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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 487 records · Page 27Linked to original sources

Factors affecting sperm motility. IX. survival of spermatozoa in various biological media and under different gaseous compositions.

The role of various environmental conditions on sperm motility and their survival was investigated by incubating washed human spermatozoa in various biologic or artificial media and under different atmospheric compositions. When sperm were analyzed by the multiple exposure photography technique for objective motility determination, it was found that none of the investigated biologic media induced any immediate stimulatory effect on the tested spermatozoa. Exchange of seminal fluid between normal and oligoasthenospermic specimens did not reveal any beneficial or harmful effect on sperm motility. Sperm did not survive for more than 24 hours when kept in their original seminal fluid under any circumstances. The most favorable media tested for prolonged sperm survival were pure human umbilical cord serum or Ham's solution containing 0.5% human albumin. However, even in these media sperm did not survive much beyond 24 hours unless incubated in an atmosphere containing 5% CO2 or a triple mixture of 90% N2, 5% O2, and 5% CO2. Only under these circumstances could sperm stay alive, in some cases up to 5 days.

Carbon Dioxide↗

The electrophysiologic effects of oral cibenzoline.

Five male patients with chronic stable ventricular arrhythmias underwent a placebo controlled ascending dose study with oral cibenzoline, a new type 1 antiarrhythmic drug. Ambulatory ECG (Holter) recordings and electrophysiologic studies were done while on placebo and on the maximum dose of cibenzoline. Drug toxicity, manifested by vomiting and QRS widening, accompanied by very high serum cibenzoline concentrations, was seen in two patients. A major reduction (greater than 85% in ventricular premature beats occurred in three patients including two in whom only relatively low serum concentrations had been achieved. Cibenzoline caused significant increases in AH (97 +/- 26 vs. 110 +/- 23 msec, p less than 0.01) and HV (59 +/- 7 vs. 78 +/- 7 msec, p less than 0.02), a major but statistically not significant increase in QRS (99 +/- 12 vs. 128 +/- 27 msec, NS) but QT (38 +/- 2 vs. 38 +/- msec) and QTc (42 +/- 1 vs. 44 +/- 3 msec) were essentially unchanged, even in toxic patients. Cibenzoline had no consistant effect on sinus cycle length, sinus node recovery time, or the relative, functional or effective refractory periods of the atrium and AV node. We conclude that cibenzoline has potent type 1 effects in prolonging HV but may be unique in not affecting QT or QTc, even at toxic levels. Its effects upon AH were unexpected and warrant further study.

Aged↗

Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus.

Nonenzymatic glucosylation interferes with recognition of low density lipoprotein (LDL) by its receptor and markedly decreases the rate of plasma clearance of glucosylated LDL, both in experimental animals and in normal human subjects. However, in selected diabetic subjects we have observed a paradoxical increase in the clearance of glucosylated LDL, suggesting the possibility of immune-mediated clearance. Immunoassay demonstrated antibodies specific for glucosylated LDL in the preinjection plasma of each of four such diabetic subjects studied. These antibodies cross-react with other glucosylated proteins and recognize specifically the glucosylated lysine epitope--i.e., glucitollysine . These data suggest that nonenzymatic glucosylation of plasma or structural proteins may render them immunogenic and result in production of autoantibodies that recognize not only the particular immunogen but also many other glucosylated proteins, including glucosylated tissue proteins. These findings may be relevant to the increased prevalence of immune complexes in plasma of diabetic subjects and the late complications of diabetes mellitus.

Antigen-Antibody Complex↗

Neuronal influence on glial enzyme expression: evidence from mutant mouse cerebella.

The developmentally regulated enzyme sn-glycerol-3-phosphate dehydrogenase (GPDH; EC 1.1.1.8) is characteristically present in relatively high levels in mature Bergmann glia of the mouse cerebellum. Preliminary studies identified several neurological mouse mutants with reduced glial enzyme activity. Immunohistochemical examination of GPDH expression in three mutants (lurcher, nervous, and Purkinje cell degeneration) revealed a positive correlation between glial enzyme expression and Purkinje cell presence. Whereas GPDH immunoreactivity appears normal in Bergmann glia from all three mutants at early times, immunoreactivity diminishes fairly rapidly after Purkinje cell loss, first in the Bergmann glia somas and then in the processes. Loss of immunoreactivity is uniform throughout the cerebellar cortex in lurcher and Purkinje cell degeneration where the entire Purkinje cell populations die. In nervous mice, in which some Purkinje cells survive, GPDH immunoreactivity is patchy throughout the cortex; it is present only where Purkinje cells remain. In contrast, Bergmann fibers appear uniformly distributed throughout the cortex of mutant cerebella, as demonstrated by immunostaining for the presence of glial filaments. This observation suggest that the loss of GPDH immunoreactivity is not a result of glial cell death. These results support the idea that GPDH expression in Bergmann glia depends upon their sustained interaction with adjacent Purkinje cells.

Animals↗

Some difficulties inherent in the interpretation of dietary data from free-living populations.

Isocaloric adjustments of diet in metabolic experiments tend to induce negative correlations. In free-living populations, on the other hand, the absolute amounts of major nutrients consumed are positively correlated with total calorie intake and with each other. In general, these positive correlations are fairly strong. Relative amounts of nutrients consumed tend to be weakly and negatively correlated with total calories and each other. Because of these intercorrelations conclusions drawn from cross-sectional population data are ambiguous, at best, and misleading, at worst. Beyond that, the correlation between the intakes of specific nutrients with total calorie intake introduces the possibility that dietary variables may to some degree be surrogates of some nondietary variables; in particular, of physical activity. Unless the questions being asked in population studies are precisely formulated, with a careful consideration of the biological issues and the statistical limitations, biased conclusions are likely to result.

Adult↗

Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.

The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.

Arrhythmias, Cardiac↗

Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation, or carbamylation: generation of antibodies specific for derivatized lysine.

We previously showed that immunization of guinea pigs with reductively glucosylated guinea pig low density lipoprotein (LDL) or albumin resulted in the formation of antibodies specific for the glucosylated protein. The present studies were done to determine if modifications of homologous LDL or albumin, other than addition of carbohydrate, would also render these proteins immunogenic. We found that derivatization of lysine residues of guinea pig LDL or albumin by carbamylation, acetylation, ethylation, or even methylation rendered them immunogenic in guinea pigs. In addition, the specificity of the antibodies was strikingly influenced by whether modified homologous LDL or modified homologous albumin was used as the immunogen. Antibodies generated against modified LDL were directed almost exclusively against the derivatized lysine residues (i.e., carbamyllysine, acetyllysine, or methyllysine) and hence reacted equivalently with other modified proteins that contained the same lysine derivative. However, antibodies generated against guinea pig albumin (or fibrinogen) modified in the same ways reacted primarily with the modified protein used as immunogen, and not with the free lysine derivative, or with other similarly modified proteins. Each of the modifications referred to above could potentially occur in vivo. Therefore, the findings presented may be relevant to autoantibody formation and immunopathogenetic mechanisms in certain diseases.

Acetylation↗

Putaminal hemorrhage presenting as dysarthria-clumsy hand syndrome.

A patient with chronic hypertension presented clinically with the dysarthria--clumsy hand syndrome. A CT scan demonstrated putaminal hemorrhage sparing the internal capsule. This case provides additional evidence that lacunar syndromes may not be due to lacunar infarction. The localization of dysarthria--clumsy hand appears similar to that of ataxic hemiparesis.

Cerebral Hemorrhage↗

Hand muscle atrophy in multiple sclerosis.

The occurrence of muscular atrophy in multiple sclerosis (MS) has been considered unusual and classically has been ascribed to disease involving the motor unit. Nine patients with MS in a single clinic were found by strict criteria to have focal hand muscle atrophy associated with weakness. None had electrodiagnostic evidence of either anterior horn cell or axonal abnormalities. These observations indicate that focal muscular atrophy is common in MS; it may often occur as a result of relative disuse resulting from disease of central pathways involved in motor control.

Adult↗

The use of early chick embryos in experimental embryology and teratology: improvements in standard procedures.

The chick embryo is a convenient experimental system for embryologic and teratologic studies. However, windowing eggs during the first day of incubation, a procedure that is required to expose embryos in ovo, frequently results in dysmorphogenesis. The frequency and severity of the particular anomalies caused by windowing are greater the younger the embryo at the time this procedure is done. At all stages examined, dysraphic defects of the neural tube are the most common anomaly present following windowing. Defects of the neural tube are virtually eliminated if the air space introduced over the embryo by windowing is filled with albumen or saline, and the egg (with its window sealed with tape) rotated 180 degrees, so that the embryo rests subjacent to an undisturbed area of the shell. Subblastodermic injection of saline, a vehicle often used for teratogenic agents, has no adverse effects when eggs are subsequently filled with albumen or saline and rotated. Furthermore, known teratogens (e.g., colchicine, hyaluronidase) injected subblastodermically after windowing are active in eggs that are then filled with albumen or saline and rotated. Finally, the addition of albumen or saline, followed by rotation, may be delayed up to 3 hours without reducing the restorative effects of these two procedures. Our modified procedures for the handling of windowed eggs significantly increase the value of young chick embryos for studies of early developmental events.

Animals↗

Assessment of health needs and willingness to utilize health care resources of adolescents in a suburban population.

We investigated whether adolescents living in a middle-class suburb believed that their health needs were being met, and the extent to which they were willing to utilize local health care resources for a range of problems. Self-administered, anonymous questionnaires were completed by 649 students in grades 9 through 12. The mean age of respondents was 15.4 years; 52% were female, and 95% white. They had ready access to medical care: 90% used a specific private physician. From a list of 15 health problems, 60% indicated that they had seen a health provider for at least one of them, most often for stomach pains (22%), headaches (18%), and coughing (16%). From an identical list, 48% indicated that there was at least one problem for which they had never seen a health provider but would like to, most often for a weight problem (14%), birth control (10%), and emotional upset (9%). Although 20% regularly used illegal drugs, 24% were sexually active, and 38% thought they had a weight problem, only 1%, 4%, and 10%, respectively, had sought care for these matters. A majority of students would not choose to go to a private physician for care related to sexuality, substance abuse, or emotional upset, and would not be willing to seek care for these problems with their parents' knowledge. Ready access to private primary care did not assure attention to important health needs among these suburban adolescents.

Adolescent↗

Penicillamine: review and cutaneous manifestations.

D-Penicillamine, a heavy metal chelator used in the treatment of Wilson's disease and other conditions, may be associated with both noncutaneous and cutaneous side effects. Some of the cutaneous lesions are due to a toxic-metabolic effect on connective tissue; some may be explained on the basis of autoimmunity; some are acute sensitivity reactions, and some are secondary to unknown mechanisms. The types of cutaneous manifestations may, in some instances, be correlated with the disease being treated and the dosage and duration of penicillamine therapy.

Autoimmune Diseases↗

Nonenzymatic glucosylation of homologous low density lipoprotein and albumin renders them immunogenic in the guinea pig.

Nonenzymatic glucosylation of low density lipoprotein (LDL) and other plasma and structural proteins is enhanced in diabetics. Because conjugated carbohydrates are known to play an important role in the immunogenicity of proteins, we sought to determine if glucosylation of LDL (yielding Glc-LDL) and albumin would make them immunogenic. Therefore, we immunized guinea pigs with homologous glucosylated proteins and measured antibody response by solid-phase radioimmunoassay. Glucosylation of LDL in the presence of cyanoborohydride yields glucitol-lysine as the glucose adduct. Immunization with this Glc-LDL yielded a high-titered antiserum that reacted specifically with guinea pig Glc-LDL but not native LDL. Glucitol-lysine was an effective competitor for binding to the antibody, as were other reductively glucosylated human proteins. Glucosylation of LDL by incubation with glucose in the absence of a reducing agent yields fructosyllysine as the glucose adduct. This product, which has been demonstrated in human plasma, was also immunogenic, though the antiserum produced was of lower titer and affinity. Homologous glucosylated albumin was also immunogenic. These data suggest that nonenzymatic glucosylation of proteins could lead to autoantibody production and the formation of immune complexes in diabetic plasma and tissues.

Animals↗