Biomedical subjects
Publications and source records attributed to M Kirsch.
Dogs with spontaneous Diabetes mellitus were checked at regular intervals for protein excretion in the urine. A large number of dogs developed a proteinuria, very marked in some cases, with excretion of primarily macroproteins.
A number of light adaptive changes of teleost horizontal cells are mediated by dopamine D1 receptors coupled positively with the cAMP second messenger system. Spinules, finger-like extensions from horizontal cell dendrites directed towards the cone pedicle cytoplasm, are formed in response to a stimulation of D1 receptors. We studied the second messenger mechanism associated with this process using isolated dark-adapted cyprinid retinae. Increasing intracellular cAMP concentrations by adding a membrane permeable analogue, or by stimulating the adenylate cyclase and simultaneously blocking the degradation of cAMP, resulted in a significant increase of spinule numbers in spite of the absence of light. In contradistinction to using isolated retinae for pharmacological experiments, injection of drugs into the vitreous had inconsistent or negative results.
C-11 acetate has recently been introduced as a tracer of myocardial oxidative metabolism with the use of positron emission tomography. To evaluate this approach in the pressure- or volume-loaded heart, C-11 acetate clearance rate constants were determined in 22 patients with chronic aortic valve disease and in nine normal subjects. Global myocardial C-11 clearance was significantly higher in patients with predominant aortic stenosis (n = 11) or aortic regurgitation (n = 11) than in normal subjects (0.069 +/- 0.017 min-1 and 0.072 +/- 0.010 min-1 compared with 0.050 +/- 0.004 min-1, p less than 0.05) and correlated significantly with the rate-pressure product corrected for mean aortic valve gradient (r = 0.73, p = 0.0001) for all studies. However, analysis of patient subgroups demonstrated that this correlation held only for aortic stenosis (r = 0.79, p less than 0.005 for gradient-corrected rate-pressure product). Additionally, C-11 clearance was strongly correlated with the product of heart rate and mean wall stress in patients with aortic stenosis (r = 0.89, p less than 0.005) but not in patients with aortic regurgitation. Normalization of C-11 acetate clearance rate constants for gradient-corrected rate-pressure product were significantly lower in patients with loaded ventricles, particularly in the presence of a low ejection fraction, compared to normal subjects. Possible mechanisms include myocardial adaptation through hypertrophy or depressed contractility, which would both tend to reduce oxygen consumption under any given load. Serial comparison of C-11 acetate kinetics and noninvasive indexes of oxygen demand may provide assessment of disease progression in pathologic ventricular loading.
Cardiac ascites is a rare condition. Diagnosis is aided by liver histology, which characteristically shows diffuse hepatic congestion affecting the centrilobular region. In our case of refractory ascites due to constrictive pericarditis, diagnosis was delayed because centribular hepatic congestion was absent histologically. Contrary to numerous published reports, diffuse hepatic congestion is not uniformly present in cardiac ascites. Constrictive pericarditis is curable and should be considered in all cases of unexplained ascites, regardless of atypical hepatic histology.
The negative feed-back interaction between horizontal cells (HCs) and cones in the cyprinid fish retina is thought to be mediated by horizontal cell spinules. These are "plastic" structures, largely absent from the dark-adapted retina and formed anew during light adaptation. We have previously shown that horizontal cell feed-back is similarly enhanced by light adaptation. The role of the interplexiform cell transmitter dopamine in both processes has been studied in the roach retina. Application of dopamine to dark-adapted retinae induced spinule formation in a dose-dependent way. The effect of dopamine was mimicked by dibutyryl-cAMP and suppressed selectively by D1 receptor antagonists. The effect of light in inducing spinule formation was lost in retinae depleted of endogenous dopamine. However, application of exogenous dopamine to these retinae triggered normal spinule formation. For all pharmacological treatments used, there was a strong correlation between spinule number and degree of feed-back activity in biphasic horizontal cells. Thus, when the spinule content of the cone pedicles was high, biphasic horizontal cell responses exhibited strong depolarizing components and vice versa. It is concluded that light-evoked formation of spinules in HC dendrites involves the action of dopamine upon D1 receptors. Spinules, in turn, are likely to be presynaptic terminals mediating the dynamic negative feed-back effect of horizontal cells upon cones.
Using high-performance liquid chromatography combined with electrochemical detection (HPLC-ED) we measured the content of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) as well as the activity of tyrosine hydroxylase in the retina of a teleost fish during a normal 12 h dark-light cycle. All 3 parameters showed a distinct diurnal pattern with oscillations during phases of changing illumination and more stable levels throughout the light and dark phase. While tyrosine hydroxylase activity levels roughly paralleled dopamine values, the time course of DOPAC content was a mirror image of dopamine levels. The results suggest that changing dopamine levels provide an adaptational signal for the retinal neural network; its metabolism seems at least in part to be controlled by endogenous factors.
In BALB/c mice, successful defense against visceral leishmaniasis is T cell dependent, expressed by tissue granuloma formation, and probably mediated by macrophages activated by cytokines, including gamma interferon (IFN-gamma). C57BL/6 ep/ep (pale ear) mice, which reportedly exhibit impaired IFN-gamma production, were challenged with Leishmania donovani to determine the outcome of infection in a euthymic host with an apparent defect in lymphokine secretion. In BALB/c and normal C57BL/6 mice, L. donovani liver burdens peaked at 2 weeks and were largely eliminated by 4 weeks. In contrast, in pale ear mice, infection progressed until after 4 weeks and persisted at high levels at 8 weeks. The failure to resolve hepatic infections was not related to deficiencies in (i) Thy-1+, L3T4+, or Lyt-2+ T cells; (ii) IFN-gamma secretion; (iii) liver tissue Ia expression; (iv) macrophage antimicrobial capacity; or (v) antileishmanial antibody production. However, despite the anticipated influx of mononuclear cells into livers, these cells were not properly focused on the parasitized Kupffer cells, the inflammatory infiltrate receded prematurely, and mature granulomas failed to develop. These results suggest that there is a cellular immune defect at the tissue level and emphasize the critical role of granuloma formation in successful resolution of systemic intracellular infections.
Small bowel bacterial overgrowth is a syndrome manifested by malabsorption, weight loss, and diarrhea. Human intestinal flora is part of a complex ecosystem regulated by host mechanisms, environmental factors, and bacterial interactions. Numerous conditions can tilt this balance to favor bacterial contamination of the gut. Knowledge of intestinal microbial control enables the clinician to better understand the pathophysiology and the clinical features of this disorder. Current strategies in diagnosis and therapy are discussed.
The humanus amorphus or acardiac twin is a very rare anomaly found only in monocygotic multiple pregnancies. In 8 twin pregnancies observed from 1977 to 1988 at the Charité-Hospital the findings of perinatal imaging diagnostics (sonography, amniofetrography, postnatal radiography) have been presented. For the prenatal diagnosis, especially for continuous prenatal control in these high-risk pregnancies, sonography seems to be the suitable method. However, an exact classification and morphological description of such monstrosities will be possible only by postnatal radiography (eventually in combination with a transumbilical angiography). Six ouf of eight cases were classified as an acephalous type, and two as an acardius anceps fetus.
Hepatic portal venous gas is associated with numerous conditions and traditionally has been regarded as an ominous prognostic sign. There are several reports of hepatic portal venous gas occurring in patients with inflammatory bowel disease after or during the performance of colonic diagnostic studies. We report an unusual case of Crohn's disease whose initial presentation included hepatic portal venous gas. The literature of hepatic portal venous gas associated with inflammatory bowel disease is reviewed.
In radiotherapy approved standard irradiation techniques are available for almost all tumor localizations that has to be adapted to individual anatomic situations with the concrete particular case. A possibility is shown that allows an anatomic adaptation of four types of parameters for four coplanar irradiation fields in maximum with permissible expenditure of time. During the dose adaptation process the estimation of the separate dose distribution is done for the target area and for risk organs according to given criteria by an added measure function value that is calculated from measure function values for the areas to be estimated.
Starting point for automatic adaptation of a dose distribution is a starting variant which parameters values are fixed as a matter of experience. On base of this starting variant a limited number of variants is produced and the "quality" of the attained dose distribution in each case is expressed by an added measure function value. A gradual improvement of adaptation of dose distribution to individual geometry of patients is done by pointed search of new parameter values for field breadths, field beginning points, field weights, and field insolation directions.
For the concrete case of a central bronchial carcinoma the method, explained in parts I and II, is applied for an automatic dose adaptation. In result a dose distribution is found which has a better adaptation of target area isodoses opposite the starting variant and results in a lower exposure of risk regions altogether.
In retinae of lower vertebrates, negative feed-back interactions between horizontal cells (second-order neurones), and cone photoreceptors lead to generation of spectrally multi-phasic light-evoked responses (S-potentials) in horizontal cells. Spinules (finger-like extensions of horizontal cell dendrites) have been suggested to mediate these interactions in retinae of teleost fish. We have studied whether prevention of light-dependent spinule formation would indeed affect an S-potential component (the red-sensitive depolarization in H2 horizontal cells), known to depend on such negative feed-back. Haloperidol was used as a dopamine antagonist to suppress light-induced formation of spinules in retinae of the cyprinid fish, the roach. In normal (untreated) retinae, biphasic S-potentials were strongly depolarizing and horizontal cell dendrites possessed abundant spinules. However, following application of haloperidol to the vitreous prior to light adaptation, spinule formation was suppressed, and concomitantly, red-sensitive depolarizing S-potentials remained significantly under-developed. The results are consistent, therefore, with the idea that spinules mediate the negative feed-back interaction between horizontal cells and cones.
Morphological and functional differentiation of dopamine (DA) neurons was compared in dissociated cultures from gestational day 14 rat mesencephalon and diencephalon. Numbers of tyrosine hydroxylase-immunoreactive (TH-IR) neurons relative to all neurons were 4 and 1.7 times higher in mesencephalic than in diencephalic cultures at 6 and 13 days in vitro (DIV), respectively. Morphological maturation of diencephalic DA neurons was retarded in comparison to mesencephalic DA neurons. There were gross differences in soma size and length of processes between the two types of DA neurons, the appearance of which was strongly reminiscent of DA cell types described in vivo. Functional maturation of DA neurons was quantified by measuring uptake and Ca2+-dependent K+-stimulated release of [3H]DA per TH-IR neuron. As early as 6 DIV, DA uptake by mesencephalic DA neurons was saturable, was sensitive to benztropine and reserpine, and could be displaced by unlabeled DA. Twenty to 30% of the radioactivity accumulated could be released upon depolarization within a period of 5 min. At 6 DIV, influx of [3H]DA into diencephalic DA neurons was almost insensitive to benztropine, reserpine and unlabeled DA. Even after 13 DIV, diencephalic DA uptake was characterized by a markedly lower initial velocity, a longer time needed to reach saturation, a lower uptake capacity, and a lower sensitivity to benztropine than mesencephalic DA uptake. The releasable pool was very small and did not increase between DIV 6 and 13. The results demonstrate that mesencephalic DA neurons in vitro differentiate considerably faster than diencephalic DA neurons and gain functional competence very early in brain development. Comparison with data on adult nigrostriatal and hypothalamic DA systems suggests that the in vitro differences reflect a fundamental regional diversity of DA neurons.
Action spectra for light induced cone contraction are described for the two spectral cone types of a dichromatic (red/green) cichlid species (Aequidens pulcher). Criterion response thresholds (50% of maximal response amplitude) were determined for seven wavelengths. After correcting for absorption by cornea and lens, the resulting action spectra were compared with the absorption spectra of the rod and cone visual pigments. We find (i) that the action spectra of red and green sensitive cones are almost identical and (ii) matched most closely the absorption spectrum of the rod visual pigment. We therefore conclude that light adaptive cone contraction is triggered by light absorption in rods, which in the dark adapted state are located next to the external limiting membrane and are therefore in an optimal position to capture the incident light during early dawn. Possible mechanisms of signal transfer from rods to cones are discussed.
The release of endogenous dopamine from teleost retinae was studied using high-performance-liquid-chromatography and electrochemical detection. Dopamine was measured in superfusates of isolated retinae after stimulation with flickering light as well as in the presence of GABA, L-glutamate, kainate or taurine. The effect of the receptor antagonists bicuculline, picrotoxin and kynurenic acid was also tested in retinae kept in the dark. We report a low level, basal release of dopamine in the dark (20 pg x 10 min-1/retina), which is transiently increased by stimulation with flickering light. This light evoked release of dopamine is inhibited by GABA and L-glutamate, whilst antagonists of these retinal transmitters stimulate release in the dark.
A report of ibuprofen-associated lipoid nephrosis without interstitial nephritis is presented. Previous reported cases had incomplete biopsy descriptions or concurrent interstitial disease. The patient responded to withdrawal of ibuprofen.