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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 127 records · Page 7Linked to original sources
PubMed1994

Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's disease.

Antibodies to different phosphorylated and non-phosphorylated tau epitopes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughout the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed extracellular tangles (Type 3) were characterized by the presence of epitopes associated with the microtubule binding region and the COOH-terminus. These three types of tangles, found in situ in hippocampus, could be created experimentally by proteolytic treatment of brain sections. These findings suggest that three stages of neurofibrillary degeneration can be understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phosphorylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.

Alzheimer Disease↗
PubMed1994

Influence of digoxin-like immunoreactive factor on late complications in patients with diabetes mellitus.

The aim of this study was to compare the intensity of typical late complications in diabetic patients (n = 65, 28 type I, 37 type II) who were not on glycoside drugs with low vs. high serum levels of digoxin-like immunoreactive factor (DLIF: group I, n = 42, DLIF < or = the detection limit of 0.2 ng ml-1; and group II, n = 23, mean +/- SEM: 1.17 +/- 0.31 [0.25-4.96] ng ml-1). For detection of nephropathy, urinary albumin excretion (24 h) and creatinine clearance tests were used. For coronary heart disease a questionnaire and standard ECG; for peripheral occlusive vascular disease a questionnaire; for eye disease a fundoscopy; for neuropathy a neurological score system; and for autonomic neuropathy a standardized test battery was employed. Patients with high DLIF levels showed better test results in vibratory perception (95.7 +/- 1.5 vs. 82.8 +/- 3.8%, normal finding = 100%, 2p = 0.016), had better percentile localizations concerning maximal pupillary area in darkness (28.4 +/- 6.6 vs. 8.1 +/- 1.8%, 2p = 0.0004), contraction velocity at 1 s (21.5 +/- 5.8 vs. 8.0 +/- 2.2%, 2p = 0.012), and dilation velocity at 6 s (23.0 +/- 6.8 vs. 10.5 +/- 2.5%, 2p = 0.041), had less retinopathy (with retinopathy: 26.1% vs. 64.3%, 2p = 0.0028), and better percentile localizations in the respiratory sinus arrhythmia test (68.4 +/- 7.3 vs. 44.1 +/- 4.9%, 2p = 0.0064). There was no difference concerning nephropathy, blood pressure, coronary heart disease and peripheral vascular disease. Separate analysis according to the type of diabetes confirmed the results in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression.

Cardiac hypertrophy is largely due to cardiac fibroblast growth and increased synthesis of extracellular matrix. This study has investigated the contribution of the vasoactive hormone, angiotensin II, toward this hypertrophic process. We have demonstrated that cultures of adult rat cardiac fibroblasts express AT1 but not AT2 receptors for angiotensin II. The ability of angiotensin II to stimulate phosphoinositide catabolism and to elevate intracellular calcium concentrations in these cells was blocked by losartan, a specific AT1 receptor antagonist, but not by the AT2 receptor antagonist CGP 42112. Exposure of adult cardiac fibroblasts to angiotensin II resulted in the induction of several growth-related metabolic events including c-fos protooncogene expression and increased synthesis of DNA, RNA, and protein. Angiotensin II was also found to induce collagen type I, alpha 1 chain transcript expression in cardiac fibroblasts as well as the synthesis and secretion of collagen by these cells. The data demonstrate that angiotensin II, via AT1 receptors, can stimulate cardiac fibroblast growth and increase collagen synthesis in cardiac tissue. Thus, angiotensin II may contribute toward the development of cardiac hypertrophy in conditions of hypertension that are associated with elevated concentrations of angiotensin II.

Animals↗
PubMed1994

Should oral steroids be the primary treatment for allergic fungal sinusitis?

A case of Allergic Fungal Sinusitis successfully controlled with oral corticosteroids followed by endoscopic sinus surgery is presented. The clinical diagnosis of AFS is emphasized. Endoscopic sinus surgery is preferable to open sinus techniques since the underlying mucosal disease is reversible. A prospective study is needed to determine the most appropriate treatment for this unique clinical disorder.

Administration, Oral↗
PubMed1994

[Deforming idiopathic ankylosis of the coffin joint in young cattle].

Case reports are given of a deforming ankylosis of the distal interphalangeal joints in two juvenile cattle of the breed German Simmental. In one animal all distal interphalangeal joints were affected; in the second animal the coffin joints of the forelimbs and the lateral coffin joints of the hindlimbs were ankylosed or in the process of being bridged by bone. The condition was painful, resulting in lameness and loss of weight. Clinical, radiological and pathological-anatomical features are described.

Animals↗
PubMed1994

Platelet-activating factor plays an important role in reperfusion injury in myocardium. Efficacy of platelet-activating factor receptor antagonist (CV-3988) as compared with leukocyte-depleted reperfusion.

Although platelet-activating factor has been implicated in the pathogenesis of neutrophil-induced reperfusion injury, it has other mechanisms of direct deleterious hemodynamic effect. In this study we evaluated the definitive role of platelet-activating factor in myocardial reperfusion injury. Porcine hearts that underwent 60 minutes of normothermic ischemia with cardioplegia and 60 minutes of reperfusion under cardiopulmonary bypass were divided into three groups according to the methods of 15 minutes of controlled reperfusion: whole blood reperfusion group (n = 6), leukocyte-depleted reperfusion group (n = 6), and platelet-activating factor receptor antagonist (CV-3988) group (n = 6). At 60 minutes of reperfusion, the percentage of recovery of maximum slope of the pressure-volume relationship measured with intraventricular balloon, malondialdehyde value in coronary sinus blood, tissue adenosine triphosphate, and percentage of spontaneous defibrillation were evaluated. The receptor antagonist group showed significantly better recovery of maximum slope of the pressure-volume relationship than did the whole blood reperfusion group. Moreover, the receptor antagonist group showed significantly less release of malondialdehyde in the coronary sinus, higher values of adenosine triphosphate in the myocardium, and a higher percentage of spontaneous defibrillation than did the whole blood reperfusion group. On the other hand, the leukocyte-depleted reperfusion group showed no significant differences of maximum slope of the pressure-volume relationship, malondialdehyde, adenosine triphosphate, or spontaneous defibrillation as compared with the whole blood group. These results suggest that platelet-activating factor receptor antagonist attenuated severe damage in whole blood reperfusion of the myocardium as compared with leukocyte-depleted reperfusion, which also suggests that platelet-activating factor may play a more important role in myocardial reperfusion injury than do neutrophils.

Animals↗
PubMed1994

Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease.

Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology.

Aged↗
PubMed1993

Transcriptional activation of low density lipoprotein receptor gene by angiotensin-converting enzyme inhibitors and Ca(2+)-channel blockers involves protein kinase C isoforms.

The pharmacological potency of angiotensin-converting enzyme (ACE) inhibitors (lisinopril and enalaprilat) on the transcription of low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase genes was examined in human vascular smooth muscle cells and compared with the action of Ca(2+)-channel blockers (manidipine, verapamil, and diltiazem). Analogous to Ca(2+)-channel blockers, nanomolar concentrations of enalaprilat or lisinopril stimulated the synthesis of low density lipoprotein receptor mRNA and amplified the transcription induced by recombinant platelet-derived growth factor BB. In contrast to Ca(2+)-channel blockers, ACE inhibitors did not alter the transcription of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. Platelet-derived growth factor BB stimulated the translocation of delta and epsilon isoforms of protein kinase C. Similar to Ca(2+)-channel blockers, ACE inhibitors reduced the translocation of delta and epsilon isoforms of protein kinase C. Furthermore, ACE inhibitors and Ca(2+)-channel blockers inhibited platelet-derived growth factor BB-induced transcription of c-fos and c-jun genes. The findings suggest that increased de novo synthesis of mRNA low density lipoprotein receptor apparently involves the participation of delta and epsilon isoforms of protein kinase C and transcription factors c-Fos and c-Jun.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Evidence of subtypes of Alzheimer's disease and implications for etiology.

OBJECTIVE: Because age of onset does not reliably define two subtypes of Alzheimer's disease, classification based on the severity of neuronal degeneration was tested. DESIGN: Numbers of extracellular tangles and pyramidal neurons in the hippocampus were used to group patients. PATIENTS: The study population consisted of 46 elderly patients satisfying DSM-III criteria for dementia and NINCDS-ADRDA criteria for definite Alzheimer's disease after death. RESULTS: Univariate logistic regression analysis showed the numbers of neurofibrillary tangles and pyramidal neurons and the duration of dementia were significantly associated with grouping based on the presence of abundant extracellular tangles. Ninety-one percent of patients were correctly classified as compared with 85% correctly classified by age of onset data. Odds ratios showed that increasing numbers of neurofibrillary tangles predicted greater severity of neuronal loss. CONCLUSION: The results of the study indicate the importance of neurofibrillary degeneration, not the deposition of amyloid, in the pathogenesis of Alzheimer's disease. They support a classification of Alzheimer's disease related more closely to the severity of neurofibrillary degeneration than to age at onset.

Age Factors↗
PubMed1993

p-ANCA of undefined specificity in ulcerative colitis: correlation to disease activity and therapy.

Sera of 108 patients with chronic inflammatory bowel disease (IBD) and 13 sera from patients with other gastrointestinal diseases were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. 37 out of 64 sera (58%) from patients with ulcerative colitis (UC) produced a fine granular and perinuclear ANCA staining pattern ("snowdrift-like" p-ANCA) clearly different from the cytoplasmic ANCA fluorescence (c-ANCA) seen in active Wegener's granulomatosis (WG) and the typical p-ANCA pattern produced by anti-myeloperoxidase (MPO) autoantibodies. Only 1 of 44 sera from patients with Crohn's disease (CD) and none of the control sera showed positive "snowdrift-like" p- ANCA reactions. 31 out of the 37 p-ANCA positive sera (84%) were obtained from patients with high disease activity with and without longterm high dose steroids. p-ANCA titers became negative after longterm steroid therapy and following complete colectomy.

Adult↗
PubMed1993

Development of thyroid gland volume during the first 3 months of life in breast-fed versus iodine-supplemented and iodine-free formula-fed infants.

The spontaneous development of thyroid gland volume (TGV) during the first 3 months of life was studied in entirely breast-fed infants (n = 21) and compared to those fed an iodine-supplemented formula (n = 19), an iodine-free formula (n = 5), or partially breast-fed in addition to an iodine-free (n = 4) or an iodine-supplemented formula (n = 16). The TGV of the infants and their mothers was determined sonographically in addition to their urinary iodine concentrations 5-7 days postpartum and 3 months later. In ten additional lactating mothers the breast milk concentrations of thyroid hormones and iodine were determined. It was shown that at 3 months of age an infant consuming about 1000 ml breast milk per day receives about 2 micrograms thyroid hormones and 55 micrograms iodine per day. At the end of their first week of life the infants showed a TGV between 0.28 and 1.5 ml (median 0.61 ml) and a urinary iodine concentration between 0.03 and 16.3 micrograms/dl (median 3.0 micrograms/dl). At 3 months of age the TGV of the breast-fed infants had decreased by a median of 0.24 ml (= -34%; median of percentage changes) whereas those fed a formula without iodine had increased by a median of 0.26 ml (= +50%; median of percentage changes). Those receiving an iodine-supplemented formula showed a TGV reduction of 0.14 ml (= +2%; median of percentage changes). The TGV development of the partially breast-fed infants lay between those being exclusively breast or formula fed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Manidipine affects rPDGF-BB-induced gene transcription of low-density lipoprotein receptors and 3-hydroxy-3-methylglutaryl coenzyme A reductase in human mesangial cells.

The effects of manidipine, a newly developed Ca2+ channel blocker, on recombinant platelet-derived growth factor BB (rPDGF-BB)-induced transcription of the low-density lipoprotein receptor and the 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in human mesangial cells are reported. The transcription of the rPDGF-BB-induced gene of the low-density lipoprotein receptor was enhanced and maintained over a longer period, whereas the transcription of the 3-hydroxy-3-methylglutaryl reductase gene was blocked by manidipine at nanomolar concentrations. The results suggest that aside from the ability to block manidipine's potential-operated Ca2+ channels, manidipine also affects gene transcription of relevant proteins involved in the regulation of cholesterol metabolism at concentrations close to those efficacious for clinical therapies. This may further explain the antiinflammatory and organ-protective activities of the compound.

Calcium Channel Blockers↗
PubMed1993

Inhibition of receptor-mediated platelet activation by nedocromil sodium.

BACKGROUND: Platelet activation by platelet activating factor (PAF) seems to be involved in the inflammatory process in asthma and may serve as a possible target for the antiinflammatory drug nedocromil sodium, which is known to inhibit cell activation by different stimuli. METHODS: We investigated the effect and the mode of action of nedocromil sodium on platelet activation by PAF. In a set of healthy volunteers (n = 45) we investigated seven different parameters of platelet activation by PAF, thrombin, and Ca(2+)-ionophore. RESULTS: Nedocromil sodium inhibited: (1) PAF-induced "shape change" reaction up to 78% (50% inhibitory concentration [IC50]: 3 x 10(-9) mol/L), thrombin-mediated "shape change" up to 80% (IC50 2 x 10(-8) mol/L), but not the Ca(2+)-ionophore-dependent reaction, (2) platelet aggregation by PAF up to 85% (IC50 2 x 10(-9) mol/L); (3) release of thromboxane B2 up to 82% (IC50 5 x 10(-9) mol/L); (4) formation of inositol 1,4,5-triphosphate by PAF (IC50 3 x 10(-7) mol/L), by thrombin (IC50 1 x 10(-7) mol/L), but not by Ca2+ ionophore; (5) increase of intracellular free calcium (IC50 4 x 10(-7) mol/L); (6) formation of diacylglycerol (IC50 9 x 10(-9) mol/L), and (7) translocation of protein kinase C (IC50 1 x 10(-7) mol/L). CONCLUSIONS: In the concentration range of the IC50 values found in these experiments, nedocromil sodium reduced PAF binding to platelets by only 10% to 20%, such that this interference cannot explain the observed effects of the compound. Inhibition of receptor-mediated platelet activation at an early stage in the signal transduction pathway, and without effect on Ca(2+)-ionophore-induced platelet activation, suggests an action of nedocromil sodium at the level of the cell membrane.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Who becomes an "at-risk" student? The predictive value of a Kindergarten Screening Battery.

This study was undertaken to determine whether a preschool screening instrument could predict whether kindergarten students would later be retained, referred to special education, or placed in special education. The results of Early Prevention of School Failure (EPSF) screening on 161 kindergarten students were examined. Students who had been retained, referred to special education, or placed in special education demonstrated significantly lower EPSF pretest scores except in the gross motor modality. All EPSF modalities were statistically significant predictors of students' status; however, other factors such as family support network, preschool experiences, and motivational factors must be considered in evaluating whether a student is "at risk" of later school failure.

Child↗
PubMed1993

Clinical and biochemical characteristics of acromegalic patients harboring gsp-positive and gsp-negative pituitary tumors.

A subgroup of growth hormone (GH)-secreting pituitary tumors carries somatic mutations within the gene coding for the alpha subunit of the stimulatory heterotrimeric guanosine 5'-triphosphate-binding protein, Gs alpha. These so-called gsp mutations result in constitutively activated Gs alpha and the signal transduction cascade downstream of it, with eventual markedly and continuously elevated cyclic adenosine monophosphate levels as a result of constitutive adenylyl cyclase activity. It is this elevation of intracellular cyclic adenosine monophosphate that is thought to be the cause of excessive GH secretion and somatotroph proliferation. We examined the clinical and biochemical characteristics of acromegalics harboring gsp-positive and gsp-negative pituitary tumors. Of 19 tumors studied, 8 (42%) were gsp positive. There was a slight tendency for basal GH levels in serum to be lower and to be further reduced by an oral glucose tolerance test in gsp-positive patients. However, there was no difference between the two groups in terms of clinical features, tumor size, mitotic activity (as assessed by cytosolic deoxyribonucleic acid polymerase and KI-67 staining), and in vitro GH response to GH releasing factor. We conclude that there is, in general, little difference in the clinical and biochemical characteristics between gsp-positive and gsp-negative human pituitary GH-secreting tumors.

Acromegaly↗