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Biomedical subjects

P Schmidt

Publications and source records attributed to P Schmidt.

At least 145 records · Page 8Linked to original sources

Screening of a mouse/human Y-chromosomal cosmid library for gene candidates and markers by using (short) oligonucleotide probes.

A comprehensive approach is described for the identification of sequences of interest from a human Y chromosomal cosmid library via (short) consensus oligonucleotide probes. It involves the ordering of cosmid clones grown in microtiter plates onto small filter membranes by a robot workstation. A high number of the clones are characterized by their repetitive sequence content, either by ubiquitously interspersed simple tandem blocks or by Y-specific elements. The Y chromosomal repeat (DYZ2) appears underrepresented in the library. In contrast many novel microsatellite marker systems can now be developed for the Y chromosome on the basis of the simple repeat blocks described here. Though novel genes were not yet delineated so far, a number of candidate sequences with high coding potential and other interesting characteristics are described.

Animals↗

Treatment of malignant testicular tumors in childhood: results of the German National Study 1982-1992.

The German Cooperative Protocol for treatment of testicular germ cell tumors in childhood registered 106 patients from January 1982 through February 1992. Sixty-one patients suffered from yolk sac tumors (YST); 25 patients from differentiated teratomas (TD); 19 patients from malignant teratomas of either intermediate (MTI), undifferentiated (MTU), or trophoblastic type (MTT), and 1 patient from a seminoma. A stratified chemotherapy based on stage and histology was administered in addition to unilateral orchiectomy: Standard chemotherapy consisted of four treatments with vinblastine, bleomycin, and cisplatinum. If viable tumor was suspected after two treatments with standard chemotherapy, a delayed explorative laparotomy was done. There were two options based on the histological findings: In case of complete tumor regression, the standard chemotherapy was continued. In case of incomplete tumor response, patients received a salvage chemotherapy consisting of three treatments with VP 16 (etoposide), ifosfamide, and cisplatinum. In addition three injections with VP 16 were given as a maintenance therapy. The following results were obtained: YST: 59 patients with stage I. Forty-nine patients were followed according to "wait and see" policy. Eight of these needed a delayed standard chemotherapy. The relapse free survival of all 61 patients in 100%. Median observation time is 49 months. TD: Twenty-five patients had stage I. No chemotherapy was given. The relapse free survival is 100%. Median observation time is 48 months. Malignant teratomas (MTI, MTU, MTT): 8 patients had stage I. Three of these received adjuvant chemotherapy and 5 lymphadenectomy without chemotherapy. All patients survived without relapse. Nine patients had stage II and received standard chemotherapy. Four of these patients had a delayed explorative laparotomy leading to a salvage therapy in two patients. All patients survived relapse free. Two patients had stage III. Of these 1 received standard chemotherapy and is well. One patient suffering from MTU stage IIIA died due to candida septicemia during salvage therapy. Median observation time of the entire group is 60 months.

Antineoplastic Combined Chemotherapy Protocols↗

A general enhancement scheme in heteronuclear multidimensional NMR employing pulsed field gradients.

General pulse sequence elements that achieve sensitivity-enhanced coherence transfer from a heteronucleus to protons of arbitrary multiplicity are introduced. The building blocks are derived from the sensitivity-enhancement scheme introduced by Cavanagh et al. ((1991) J. Magn. Reson., 91, 429-436), which was used in conjunction with gradient coherence selection by Kay et al. ((1992) J. Am. Chem. Soc., 114, 10663-10665), as well as from a multiple-pulse sequence effecting a heteronuclear planar coupling Hamiltonian. The building blocks are incorporated into heteronuclear correlation experiments, in conjunction with coherence selection by the formation of a heteronuclear gradient echo. This allows for efficient water suppression without the need for water presaturation. The methods are demonstrated in HSQC-type experiments on a sample of a decapeptide in H2O. The novel pulse sequence elements can be incorporated into multidimensional experiments.

Amino Acid Sequence↗

Basic experimental studies on corpus cavernosum electromyography and smooth-muscle electromyography of the urinary bladder.

In contrast to the extensive work on in vitro experiments for elucidation of the electrical properties of smooth musculature, the acquisition of knowledge on electrical signal behaviour from smooth-muscle cells in an in vivo situation remains very limited and rare. Smooth-muscle electromyographic recording from the smooth musculature of the genitourinary tract, in particular from the penile cavernous bodies and the urinary bladder, has recently become one of the most interesting issues in both impotence research as well as neurophysiological assessment of the urinary bladder. However, the inadequate available data on corpus cavernosum and EMG recordings remains controversial due to the significant discrepancy between basic physiology of the smooth musculature, technical prerequisites and the expected clinical impact from the smooth-muscle EMG of genitourinary organs. This article is an attempt to describe the fundamentals of smooth-muscle EMG signal behaviour and the technical prerequisites for data acquisition and analysis of electrical activity from smooth-muscle cells of the cavernous bodies and urinary bladder. A description is given of the technical aspects, including methodology and interpretation of the recorded data, and also of the possible interference by artefacts (endogeneous and exogeneous) that might limit the clinical relevance of this encouraging method. The advantages, pitfalls and limitations of online analogous data registration and the possibility of computer-assisted smooth-muscle electrical activity recording and analysis are demonstrated by basic in vivo studies on cavernous bodies and also the detrusor muscle.

Animals↗

Calcitonin gene-related peptide (CGRP) in the nipple of the rat mammary gland.

The distribution of nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) was investigated by immunohistochemistry in nipples and mammary glands from lactating and non-lactating rats and compared to the immunoreactivity of other neuropeptides including substance P (SP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM). The study revealed an extensive innervation of the mammary nipples, in which CGRP-immunoreactive (IR) nerve fibres were abundantly present in the epidermis, dermal connective tissue and intralobular connective tissue of the mammary gland parenchyma. Several of the dermal CGRP-IR fibres seemed to follow blood vessels, or formed "ringlet-like" structures. The latter were mostly observed in the dermal connective tissue of the nipple from the lactating rat and may have a mechanoreceptive function, e.g. for the suckling stimuli. The location of SP-IR appeared to be comparable to CGRP-IR, but in fewer fibres. Dense NPY-IR networks of nerve fibres were closely associated with the fascicles of smooth musculature in the core of the nipple base. In contrast, VIP-IR fibres were only sparsely present, and SOM-IR was not detected in the mammary nipples. The immunoreactive content of CGRP and SP was determined by radioimmunoassays. The total amount of immunoreactive CGRP was significantly higher in the nipples from the pregnant and the lactating rats when compared to SP. The maximum concentration of CGRP (65.9 +/- 4.0 pmol/g) measured in the nipples of the pregnant (day 10) rats exceeded almost ninefold the maximum concentration of SP (7.7 +/- 2.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cosmic dosimetry using TLD aboard spacecrafts of the "Cosmos" series.

Thermoluminescent (TL) detectors were used for dosimetric investigations on the outer surface as well as inside Soviet spacecrafts of the "Cosmos" series. At the outer surface, ultrathin TL detectors, based on CaF2-PTFE and LiF, were arranged in special stacks and exposed to unshielded cosmic radiation. The strong decrease of dose within a few mg/cm2 demonstrates that weakly penetrating radiation is dominating in the radiation field under investigation. On the basis of glow curve analysis of LiF thermoluminescent detectors it could be shown, that the high doses are caused by electrons.

Cosmic Radiation↗

Investigation of the low-energy component of primary cosmic radiation on the outside of spacecrafts.

We have developed a method to investigate the low-energy radiation environment on the outside of spacecrafts. Thereby, ultra-thin thermoluminescent (TL) detectors on the base of CaF2:Mn-PTFE are arranged in stacks and exposed to the unshielded cosmic radiation. The dose distribution within a stack is determined by successive evaluation of the thin TL sheets. The analysis of LiF thermoluminescent detector glow curves permits conclusions on the dose contribution caused by either low-energy electrons or by protons. The method was applied aboard Russian COSMOS spacecrafts as well as the MIR station. It was shown that along low-earth orbits dose rates up to 10 Gy/day within the first few mg/cm2 are typical, mainly as a result of the electron impact.

Cosmic Radiation↗

In-situ hybridization for demonstration of equine herpesvirus type 1 DNA in paraffin wax-embedded tissues and its use in horses with disseminated necrotizing myeloencephalitis.

The detection of equine herpesvirus type 1 (EHV-1) in infected cell cultures, and in tissues taken at necropsy, by the in-situ hybridization technique is described. A 4.9 kb Bam HI fragment of EHV-1 vaccine strain RacH was used as a probe after labelling with [alpha-32P] thymidine 5'-triphosphate ([32P]TTP) or digoxigenin-deoxyuridine 5'-triphosphate (dUTP). Both probes specifically detected EHV-1 DNA in either cytospin or paraffin wax-embedded preparations of infected cells. The digoxigenin-labelled probe was further used to examine tissue sections of equine fetuses which had been aborted due to EHV-1 infection. In all cases positive hybridization signals were mainly associated with the nuclei. Positive results were confirmed by immunostaining of EHV-1 antigen in adjacent sections. However, both methods failed to detect EHV-1 in spinal cord sections of six horses suffering from disseminated necrotizing myeloencephalitis (DNM). These results support the hypothesis that DNM is not caused by a productive viral infection of parenchyma of the nervous system but is immunologically mediated.

Animals↗

Clinical in vitro endothelialization of femoropopliteal bypass grafts: an actuarial follow-up over three years.

PURPOSE: The creation of an endothelial coverage on prosthetic vascular surfaces may improve the performance of synthetic small diameter vascular grafts. In vitro lining with cultured autologous endothelial cells offers a confluent endothelium at the time of implantation. METHODS: Between June 1989 and December 1991, 49 patients who had no saphenous vein available entered the study. Indication for operation was disabling claudication in 37 patients and critical ischemia in 12 patients. With a random 1:2 assignment, 33 patients were admitted to the endothelialized group and 16 control patients received an untreated polytetrafluoroethylene prosthesis. Cultured autologous endothelial cells from the external jugular vein were confluently lined onto polytetrafluoroethylene grafts precoated with fibrinolytically inhibited fibrin glue. The follow-up was based on angiography, platelet labeling studies with indium 111-labeled oxine, assessment of the ankle-brachial index, and duplex sonography. RESULTS: First-passage mass cultures of 16 million endothelial cells-required for the confluent lining of a 70 cm long 6 mm graft-were reached 25.1 +/- 11.2 days after vein excision. Growth failure occurred in 27.3%. After 32 months, the actuarial patency was 84.7% for endothelialized grafts and 55.4% for control grafts (p < 0.041 by Breslow test; p < 0.068 by Mantel-Cox test). The ankle-brachial index was continually diverging, reaching significantly lower values in the control group at 24 months (0.98 +/- 0.14 in the endothelialized group versus 0.70 +/- 0.12 in the control; p < 0.0023). The uptake of indium 111-labeled platelets--measured at 9 days, 3 months, 6 months, and 12 months--was significantly lower in the endothelialized group during the entire observation period.

Actuarial Analysis↗

Antegrade-retrograde urethrotomy for treatment of severe strictures of the urethra: experience and literature review.

In cases of urethral stricture that are nonpassable when using conventional internal urethrotomy, open urethroplasty can be avoided by performing combined antegrade-retrograde urethrotomy (ARUT). A rigid cystoscope is guided through a dilated suprapubic cystostomy channel toward the stricture in the membranous or bulbar urethra. A urethrotome is inserted in retrograde fashion, and the "cut to the light" procedure is performed. Using the ARUT method, realignment was achieved in nine patients; four of whom had strictures induced by trauma or urethritis and five of which were the result of previous transurethral management. Recurrent stricture in four of seven cases necessitated further urethrotomy. There was no recurrence in five of seven patients for at least 5 months subsequent to the last treatment. All patients were spared open surgery. The antegrade-retrograde technique was described in 1978, but to date, only 70 cases have been reported in the literature. The primary success rate is 25%. Successful retreatment following recurrence was observed in 65%. We recommend ARUT as a first-choice treatment for severe strictures of the bulbar and membranous urethra.

Adult↗

Changing indications for penetrating keratoplasty.

The indications for penetrating keratoplasty have changed over the past several years. One hundred and eighty cases of penetrating keratoplasty performed in the Department of Ophthalmology, Naestved Centralsygehus, Denmark, from January 1984 to December 1993, were analysed. Overall pseudophakic bullous keratopathy was the most common indication for penetrating keratoplasty (28.3%). This was followed by keratitis (13.9%), Fuchs' dystrophy (13.9%), regraft (11.1%), aphakic bullous keratopathy (10.0%) and keratoconus (6.7%). Pseudophakic bullous keratopathy was the most common indication for penetrating keratoplasty in 1989 and in each year from 1991 to 1993. Before 1989 the most common indications were keratitis (18.0%) and aphakic bullous keratopathy (14.8%). The emergence of pseudophakic bullous keratopathy, as the most common indication for penetrating keratoplasty, correlates well with the dramatic increase in the number of cataract extractions with intraocular lens implantation performed since the early 1980s. Especially semiflexible, closed-loop anterior chamber lenses used in our department in the early years of the period, have been the cause of subsequent corneal edema.

Adolescent↗

Role of nitric oxide in neurally induced pancreatic exocrine secretion in pigs.

Formation of NO, enzymatically catalyzed by NO synthases in both endothelial cells and autonomic nerves, seems to explain some noncholinergic nonadrenergic tissue reactions. We studied the possible role of NO in vagally induced pancreatic exocrine secretion using isolated perfused porcine pancreas (n = 11) with intact vagus nerve (VN) supply. Electrical stimulation of the VN (8 Hz, 10 mA) and infusions of vasoactive intestinal polypeptide (VIP, 2 x 10(-9) M) were carried out before and after addition to the perfusate of the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or NG-nitro-L-arginine (L-NNA, 10(-5) M) with and without further addition of L-arginine (10(-3) M). We also studied the effects of L-arginine alone and of sodium nitroprusside (10(-4) M). In all experiments VN and VIP caused a profuse exocrine secretion (43 +/- 7 and 44 +/- 11 times basal secretion). The inhibitors increased vascular resistance approximately twofold but had no effect on the vascular relaxation caused by VIP and VN. The exocrine fluid response to VN was reduced to 19 +/- 5 and 4.7 +/- 1.8% (L-NAME and L-NNA), and response to VIP was reduced to 54 +/- 12 and 35 +/- 13%. Protein and bicarbonate outputs largely paralleled flow rate. Addition of L-arginine (no effects alone) to L-NAME restored the responses to VN (to 100 +/- 21% of controls) and increased VIP responses (to 65 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelin-1 potentiates ADP-induced platelet aggregation in chronic renal failure.

The effect of preincubation of heparinized whole blood with endothelin-1 (ET-1) on the ADP (adenosine diphosphate) and epinephrine-induced platelet aggregation was examined in 20 healthy donors compared with 20 patients with chronic renal failure (CRF). ET-1 significantly stimulated ADP-induced aggregation in CRF: EC (effective concentration)25 = 2.3 +/- 0.20 with ET-1 vs. 2.7 +/- 0.22 mumol/L without ET-1; EC50: 3.8 +/- 0.18 with ET-1 vs. 4.4 +/- 0.24 mumol/L without ET-1; and EC75: 5.7 +/- 0.22 with ET-1 vs. 6.4 +/- 0.21 mumol/L without ET-1). In healthy donors only the EC25 was significantly increased: EC25 = 2.5 +/- 0.13 with ET-1 vs. 2.8 +/- 0.20 mumol/L without ET-1. No significant influence of ET-1 in epinephrine-induced aggregation was observed in CRF or in healthy donors. The basal values of determined ET-1 were significantly elevated in CRF: 6.99 +/- 0.29 pmol/mL vs. 5.65 +/- 0.33 pmol/mL in healthy donors. The high endogenous level of ET-1 in CRF patients together with an observed higher endogenous plasma level of cAMP (58 +/- 5.2 nmol/L compared to 29 +/- 2.0 nmol/L in healthy donors) may explain the enhanced pharmacological interaction of ET-1 and ADP in CRF patients. The data suggest that positive agonist interaction between ET-1 and ADP may result from effects on the concentrations of cAMP within the platelet rather than from direct interaction on the membrane receptors or the transmembrane coupling mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Highly sensitive northern hybridization of rare mRNA using a positively charged nylon membrane.

The effect of different RNA fixation methods using Hybond-N and Hybond-N+ nylon membranes in Northern blot experiments was analyzed with human glyceraldehyde-3-phosphate dehydrogenase and human interleukin-3 receptor alpha-subunit as radioactive labeled DNA probes. Highest sensitivity could be achieved by mild alkaline fixation of RNA to positively charged Hybond-N+ nylon membrane. Fixation by UV light resulted in reduced sensitivity in comparison with alkaline treatment. Fixation of RNA to Hybond-N or -N+ membranes by baking for 2 h at 80 degrees C resulted in a strong decrease in sensitivity and should be avoided when using modified nylon membranes in Northern hybridizations.

Blotting, Northern↗

[Inheritance of notched ears in Highland cattle].

The present study describes an anomaly of the pinna of the ear and its distribution in Highland Cattle. The investigation is based on a questionnaire survey in farms in Bavaria keeping robust breeds and on registering data in 15 selected farms. In the year 1991, there were registered 548 Highland stud book cows in 108 farms. In four herds animals of the breed Highland Cattle were observed which showed crop ears. Always both ears were affected and this ear defect could be already observed in newborn calves. Crop ears appeared in very different forms. In some cases only small changes of the external ear could be recognized, in more severe cases, grooves in the external ear could be found and in the most severe case, the external ear was totally deformed and drastically reduced in size. In one herd, 45 animals out of the progeny of 46 of one affected breeding bull showed crop ears. The pedigrees indicated that this defect of the ear pinna is inherited and a single autosomal gene with nearly additive (incomplete dominant) action may be involved. Homozygote recessive animals are free from crop ears, animals homozygote for the mutated allele carry totally deformed external ears and heterozygote animals do not show as severe forms of crop ears as homozygote ones.

Animals↗

[Two traffic accidents after heroin consumption with fatal outcome].

We report on 2 road accidents where 4 people--drivers and front-seat passengers--were injured so badly that they consequently died. All four had consumed heroin, in addition to which both passengers had also consumed cocaine and dihydrocodeine respectively. The blood samples of one of the drivers was only taken after the onset of intensive medical treatment including infusions and transfusions. Nevertheless the result of the analysis clearly showed that the driving ability had been impaired by heroin. In the remaining cases the opiat concentrations were so high that they could have justified a fatal intoxication in themselves. This applies especially to one of the passengers who displayed an unconjugated morphine blood concentration of 0.96 m/l. However, also in this case at the time of the accident the blood circulation and heartbeat did not stop immediately.

Accidents, Traffic↗