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Biomedical subjects

L Fischer

Publications and source records attributed to L Fischer.

At least 127 records · Page 7Linked to original sources
PubMed1991

Characterization of Sp-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole- 3',5'-monophosphorothioate (Sp-5,6-DCl-cBiMPS) as a potent and specific activator of cyclic-AMP-dependent protein kinase in cell extracts and intact cells.

A newly designed cyclic AMP (cAMP) analogue, Sp-5,6-dichloro-1-beta-D- ribofuranosylbenzimidazole-3',5'-monophosphorothioate (Sp-5,6-DCl-cBiMPS), and 8-(p-chlorophenylthio)-cAMP (8-pCPT-cAMP) were compared with respect to their chemical and biological properties in order to assess their potential as activators of the cAMP-dependent protein kinases (cAMP-PK) in intact cells. Sp-5,6-DCl-cBiMPS was shown to be both a potent and specific activator of purified cAMP-PK and of cAMP-PK in platelet membranes, whereas 8-pCPT-cAMP proved to be a potent activator of cAMP-PK and cyclic-GMP-dependent protein kinase (cGMP-PK) both as purified enzymes and in platelet membranes. Sp-5,6-DCl-cBiMPS was not significantly hydrolysed by three types of cyclic nucleotide phosphodiesterases, whereas 8-pCPT-cAMP (and 8-bromo-cAMP) was hydrolysed to a significant extent by the Ca2+/calmodulin-dependent phosphodiesterase and by the cGMP-inhibited phosphodiesterase. The apparent lipophilicity, a measure of potential cell-membrane permeability, of Sp-5,6-DCl-cBiMPS was higher than that of 8-pCPT-cAMP. Extracellular application of Sp-5,6-DCl-cBiMPS to intact human platelets reproduced the pattern of protein phosphorylation induced by prostaglandin E1, a cAMP-increasing inhibitor of platelet activation. In intact platelets, Sp-5,6- DCl-cBiMPS was also more effective than 8-pCPT-cAMP in inducing quantitative phosphorylation of the 46/50 kDa vasodilator-stimulated phosphoprotein (VASP), a major substrate of cAMP-PK in platelets. As observed with prostaglandin E1, pretreatment of human platelets with Sp-5,6-DCl-cBiMPS prevented the aggregation induced by thrombin. The results suggest that Sp-5,6-DCl-cBiMPS is a very potent and specific activator of cAMP-PK in cell extracts and intact cells and, in this respect, is superior to any other cAMP analogue used for intact-cell studies. In contrast with 8-pCPT-cAMP, Sp-5,6-DCl-cBiMPS can be used to distinguish the signal-transduction pathways mediated by cAMP-PK and cGMP-PK.

Animals↗
PubMed1991

The clinical significance of absent or reverse end-diastolic flow in the fetal aorta and umbilical artery.

The clinical utility of Doppler blood flow investigations of the fetal and fetoplacental vessels is still under debate as far as timing of the delivery is concerned. However, in cases of absent or reverse end-diastolic flow, fetal compromise is usually very severe. As a consequence, we have investigated the possibility of using this information as a guide to obstetrical management. Altogether, 32 fetuses with absent or reverse end-diastolic flow in the fetal descending aorta and/or umbilical artery were studied. Reverse flow was observed in 11 cases and absence of end-diastolic flow in 21 cases. The two groups are considered separately. No significant difference was found in the mean gestational age at delivery. However, a highly significant difference was found in the mean birth weight and perinatal mortality rate. All the cases of perinatal mortality were encountered in the group presenting with reverse flow (mortality rate, 63.6%). All the live fetuses were delivered by Cesarean section and no neonatal mortality was observed in this group. Two cases of handicap were observed, one in each group. In our experience, reverse flow indicates the necessity for immediate delivery if no other clinical contraindications are present. Absence of end-diastolic flow can be observed for longer periods without adverse outcome. Absence of end-diastolic flow always precedes the appearance of fetal distress. Therefore, we believe that, after exclusion of conditions such as fetal abnormalities or extreme prematurity, a planned delivery should be considered.

Journal Article↗
PubMed1991

Effects of age, gender, and education on cognitive tests in a rural elderly community sample: norms from the Monongahela Valley Independent Elders Survey.

A random sample of 1,350 persons aged 65 years and older in a rural community underwent cognitive screening as part of a survey to establish a population-based registry of dementing disorders. The screening battery included the neuropsychological tests of the assessment protocol used in the National Institute on Aging multicenter Consortium to Establish a Registry for Alzheimer's Disease (CERAD). This paper reports a large body of normative neuropsychological data from this sample with members of relatively low socioeconomic status. Age, sex, and educational level were found to have statistically significant effects on test scores. The implications of these findings for the establishment of screening cutoff scores are discussed.

Aged↗
PubMed1990

Inhibition of cGMP-dependent protein kinase by (Rp)-guanosine 3',5'-monophosphorothioates.

The activation of the cGMP-dependent protein kinase and cAMP-dependent protein kinase by the diastereomers of guanosine 3',5'-monophosphorothioate, (Sp)-cGMPS and (Rp)-cGMPS, and 8-chloroguanosine 3',5'-monophosphorothioate, (Sp)-8-Cl-cGMPS and (Rp)-8-Cl-cGMPS, was investigated using the peptide Kemptide as substrate. The (Sp)-diastereomers, which have an axial exocyclic sulfur atom, bound to the cGMP-dependent protein kinase and stimulated its phosphotransferase activity. In contrast, the (Rp)-isomers, which have an equatorial exocyclic sulfur atom, bound to the enzyme without stimulation of its activity. (Rp)-cGMPS and (Rp)-8-Cl-cGMPS antagonized the activation of the cGMP-dependent protein kinase with a Ki of 20 microM and 1.5 microM, respectively. (Rp)-cGMPS also antagonized the activation of cAMP-dependent protein kinase with a Ki of 20 microM. In contrast, (Rp)-8-cGMPS ws a weak inhibitor of the cAMP-dependent protein kinase with a Ki of 100 microM. (Rp)-8-Cl-cGMPS appears to be a rather selective inhibitor of the cGMP-dependent protein kinase and may be a useful tool for studying the role of cGMP in broken and intact cell systems.

Animals↗
PubMed1990

[A clarification system for completing suicidal thoughts].

To improve the prediction of suicidal risk one has to understand the suicidal thoughts in individuals. We formalized these ideas and integrated them into an understanding system. In such a system the ideas concerning suicide cooperate in such a way so that the suicidal attempt appears to be the optimal solution for this patient. We discuss the question whether such an idiographic understanding system may help to understand other patients too.

Expert Systems↗
PubMed1990

Changes in electrical impedance of the vaginal medium during the menstrual cycle of female rhesus monkeys (Macaca mulatta).

Changes in electrical impedance of the vaginal medium during the menstrual cycle were recorded in female Rhesus monkeys using electrical probe and were correlated with estradiol-17 beta and progesterone plasma concentrations. A gradual decrease in impedance was observed during the follicular phase, the lowest values being observed between days 12-17 of the cycle. Impedance increased again during the first third of the luteal phase until day 21. The reversal of the impedance gradient's sign was nearly concomitant with the appearance of a detectable plasma progesterone concentration. These results support the use of vaginal impedance measurements as a help for the diagnosis of the periovulatory time in the female Rhesus monkey.

Animals↗
PubMed1989

Late radiation injury of the colon and rectum. Surgical management and outcome.

After a median latency of 2 years, the initial late colorectal radiation injuries in 182 patients were: stricture (37 percent), minor lesions (36 percent), rectovaginal fistula (22 percent), and gangrene or other fistulas (5 percent). Due to progression, new colorectal injuries, primarily stricture (55 percent) and fistula (42 percent), occurred in 68 patients (37 percent). Resection provided the best results. However, the resectability rate was low (46 percent) and resection was primarily performed in patients with a circumscript well-defined stricture of the proximal rectum or sigmoid colon with an anastomotic leakage rate of 5 percent. The prevailing management of 78 patients with fistula or stricture with synchronous fistula was defunctioning colostomy, primarily end-sigmoidostomy, providing fair results in half of the patients. Stomal complications occurred in 15 percent. The radiation-induced colorectal mortality was 8 percent. Colorectal fistula and associated radiation injuries of the urinary tract, and especially of the small bowel, were the major determinants of fatal outcome, yielding an overall radiation-induced mortality of 25 percent. After a median observation time of 13 years, half of the patients were alive at follow-up; 56 percent of these had a fair outcome whereas the remaining patients continued to have mild symptoms responding to conservative measures (34 percent) or disabling symptoms (10 percent).

Adult↗
PubMed1989

Reliable assessment of cognitive impairment in dementia patients by family caregivers.

Caregivers (n = 53) of patients with mild to moderate dementia administered a modified version of a cognitive examination at home to their patients. Comparisons between caregiver-administered examinations and the associated clinical examinations revealed a high degree of interrater reliability that was not affected by age or level of education of the caregiver. Reliable assessment of cognitive functioning by caregivers can provide clinicians with an alternative method for monitoring cognitive function of dementia patients.

Aged↗
PubMed1989

Late radiation injuries of the small intestine--management and outcome.

A series of 86 patients with late radiation-induced lesions, mainly stricture, of the small bowel is reviewed. The median interval from radiotherapy to manifestation of enteropathy was 2 (1/4 to 43) years. Progression of the lesions necessitated further treatment in 35 of the 70 patients who survived the initial attack. Bowel resection was followed by leakage from 12% of ileo-ileal and ileo-colic anastomoses. Mortality was 34% from the enteropathy and 8% from coexisting damage to the rectum or urinary tract. Factors significantly influencing mortality were pre-irradiation laparotomy, emergency surgery, and surgery to deal with a segment of irradiated intestine left in situ at initial operation. Age, stage of primary malignancy and coexisting rectal or urinary tract lesions did not significantly influence the outcome. After a median of 10 years' observation the outcome was classified as favourable in only 28% of cases, while 30% had slight to moderate symptoms or had died of unrelated causes. When surgery is required for radiation-related lesions of the small intestine, the aim should be a one-stage definitive procedure, as management of subsequently progressing lesions is associated with substantially increased mortality.

Adolescent↗
PubMed1987

Octopamine action on the contractile system of crustacean skeletal muscle.

1. In the opener muscle of walking legs of crayfish (Astacus leptodactylus) octopamine (OA) greatly enhances the contractions resulting from brief applications of L-glutamate or of elevated K-concentrations. Synephrine is as effective as OA. 2. In the case of potentiation of responses to high-K applications a presynaptic component of the OA action was excluded by first desensitising the muscle fibres to the action of the natural transmitter, using a high concentration (1 mM) of glutamate. 3. The Ca-antagonists Co, Ni and Mn (1 mM) reduced the effects of glutamate and of elevated K to about one-half. In preparations treated with OA, the same Ca-antagonists also depressed the potentiated contractural responses to glutamate and to elevated K, again to about one-half. 4. OA also enhanced contractions resulting from the application of caffeine. 5. With 5-hydroxytryptamine (5-HT) application, the same postsynaptic effects were obtained as described for OA, except that the 5-HT actions were much weaker. 6. With OA, maximal effects were obtained with concentrations of 5 x 10(-6)-10(-5) M; maximally effective concentrations of 5-HT were around 10(-5) M. 7. The lowest effective concentrations of OA were around 10(-8) M; those of 5-HT were around 10(-7) M. 8. In the same preparation, 5-HT is far more effective in enhancing transmitter release (presynaptic action) than OA, the lowest effective concentration being around 10(-11) M while no presynaptic effects of OA were seen at concentrations below 10(-8) M, in some cases even below 10(-5) M.

Animals↗
PubMed1985

Psychiatric aftercare in a metropolitan setting.

In the face of the trend toward brief hospitalization, rising re-admission rates and other indices of poor community adjustment, concern has developed about the adequacy of psychiatric aftercare services. The authors report on a comprehensive study of psychiatric aftercare in a large metropolitan area (population 2.5 million). The study followed prospectively a group of 747 patients, representative of a significant proportion of patients in the care system. The findings document inadequacies in hospital-based discharge planning, unbalanced use of aftercare services and poor patient outcomes six months and two years post-discharge. The study found heavy reliance on medical/therapeutic aftercare services with a relative neglect of housing, vocational/educational, financial and social/recreational services. Despite the large volume of medical/therapeutic service use, the patient group had a high readmission rate, high levels of symptomatology and poor social adjustment on follow-up. The authors suggest that community-based practitioners with specialized training in psychiatric rehabilitation would improve the system of aftercare.

Adult↗
PubMed1984

[How useful is the ultrastructural study of the cilia of the respiratory tract in the diagnosis of an immotile cilia syndrome?].

The immotile cilia syndrome (ICS) comprises a range of congenital defects of the ciliary apparatus most probably transmitted by autosomal recessive inheritance. Because cilia occur mainly in the respiratory and genital tract, the clinical symptoms of ICS are most commonly chronic sinusitis, bronchitis, bronchiectasis and male sterility. The syndrome can be associated with a situs inversus and is then called Kartagener's syndrome. We studied the ciliary ultrastructure in airway biopsies of 5 patients suffering from chronic upper and lower respiratory tract infections. With the single exception of one female patient with confirmed ICS diagnosis (Kartagener's syndrome) the etiology of the recurrent infections was unknown. The following ciliary defects were observed: missing dynein arms, radial spoke defects, missing nexin links, microtubular transpositions, compound cilia, supernumerary, absent, or incomplete microtubules, lack of ciliary orientation and various abnormal patterns of microtubular arrangement. In no instance did a patient show only a single anomaly; defects were always combined. Missing dynein arms, radial spoke defects and microtubular transpositions have frequently been described as lesions specific for ICS. Whenever these lesions were found simultaneously in both the respiratory and genital tracts, their genetic origin cannot be doubted. In our confirmed ICS patient the outer dynein arms were not missing but were reduced in number and length in a large number of cilia. The biopsy was, however, obtained from the heavily infected maxillary sinus and it is known that inflammation can lead to a loss of dynein arms. In the light of our investigations and of a review of the published cases of ciliary anomalies, it is concluded that none of the above defects in itself is specific for ICS. They may all occur as secondary lesions or sporadically as varieties in otherwise healthy subjects. It therefore appears questionable whether ICS can be diagnosed from the ciliary ultrastructure of a single airway biopsy. Assessment of ICS cannot be based simply on the ultrastructural demonstration of a particular ciliary defect, but necessitates additional considerations particularly regarding the origin of the biopsy, the sampling procedures and quantitation of defects. It appears necessary to investigate samples from different parts of the airways and quantitatively analyze the prominent lesions.

Abnormalities, Multiple↗
PubMed1984

A note on stability in force applied to control a repetitive task with the legs.

The forces applied to pedals during cycling were collected every 40 ms from approximately 29,000 movement repetitions. Intra-cycle mean values of force and its variability were significantly correlated, supporting Schmidt's impulse variability theory of within-movement activities of the legs. In addition, as mean forces approached peak values, coefficients of variation decreased. From averages taken minute by minute, intra-cycle forces were seen to rise or fall in concert, implying that the pattern as a whole constituted a significant neuro-muscular unit of control.

Journal Article↗
PubMed1984

[Neutralizing virus antibodies in human immunoglobulins for intravenous use].

Neutralizing antibodies against measles, poliomyelitis, rubella, herpes simplex, influenza and vaccinia viruses were measured in batches of a representative selection of human immunoglobulins for intravenous use licensed in the Federal Republic of Germany. Rubella antibodies were also examined by haemagglutination-inhibition tests. Where available, reference preparations were used, and antibody levels expressed in I. U. All preparations contained significant amounts of the examined antibodies, with relatively low variation from one batch to the other. In most cases activity data specified by the manufacturers could be confirmed. However, differences between the various preparations were sometimes important, some of them relating mainly to individual antibodies, others more or less to the whole range. Some striking findings are emphasized with consideration of manufacturing and control problems.

Antibodies, Viral↗