Biomedical subjects
P Schmidt
Publications and source records attributed to P Schmidt.
Detection of deep venous thrombi and pulmonary embolus with technetium-99m-DD-3B6/22 anti-fibrin monoclonal antibody Fab' fragment.
UNLABELLED: Technetium-99m-labeled anti-fibrin DD-3B6/22 Fab' monoclonal antibody fragments, which specifically target human cross-linked fibrin with high affinity, were evaluated in humans for safety and their capacity to detect deep vein thrombi and pulmonary embolism. METHODS: Twenty patients with proven deep-vein thrombosis, documented by contrast venography, or venous duplex scan, were injected with a 600 MBq (0.5 mg) dose of antibody. Planar images of the lower limbs were recorded at 0, 2, 6 and 24 hr and chest scintigrams were recorded at 6 and 24 hr. RESULTS: All venography documented thrombus sites, calves, popliteal and femoral, were detected with the radioimmunoconjugate. For the venous duplex scan-proven thrombus sites, all except two calf thrombi in two patients with bilateral disease and other positive sites were detected. Five patients had bilateral deep-vein thrombosis with multiple sites being visualized with the radioimmunoconjugate in the calf, popliteal and femoral regions. One case of pulmonary embolus was also definitively demonstrated. Documented thrombus sites were detected at 2 and 6 hr postinjection. Nineteen patients were on heparin. No adverse reactions to the injected dose were observed and one low titer human anti-mouse antibody response may have occurred. CONCLUSION: The results indicate that 99mTc-DD-3B6/22 Fab' has potential for noninvasive detection of deep-vein thrombosis and pulmonary embolism.
Indications for a central innervation of the bovine pineal gland with substance P-immunoreactive nerve fibers.
An antiserum, raised in rabbits, against substance P was used in an immunohistochemical investigation of the bovine pineal gland. A moderate innervation of all parts of the bovine pineal gland with substance P-immunoreactive nerve fibers was demonstrated. The immunoreactive nerve fibers were located throughout the pineal gland, both perivascularly, intraparenchymally, and with few fibers in the pineal capsule. Within the habenular nucleus, a large number of substance substance P-immunoreactive perikarya were present. From these perikarya processes extended towards the pineal stalk and gland. Some substance P-immunoreactive nerve fibers were located in the stria medullaris and in the posterior commissure. The anatomical location of the substance P-immunoreactive nerve fibers in the pineal gland and stalk strongly indicates that, in this species, substance P-immunoreactive pinealopetal nerve fibers originate from perikarya in the brain, probably from the medial habenular nucleus.
Microsatellite and HLA class II oligonucleotide typing in a population of Yanomami Indians.
We have used three different microsatellites (on chromosome 12 and Y) together with HLA class II oligonucleotide typing (DQA and DQB) to analyze families of Yanomami indians settling in villages in Southern Venezuela. There exist complex networks of biological relationship between villages as a result of wife exchange, village fissioning and changing patterns of alliances associated with inter-village warfare. Social status in this society is largely determined by the kinship system. Polygyny is common, especially among headmen, with additional wives, frequently being chosen among the sisters of the first wife. Our preliminary results mainly obtained from inhabitants of the village HAP show the expected allele distribution in populations with a high degree of consanguinity: (i) deficiency of observed heterozygotes at the autosomal loci and (ii) almost all men carry the same Y chromosomal allele. Nevertheless in the Yanomami village two thirds of the described autosomal microsatellite alleles were identified. Several paternities were clarified.
Effect of intestinal inhibitory peptides on vagally induced secretion from isolated perfused porcine pancreas.
Several gastrointestinal peptides inhibit pancreatic secretion in intact animals, but fail to do so in isolated pancreas preparations. Using isolated perfused porcine pancreas with intact innervation, we studied the influence of such peptides (somatostatin, peptide YY, glucagon-like peptide-1, oxyntomodulin, neuropeptide Y, galanin, and calcitonin gene-related peptide) on vagally induced secretion and on release of vasoactive intestinal polypeptide (VIP), a neuropeptide involved in fluid and bicarbonate secretion. In control experiments electrical vagus stimulation increased flow of juice from 0.9 +/- 0.1 to 37.3 +/- 5.6 ml/h and protein output from 43 +/- 5 to 1,244 +/- 336 mg/h (mean +/- SD). With somatostatin-14 at 10(-10) mol/L, the fluid response was reduced to 64 +/- 11% of controls, protein concentration to 78 +/- 3.8%, and protein output to 50 +/- 5% (p < 0.05). At 10(-8) M the response was almost abolished. VIP release, which in control experiments increased from 0.2 +/- 0.05 to 2.1 +/- 0.4 pmol/min, was similarly reduced (p < 0.01). Galanin at 10(-8) M inhibited the fluid response to 54 +/- 7% of controls, protein output to 51.7 +/- 11%, and VIP release to 54 +/- 6% (p < 0.01). None of the other inhibitory peptides affected vagus responses. It is concluded that somatostatin and galanin inhibit pancreatic secretion through interaction with intrapancreatic ganglia. The other peptides act on extrapancreatic, possibly central sites.
Spinal dysmyelination in new-born brown Swiss x Braunvieh calves.
In four new-born Braunvieh calves suffering from connate recumbency and body tremor, a hitherto not described myelination disorder of the spinal cord was examined. Bilateral symmetric hypo- as well as demyelination in several spinal tracts were the most conspicuous findings, affecting the ascending gracile funiculus, the ascending dorsolateral spinocerebellar tract, and the mainly descending sulcomarginal tract. Deficient myelin production, loss of myelin, consecutive axonal degenerations, and prominent astrogliosis within these tracts were the histological hallmarks of the disease. This possibly inherited primary myelination disorder of the spinal cord differs markedly from known hereditary neurological diseases in Brown Swiss and Braunvieh cattle, respectively, i.e. the weaver-syndrome and the spinal muscular atrophy.
Chicken egg antibodies for immunohistochemical labeling of growth hormone and prolactin in bovine pituitary gland.
We describe the production of polyclonal chicken antibodies specific for bovine growth hormone (bGH) and prolactin (PRL). Antibodies were generated by immunization of laying hens with recombinant bGH (rbGH), pituitary derived bGH (pbGH), and ovine PRL (oPRL). After the lipoprotein fraction was removed by dextran sulfate precipitation the antibodies were isolated from the egg yolks by ammonium sulfate precipitation. Immunization with rbGH and oPRL generated large amounts of specific antibodies, as revealed by ELISA and Western blot analysis. Antibodies against pbGH showed pronounced crossreactions with oPRL. The antibodies against rbGH and oPRL were well suited for sensitive and specific labeling of the GH- and PRL-synthesizing cells in bovine pituitary glands by immunohistochemistry. In addition, a quick and sensitive procedure for demonstration of both bGH- and PRL-synthesizing cells in a single paraffin section by double immunohistochemistry is presented. The chicken anti-bGH antibodies showed excellent results in combination with rabbit anti-PRL antibodies. The main advantage of avian antibodies in double immunostaining methods is the lack of crossreactions between avian antibodies and mammalian immunoglobulins and receptors which bind to the crystalline fragment of mammalian immunoglobulins (Fc receptors).
Cerebrovascular changes following administration of gammaglobulins against substance P or calcitonin gene related peptide in monkey with subarachnoid haemorrhage.
Cerebrovascular changes after intrathecal (ith) administration of gammaglobulins against substance P (SP) or calcitonin gene-related peptide (CGRP) were investigated before and following a simulated subarachnoid haemorrhage (SAH) in the squirrel monkey. The SAH was produced by injection of homologous blood into the interpeduncular fossa and the cisterna magna. The gammaglobulins were given both prior to the blood injections and daily in 5 days post-SAH. The effect of the gammaglobulins was examined by angiography pre-SAH and at 10 min and at 6 days post-SAH, i.e. the time points for maximal acute and late spasm in the present model. Cerebral blood flow (CBF) was measured under general anesthesia at day 6 post-SAH with an autoradiographic technique. Five of nine animals treated with CGRP antigammaglobulin died from respiratory failure. Four animals received SP antigammaglobulin and two control animals received normal globulin. SP antigammaglobulin per se had no effect on baseline arterial diameter, while CGRP antigammaglobulin significantly reduced the diameter of the arteries. SP antigammaglobulin prevented the occurrence of acute spasm and significantly reduced the degree of late spasm. Moreover, the reduction in CBF noted in the control SAH animals was significantly reduced. In contrast, CGRP antigammaglobulin treatment had no effect on the degree of spasm and did not cause any change in CBF as compared to controls. The finding that CGRP but not SP antigammaglobulin significantly reduces the arterial diameter in conjunction with our previous demonstration that a post-, but not preganglionic trigeminal lesion reduces the baseline arterial diameter, indicates that CGRP could be the transmitter involved in a peripheral axon reflex. The function of SP might be as a neurotransmitter conveying information to the brainstem. The transmitter role is supported by the effect of SP antigammaglobulin impairing SP containing neurons and, in that way, mimicking a bilateral trigeminal rhizotomy.
Non-endemic Burkitt's lymphoma in a patient with Bloom's syndrome.
Bloom's syndrome is an autosomal recessive disorder characterized by intrauterine growth retardation, typical physical signs, immunodeficiency and an increased risk of developing neoplasms at a young age, compared to the general population. Factors possibly involved in the pathogenesis of non-endemic Burkitt's lymphoma in a five year old girl with Bloom's syndrome are discussed. These include immunodeficiency, upregulated c-myc expression and an Epstein-Barr viral infection.
[Antegrade-retrograde urethrotomy in therapy of high degree urethral stricture].
In the case of urethral stricture which is non-passable by conventional "cold knife" urethrotomy, open urethroplasty can be avoided by combined antegrade-retrograde urethrotomy (ARUT). A rigid cystoscope is guided, through a dilated, suprapubic cystostomy channel, to the stricture in the membranous or bulbular urethra. A urethrotome is inserted in the retrograde direction and the "cut to the light" procedure is adopted. Using the ARUT method, successful realignment was achieved in 9 patients; 4 strictures were trauma- or urethritis-induced and 5 were the result of transurethral management. Recurrent stricture in 4 out of 7 cases (57%) required further urethrotomy. There was no recurrence in 4 out of 7 patients for at least 5 months subsequent to the last treatment. All patients were spared open surgery. The antegrade-retrograde technique exists since 1978. Up to date, 63 cases have been mentioned in the literature. The primary therapy success rate is 25%. Successful retreatment following recurrence was observed in 65%. We recommend ARUT as first-choice treatment for severe strictures of the bulbular and membranous urethra.
[Interpretation of blood gas analyses].
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[Environmental medicine group diagnosis of children--studies from 1982 to 1990. Review].
In the period of 1982-1990 a total of 5760 children (2893 boys, 2816 girls) were examined in the frame-work of the Clean Air Programme Rhine-Main: from the polluted Rhine-Main area 2511 children (Wiesbaden 1682, Frankfurt since 1985, 825), from the control areas 3153 children (Freiburg area 1937, Starnberg area 1316). Healthy children living in the industrialised Rhine-Main area exhibited alterations of the following parameters compared with healthy children living in the less polluted control areas: Long-term alterations, enlarged and fissured, rough palatine tonsils, palpably enlarged cervical and mandibular lymph nodes, Short-term alterations, erythrocyte count: from 1981-1988 relatively smaller numbers, from 1988-1990 equalized to the scatter range of controls, hemoglobin values: corresponding to erythrocyte counts, activity of lymphocyte nucleoli: increased until 1985, later on equalized, lymphocyte count: reduced, T8-suppressor cell count: decreased, chemiluminescence of granulocytes: increased, palatine tonsils: altered microbial contamination with contact germs, altered physiological resident flora, heavy metals (Pb, Cd) in hair: from 1982-1990 increased, then slowly reduced corresponding to the results of the ambient air analyses. These findings indicate an increased inclination for reaction of the healthy juvenile organism in the sense of biological adaptation to long-term stress, i.e. living for years in an area with air pollution, and are also in good agreement with the measuring values characterising the ambient air quality.
[Inservice training: resuscitation. Planning and execution of seminars].
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Nervous control of the release of substance P and neurokinin A from the isolated perfused porcine ileum.
Using isolated perfused porcine ileum we studied the release of substance P (SP) and neurokinin A (NKA) in response to electrical stimulation of the mixed periarterial nerves and to infusion of different neuroactive agents. Nerve stimulation (8 Hz) had no significant effect on the release of SP and NKA. Nerve stimulation also had no effect on the release of SP and NKA during infusion of atropine (10(-6) M) or phentolamine (10(-5) M), whereas a significant increase (from 8.2 +/- 1.9 to 20.1 +/- 4.6 pmol/l for SP and from 12.3 +/- 2.7 to 34.2 +/- 7.7 pmol/l for NKA, n = 7) was observed during nerve stimulation after pretreatment with both atropine and phentolamine. This increase was abolished by hexamethonium (3 x 10(-5) M). Also acetylcholine infusion causes a significant release of SP and NKA after infusion of both atropine and phentolamine (to 172 +/- 56% and 232 +/- 69% of basal release, n = 7), an effect that was abolished by hexamethonium infusion. Infusion of atropine alone increased the release of SP and NKA significantly (to 337 +/- 92% and 386 +/- 124% of basal output, n = 5). Norepinephrine (10(-6) M) inhibited the release of SP and NKA (to 69 +/- 6% and 80 +/- 6% of basal release, n = 7). Our results suggest that the SP- and NKA-producing neurons receive intrinsic tonic muscarinic inhibitory impulses, extrinsic nicotinic excitatory impulses, and extrinsic adrenergic inhibitory impulses.
Isolation of cold agglutinins in Eperythrozoon suis-infected pigs.
A simple and reliable procedure is described for isolating the cold agglutinins associated with Eperythrozoon suis-infection in swine. After initiating microagglutination by cooling the blood samples, the erythrocytes were separated by density-gradient centrifugation using Ficoll-Paque, resuspended in RPMI-medium and warmed to 40 degrees C. The cold agglutinins could be removed from the supernatant by a subsequent centrifugation. Double immunodiffusion, polyacrylamide gel electrophoresis and immunoblotting showed that the cold agglutinins isolated consisted of IgM antibodies exclusively. Their ability to induce agglutination in cooled erythrocytes from healthy pigs confirmed that they were genuine cold agglutinins. The method paves the way for more detailed investigation into the mechanisms of this agglutinating disease.
On the potential of simple repetitive DNA for fingerprinting in clinical, forensic, and evolutionary dynamic studies.
The purpose of this review is to discuss critically the practical meaning of a specific genome component, simple repetitive desoxyribonucleic acid (DNA) sequences as clinical and forensic and diagnostic and research tools. Previously, multilocus DNA fingerprinting was the major technology employed to visualize such simple repeat sequences. This technique enables many polymorphic loci to be simultaneously detected thus yielding vast amounts of information. With the advent of enzymatic DNA amplification via the polymerase chain reaction (PCR), individual simple repeat loci can be demonstrated, theoretically even from single DNA molecules and so a wealth of additional approaches have also become feasible. In general investigating, small, known, single copy parts of genomes have not posed truly insurmountable problems if enough material was available. There have even been a few (anecdotal) reports on the amplification of simple repeats from ancient DNA (see, e.g. [30]. Here we would like to after a solid basis for an earnest discussion of the applications of these simple repetitive sequences using various methodological approaches relevant for clinical diagnosis, setting aside the obvious unsolved mysteries of their biology.
Non-vasopressinergic, non-oxytocinergic neuropeptides in the rat hypothalamo-neurohypophyseal tract: experimental immunohistochemical studies.
The hypothalamo-neurohypophyseal tract is known to contain the classical neurohypophyseal hormones vasopressin and oxytocin. Additionally, dynorphin, methionine- and leucine-enkephalin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), and galanin are co-stored with vasopressin and/or oxytocin. Recent immunohistochemical studies have revealed the existence of a low to moderate number of substance P-, vasoactive intestinal peptide (VIP)-, neuropeptide Y (NPY)- and somatostatin-immunoreactive nerve fibers within the rat neurohypophysis. VIP-, substance P- and NPY-immunoreactive fibers were distributed throughout the organ, whereas somatostatin-immunoreactive fibers were present in the proximal part of the organ. The positive nerve endings were either large in size resembling classical nerve terminals related to perivascular spaces, or smaller similar to peptidergic fibers as described in the CNS. These results indicate that these neuropeptides may be either co-stored with the classical neurohypophyseal hormones or contained in another system of afferents to the organ. The probably distinct functional roles of these neuropeptides in the physiology of the neurohypophysis are discussed.
Somatostatin restraint of gastrin secretion in pigs revealed by monoclonal antibody immunoneutralization.
We studied the functional coupling between antral somatostatin and gastrin cells in isolated perfused porcine antrum using immunoneutralization with monoclonal antibodies against somatostatin. Their binding affinity was 10(11) l/mol, and the final binding capacity was 11.7 nmol/ml. Antibody infusion within 1 min increased gastrin secretion, reaching a rate of 349 +/- 64% (means +/- SE, n = 7) of basal secretion (59 +/- 5 pmol/l) after 5 min. The effect of somatostatin at 10(-9) mol/l, which inhibited gastrin secretion from 58 +/- 11 to 14 +/- 3 pmol/min (n = 4), was abolished by antibody infusion. Electrical stimulation of the vagus nerves (n = 7) performed during antibody infusion increased gastrin secretion from 224 +/- 61 to 328 +/- 55 pmol/min, not significantly different from the increase in control experiments from 43 +/- 9 to 118 +/- 20 pmol/min, indicating that the vagal stimulation of gastrin secretion does not depend on mechanisms involving somatostatin. We conclude that paracrine antral somatostatin secretion is one of the most important factors regulating basal gastrin secretion in pigs.