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Biomedical subjects

J Schwarz

Publications and source records attributed to J Schwarz.

At least 163 records · Page 9Linked to original sources

Folinic acid therapy fails to improve early Parkinson's disease: a two week placebo controlled clinical trial.

Folinic acid (15 mg bid, po) was administered in a two week, double-blind, placebocontrolled, cross over clinical trial in 5 patients with Parkinson's disease (Hoehn and Yahr stage I or II). 4 patients had not been on L-dopa treatment prior to entering this trial and one patient was on a small dose of L-dopa. No significant improvement could be detected in this pilot study by clinical evaluation and motor performance assessed by a computer assisted motor performance test.

Adult↗

Molecular cloning and functional expression of mouse connexin40, a second gap junction gene preferentially expressed in lung.

From a mouse genomic library, a clone has been isolated that codes for a connexin-homologous sequence of 358 amino acids. Because of its theoretical molecular mass of 40.418 kD it is named connexin40 (Cx40). Based on both protein and nucleotide sequence, mouse Cx40 is more closely related to mouse Cx43 (alpha subgroup of connexins) than to mouse Cx32 (beta subgroup). The highest overall homology detected, however, was to chick Cx42 (67% amino acid and 86% nucleotide identity), raising the possibility that Cx40 may be the mouse analogue. The coding region of Cx40 is uninterrupted by introns and is detected as a single copy gene in the mouse genome. High stringency hybridization of Northern blots with the coding sequence of Cx40 identified a single transcript of 3.5 kb that is at least 16-fold more abundant in lung-similar to mouse Cx37-than in other adult tissues (kidney, heart, and skin). In embryonic kidney, skin, and liver the level of the Cx40 transcript is two- to fourfold higher than in the corresponding adult tissues. Microinjection of Cx40 cRNA into Xenopus oocytes induced functional cell-to-cell channels between pairs. These channels show a symmetrical and markedly cooperative closure in response to transjunctional voltage (Boltzmann parameters of Vo = +/- 35 mV; A = 0.32) which is also fast relative to other connexin channels recorded similarly (tau = 580 ms at Vj of +/- 50 mV). Although Cx40-expressing oocytes did not couple efficiently with oocytes expressing endogenous connexins, they did couple well to Cx37-expressing oocytes. The heterotypic channels which formed had voltage-gating properties modified from those of the original homotypic forms. Transfection of mouse Cx40 DNA, under control of the SV-40 early promoter, into coupling-deficient human HeLa or SK-Hep-1 cells resulted in expression of the expected transcript and restoration of fluorescent dye transfer in transfected clones.

Amino Acid Sequence↗

123I-iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism.

We used 123I-iodobenzamide-single photon emission computed tomography (IBZM-SPECT) in a prospective study to investigate 38 patients with parkinsonism (Hoehn and Yahr stage I to III) not previously treated with dopamimetic drugs. Thirty-four patients only showed symptoms of Parkinson's disease, and four patients showed, in addition, subtle clinical signs of progressive supranuclear palsy or multisystem atrophy. IBZM is a dopamine D2 receptor antagonist detectable by SPECT. We compared IBZM-SPECT results with clinical response to subcutaneous injections of the D1/D2 dopamine receptor agonist apomorphine (38 patients) and long-term dopamimetic therapy (31 patients). IBZM-SPECT results predicted a positive or negative response to apomorphine in 30 of 34 patients (apomorphine response in four patients was equivocal) and response to dopamimetic therapy in 27 of 31 patients. Thus, imaging of dopamine D2 receptors using readily available IBZM-SPECT seems to distinguish between L-dopa-responsive (most likely Parkinson's disease of Lewy body type) and L-dopa-unresponsive parkinsonism in patients not previously treated with dopamimetic drugs.

Adult↗

Evaluation of the effects of low molecular weight heparin on inflammation and collagen deposition in chronic coxsackievirus B3-induced myocarditis in A/J mice.

Coxsackievirus, Group B, type 3 (CVB3) infection of A/J male mice induces chronic myocarditis with increased interstitial fibrosis and collagen deposition. Heparin, a naturally occurring sulfated glycosaminoglycan, has both anti-inflammatory and antifibrotic activities besides its well-known anticoagulant activity. This study determined whether heparin treatment could decrease either cardiac inflammation or fibrosis in chronic CVB3-induced myocarditis. Control mice were either untreated or treated with heparin (4 micrograms/g body weight, subcutaneously 5 times weekly) beginning 2 days before infection of other groups. Additional groups received either virus only (1 x 10(4) plaque-forming units [PFU]), virus followed by heparin beginning 14 days after CVB3 inoculation, or virus and heparin beginning 2 days before CVB3 inoculation. Animals were sacrificed 14, 28, and 58 days after infection. Heparin treatment begun either before or after virus inoculation reduced animal mortality by approximately 20%. Heparin did not alter virus infection or replication in the heart. Histologically, only animals treated with heparin before virus inoculation showed reduced myocardial inflammation, and only at day 58. However, heparin treatment begun either before or after virus infection significantly decreased collagen deposition in the heart (fibrosis).

Animals↗

[Drug modification of post-traumatic edema of the extremities by the proteinase inhibitor aprotinin. An animal experiment study].

Posttraumatic edema remains a serious problem in traumatology. Unrecognized or improperly treated, edema poses a threat to the survival of any extremity, particularly the hand, where a number of intricate functional structures are at stake. This study, as well as other recent clinical and experimental work, show that aprotinin, a proteinase inhibitor, is valuable in the treatment of posttraumatic edema, provided it is given as early as possible and in an adequate dosage.

Animals↗

[Design of and involvement in an interventional study on health education in basic schools: the Pforzheim Study].

We report the design and the determinants of participation in a controlled, randomized trial evaluating the efficiency of a school-based health education and promotion program. The health education program "Gesund leben macht Spass" ("Healthy living is fun") was developed by the AOK Pforzheim, a statutory health insurance organization in South West Germany. In this 7 week program, the body structure is presented systematically, and the children themselves are asked to correlate structure with function. During the fall of 1988, 490 pupils in 22 third grade level classes at 11 primary schools in Pforzheim and vicinity were invited to participate in a health survey (378 consenting parents = 77.1%). Ten schools with 19 classes and 413 students were admitted to the study (333 participating students = 80.6%). One year later, 290 children (70.2%) were available for follow up. Both examinations covered body weight and height, blood pressure level, total cholesterol, and the assessment of health related knowledge, attitudes and behavior by a repeat questionnaire. Parental consent rates in participating schools varied between 66.7% and 100%. Initial student participation was distinctly higher in schools in a rural (85.2%) as compared to an urban environment (73.2%), and among children of German nationals (83.2%) as compared to children of other nationalities (70.9%). After one year, participation rates in these groups approached each other. Schools in the intervention and control groups were similar in sociodemographic characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

SPECT imaging of dopamine D2 receptors with 123I-IBZM: initial experience in controls and patients with Parkinson's syndrome and Wilson's disease.

123I-(S-)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide (123I-IBZM) is a highly selective CNS D2 dopamine receptor ligand suitable for SPECT. This study reports on IBZM-SPECT findings in 60 patients including eight controls and 52 patients presenting with disorders of the dopaminergic system, including idiopathic Parkinson's syndrome (IPS) (n = 18), Parkinson's syndromes of other aetiology (PS) (n = 24) and Wilson's disease (n = 10). SPECT was performed 2 h p.i. of 185 MBq 123I-IBZM. For semiquantitative evaluation basal ganglia to frontal cortex ratios (BG/FC ratios) were calculated. In controls BG/FC ratios of 1.55 +/- 0.05 S.D. were observed. Findings in IPS patients (BG/FC ratio: 1.51 +/- 0.05) were not different from controls. In PS patients striatal IBZM binding (BG/FC ratio: 1.35 +/- 0.11) was significantly (P less than 0.001) lower compared to the control and IPS groups. Asymptomatic patients with Wilson's disease presented normal IBZM binding. In those with neurologic symptoms IBZM fixation was markedly reduced. IBZM-SPECT has shown to be a suitable means for in vivo imaging of striatal dopamine D2 receptors in controls and various disorders of the dopaminergic system. Our preliminary data suggest that IBZM-SPECT is potentially useful for discriminating between IPS and PS (sensitivity: 100%; specificity: 83%). In patients with Wilson's disease IBZM accumulation seems to correlate with the presence of neurologic symptoms.

Adolescent↗

Cardiac myofibroblasts express alpha smooth muscle actin during right ventricular pressure overload in the rabbit.

A number of changes occur in contractile proteins and mechanical performance of the heart within 2 weeks of right ventricular pressure overload in 8- to 12-week-old rabbits. These changes are accompanied by increases in collagen concentration and the ratio of type I to type III collagen. The purpose of the present study was to evaluate the evolution of these connective tissue changes morphologically and to characterize the interstitial cells that might be responsible. The myocardium is infiltrated by mononuclear inflammatory cells 2 days after banding, accompanied by focal myocyte necrosis. By 7 days, the inflammatory infiltrates subside and the damaged myocytes seen at 2 days are replaced by new collagen and a population of spindle-shaped cells, with ultrastructural features of myofibroblasts. A significant proportion of these cells contain alpha smooth muscle actin by immunohistochemical analysis. At 14 days, there is a large increase in stainable collagen with complex remodeling and reduplication of the collagen fiber network of the interstitium. Alpha smooth muscle actin-containing myofibroblasts persist, but their immunoreactivity appears reduced compared with day 7. The authors hypothesize that the interstitial fibroblasts that acquire smooth-muscle-like features in this model play a critical role in the heart's response to severe and sudden mechanical stress and are at least partly responsible for the changes in connective tissue that occur as a result of pressure overload in this model.

Actins↗

[Analysis of environmentally-conditioned and genetic influences on the frequency of hip joint dysplasia in German Shepherd dogs].

The importance of environmental and genetic influences on the frequency of hip dysplasia was studied in 10,595 German shepherd dogs. Systematic effects were analysed using mixed linear and mixed nonlinear threshold models. Following effects were regarded in the models applied: sire and mother of the dog as random effects, age at x-raying, sex, birth year and season of the x-rayed dogs, litter size, percentage of x-rayed dogs in each litter and sex ratio of the litter as fixed effects. Sire, mother, sex and age at x-raying showed significant influence on the occurrence of hip dysplasia. The heritability estimates in a hierarchical data design (sire, mother within sire) for the polychotomous trait hip dysplasia were for full sibs h2 = 0.30, for maternal half sibs h2 = 0, 48, and for paternal half sibs h2 = 0.11. Only the heritability estimates of the paternal half sibs seem to be reliable because kennel and breeder effects are confounded with the mother effect. Analysing the frequency of hip dysplasia as all-or-none traits, the heritability estimates were usually lowered by 50%. Selection programmes to reduce frequency of hip dysplasia can be improved if the estimation of breeding values with respect to environmental effects and frequency of hip dysplasia in all relatives will be implemented.

Analysis of Variance↗

Gangliosides prevent MPTP toxicity in mice--an immunocytochemical study.

The role of gangliosides in preventing neuronal degeneration was examined in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse parkinsonian model. Intraventricular injections of a ganglioside mixture prior to MPTP treatment reduced MPTP's toxicity on tyrosine hydroxylase-positive neurons in the substantia nigra. This raises the interesting possibility that early ganglioside administration may be beneficial in the treatment of neurodegenerative disorders.

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

Progressive interstitial collagen deposition in Coxsackievirus B3-induced murine myocarditis.

Myocardial fibrosis can be produced in certain inbred strains of mice after coxsackievirus B subtype 3 (CVB3) infection. The mechanism responsible for this interstitial matrix alteration is unknown. The presumption is that fibrosis occurs in areas of myocyte damage and inflammation associated with viral infection, analogous to scar formation after cell injury in other organ systems. To test this hypothesis, we examined the hearts of A/J strain mice infected with three CVB3 variants (Crowell [CVB3-CR], Woodruff [CVB3-WD], and Lerner [CVB3-LR]), each known to cause different degrees of acute myocardial injury. With these three variants, virus was present in the heart until day 28 after inoculation but was absent thereafter. Fourteen days after inoculation, inflammation with myocyte necrosis was seen in discrete foci throughout the myocardium with all three variants. Collapse and disorganization of the usually delicate connective tissue matrix identifiable by silver impregnation was seen in these areas of myocyte injury. Persistent, diffuse lymphocytic infiltration of the myocardium was seen 55 days after inoculation with CVB3-WD and CVB3-LR, but hearts initially infected with CVB3-CR showed only rare interstitial lymphocytes comparable to uninfected control hearts. The focal scars produced by myocyte necrosis 14 days after inoculation were accentuated and heavily collagenized 55 days after inoculation with CVB3-WD and CVB3-LR; however, these foci were indistinct 55 days after inoculation with CVB3-CR. Furthermore, the usually delicate network of interstitial collagen fibers surrounding individual myocytes became thickened throughout the heart 55 days after inoculation with CVB3-WD and CVB3-LR, away from visibly scarred areas produced early after infection with these variants. This diffuse reticulin thickening was not seen after infection with the Crowell variant. Only the virus variants associated with persistent interstitial inflammation at day 55 developed major collagen matrix alterations and interstitial fibrosis. We conclude that this persistent interstitial lymphocytic infiltration reflects altered immune function related to specific virus variants in this animal strain. We postulate that these lymphocytes are part of a delayed immunopathogenic response uncoupled from the original viral injury and inflammatory damage. Potential mechanisms by which this interstitial lymphocytic infiltration results in fibrosis are discussed.

Animals↗

A team approach to prevocational services.

This paper presents a chronology of legislative mandates for vocational rehabilitation, discusses their impact on occupational therapy, and describes relationships between special educators and vocational agencies. The Career Training Workshop, a prevocational program developed and used successfully by a North Carolina school district, is described here as an example of one effort to prepare students with disabilities for employment.

Activities of Daily Living↗

[Experimental studies of the prevention of postoperative adhesions].

Female wistar rats were used for the testing of different substances to prevent postoperative intraabdominal adhesions. It could be demonstrated that the best results were obtained by dextran 70 with a concentration of 10%. Good effects were seen also by contrykal (aprotinin) and hylase (hyaluronidase). By the combination of dextran 70 30% with contrykal the spread of adhesions was very low but the effect was not significant better than with dextran 70 10% alone. For the prevention of intraabdominal adhesions operative techniques with minimal lesions are important too of the peritoneal epithelium.

Animals↗

[Electrophysiologic and histomorphological studies on the nervus ischiadicus of rats. I. The uninjured nerves].

We report in the model described above on measurements of striking features of the normal sciatic nerve of adult male Wistarrats (250-300 g). Electrophysiological parameters were measured by means of an Electromyoneurograph (needle stimulation). The calculation of the maximum motor nerve conduction velocity results in a mean value of 59.6 ms-1. The mean compound action potentials of the foot muscle are 9.2 mV (proximal stimulated) and 10.1 mV (distal stimulated). Counting out 10011 nerve fibres in Light Microscoping Findings for histological studies we got a nearly Normal distribution of the fibre diameters with a mean fibre diameter of 7.09 microns. The corresponding density of nerve fibres is 8700.4 mm-2. The calculated percentage of neural tissue, related to the surrounding connective tissue is about 36.32%.

Action Potentials↗

Positive effect of direct current on cytotoxicity of human lymphocytes.

Normal or leukemic human lymphocytes treated with direct current (DC) showed enhanced antileukemic cytotoxicity. The enhancing effect of DC-treated lymphocytes was dependent on current density and time exposure. A desirable effect was achieved with current densities ranging from 5 to 10 mA/cm2 at a short exposition time (5--10s). Enhanced lymphocyte cytotoxicity occurred after a 48 h cultivation at 37 degrees C in a humidified atmosphere containing 5% CO2 and was proved by the increased number of trypan blue stained target cells, tumor-binding cells, and lymphocytes with activated nucleoli. Lymphocyte cytotoxicity measured immediately after DC-treatment was not enhanced. Furthermore, the cytotoxic effect was potentiated using media conditioned with interleukin-2 (IL-2) or cytosol fraction (F3) isolated from human leukemic cells. Such in vitro stimulated cytotoxic cells displayed reactivity against K 562 cells as well as fresh leukemic cells of allogeneic origin. Of considerable clinical interest is the observation that lymphocytes treated with DC in IL-2 or F3 conditioned media may enhance antileukemic cytotoxicity in peripheral lymphocytes of patients with hematological malignancies.

Cytosol↗

Influence of "calcium2+-channel blockers" on exocrine pancreatic secretion by isolated rat acini.

Cytoplasmic Ca2+ is regarded as an intracellular messenger for acetylcholine- and cholecystokinin (CCK)-stimulated pancreatic enzyme secretion. We investigated in the in vitro model of isolated rat pancreatic acini whether or not Ca2+-channel blockers are able to inhibit Ca2+-mediated enzyme secretion. Isolated rat pancreatic acini were prepared via collagenase digestion. The effect of various Ca2+-channel blockers on amylase secretion stimulated by various secretagogues was monitored. Verapamil, but not nitrendipine, dose-dependently reduced CCK8- and carbachol-stimulated enzyme secretion. Higher doses of either CCK8 or carbachol could not reverse the inhibition caused by verapamil. Amylase secretion stimulated by the ionophore A23817 was not altered by verapamil. Verapamil augmented enzyme secretion stimulated by secretagogues which work through cAMP as second messenger. 3H-N-methylscopolamine- and 125I-Bolton-Hunter-CCK8-binding to pancreatic acini was dose-dependently inhibited by verapamil, but the inhibition curves did not parallel the inhibition curves with unlabeled receptor agonists. Thus, the impairment of exocrine pancreatic amylase secretion by verapamil is probably not due to its known "Ca2+-channel" blocking abilities in other tissues but is rather caused by noncompetitive effects on the level of muscarinic receptors and receptors for CCK.

Amylases↗

Receptors for neuropeptides are induced by exogenous poly(A)+ RNA in oocytes from Xenopus laevis.

Receptors for the hormones vasopressin, angiotensin II, and thyrotropin-releasing hormone have been studied electrophysiologically in Xenopus laevis oocytes previously injected with poly(A)+ RNA from the respective receptor-containing tissues. The injected oocytes responded to the hormones by demonstrating oscillations in membrane currents as recorded by the voltage-clamp method. The response was dependent on the hormone concentrations and detectable between 5 and 1000 nM concentrations. Size fractionation of poly(A)+ RNA from the respective tissues showed that the mRNAs encoding the three hormone receptors were larger than 18S rRNA, suggesting a length of at least 2 kilobases. When vasopressin was added to the oocyte bath, an inward membrane current was generated in oocytes injected with rat poly(A)+ RNA from liver but not from kidney. This suggests that the V1-type (liver), not the V2-type (kidney), vasopressin receptor can be expressed and electrophysiologically identified in the oocyte. A V1-specific, but not a V2-specific, antagonist suppressed the vasopressin-dependent effect. Application of angiotensin II to liver poly(A)+ RNA-injected oocytes elicited oscillations in membrane current, indicating that these oocytes also expressed receptors for angiotension II; the antagonist [Sar1, O-methionyl-Tyr4]angiotensin II blocked this effect. Poly(A)+ RNA from tumor-derived GH3B6 cells, known to contain receptors for thyrotropin-releasing hormone, injected into oocytes induced receptors responding to thyrotropin-releasing hormone; the drug chlordiazepoxide suppressed the thyrotropin-releasing hormone response.

Action Potentials↗