populations of neurons in the pars compacta of the substantia nigra (SNc) and ventral tegmental area (VTA). X-ray film and liquid emulsion autoradiography of brain sections hybridized with an 35S-labelled synthetic 45-mer antisense human TH oligonucleotide probe showed strong hybridization signals and dense populations of TH mRNA expressing cells in the SNc and VTA at all levels, in the control marmoset brain. In the MPTP-treated brain, there was a substantial reduction of TH mRNA in the ventral midbrain. The loss of TH mRNA-expressing cells amounted to 98% in the lateral SNc, 88% in the medial SNc and 33% in the VTA. In situ hybridization of adjacent sections with an 35S-labelled synthetic 45-mer antisense human CCK oligonucleotide probe showed a weak hybridization signal for CCK mRNA in the ventral midbrain of the control brain. Emulsion autoradiography demonstrated CCK mRNA expressing cells in the SNc and VTA at all levels with the number of cells in the VTA similar to that for TH mRNA. However, the number of cells in the SNc expressing CCK mRNA was a fraction (1/4) of that expressing TH mRNA; moreover, the level of expression per cell was substantially less than that for TH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Limits of cryofixation as seen by Fourier transform infrared spectra of metmyoglobin azide and carbonyl hemoglobin in vitrified and freeze-concentrated aqueous solution.

The limits of cryofixation were probed by investigating metmyoglobin azide and carbonyl hemoglobin in approximately 5 wt% aqueous solution by Fourier transform infrared spectroscopy. Spectra of solutions cooled slowly and recorded in steps between 295 K and 190 K are compared with those obtained by "hyperquenching" either into their glassy states at 80 K, or into freeze-concentrated solution at 170 K. For metmyoglobin azide we conclude from an analysis of its covalently and ionically bound azide that it is impossible to freeze-in its high-spin/low-spin equilibrium even by hyperquenching, and that its vitrified state must correspond to a temperature T < 226 K for the Fe(II) site of the protein. In the amide I spectral region of carbonyl hemoglobin (HbCO), a band at approximately 1654 cm-1 due to alpha-helical structures is the dominant band in spectra recorded at ambient temperature and in the vitrified state, but in the spectrum of HbCO quenched at similar rates into a freeze-concentrated state, a band at approximately 1650 cm-1, tentatively assigned to unordered structures, becomes the dominant feature. This band is absent in the spectra of freeze-concentrated samples obtained by heating a vitrified sample to 170 K. We surmise that HbCO is dehydrated by freeze-concentration to a larger extent in solution quenched rapidly at 170 K than in a vitrified solution heated to 170 K, and that this dehydration is the primary cause for HbCO's perturbation. We conclude that freeze-concentration induced by heating a vitrified solution can cause less perturbations of a protein than does quenching into a freeze-concentrated state. Therefore it can be advantageous for the practice of freeze-etching to vitrify first a solution by "hyperquenching" and thereafter freeze-etch at e.g. approximately 170 K.

Animals↗