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Biomedical subjects

G Schmidt

Publications and source records attributed to G Schmidt.

At least 343 records · Page 19Linked to original sources

Isolation and characterization of coliphage omega 18A specific for Escherichia coli O18ac strains.

The bacteriophage omega 18A, specific for Escherichia coli O18ac strains, was isolated from sewage. The results of host range and conjugation experiments showed that the sensitivity of bacteria to the phage is associated with the presence of O18ac antigens. With some of the O18 strains the phage omega 18A produces clear lysis on bacterial lawns only when applied at a high multiplicity and moreover the phage does not multiply. With the help of the phage omega 18A, E. coli O18ac strains could be divided into two serologically distinct subgroups called O18A and O18A1. E. coli strains belonging to the subgroup O18A are sensitive to phage omega 18A whereas bacteria of subgroup A1 are resistant.

Antigens, Bacterial↗

Tricyclic compounds as selective antimuscarinics. 1. Structural requirements for selectivity toward the muscarinic acetylcholine receptor in a series of pirenzepine and imipramine analogues.

The M1-selective antiulcer drug pirenzepine (1) is a tricyclic compound with close resemblance to tricyclic psychotropic agents such as imipramine (2). Despite this fact, pirenzepine is devoid of any psychotropic effects, exhibiting measurable antagonistic effects in biochemical assays and receptor binding studies only toward the muscarinic receptor system. To understand how different groups in these tricyclic molecules affect binding affinities, a set of nine compounds structurally related to pirenzepine (1) and imipramine (2) has been selected for analysis, comprising three different tricycles and three different side chains. The compounds were tested for their affinity to the imipramine and muscarinic receptors in homogenized rat cortex tissue. The result of these studies suggests that it is the nature and placement of accessory groups that determine the differences in receptor recognition and the binding process. In the case of pirenzepine (1), preferential binding toward the muscarinic receptor is brought about by the endocyclic amide group, by the positioning of the protonated N atom of the side chain, and to a minor extent by the exocyclic amide group. From these findings a putative model for the explanation of selective binding of pirenzepine (1) to the muscarinic receptor has been derived.

Animals↗

Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies.

The detection of early micrometastasis or disseminated single tumor cells poses a problem for conventional diagnosis procedures. Using a panel of monoclonal antibodies against cytokeratin and the 17-1A epithelial antigen we identified immunocytochemically tumor cells in bone marrow of patients with breast cancer (n = 155) and colorectal cancer (n = 57) at the time of surgery of the primary tumor. Monoclonal antibody CK2, recognizing the human cytokeratin component 18 in simple epithelia, appeared to be the most suitable reagent because of its negative reaction with bone marrow samples of the noncarcinoma patients (n = 75). Its specificity was further demonstrated in a double-marker staining procedure using an anti-leukocyte common antigen monoclonal antibody (T200) as counterstain. A comparative analysis showed that immunocytology was clearly superior to conventional cytology (n = 212) and histology (n = 39). In 9.5-20.5% of patients without distant metastasis, tumor cells could be detected in bone marrow. We found a significant correlation between tumor cells in bone marrow and conventional risk factors, such as distant metastasis or lymph node involvement. In a first approach toward immunotherapy we demonstrated in 3 patients that infused monoclonal antibody 17-1A can label single tumor cells in bone marrow in vivo. We then used this approach to follow up 7 patients undergoing 17-1A therapy in an adjuvant clinical trial.

Antibodies, Monoclonal↗

Interaction of small dermatan sulfate proteoglycan from fibroblasts with fibronectin.

Immunogold labeling was used to localize the core protein of small dermatan sulfate proteoglycan (DS-PG) on the surface of cultured human fibroblasts. At 4 degrees C, DS-PG core protein was uniformly distributed over the cell surface. At 37 degrees C, gold particles either became rearranged in form of clusters or remained associated with fibrils. Double-label immunocytochemistry indicated the co-distribution of DS-PG core protein and fibronectin in the fibrils. In an enzyme-linked immunosorbent assay, binding of DS-PG from fibroblast secretions and of its core protein to fibronectin occurred at pH 7.4 and at physiological ionic strength. Larger amounts of core protein than of intact proteoglycan could be bound. Fibronectin peptides containing either the heparin-binding domain near the COOH-terminal end or the heparin-binding NH2 terminus were the only fragments interacting with DS-PG and core protein. Competition and replacement experiments with heparin and dermatan sulfate suggested the existence of adjacent binding sites for heparin and DS-PG core protein. It is hypothesized that heparan sulfate proteoglycans and DS-PG may competitively interact with fibronectin.

Cell Membrane↗

Magnetic resonance imaging in evaluating focal liver lesions.

We report the results of magnetic resonance imaging (MRI) of the liver in 46 patients with various previously confirmed focal lesions. A characteristic signal pattern was found in hemangiomas (n = 11), with marked signal hyperintensity on T2 and proton weighted images as compared to normal liver tissue. Cysts (n = 7) also showed marked hyperintensity on T2 images, but could easily be differentiated by a lesser intensity on proton weighted images and signal hypointensity on T1 weighted images. Primary liver tumors (n = 4), metastatic liver disease (n = 18), focal nodular hyperplasia (n = 5), and liver adenoma (n = 1) revealed a weak signal hyperintensity on T2 images, with varying signals in T1 and proton weighted modalities. These data combined with other recent communications in the literature indicate that MRI is a promising diagnostic technique in the detection of focal liver lesions and that it may offer a high degree of specificity in the diagnosis of hepatic hemangiomas and benign cysts.

Cysts↗

GABA suppresses stimulation-induced release of [3H]-noradrenaline from sympathetic nerve fibres in bovine ovarian follicles.

1 Strips from the bovine ovarian follicle wall were incubated in Krebs-Ringer solution containing [3H]-noradrenaline in order to saturate sympathetic nerve fibres with radiolabelled transmitter. This allowed the study of field stimulation-evoked transmitter release. 80.3 +/- 3.9% of the tritium released upon stimulation (10 Hz, pulse duration 1 ms, 10 V between the electrodes) was noradrenaline. 2 The stimulated release of tritium was totally blocked in calcium-free, EGTA (1 mM) containing medium or by 1 microM tetrodotoxin. Chemical sympathectomy (6-hydroxydopamine treatment) in vitro reduced the tritium content of the strip by 85%. The neuronal amine uptake blocker desipramine (0.6 microM) was almost equally effective in inhibiting the incorporation of tritium. The extraneuronal amine uptake blocker normetanephrine (10 microM) reduced the tritium content by 30%. Together, the results suggest that the electrically evoked release of tritium reflects the release of [3H]-noradrenaline from sympathetic nerve fibres. 3 gamma-Aminobutyric acid (GABA) concentration-dependently reduced the electrically evoked tritium release. Also the GABAB-receptor agonist baclofen (30 microM) reduced the stimulated tritium release whereas muscimol (100 microM), a GABAA-receptor agonist, failed to affect the release. 4 The selective GABAA-receptor antagonist bicuculline (3 and 100 microM) did not block the effect of GABA, while 3-amino-1-propanesulphonic acid (3-APA), a blocker of GABAB-receptors reversed the inhibitory effect of GABA. The results suggest that neuronal GABAB-receptors are involved in the GABA-evoked suppression of stimulated noradrenaline release.

Animals↗

Characterization of presynaptic 5-HT receptors on adrenergic nerves supplying the bovine ovarian follicle.

1. The effects of 5-hydroxytryptamine (5-HT) on contraction and release of [3H]-noradrenaline were investigated in vitro in bovine ovarian follicle strips. Using available selective agonists and antagonists, an effort was made to characterize the type of receptor mediating the inhibitory effect of 5-HT on neurogenic contraction and release of [3H]-noradrenaline by electrical field stimulation. 2. 5-Hydroxytryptamine inhibited the neurogenic contraction and release of [3H]-noradrenaline evoked by electrical field stimulation in a concentration-dependent manner. Like 5-HT, 5-carboxamidotryptamine (5-CT) and methysergide reduced the transmitter release as well as the neurogenic contraction, whereas 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) failed to inhibit both responses in concentrations up to 0.1 microM. 3. The 5-HT (1 microM)-induced inhibition of contractile responses was more evident during stimulation at low frequencies (4 and 8 Hz) than during high frequency electrical stimulation (16 and 32 Hz). 4. Methiothepin (1 microM) and methysergide (10 microM) significantly antagonized the inhibitory effect of 5-HT on the electrically evoked release of tritium, whereas cyanopindolol, MDL 72222 and ketanserin (all 0.1 microM) were without effect. In addition, ketanserin, MDL 72222, cimetidine, pyrilamine, atropine, propranolol and indomethacin were without effect on the 5-HT-induced inhibition of the neurogenic contraction. 5. It is suggested that 5-HT inhibits the electrically evoked transmitter release from adrenergic nerves in the bovine ovarian follicle wall via prejunctional 5-HT1-like receptors. This was based on the findings that 5-CT was a potent agonist, methiothepin an antagonist and the lack of effect of MDL 72222, cyanopindolol and ketanserin.

Animals↗

Physiological pacing: present status and future developments.

With the increasing tendency to implant pacemakers not only for life-threatening bradycardias but also for improving cardiodynamics in patients with bradycardia, it soon became apparent that classical VVI pacing is not truly able to optimize circulatory performance. Experience has shown that with ventricular pacing augmentation of cardiac output takes place only initially but is not maintained on a long-term basis, exercise capacity remains markedly reduced, there is only an unsatisfactory influence on the degree and course of heart failure and, in an occasional patient, cardiac function may even deteriorate as compared to the situation prior to pacing. Because the disappointing hemodynamic effect of fixed rate ventricular stimulation was at least partly due to the "unphysiological" mode of pacing provided by those systems which fail to restore AV synchrony and to increase heart rate with changing metabolic requirements, so called physiological pacemakers were developed. These pacing systems either maintain AV-synchrony and/or reestablish some way to adapt the pacing rate (Table I). This study delineates the hemodynamics of the paced heart with special reference to the role of AV relationship and rate control; it describes the clinical experience with physiological pacing and provides some ideas leading to present and future developments for rate adaptive pacing systems.

Atrial Fibrillation↗

Densitometric analysis of Western blot (immunoblot) assays for human immunodeficiency virus antibodies and correlation with clinical status.

Western blot assays for antibodies directed against components of human immunodeficiency virus (HIV) associated with acquired immunodeficiency syndrome (AIDS) were examined with a densitometer and integrator. Antibody responses to seven HIV proteins were determined from the areas under the peaks of bands on blots from 430 seropositive individuals. Antibody responses corresponded qualitatively and quantitatively with clinical status. The Western blot assays examined were done on single specimens from individuals in one of four clinical states: asymptomatic with no risk factor identified, asymptomatic with risk factor(s) identified, AIDS-related complex, and AIDS. The ratios of gp41 antibody to p24 antibody and of gp41 antibody to total HIV antibodies increased, and the number of total HIV antibodies decreased progressively in these populations. Parameters were assigned to characterize the typical response found in AIDS: gp41 antibody/p24 antibody ratio, greater than or equal to 2.0; gp41 antibody/total HIV antibodies ratio, greater than or equal to 0.30; and number of total HIV antibodies, less than or equal to 25.0 signal units. Parameter match increased with progression of clinical status. These parameters were applied in a brief follow-up study of 34 HIV-infected asymptomatic individuals who developed AIDS-related complex or AIDS. Initial specimens showed a stronger correlation than our population data base had predicted, suggesting that the parameters have prognostic value. Densitometric analysis of antibody responses on Western blot assays of single or serial specimens should prove useful to physicians in staging and monitoring HIV-infected individuals and in predicting which individuals will progress to AIDS.

AIDS-Related Complex↗

Histamine stimulates progesterone synthesis and cyclic adenosine 3',5'-monophosphate accumulation in isolated preovulatory rat follicles.

The effect of histamine on progesterone synthesis and cyclic adenosine 3',5'-monophosphate (cAMP) accumulation was studied in superfused and incubated follicles dissected free from immature rats treated with pregnant mare serum gonadotrophin (PMSG). Histamine, like LH, increased the progesterone synthesis, but to a smaller extent. The H2-antagonist, cimetidine, inhibited completely the histamine-induced progesterone increase while the H1-antagonist, pyrilamine, as well as propranolol and atropine did not affect the initial response but modified its duration. The specific H2-agonist, 4-methylhistamine, but not the H1-agonist, 2-methylhistamine, mimicked the effect of histamine on progesterone synthesis. In the presence of the phosphodiesterase inhibitor, IBMX, histamine increased tissue levels of cAMP. These results suggest that histamine stimulates progesterone synthesis via the H2-receptor with cAMP acting as secondary intracellular messenger.

1-Methyl-3-isobutylxanthine↗

A simple and reproducible staining procedure to assess characteristic effects of some fixatives.

The standardized Romanowsky-Giemsa-Stain, adapted for use in histology, is recommended as a suitable technique to assess effects of fixatives. The stain consists of two dyes only--Azure B and Eosin Y--but gives a polychrome and reproducible staining pattern. Most important is the colour purple which results from Azure B-Eosin Y molecular interaction. A collection of fixative effects on the RG-staining pattern is given. They are not easily revealed by other equally simple histochemical techniques. Of special interest is the fixative-dependent development of the colour purple on various biological substrates. For instance, both formaldehyde and acrolein allow the generation of this colour on collagen fibers but only after formaldehyde, hardly after acrolein, will the full colour purple appear on chromatin. A list of substrates, RNA among them, is presented which will not stain purple after any of the fixatives employed. The results are briefly discussed.

Animals↗

[Spontaneous variability of ventricular extrasystoles: criteria for validating anti-arrhythmia therapy in relation to the length of the control interval].

Calculations about the variability of PVCs are usually based upon the results of two Holter ECGs, either successive ones or separated by a short interval. No studies are available indicating whether the criteria calculated for short control intervals also holds true when evaluating chronic antiarrhythmic treatment over longer control periods. This study was performed to investigate the influence of the length of the control interval on the spontaneous variability and thus on the reduction of PVCs required to secure an antiarrhythmic effect. In a prospective study, 444 ambulatory ECGs were obtained in 90 patients with CAD or IDC and untreated ventricular arrhythmia of Lown grade IV. Patient follow-up was carried out over an average of 181 +/- 297 days. The degree of arrhythmia was expressed as the mean hourly PVC rate. The variability of PVC counts between two Holter ECGs was defined as the logarithm of the quotient PVCday 2(n + 1)/PVCday 1(n + 1). The spontaneous distribution of variability quotients was defined separately (mean +/- 2 SD) for each of four ranges of control intervals (0-6 days, 7-89 days, 90-364 days, greater than or equal to 365 days). The per cent reduction (R) in PVC frequency necessary to establish drug efficacy, was calculated according to the formula R (%) = 10(0)-10(-2SD) X 100, whereas the percentage change necessary to prove aggravation of arrhythmia (A) was assessed by the formula A (%) = 10(0)+10(+2SD X 100. R increased from 63% (0-6 days), 81% (7-89 days), 93% (90-364 days) to 98% (greater than or equal to 365 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

[Sickle cell disease in the People's Republic of Angola. 1. Epidemiology and clinical aspects].

In a period of 6 years 819 children affected with drepanocytosis (S. E.) were treated at the children's clinic in Luanda. At the time of diagnosis the age of the 457 boys amounted to 3.4 +/- 2.7 years and that of girls to 4.3 +/- 3.4 years. The age distribution shows that 40.2% of the patients were in their first 2 years of life. Conditions of crisis which affected 70% of the diseased children are typical of this disease. The family anemnesis demonstrated that 13.6% of all brothers and sisters covered were HbSS positive. 34.1% of them died at an age of 3.5 +/- 3.5 years (boys) or 2.4 +/- 2.3 years (girls) respectively. The physical development measured in the body mass shows that it is significantly diminished in comparison with healthy children of the same age. The characteristic symptom of this disease, splenomegaly, existed in 27.8% of the children with a mean age of 2.8 +/- 2.3 years. In one age group of 4.4 +/- 2.6 years it could even be identified in 11.3% of the cases.

Anemia, Sickle Cell↗

[Sickle cell disease in the People's Republic of Angola. 2. Behavior of laboratory parameters].

In 819 children the Hb concentration, its dependence on the course of disease, the impact of various crises on Hb values and the behaviour of MCHC were evaluated. In the mean there was an anemia of 4.65 +/- 0.5 Hb mmol/l. In the course of 6 years a significant decline anemia of 4.65 +/- 0.5 Hb mmol/l. In the course of 6 years a significant decline of the Hb concentration could be observed. Only those crises connected with severe clinical symptoms (third degree) coincide with a significant Hb decrease. Every second child with a mean Hb value of 2.3 mml/l was transfused. In nearly half the cases there is a normochromic anemia, in 45.7% a hypochromic one. The mean serum bilirubin concentration lay at 31.6 mumol/l and increased with growing age of disease. The anemia has negative effects on the cardio-circulating system. The thorax-heart quotient shows a positive correlation to the degree of anemia.

Anemia, Sickle Cell↗

[Incidence of B streptococcal diseases and colonization--a clinico-epidemiological study].

The incidence of newborn infections caused by group B streptococci (GBS) has risen significantly in recent years. In 1983 and 1984 ten GBS diseases of the newborns were registered in the Department of Neonatology of the University Hospital (Charité). This is a morbidity of 1.2 per 1,000 live births. Eight infants showed an early onset and 2 a late onset type. Three of the neonates died. These were term infants with a birth weight of more than 2,500 g. The isolated types in these cases were Ia, Ia/c and III. In 1983 and 1984 430 nonselected women between the 34th and 40th weeks of gestation were examined for GBS colonization. One rectal, vaginal and cervical swab was collected from each women and cultured both in a selective broth medium and a selective blood agar plate. The colonization rate was 11.4% in pregnant women. The most frequent colonized region was the rectum, followed by vagina and cervix. Cultures from infants were obtained from throat, left and right ear. 2.7% of the newborns were positive for GBS. The most frequent isolated types are III/R and Ia. In all cases, positive for maternal and neonatal colonization, the isolated types were identical.

Bacteriological Techniques↗

Recurrence of acute lymphoblastic leukemia in donor cells after allogeneic marrow transplantation associated with a deletion of the long arm of chromosome 6.

This report concerns a woman who experienced a relapse of acute lymphoblastic leukemia (ALL) associated with an interstitial deletion of the long arm of chromosome 6 in donor cells more than 4 years after allogeneic bone marrow transplantation (BMT). Direct bone marrow preparations revealed the presence of two leukemic clones 46,XY,del(6)(q23q25) and 45,X,-4,del(6)(q23q25),+8,-15,-21,+i(21q), +mar, the former clearly indicating that male donor cells were involved in the malignant process. Relapse as evidenced by these chromosome anomalies was confined to metaphases from directly prepared marrow cells and phytohemagglutinin (PHA)-stimulated peripheral blood cells. Cytogenetic analyses of T cell colonies gave predominantly normal donor karyotypes (65 of 69 mitoses) along with three host mitoses and a single donor metaphase carrying the 6q- anomaly. The marrow stroma, as represented by first-passage adherent layer cells from long-term marrow cultures, showed 17 of 19 host metaphases. One of two donor cells found within the stromal elements exhibited a 6q- chromosome. In the subsequent remission mitoses derived from myeloid and lymphoid cells were exclusively of donor origin, and chromosomal abnormalities could no longer be detected. Stromal elements remained host-derived (14 of 16 mitoses).

Acute Disease↗