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Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 19 recordsLinked to original sources

Age-related changes in kynurenic acid production in rat brain.

Two separate in vitro assays were used to examine the biosynthesis of the broad spectrum excitatory amino acid receptor antagonist kynurenic acid (KYNA) during the life span of the adult rat. Assessment of KYNA's anabolic enzyme kynurenine aminotransferase revealed steady increases between 3 and 24 months of age in all five brain regions examined. No changes were observed in the liver. The changes were particularly pronounced in the cortex and in the striatum where enzyme activity increased three-fold during the period studied. KYNA production from its bioprecursor L-kynurenine was also investigated in tissue slices and was found to be significantly enhanced in the cortex and hippocampus of old animals. The effect of depolarizing agents or sodium replacement was virtually identical in tissues from young and old rats. These data, which are in excellent agreement with reports on an age-dependent increase of KYNA concentration in brain tissue, suggest an enhanced KYNA tone in the aged brain. Together with the reported decline in cerebral excitatory amino acid receptor densities with age, increased production of KYNA may play a role in cognitive and memory dysfunction in old animals.

Aging

Localization of kynurenine aminotransferase immunoreactivity in the rat hippocampus.

The localization and distribution of kynurenine aminotransferase (KAT), the biosynthetic enzyme of the excitatory amino acid receptor antagonist, kynurenic acid, was studied in the rat hippocampal formation with immunohistochemical methods. The enzyme was found mainly in glial cells that could be distinguished as 3 types on the basis of their shapes and locations. Typically, these cells shared the morphological features of astrocytes and exhibited glial fibrillary acidic protein immunoreactivity as demonstrated by a double-labeling technique. The distribution of KAT-containing glial cells was heterogeneous throughout the hippocampal formation. In the hippocampus, the stratum lacunosum-moleculare of Ammon's horn and the hilus contained a higher density of KAT-positive glial cells than other regions, whereas the lowest density of KAT glial cells was observed in the granule cell layer of the dentate gyrus and in the stratum radiatum of CA subfields. In the subicular complex, the density of KAT-containing glial cells was generally higher in the superficial than in the deep layer. Hippocampal neurons exhibiting KAT immunoreactivity, distinguished as nonpyramidal cells, were very few in number and mainly distributed in strata oriens and pyramidale of Ammon's horn. Substantially more KAT-positive neurons were observed in layers II and III of the subicular complex. The organization of cellular elements containing KAT may be of relevance for the function and possible dysfunction of kynurenic acid in the rat hippocampal formation.

Animals

Analysis of infectious complications occurring after solid-organ transplantation.

To improve our understanding of posttransplant infections, we analyzed bacterial, viral, fungal, parasitic, and other infections in 604 consecutive recipients of kidney (n = 518), kidney-pancreas (n = 82), kidney-liver (n = 3), or kidney-islet (n = 1) allografts (355 cadaveric, 14 living-unrelated, 235 living-related donors) who also received cyclosporine, azathioprine, and prednisone immunosuppression. Recipients of cadaveric grafts received additional induction immunosuppression (antilymphocyte globulin or murine monoclonal antibody OKT3). Rejection episodes were treated with high-dose steroids, and either antilymphocyte globulin or OKT3 was administered when clinically indicated. Perioperative antibiotics and posttransplant prophylactic acyclovir sodium or ganciclovir sodium, trimethoprim-sulfamethoxazole, and clotrimazole or nystatin (Mycostatin) were administered to all recipients. Two hundred thirteen patients (35.3%) were found to have had no identifiable infections, while 391 (64.7%) had either isolated bacterial (97 [16.1%]), viral (53 [8.8%]), or fungal (34 [5.6%]) infections or combination (concurrent or sequential) infections with bacterial plus viral (46 [7.6%]), bacterial plus fungal (66 [10.9%]), viral plus fungal (20 [3.3%]), bacterial plus viral plus fungal (64 [10.6%]), or bacterial plus viral plus fungal plus parasitic (11 [1.8%]) pathogens in the posttransplantation period. Renal allograft survival (percentage, actuarial method) was diminished in patients with infections at both 1 year (91% vs 83%) and 3 years (81% vs 76%) after transplantation, as was actuarial patient survival (1 year, 97% vs 92%; 3 years, 93% vs 88%). We conclude that infection remains a major cause of both patient demise and allograft loss following successful solid-organ transplantation.

Adolescent

The amniotic fluid compartment: the fetal habitat.

This study begins with a phylogenetic overview of the fetal membranes in terrestrial vertebrates. It is, of course, well known that the human amnion differs very little from that of other recent members of the phylum, although during evolution the development of the placenta has brought about extensive changes in the chorion. Much of the structure and many of the functions of both the amnion and chorion laeve can be interpreted from a comparative point of view (e.g., production of lipids). The next section deals with the ontogeny of the human amniotic sac, and the histogenesis and functional structure of the fetal membranes. It concludes with a structural analysis of the single layers of the fetal membranes at the end of pregnancy. Light and electron microscopy and histochemical examination are combined with experimental investigations; the striking differences and departure from any possible "norm", however, made the interpretation of morphological findings particularly difficult. Explanations for these differences are put forward: the texture of the connective tissue elements is only approximately determined and therefore gives rise to many irregularities; differences in the structure of cells depend upon their functional state; and the cells exist in groups which reciprocally exchange functional activity with each other. It is emphasized that the amniotic epithelium produces lipids which then appear in the same composition in the amniotic fluid. The fibroblasts in the amniotic connective tissue may, when necessary, be transformed into phagocytes (the so-called Hofbauer cells). Within the fetal membranes one can also observe glucose metabolism which, apart from the supply of local energy and the storage of glycogen, is concerned with production of phospholipids, triglycerides, glycoproteins, proteoglycans, and collagen (types I, III, and IV). A similar process of glucose metabolism is found in the trophoblast, especially the building-up of an extracellular matrix (the so-called fibrinoid), which seems to play a part in the formation of an immune barrier. An attempt is made to correlate the various differentiated cells of the trophoblast with particular functions. The vacuolated cells obviously store glucose. Others, as lectin-binding investigations have shown, are concerned with production of the extracellular matrix. They produce a three-dimensional latticework between the cells, and reach out as far as the borders of the chorionic connective tissue. In this regard, the microtexture of the amniotic and chorionic connective tissue provides a basis for a more precise understanding of their mechanical stability.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid

Scotopic versus photopic pattern onset-offset electroretinograms.

We investigated the contribution of rods and cones to the human pattern electroretinogram to onset and offset checkerboards of different spatial frequency and wavelength in a 39 degrees x 39 degrees field. Under strictly scotopic conditions, there was a negative potential at onset and a positive potential at offset, whereas under photopic conditions, there was a positive potential at onset and a negative/positive potential at offset. Thus, the waveform to pattern onset (offset) was that of the luminance electroretinogram to decreasing (increasing) luminances. For pattern onset, the sensitivity difference 486-601 nm under scotopic and photopic conditions closely followed the luminosity function of rods and cones. The amplitude of the scotopic onset response increased with check size up to 3 degrees 30' and that of the photopic onset response, up to 30'. With larger checks, the scotopic and photopic onset response markedly decreased. This indicates antagonistic center-surround organization of the receptive fields under both scotopic and photopic conditions. By contrast, the offset response monotonically increased with check size under scotopic and photopic conditions, which suggests a luminance component in the pattern electroretinogram. Consequently, the pattern electroretinogram to reversing checkerboards has to be regarded as a mixture of both pattern- (contrast) and luminance-specific components.

Adolescent

Time-resolving luminescence techniques for possible detection of forest decline. I. Long term delayed luminescence.

Needles from spruces at different environmental and physiological conditions were analyzed by long term delayed luminescence in the seconds-range (LDL) using a novel set-up with on-line computer and a specially written computer program. Upon red light induction, the LDL-kinetics showed a super-position of three exponentially decaying components ("fast", "medium" and "slow") with reaction constants of kf = 5-15 s-1, km = 0.8-1.8 s-1 and ks = 0.13-0.23 s-1, ks-values are fairly independent of the individual tree and quite stable throughout the whole year. They are also independent of the status and localization, i.e. the physiological situation of the individual tree. However, km- and kf-values as well as the related amplitudes Am and Af exhibit a general, significant seasonal variation and obviously are correlated with the damage class or the environmental situation of the individual tree. Therefore, the measurement of long term delayed luminescence might offer a valuable piece of information in search of an early detection of forest decline.

Ecology

Time-resolving luminescence techniques for possible detection of forest decline. II. Picosecond chlorophyll fluorescence.

Needles from spruces at different environmental and physiological conditions were analyzed by picosecond fluorescence spectroscopy using a novel laser diode and single photon counting detection. The decay curves of chlorophyll fluorescence showed a superposition of three exponentially decaying components with time constants of T1 = 100-200 ps, T2 = 300-500 ps and T3 = 2.0-3.5 ns. A high relative intensity of the long-lived component was found in damaged spruces as well as in trees showing first symptoms of yellowing, needle loss or parasite infection, although all measurements were carried out with green needles which appeared visually intact. Therefore, fluorescence spectroscopy with subnanosecond time resolution seems to be a valuable attempt for an early detection of forest decline.

Chlorophyll

Pentylenetetrazol kindling and factors of glutamate transmitter metabolism in rat hippocampus.

Male Wistar rats administered repetitively with pentylenetetrazol developed a dose-dependent enhancement of seizure behaviour referred to as pentylenetetrazol kindling. After a daily dose of 40 mg pentylenetetrazol/kg or physiological saline (control rats) injected intraperitoneally for a period of two weeks, hippocampal tissue was studied autoradiographically for high-affinity uptake of [3H]glutamate and, by activity staining, for aspartate aminotransferase and glutamate dehydrogenase. Most prominent changes were found in neuropil areas known to be endowed with glutamatergic structures. The uptake capacity of glutamate decreased by 48% (maximum rate), whilst activities of aspartate aminotransferase and glutamate dehydrogenase elevated to 140 and 130%, respectively. Cytochrome c oxidase activity was found to be unaffected. The findings indicate an important role of factors of the glutamate metabolism in the kindling process with respect to the production, utilization, and availability of transmitter glutamate.

Animals

Radioiodination of S-type lipopolysaccharide. Possibilities and limitations of labelling of the carbohydrate chain by periodate oxidation.

S-type Lipopolysaccharide (LPS) from E. coli O 139:K 82 (B) was radiolabelled by coupling 125I-tyramine to the carbohydrate chain of LPS after oxidation of sugar residues carrying vicinal hydroxy groups, with sodium metaperiodate. The specific activity amounted to 1.3 kBq/microgram LPS. As LPS is a mixture of molecules with different carbohydrate chain lengths that are associated to large micelles of high kinetic stability, the preparation and the properties of the tracer exhibit some peculiarities. Most important, partial cleavage of the carbohydrate chains of LPS is caused on radioiodination by the procedure described. As a consequence, the tracer differs markedly from the starting LPS with respect to carbohydrate chain length distribution. Another feature of special interest is the variation of the specific activity (radioactivity/unit mass) for LPS molecules of different carbohydrate chain lengths. Because of the kinetic stability of LPS micelles, the equilibration of radioiodinated and non-radioactive LPS aggregates requires their solubilization by a detergent and its subsequent removal by dialysis. It could be demonstrated that short-chain LPS molecules predominantly associate to larger micelles than long-chain molecules. Regardless of these restrictions, the 125I-LPS proved to be useful for certain analytical purposes.

Carbohydrate Metabolism

[Use of computer-assisted image analysis for the detection of immunohistochemical receptor status in breast cancer. Immunohistochemical densitometry receptor analysis--IRDA].

A method for the evaluation of the immunohistochemical staining score of steroid receptors in breast cancer using computer-based image analysis is presented. The optical density of tumour cell nuclei was measured using kryostat sections and, using a control section as reference, an objective threshold for specific staining was defined. In intensively stained sections, a good correlation with visual scoring was achieved, but in 9 out of 16 sections, which were regarded as receptor-negative by visual scoring, a specific receptor-positive staining was demonstrated by image analysis. Next to the percentage of positive cells (PP) and the mean staining intensity (SI), a histogram of the receptor concentration in positive nuclei was calculated. The method allows, besides an objective evaluation and documentation, an exact definition of a threshold for specific receptor measurement and furthermore shows the pattern of receptor concentration in the tumour cell nuclei. Hence, the method could contribute towards a more widespread use of immunohistochemical receptor analysis.

Breast

[Noninvasive function tests in the evaluation of vascular reactivity in pregnancy and pregnancy-induced hypertension].

At present, there is an increasing discussion regarding the change of the prostacyclin/thromboxane ratio as an aetiological factor of pregnancy-induced hypertension (PIH). By means of videophotometric capillaroscopy in the capillaries of the nailfold, it is possible to visualise the resulting changes in the microcirculation. This method employs a special illumination microscope (magnification of the optical system x 560). Red blood cell velocity is measured under test conditions and microcirculatorical reaction capacity on ischaemic stress. Studies were conducted on healthy non-pregnant women and on healthy pregnant women as well as on patients suffering from pregnancy-induced hypertension. A markedly reduced velocity of red blood cells in patients with pregnancy-induced hypertension was seen as a sign of vasoconstriction, namely, 0.53 mm/sec. versus 0.74 mm/sec. Furthermore, these patients have a higher reactivity to ischaemic stress, probably also as a result of the already existing vasoconstriction; however, the duration of the hyperaemic phases is reduced in pregnancy-induced hypertension. By this method, an insight can be gained into microcirculation in pregnancy and in pregnancy-induced hypertension. In addition, as preliminary studies have already shown, the influence exercised by different medications on microcirculation can be assessed.

Blood Flow Velocity

[Experiences up to now with the ultrasound dissection instrument in gynecologic oncology].

The energy of high frequency ultrasound is used to disrupt cellular structures. Since the water content of each individual cell is of utmost importance for the physical destruction of the cell, there may be a tissue-selective effect in respect of tissues such as epithelium (high water content) and mesenchyma (low water content). The various therapeutic modalities are described in the following four cases. Ultrasonic tumor destruction was highly effective with regard to maximum reduction of tumor masses, especially for tumor sites which could not be removed by conventional tumor surgery. Blood vessels and nerves surrounded by tumor could be carefully and completely dissected--even in advanced stages. Peritoneal metastases from an ovarian carcinoma could be removed entirely, as well as the metastases within a tumor bulk (e.g. ureter within tumor mass); also the layers of tissue which were lost could be visualized again. So far, no increase in complications during and after surgery has been observed.

Adult

[Recurrence of vulvar cancer--treatment, experiences and results].

At the University Hospitals of Heidelberg (1970-1988) and Homburg/Saar (1988-1990), 182 patients with vulvar carcinoma were treated. 51 patients had a recurrence of vulvar carcinoma and 21 patients showed a persistence of this tumour. 19 women had a second recurrence of vulvar disease. In these cases, therapy ranged from local surgery to exenteration, depending on the site and tumour extension. 18 patients underwent successful reconstructive surgery. Prognosis was better in cases with local recurrence in comparison to distant sites of metastatic progression (i.e. inguinal nodes or disseminated disease) (p less than 0.001). The five-year survival (after diagnosis of recurrent disease) for patients with early onset of recurrence (less than 20 months after initial therapy) was 28% compared to 68% for patients with late onset of recurrent disease (p less than 0.01).

Female

[Results of treatment in vulvar cancer from 1970 to 1990].

From 1970-1990, 159 patients with invasive malignant tumours of the vulva (150 squamous cell carcinomas) underwent surgery at the University Hospitals, department of gynaecology. Heidelberg (1970-1988) and Homburg/Saar (1988-1990). 73% of the patients were more than 60 years old and 3% were less than 40 years old. The mean age was 69 years. 30% of the patients had diabetes mellitus. As a standard therapy, 101 patients had radical vulvectomy with bilateral inguinal node removal in accordance with S. Way. If nodes were found to be positive, the inguinal/pelvic region was irradiated postsurgically with 40-50 Gy. The 5 years survival rate for all patients with vulvar carcinoma was 69%. For early stage carcinomas (pT1, depth of invasion < or = 1 mm) a restricted radical therapy should be considered. 9 patients with early stage carcinomas survived disease-free for a period of 70 months. Significant prognostic differences were noticed if node histology was N- as opposed to N+ (p < 0.001), if depth of invasion was < or = 1 mm as opposed to > 10 mm (p < 0.001), if stage was pT1 as opposed to pT2 to pT4 (p < 0.001) or if lymphangiosis carcinomatosa (p < 0.01) was present or not. Prognostic differences were also noticed, if cytological grading was done in accordance with Broders (p < 0.09). 27 patients had successful reconstructive surgery with local cutaneous or myocutaneous flaps at the time of initial surgery. The median recovery period after radical vulvectomy with bilateral inguinal lymph node excision was 22 days. The median recovery period after radical vulvectomy with bilateral node removal and reconstructive surgery was 25 days. Early recurrence of carcinoma (< or = 6 months after initial therapy) was 5.9%, late recurrence was 12%.

Aged

Bioavailability of vinpocetine and interference of the time of application with food intake.

In a pilot study based on an open cross-over design involving four phases, the relative bioavailability of the eburnamenine derivative vinpocetine (CAS 42971-09-5) was investigated in 8 healthy volunteers in relation to different times of drug administration relative to food intake. The substance was applied orally as 10 mg film tablets. The areas under the plasma concentration-time curves (AUC) amounted to 27.3 +/- 18.1 ng.h/ml (fasting) and 42.8 +/- 27.4 up to 54.3 +/- 38.4 ng.h/ml (non-fasting, intake before and after meal, resp.). The relative bioavailability under non-fasting conditions was found to be approx. 60 to 100% higher than under fasting conditions.

Adult

[A clinical evaluation of MAb BW 835/6 in breast and ovarian cancer].

Studies with the 99mTc-labeled murine monoclonal antibody BW 835/6 in patients suspected of breast (n = 7) or ovarian cancer (n = 8) showed insufficient depiction of primary tumors and metastases of breast cancer, but promising results in the detection of primary tumors in ovarian cancer without metastases. The small number of patients does not allow statistical analysis.

Adult