Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 433 records · Page 24Linked to original sources

PubMed1992

A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome.

A gene designated "FMR-1" has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involved in the clinical manifestation of the fragile-X syndrome and also in the expression of the cellular phenotype. A deletion including the HTF island and exons of the FMR-1 gene was detected in a fragile X-negative mentally retarded male who presented the clinical phenotype of the fragile-X syndrome. The deletion involves less than 250 kb of genomic DNA, including DXS548 and at least five exons of the FMR-1 gene. These data support the hypothesis that loss of function of the FMR-1 gene leads to the clinical phenotype of the fragile-X syndrome. In the fragile-X syndrome, there are pathogenetic mechanisms other than amplification of the CGG repeat that do have the same phenotypic consequences.

Base Sequence↗

PubMed1991

Influenza A virus infection of macrophages. Enhanced tumor necrosis factor-alpha (TNF-alpha) gene expression and lipopolysaccharide-triggered TNF-alpha release.

We have previously shown that infection of macrophages by influenza A virus is capable of priming for a high TNF-alpha production in response to LPS. The present study was designed to examine in more detail TNF-alpha gene expression and TNF-alpha protein release of virus-infected, murine PU5-1.8 macrophages in the presence or absence of low and by itself rather inefficient concentrations of LPS (10 ng/ml). Although influenza A virus infection alone induced a massive TNF-alpha mRNA accumulation, translation into the bioactive TNF-alpha protein was low as intra- and extracellularly determined by bioassay, specific ELISA and Western blot. However, when LPS was added simultaneously or up to 4 h after infection, a high TNF-alpha production was initiated. The virus-induced TNF-alpha mRNA accumulation appeared to be due to both transcriptional and post-transcriptional changes: an enhanced TNF-alpha gene transcription as determined by nuclear run-on transcription assay and a markedly prolonged half-life of TNF-alpha mRNA as shown in actinomycin D-treated macrophages. These findings imply that influenza A virus may 1) either directly or indirectly stimulate TNF-alpha gene transcription activators or may interfere with labile transcription repressor proteins and 2) may stabilize TNF-alpha mRNA by delaying its degradation. Both mechanisms, taken together, prime influenza A virus-infected macrophages for a high TNF-alpha release in response to LPS which, as clinical cases show, may adversely affect patients with combined influenza A virus and bacterial infections.

Animals↗

PubMed1991

Involvement of pertussis toxin-sensitive G-proteins in the hormonal inhibition of dihydropyridine-sensitive Ca2+ currents in an insulin-secreting cell line (RINm5F).

Adrenaline inhibits insulin secretion via pertussis toxin-sensitive mechanisms. Since voltage-dependent Ca2+ currents play a key role in insulin secretion, we examined whether adrenaline modulates voltage-dependent Ca2+ currents of the rat insulinoma cell line, RINm5F. In the whole-cell configuration of the patch-clamp technique, dihydropyridine- but not omega-conotoxin-sensitive Ca2+ currents were identified. Adrenaline via alpha 2-adrenoceptors inhibited the Ca2+ currents by about 50%. Somatostatin which also inhibits insulin secretion was less efficient (inhibition by 20%). The hormonal inhibition of Ca2+ currents was not affected by intracellularly applied cAMP but blocked by the intracellularly applied GDP analog guanosine 5'-O-(2-thiodiphosphate) and by pretreatment of cells with pertussis toxin. In contrast to adrenaline and somatostatin, galanin, another inhibitor of insulin secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner. Immunoblot experiments performed with antibodies generated against synthetic peptides revealed that membranes of RINm5F cells possess four pertussis toxin-sensitive G-proteins including Gi1, Gi2, Go2, and another Go subtype, most likely representing Go1. In membranes of control but not of pertussis toxin-treated cells, adrenaline via alpha 2-adrenoceptors stimulated incorporation of the photo-reactive GTP analog [alpha-32P]GTP azidoanilide into pertussis toxin substrates comigrating with the alpha-subunits of Gi2, Go2, and the not further identified Go subtype. The present findings indicate that activated alpha 2-adrenoceptors of RINm5F cells interact with multiple G-proteins, i.e. two forms of Go and with Gi2. These G-proteins are likely to be involved in the adrenaline-induced inhibition of dihydropyridine-sensitive Ca2+ currents and in other signal transduction pathways contributing to the adrenaline-induced inhibition of insulin secretion.

Animals↗

PubMed1991

[Combined uni- and multicenter double-blind studies in hypertensive patients. Comparison of blood pressure measurements].

In a double-blind study to investigate the antihypertensive effect of a fixed triple combination with 0.05 mg reserpine, 2.5 mg clopamide and 0.4 mg dihydroergocristine in comparison to a fixed double combination with 0.05 mg reserpine and 2.5 mg clopamide, a patient subgroup of 34 patients followed a unicenter (central unit, 'institute') as well as a multicenter (established physicians) study design. The patients visited both investigation units on the day of admission to the study (week 0), after four weeks and after eight weeks of therapy (after the morning intake of the drugs). The paper in hand looks at the results of this subgroup with respect to the conformity of blood pressure values in the two investigative units. The analyses confirm the already published results of the entire study: Both combinations proved to be highly effective antihypertensive drugs. The triple combination showed therapeutical advantages for systolic blood pressure after four weeks, for diastolic pressure after eight weeks of therapy at the 'institute' as well as, although less distinct, in the medical offices. A comparison of the individual values did not show a convincing coherence of the measurements between institute and offices. All investigated possible systematic sources of error (different methods of measurement, days or times of measurement) could be excluded by correlation statistics as a reason for the divergences. The results show the necessity--particularly in multicenter studies--of a careful documentation of all accompanying data (e.g. method or time of measurement) as well as a greatest possible standardization of investigation (e.g. identical measuring apparatus and investigator.)

Antihypertensive Agents↗

PubMed1991

[Considerations on the use of the construct "Quality of life" as a goal variable in clinical research].

In recent years the importance of the assessment of quality of life increased, especially in palliative therapy. Commonly used concepts of quality of life comprise of several dimensions, e.g. somatic disorders, functional status, well-being and social interaction. We developed an 18-item questionnaire, self-administered by the patients, and compared the results of 66 'healthy' subjects with two clinical samples: 126 patients with inoperable non-small-cell lung cancer and 19 patients under dialysis. The results indicate the questionnaire as a sufficiently reliable and valid method for the assessment of 'quality of life'. On the other hand, there are several problems concerning an adequate interpretation when regarding our clinical data. For example, the cancer patients show a significantly more positive self-assessment concerning well-being and activity, compared to 'healthy' subjects.

Adult↗

PubMed1991

[Resection of liver metastases of colorectal carcinoma: claims and reality].

Results of resection of potentially operable liver metastases from colorectal carcinomas were evaluated by analysis of 50 publications between 1985 and 1990, as well as own datas (88 patients). Average 1, 3 and 5-year survival rates without treatment were 71 +/- 14%, 18 +/- 10% and 3 +/- 4%, respectively. The extent of metastasization at the time of diagnosis was the decisive prognostic factor. After resection of metastases 80 +/- 21% of patients survived for 1 year, 43 +/- 12% for 3 years and 28 +/- 11% for 5 years. But only a small group of patients, those with single and small metastasis, limited to one liver lobe and without extrahepatic tumour deposits, clearly profited from resection, as long as this could be accomplished with a wide enough margin of safety. Studies on growth characteristics of metastases suggest that in a large proportion of the remaining patients the natural history of the disease is not significantly changed by the operation.

Colorectal Neoplasms↗

PubMed1991

A radioiodinated linear vasopressin antagonist: a ligand with high affinity and specificity for V1a receptors.

A linear vasopressin antagonist, Phaa-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (Linear AVP Antag) (Phaa = Phenylacetyl), was monoiodinated at the phenyl moiety of the tyrosylamide residue at position 9. This antagonist appeared to be a highly potent anti-vasopressor peptide with a pA2 value in vivo of 8.94. It was demonstrated to bind to rat liver membrane preparations with a very high affinity (Kd = 0.06 nM). The affinity for the rat uterus oxytocin receptor was lower (Ki = 2.1 nM), and affinities for the rat kidney- and adenohypophysis-vasopressin receptors were much lower (Ki = 47 nM and 92 nM, respectively), resulting in a highly specific vasopressin V1a receptor ligand. Autoradiographical studies using rat brain slices showed that this ligand is a good tool for studies on vasopressin receptor localization and characterization.

Amino Acid Sequence↗

PubMed1991

Mapping of a carotenogenic gene cluster from Erwinia herbicola and functional identification of six genes.

Six genes have been mapped and identified by hybridization or by carotenoid analysis of deletion mutants on a 9 kb chromosomal fragment originating from Erwinia herbicola Eho 10. These genes include crtB, E and I which have been formerly described for Rhodobacter, and three new ones: crtZ encoding lycopene cyclase, crtH for beta-carotene hydroxylase, and crtG for zeaxanthin glycosilase. Their arrangement on the plasmid has been elucidated.

Carotenoids↗

PubMed1991

Receptors for neurohypophyseal hormones along the rat nephron: 125I-labelled d(CH2)5[Tyr(Me)2, Thr4, Orn8, Tyr-NH(2)9] vasotocin binding in microdissected tubules.

A microassay was developed to measure the binding of the labelled monoiodinated analogue [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine, 4-threonine, 8-ornithine, 9-125I-tyrosylamide]vasotocin [125I-d(CH2)5[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT] to isolated nephron segments microdissected from collagenase-treated rat kidneys. When determined using 1.7 nM labelled ligand at 4 degrees C, specific binding sites (expressed at 10(-18) mol 125I-d(CH2)5[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT bound/mm tubule length) were found in medullary thick ascending limbs (MTAL), 1.67 +/- 0.49; cortical thick ascending limbs, 2.20 +/- 0.80; cortical collecting ducts, 2.39 +/- 0.86; outer medullary collecting ducts (OMCD), 2.54 +/- 0.53 and inner medullary collecting ducts, 5.33 +/- 0.40, whereas no specific binding could be detected in glomeruli and proximal tubules. Specific 125I-d(CH2)5[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT binding to OMCD was saturable with incubation time and reversible after elimination of free labelled ligand (the association and dissociation rate constants at 4 degrees C were 1.06 x 10(7) M-1 min-1 and 1.95 x 10(-2) min-1 respectively). The stereospecificity of MTAL and OMCD binding sites was assessed in competitive experiments revealing the following recognition pattern for a series of eight vasopressin analogues:dDAVP greater than AVP greater than d(CH2)5-[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT = AVT = OT greater than d(CH2)5[Tyr(Me)2]AVP = [Thr4, Gly7]OT greater than [Phe2, Orn8]VT, whereas pharmacological concentrations of insulin and glucagon did not impair radioligand binding. These results indicate that the detected labelled binding sites might correspond mainly to physiological V2 vasopressin receptors.

Animals↗

PubMed1991

Effect of respiratory training with a mouth-nose-mask in tetraplegics.

Ten tetraplegics, 8 males and 2 females, with a median age of 32 years participated in a scheduled 6 weeks training programme with a respiratory muscle training mouth-nose-mask (RMT-mask) with a fixed expiratory and an increasing inspiratory resistance set by the tetraplegic in accordance to his/her increasing ability during the training period. During the 6 weeks the tetraplegics required to use the RMT-mask for 15 minutes three times a day. Before and after each training session they measured peak flow (PEF). Lung volumes, ventilatory and diffusion capacity were measured before and after the 6 weeks training period. The training resulted only in a significant change in the PEF, which increased with 11% from 371 l/min before to 412 l/min in average after the 6 weeks of training (p less than 0.025). This statistically significant increase was confirmed by the measurements of PEF performed by the tetraplegics themselves during the training period. In addition there was an increase in PEF from before to immediately after each 15 minutes training session, this trend reached statistically significance (p less than 0.025) in the third '2 weeks period'. These results might indicate a possibility of improving the tetraplegics ability to cough by use of a simple RMT-mask, which in turn might prevent certain lung complications including pneumonia, and atelectasia.

Adult↗

PubMed1991

[Thrombolytic therapy of pulmonary artery embolism in early pregnancy with recombinant tissue-type plasminogen activator].

We report on successful thrombolytic treatment of massive pulmonary embolism in a patient in early pregnancy with recombinant tissue-type plasminogen activator (rt-PA). Therapy was started with 20 mg rt-PA intravenously over 20 minutes, followed by two further infusions of 20 mg rt-PA within the next 8 hours. Clinical symptoms and haemodynamic parameters improved 24 hours after initiation of therapy. No bleeding complications were observed and the foetus was not affected. Further thromboembolic episodes could be prevented by anticoagulation with low molecular weight heparin up to full term normal delivery.

Adult↗

PubMed1991

Sarcoid heart disease--results of follow-up investigations.

52 patients thought to have sarcoid heart involvement have been followed up. By administration of a standardized glucocorticoid therapy we demonstrated improvement of patients' symptoms, ECG disturbances, thallium scan defects of left heart muscle and there was 60-70% regression of pulmonary sarcoidosis. There was a low death rate. We conclude that our diagnostic measures are reliable, and that glucocorticoid therapy is efficacious in the early stages of the disease.

Adult↗

PubMed1991

Asymmetrical cranio-orbital facial stenosis.

Cranio-orbital facial scoliosis is the result of unilateral premature stenosis of the craniofacial skeleton. Plagiocephaly is only a subform of the syndrome. The deformity progresses unless operative treatment is given. Operative treatment is indicated for functional, aesthetic, and psychosocial reasons. We advocate early operation in infancy (3 to 6 months) consisting of wide resection of the stenosed sutures of the cranium and orbit, repositioning, and remodeling relying on the spontaneous autodynamic reshaping of the nasoethmoidal complex and the midface structures during the course of further growth. In adolescents and adults, multisegmental osteotomies and remodeling into a definitive position are necessary.

Craniofacial Dysostosis↗

PubMed1991

Increasing the vascular pedicle length in a free flap using a two-stage preliminary ectopic transfer.

The length of the vascular pedicle is critically important in the use and safety of a free flap. A lengthening of the artery and vein, until now, has been achieved through the use of either an autologous vein interposition graft or an arteriovenous loop. In such patients, the risk is nevertheless increased and does so proportionally to the increasing length of the venous interposition. We present a 30-year-old male electrician who had lost his left forearm and most of his right ulna after high-voltage electrical trauma. Lengthening of the vascular pedicle of a free fibula flap was achieved by anastomosis to the thoracodorsal vessels for 4 weeks. After this time, the flap was raised again together with the pedicle of the latissimus dorsi and used safely for reconstruction of the ulnar defect. Postoperative recovery after both operations was uneventful and the aim of reconstruction fully realized. In our opinion, this procedure provides an interesting alternative in patients in whom the length of the vascular pedicle is crucial but the designated flap has only a short pedicle.

Adult↗

PubMed1991

Peptidyl proline hydroxylation and the growth of a soybean cell culture.

Peptidyl proline hydroxylase inhibitors block the growth of cultured soybean (Glycine max) cells and bring about the disappearance of the major salt-extractable hydroxyproline-rich protein, the 33 kilodalton repetitive proline-rich protein (RPRP2). Three polypeptides of 28, 20, and 14 kilodalton that cross-react with an antibody to RPRP2 accumulate in the culture during steady-state growth. In the presence of the proline hydroxylase inhibitors, all of these repetitive proline-rich proteins disappear. These results indicate that the hydroxyproline-rich proteins play a role in cell growth, and that hydroxylation may regulate the steady-state level of at least one of these proteins by influencing its turnover.

Journal Article↗

PubMed1991

Left ventricular function and wall thickness in long-term insulin-dependent diabetes mellitus: an echocardiographic study.

Left ventricular function and wall thickness were evaluated in 111 type I diabetic subjects (mean age 25.5 +/- 9 years, mean duration of diabetes 13.4 +/- 6.2 years), using 2-D-derived M-mode echocardiography. Patients were carefully selected for the absence of major coronary risk factors or manifest cardiac disorders, and compared with 91 age- and sex-matched control subjects. Fractional shortening and the maximal velocity of cirumferential fibre shortening did not differ significantly between the two groups. Furthermore, no differences were found in the diastolic functional parameter of velocity of circumferential fibre extension. Posterior wall thickness was significantly increased in the diabetic patients compared to the controls (9.5 +/- 1.8 mm vs. 8.4 +/- 1.3 mm. P less than 0.01). As the thickness of the interventricular septum was also moderately increased (9.2 +/- 2.2 mm vs. 8.9 +/- 1.7 mm, NS), these findings provide evidence for an early structural change of the myocardium in young diabetic patients without clinically relevant functional consequences.

Adult↗

PubMed1991

Diastolic ventricular function in type 1 diabetic patients: a study using Doppler echocardiography.

The transmitral flow velocity pattern of 28 Type 1 diabetic patients and 39 age-matched healthy control subjects was studied for determination of left ventricular diastolic function. No patient had systemic hypertension, congestive heart failure, or ischaemic heart disease by clinical or electrocardiographic criteria. Echocardiographic measures of systolic ventricular function were within normal range in all subjects. The ratio of early to late transmitral peak flow velocity (ve/va) was significantly decreased in the diabetic patients (1.3 +/- 0.1 (+/- SE) vs 1.6 +/- 0.1, p less than 0.05), while other Doppler derived variables did not show any significant difference. No correlation of ve/va with duration of diabetes was found (r = -0.27), but it correlated with age in both groups (both r = -0.40, p less than 0.05). Furthermore, a significant correlation was found between ve/va and heart rate (r = -0.55 for diabetic patients, p less than 0.01; r = -0.58 for control subjects, p less than 0.01). After matching for heart rate (24 diabetic patients and 24 control subjects) no significant decrease of ve/va was observed in the diabetic group.

Adult↗

PubMed1991

Mineralization of the sulfonated azo dye Mordant Yellow 3 by a 6-aminonaphthalene-2-sulfonate-degrading bacterial consortium.

Under anaerobic conditions the sulfonated azo dye Mordant Yellow 3 was reduced by the biomass of a bacterial consortium grown aerobically with 6-aminonaphthalene-2-sulfonic acid. Stoichiometric amounts of the aromatic amines 6-aminonaphthalene-2-sulfonate and 5-aminosalicylate were generated and excreted into the medium. After re-aeration of the culture, these amines were mineralized by different members of the bacterial culture. Thus, total degradation of a sulfonated azo dye was achieved by using an alternating anaerobic-aerobic treatment. The ability of the mixed bacterial culture to reduce the azo dye was correlated with the presence of strain BN6, which possessed the ability to oxidize various naphthalenesulfonic acids. It is suggested that strain BN6 has a transport system for naphthalenesulfonic acids which also catalyzes uptake of sulfonated azo dyes. These dyes are then gratuitously reduced in the cytoplasm by unspecific reductases.

Aerobiosis↗