Biomedical subjects

S Arnold

Publications and source records attributed to S Arnold.

At least 19 recordsLinked to original sources

PubMed1997

The cDNA sequences of cytochrome c oxidase subunit VIa from carp and rainbow trout suggest the absence of isoforms in fishes.

The cDNAs of subunit VIa of cytochrome c oxidase from rainbow trout liver and carp heart are presented, revealing 82% identity of their deduced amino acid sequences. The two cDNAs are evolutionary equally distant from the livertype (VIaL) and heart-type (VIaH) of mammalian subunit VIa. The data suggest that in ectotherm fishes no isoforms of subunit VIa occur, and that the postulated tissue-specific mechanism of thermogenesis in mammals, based on interaction of ATP with subunit VIaH (Frank, V. and Kadenbach, B. (1996) FEBS Lett. 382, 121-124), is absent.

Amino Acid Sequence↗

PubMed1997

HLA markers and prediction of clinical course and outcome in rheumatoid arthritis.

OBJECTIVE: To evaluate HLA markers as early prognostic factors for disease severity in rheumatoid arthritis (RA). METHODS: HLA genotyping was carried out in a retrospective analysis of 66 RA patients and in a prospective study of 55 RA patients and 87 healthy controls using polymerase chain reaction-based methods for HLA-DRB1 specificities, DR4 alleles, and their linked DQB1 alleles, as well as HLA-B27. The clinical course of RA was assessed by clinical and radiologic scores. The impact of HLA markers was evaluated by epidemiologic means in addition to modeling using multiple logistic regression analysis. RESULTS: Shared epitope-positive (HVR3+) DR4 alleles and the HVR3 amino acid cassette QKRAA were associated with RA in both longstanding (relative risk [RR] 3.34 and 3.19) and recent-onset (RR 2.1 and 2.37) RA. In longstanding RA, radiologic evidence of severe joint destruction (Larsen score > 1.62) was seen more often in HVR3 shared epitope-positive patients than in epitope-negative patients (odds ratio [OR] = 25.67, chi 2 = 13.59, P = 0.0003). Moreover, rank sum analysis of Larsen indices indicated significantly higher ranking for the presence of the RA-associated HVR3 cassettes (QKRAA, QRRAA) when expressed on a DR4 allele (P < 0.0001). In the prospective study, DR4-positive patients had a significantly increased risk (OR = 13.75, P = 0.00083) of developing bony erosions. In addition, HVR3 epitope-positive DR4-positive individuals had significantly higher Larsen indices than did epitope-negative patients (P = 0.0083). In particular, the presence of the HVR3 epitope on DR4 resulted in an increased a posteriori likelihood (0.91) of developing early erosive disease compared with an a priori risk of 0.62. Conversely, the likelihood decreased to a minimum of 0.35 when the HVR3 epitope was absent. CONCLUSION: While the contribution of HLA typing to establishing the diagnosis of RA is limited, HLA-DR genotyping and DR4 subtype determination provide valuable markers for the prognosis of joint destruction in RA.

Adolescent↗

PubMed1997

Synergistic effect and possible mechanisms of tumor necrosis factor and cisplatin cytotoxicity under moderate hyperthermia against gastric cancer cells.

BACKGROUND: Peritoneal carcinomatosis is a difficult management problem, and intraperitoneal treatment approaches may provide an opportunity to intensify dose and minimize toxicity. The current experiments were conducted to characterize the cytotoxic effects of cisplatin (cDDP), tumor necrosis factor (TNF), and hyperthermia (HT) on a gastric cancer cell line in vitro under conditions achievable with intraperitoneal treatment. METHODS: Seoul National University gastric cancer cell line (SNU-5), a poorly differentiated gastric cancer cell line, was tested for sensitivity to various doses of cDDP, TNF, or combinations of the two at normothermia (37 degrees C) or HT (42.5 degrees C). The effect of TNF on cellular rates of cDDP accumulation, efflux, and cDDP-DNA adduct formation were evaluated using atomic absorbance spectrometry with Zeemen background correction. RESULTS: During a 2-h exposure to various doses of cDDP HT, we observed a supraadditive cytotoxicity of SNU-5 with 1 to 50 micrograms/ml of TNF (p2 = 0.0001). In the presence of the three-agent combination (HT, TNF, and cDDP) we observed statistically significant increases in total cellular accumulation of cisplatin (p2 = 0.016); a nonsignificant decrease in cellular efflux of drug (p2 = 0.098); and a 40% increase in persistent cisplatin DNA damage as measured by atomic absorption spectrophotometry (p2 = 0.06). These patterns were specifically not seen with the combinations of cDDP and HT, or cDDP and TNF. CONCLUSIONS: These data provide the experimental basis for the use of TNF and cDDP with HT in the treatment of gastric cancer and support the investigation of these agents in vivo in the regional treatment of peritoneal carcinomatosis.

Antineoplastic Agents↗

PubMed1997

Quantitative electron-spectroscopic diffraction (ESD) and electron-spectroscopic imaging (ESI) analyses of dentine mineralisation in rat incisors.

Primary crystal formations in all hard tissues are, according to our investigations, Ca-phosphate chains composed of nanometer sized particles (dots) which develop along the matrix macromolecules. In circumpulpal dentine the centre-to-centre distances between the dots inside the chains reflect the distances between the crystal nucleating sites ("active sites") along the collagen matrix macromolecule. The centre-to-centre distances at the surface of the mineralised collagen fibrils probably reflect the distances between nucleating sites of noncollagenous proteins attached to collagen. These needle-like chains of dots coalesce in lateral directions to form ribbon-like crystallites. The morphological results are supported by correlated small area diffraction studies in the same regions of dentine. We have found that the first appearing Bragg-reflection has a lattice spacing value of 0.388 nm, which corresponds to the (111) apatite value. For the earliest crystal formations the intensity of the (002) reflection is higher than that of the (300)-reflection. A maximum of the net-signal-intensity ratio of the (002) to (300) Bragg-reflection appears at the mineralisation front. This peak repeats with decreasing height 3 to 5 times with a distance range of about 8-16 microm through the whole dentine zone, which corresponds to the distances of the incremental lines, called "von Ebner lines".

Animals↗

PubMed1997

Increased oxidation of LDL in patients with coronary artery disease is independent from dietary vitamins E and C.

There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.

Aged↗

PubMed1997

Ictal motor signs and interictal regional cerebral hypometabolism.

Early motor manifestations are the main components of focal seizures involving the frontal lobe. We examined the relationship between the initial ictal motor manifestations and interictal abnormalities of cerebral glucose consumption (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of neocortical origin. Group data analysis revealed that patients with predominantly unilateral clonic seizures had a significant contralateral perirolandic hypometabolism and to a lesser degree a contralateral frontomesial hypometabolism. Patients with predominantly focal tonic manifestations showed a hypometabolism within the frontomesial and perirolandic regions that was unilateral in all patients with lateralized tonic seizures. Patients with versive seizures had mainly contralateral metabolic depressions without a consistent regional pattern. Patients with hypermotor seizures had metabolic depressions involving frontomesial, anterior cingulate, perirolandic, and anterior insular/frontal operculum areas. In all patient groups, bilateral and symmetric hypometabolism of the thalamus and cerebellum was observed. We propose that this pattern of distinctly abnormal metabolic brain regions demonstrates not only possible epileptogenic zones but also symptomatogenic brain regions as shown by the associations between clinical manifestations and sets of abnormal brain regions, particularly if epileptogenic zones are in a clinically silent neocortical brain region. The detection and possible differentiation of symptomatogenic and epileptogenic zones might improve the effectiveness of presurgical noninvasive studies.

Adult↗

PubMed1997

Effect of intra-abdominally induced pressure on the urethral pressure profiles of healthy and incontinent bitches.

OBJECTIVE: To determine whether reduced pressure transmission is of importance in the pathophysiologic mechanism of urinary incontinence in bitches. ANIMALS: 20 sexually intact, continent bitches and 21 spayed, incontinent bitches. PROCEDURE: Urethral pressure profiles before (resting) and after (stressed) insufflation of gas in the abdominal cavity were recorded in bitches under general anesthesia. Differences (stressed minus resting) were calculated for all variables. On the basis of these values, the pressure transmission ratio was determined. RESULTS: Resting pressure profiles of incontinent bitches indicated significantly (P < 0.05) lower maximal closure pressure (4.5 +/- 3.0 cm of H2O) than did those of continent bitches (11.2 +/- 7.2 cm of H2O). The intra-abdominal pressure increase lead to a shortening of total profile length, which was equal in both groups and caused an increase in maximal urethral pressure. The change in maximal urethral pressure was significantly (P < 0.05) greater in incontinent bitches (12.4 +/- 4.1 cm of H2O) than in continent bitches (8.8 +/- 4.5 cm of H2O). The profile areas and the pressure transmission ratios did not differ significantly (P < 0.05) between the 2 groups. CONCLUSION: The effect of decreased pressure transmission on the urethra is not a factor in the pathophysiologic mechanism of urinary incontinence attributable to urethral incompetence in bitches.

Abdomen↗

PubMed1997

[Von Willebrand factor concentrations in blood plasma of Bernese mountain dogs].

Many Bernese Mountain dogs have been found to exhibit an increased hemorrhagic tendency of unknown etiology. Since other bleeding disorders have been excluded by routine tests and Bernese Mountain dogs have been listed to have von Willebrand's disease (vWD), we analyzed the plasma concentration of the von Willebrand Factor (vWF) in 160 Bernese Mountain dogs that were used for breeding in Switzerland in 1992. We also evaluated the suitability of the commercial Asserachrom vWF test kit to quantitate vWF in canine plasma by comparing the plasma vWF determination with validated vWF ELISA test. The vWF plasma concentration in Bernese Mountain dogs ranged from 13% to 162%, with the Asserachrom test kit (normal range 67% to 124%). Similar values were obtained with the research vWF ELISA kit (10% to 166%), and there was a close correlation between the two test methods. In 8 of the 9 Bernese Mountain dogs with initially low vWF concentration (< 60%), the determination was repeated on another sample. Since the values were well within the normal range, a problem with the collection of blood for the first determination is suspected. We conclude that vWD does not appear to be a clinical issue in Bernese Mountain dogs in Switzerland and is, therefore, not likely to be the cause of the observed bleeding tendency. The commercially available Asserachrom vWF test kit seems suitable for the determination of canine vWF plasma concentrations. It is recommended that low vWF values will be confirmed by the determination in second samples.

Animals↗

PubMed1997

[Urinary incontinence in castrated bitches. 2. Diagnosis and treatment].

Urinary incontinence due to spaying is caused by a sphincter incompetence of the urethra. In practice the diagnosis is established by ruling out other causes of incontinence such as neurological disease, bacterial cystitis, urinary tract malformation, iatrogenic ureterovaginal fistula and neoplasia of the urinary tract. An accurate diagnosis of urethral sphincter incompetence is made by urethral pressure profilometry. A urethral closure pressure of 7.4 cm H2O allowed the differentiation of bitches with urinary incontinence, due to spaying, from healthy control dogs with a diagnostic accuracy of 91%. For therapy alpha-adrenergic drugs (Ephedrine or Phenylpropanolamine) are recommended, which result in continence in 74% and improvement in 24% of incontinent patients. In the absence of response estrogens may be used. If the medical therapy fails to achieve urinary continence, the endoscopic injection of collagen into the submucosa of the proximal urethra can be performed. This is a simple and minimally invasive procedure. It rarely leads to complications and may be repeated when necessary. The method is successful in 75% of cases.

Adrenergic alpha-Agonists↗

PubMed1996

A molecular switch in cytochrome C oxidase turns on thermogenesis in heart at low work load.

We describe a new mechanism of respiratory control by ATP on cytochrome c oxidase, which contrasts with the well known respiratory control of the electron transfer chain in mitochondria by ADP/ATP ratios. It is well established that high ADP/ATP ratios stimulate respiration and thus the synthesis of ATP in mitochondria, according to the energy requirements of the cell. Herein we describe the direct stimulation by high ATP/ADP-ratios of bovine heart (but not liver) cytochrome c oxidase activity in reconstituted vesicles. Under these same conditions it has already been shown that ATP decreases the H+/e- stoichiometry of cytochrome oxidase. Thus the observed effect of high ATP on cytochrome c oxidase would be expected to lead to partial uncoupling of energy transduction in mitochondria and to stimulation of thermogenesis.

Adenosine Diphosphate↗

PubMed1996

Thalamic metbolism and corticospinal tract integrity determine motor recovery in stroke.

We studied the role of remote metabolic depressions and pyramidal tract involvement regarding motor recovery following a first hemiparetic ischemic stroke. In 23 patients the regional cerebral glucose metabolism (rCMRGlu) was measured with positron emission tomography and the location and spatial extent of the stroke lesions were assessed by magnetic resonance imaging. Motor impairment during the acute and chronic stages (4 weeks after stroke) was determined by a motor score and recordings of magnetic evoked motor potentials. Twelve patients recovered significantly, whereas 11 patients retained a disabling hemiparesis. In contrast to patients with good motor recovery, rCMRGlu was severely depressed in the thalamus on the lesion side in patients with poor motor recovery. This patient group also showed more severe damage to the pyramidal tract on magnetic resonance images and a more pronounced reduction of the magnetic evoked motor potential amplitude. Neither the size of the stroke lesions nor the spatial extent of the lesional and remote rCMRGlu depressions outside the thalamus correlated with the thalamic hypometabolism and the improvement of the motor score. We conclude that preservation both of parts of the pyramidal tract and of the thalamic circuitry is a major determinant for the quality of hand motor recovery following acute brain ischemia in the adult.

Adult↗

PubMed1996

Orthotopic implantation of inflamed synovial tissue from RA patients induces a characteristic arthritis in immunodeficient (SCID) mice.

The objective of this work was to study in more detail the human/murine SCID arthritis model with special emphasis on characteristic features initiated by rheumatoid arthritis (RA) synovial membrane (SM) as compared to appropriate control tissues. Small tissue samples from RA-SM, healthy lymph node, healthy SM, and granulomatous tissue of human origin were implanted into the left knee joint of mice with severe combined immunodeficiency (SCID), and the joints were analysed histologically after 7 days. In addition, a time course study, including non-invasive monitoring by serological parameters (human IgM, IgG, and IL-6) and Tc-99m-scintigraphy, was performed for up to 4 weeks on RA-SM recipients. All tissue implants induced transient exudative joint inflammation while RA-SM initiated a characteristic arthritis with pannus tissue of high cellular density, erosion, multinuclear giant cells, lining cell hyperplasia, fibroblast-like cell layers, chondroideal metaplasia, and fibrin deposits. Significantly elevated levels of human immunoglobulin and characteristic signs of chronic inflammation persisted for more than 4 weeks. We conclude that the hu/mu SCID arthritis with RA-SM implants comprises features of non-specific inflammation which is also transiently seen with control tissues but develops characteristic features of chronic RA-like synovitis thereafter.

Animals↗

PubMed1996

Neurological impairment and recovery in Wilson's disease: evidence from PET and MRI.

We studied the relationship of regional cerebral glucose consumption (rCMRGlc) and striatal dopamine D2 receptor binding as assessed with positron emission tomography (PET) with the structural abnormalities of the brain in magnetic resonance images (MR), and the degree of neurological impairment in 18 patients with Wilson's disease (WD). The rCMRGlc was determined in the basal ganglia, the thalamus, the cerebral cortex, and the cerebellar hemispheres. The severity of neurological signs, defined by semiquantitative motor impairment scores, correlated highly (r = -0.80) with the reduction of striatal rCMRGlc. Clinical scores, striatal rCMRGlc, and the degree of MRI abnormalities showed no correlation with different indices of dopamine D2 receptor binding. Sequential PET measurements in three patients during treatment with chelating agents revealed a moderate increase of striatal rCMRGlc (in two patients) and a moderate to marked increase of striatal D2 receptor binding (in three patients) in association with clinical improvement. Our data suggest that the rCMRGlc represents a sensitive and objective measure for assessing and monitoring striatal and extrastriatal involvement in WD. The lack of correlation between the dopamine D2 receptor binding and striatal rCMRGlc and structural abnormalities may be explained by the wide spectrum of clinical manifestations and different responses to treatment in WD patients.

Adult↗

PubMed1996

Cerebellar hypometabolism in focal epilepsy is related to age of onset and drug intoxication.

PURPOSE: We wished to investigate the cerebellar depression of regional cerebral glucose metabolism (rCMRGlu) in patients with focal epilepsy. METHOD: In 170 consecutive patients with medically refractory, focal epilepsy the rCMRGlu was measured in cerebellum and brain. RESULTS: rCMRGlu was markedly decreased in both cerebellar hemispheres and slightly in brain. The cerebellum to brain rCMRGlu ratio was significantly decreased in patients with seizure manifestation in infancy, but was normal due to a progressive decrease in brain rCMRGlu in later age. A subgroup of patients with focal epilepsy involving the frontal lobe had a reduced cerebellum/brain rCMRGlu ratio, whereas in patients with mesiotemporal lobe epilepsy (MTLE), the rCMRGlu was decreased to the same degree in cerebellum and brain. The difference in the cerebellum/brain rCMRGlu ratio between the two groups was accounted for by the younger age of the patients with focal epilepsy involving the frontal lobe, however. In another subgroup of patients with a documented history of critical drug intoxications, the cerebellar rCMRGlu was severely decreased, resulting in a significantly reduced cerebellum/brain rCMRGlu ratio. CONCLUSION: Our retrospective study suggests that the cerebellum is particularly vulnerable in infancy to ongoing epileptic activity and high dosage of antiepileptic drugs (AEDs).

Adult↗

PubMed1996

Uterine serosal inclusion cysts in a bitch.

A six-year-old, pluriparous German shepherd dog bitch was presented with an abnormal vaginal discharge of several weeks' duration. Clinical signs and radiographic and ultrasonographic findings supported an initial diagnosis of segmental cystic endometrial hyperplasia, and ovariohysterectomy was performed. Macroscopically, the uterus appeared normal except for one large and several smaller cysts attached to its antimesometrial side. These cysts were restricted to a small area of the left uterine horn. The histological diagnosis was serosal inclusion cysts. The clinical findings, gross pathology and histopathology are described and discussed.

Animals↗

PubMed1996

Treatment of urinary incontinence in bitches by endoscopic injection of glutaraldehyde cross-linked collagen.

Thirty-two spayed bitches with urinary incontinence due to urethral sphincter incompetence, non-responsive to phenylpropanolamine administration, were treated by urethral submucosal injection of glutaraldehyde cross-linked collagen. Urinary incontinence resolved after a single injection in 19 of the bitches. Additional medication with phenylpropanolamine was necessary in five of these dogs, however. Of the 13 bitches that remained incontinent, the injections were repeated in nine. This resulted in a return to continence in five dogs, although two of these required additional medication for complete continence. The cure rate due to collagen injections alone is 53 per cent (17 of the 32 cases). A total of 41 injections were performed and no post-operative complications were observed.

Animals↗

PubMed1996

Mucolipidosis type II in a domestic shorthair cat.

A seven-month-old, female domestic shorthair cat was presented to the Veterinary Teaching Hospital, University of Zurich, with abnormal facial features, retarded growth and progressive hindlimb paresis. On physical examination the cat had a flat, broad face with hypertelorism, frontal bossing, small ears and thickened upper and lower eyelids. The corneas of both eyes were clear and the pupils were dilated. The skin was generally thickened, most prominently on the dorsal aspect of the neck. Radiography of the entire skeleton revealed a severely deformed spinal column, bilateral hip luxation with hip dysplasia, an abnormally shaped skull and generalised decreased bone opacity. The clinical features and radiographic changes were suggestive of mucopolysaccharidosis. The toluidine blue spot test on a urine sample, however, was negative for glycosaminoglycans. Further biochemical investigations revealed a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) in peripheral leukocytes and an elevation of many lysosomal enzymes in the serum of the cat which is diagnostic for mucolipidosis type II. Histology and electron microscopy of different tissues are briefly summarised. The findings of this cat, the first reported case of mucolipidosis type II are compared with other similar storage diseases described in the cat.

Animals↗

PubMed1996

Spontaneous mucolipidosis in a cat: an animal model of human I-cell disease.

A 7-month-old female cat was seen for abnormal facial features and abnormality of gait. Facial dysmorphism, large paws in relation to body size, dysostosis multiplex, and poor growth were noted, and mucopolysaccharidosis was suspected. A negative urine test for sulfated glycosaminoglycans and extreme stiffness of skin indicated a mucolipidosis hitherto unknown in animals. Deficiency of UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) activity was demonstrated in leukocytes and cultured fibroblasts, which had the appearance of inclusion cells (I-cells). Activities of a set of lysosomal hydrolases were abnormally low in fibroblasts and excessive in blood plasma. Postmortem morphology revealed lysosomal inclusions predominantly in fibroblasts but also in endothelial cells and chondrocytes, i.e., in cells of mesenchymal origin. Storage lysosomes contained oligosaccharides, mucopolysaccharides, and lipids. Tissues most affected were bones, cartilage, skin, and other connective tissues such as those in heart valves, aortic wall, and vocal cords. Parenchymal cells of liver and kidney were unaffected, as was skeletal muscle. Only a few of the cerebral cortical neurons had lipid inclusions; in sciatic nerve some axons were affected, but other peripheral nerves were normal. There were striking clinical, biochemical, and morphologic similarities between the disorder in this cat and the human I-cell disease.

Animals↗