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Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

At least 271 records · Page 15Linked to original sources
PubMed1994

Tissue-specific expression of the fibril-associated collagens XII and XIV.

Interstitial collagen fibrils form the supporting scaffold of all connective tissues. The synthesis of this framework is subject to a precise spatial and temporal regulation in order to meet the mechanical needs of every tissue type. A subgroup of non-fibrillar collagens termed FACIT seems to play a role in this regulation by providing specific molecular bridges between fibrils and other matrix components. Collagens XII and XIV represent such FACIT molecules and occur preferentially in tissues containing banded type I collagen fibrils. We have used the techniques of indirect immunofluorescence and in situ hybridization to investigate the expression patterns of the two molecules during chicken embryonic development. We detected specific differences in these patterns, which may be related to the respective functions of the two proteins within the connective tissues. Collagen XIV was expressed at very few sites in the 6-day-old embryo, but occurred in virtually every collagen I-containing tissue (skeletal muscle, cardiac muscle, gizzard, tendon, periosteum, nerve) by the end of embryonic development. In contrast, collagen XII was fairly abundant in the 6-day-old embryo but was, at later stages, restricted to only a few dense connective tissue structures (bone, tendon, gizzard). Thus, our results suggest that collagen XII and collagen XIV serve different functions during embryonic development although their structures are highly similar.

Animals↗
PubMed1994

Starvation induces differential small bowel luminal amino acid transport.

BACKGROUND: The importance of small intestinal mucosa functions has been emphasized in recent years because gut metabolism becomes better defined. One of the major activities of the enterocyte is amino acid transport, which is important not only for the organism but also for the integrity of the mucosa. Bowel rest during the postoperative period is marked by decreased calorie and protein intake with atrophy of the brush border mucosa. We sought to determine whether active amino acid transport is altered during 72 hours of fasting. METHODS: New Zealand white rabbits were fed (control) or fasted for 72 hours. Brush border membrane vesicles were prepared from scraped jejunal mucosa, and their purity was assessed by marker enzyme enrichment (17- to 25-fold). Transport of tritiated glutamine, arginine, alanine, methylamino-isobutyric acid (MeAIB), and leucine into brush border membrane vesicles was measured by rapid mixing filtration. RESULTS: Fasted animals lost on average 138 +/- 51 gm of body weight. Glutamine and arginine transport were decreased in rabbits fasted for 72 hours compared with controls; alanine, MeAIB, and leucine transport were maintained. The decrease in Glutamine transport was due to a decrease in Vmax (545 +/- 22 versus 836 +/- 93 pmol/mg protein/10 sec; p < 0.05), consistent with a decrease in the number of functional transporter proteins. Km values were similar in both groups (644 +/- 25 versus 624 +/- 18 mumol/L), indicating no change in carrier affinity. CONCLUSION: Differential changes occur in brush border amino acid transport during a 3-day period of bowel rest. The apparent gut nutritive transporters for Glutamine and arginine are decreased, although the gluconeogenic transporters for alanine, MeAIB, and leucine are maintained. These adaptive changes may help explain the difficulties seen in postoperative and critically ill patients on prolonged bowel rest.

Amino Acids↗
PubMed1994

Prodrugs of anthracyclines for chemotherapy via enzyme-monoclonal antibody conjugates.

New prodrugs of daunorubicin, 1c, 1e and 2c, including a galactopyranosyl residue linked to the N-3' of the daunosaminyl moiety through substituted o- or p-benzyloxycarbonyl groups were synthesized. Their low cytotoxicity and high stability in plasma fulfil the conditions for antibody-directed enzyme prodrug therapy (ADEPT). Enzymatic hydrolysis using alpha-D-galactosidase gives rise to daunorubicin by subsequent self-elimination of the spacers. However, elimination clearly depends on the aromatic substitution pattern, as demonstrated especially by comparison with non-substituted analogues.

Animals↗
PubMed1994

Synthesis and biological activity of 3'-deamino-3'-haloanthracyclines.

4'-O-Acetyl-3'-deamino-3'-chloro and 4'-O-acetyl-3'-deamino-3'-bromoepidaunorubicin analogs have been synthesized by condensation of daunomycinone with the corresponding hexopyranosyl chlorides. The glycosides obtained were less potent than adriamycin (ADR) in inhibiting the proliferation of tumor cells in vitro, but they have shown promising activity against a variety of multidrug resistant (MDR) cell lines.

Animals↗
PubMed1993

Microinjections of the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-cyclopentane-1,3-dicarboxylate (trans-ACPD) into the amygdala increase the acoustic startle response of rats.

The present study examined the effect of intraamygdaloid application of the metabotropic glutamate receptor agonist trans-ACPD on the acoustic startle response. Trans-ACPD led to a disruption of between-session habituation which is normally seen after repeated testing after injections of the vehicle into the amygdala. More specifically, a statistically significant increase of the magnitude of the startle response was observed 4 h after injection of 30 nmol of trans-ACPD into the central amygdaloid nucleus. The present findings suggest a role for the metabotropic glutamate receptor in the amygdala in the enhancement of the acoustic startle response.

Acoustic Stimulation↗
PubMed1993

Oestrogen receptor occurrence in the male mouse brain: modulation by paternal experience.

Paternal behaviour (pup-searching and retrieving of pups) was studied in male house mice with different experience in pup care and oestrogen receptor immunoreactive (ER-IR) cells were localized and quantified in their brains. Experience with pups induced paternal behaviour and correlated with (a) the occurrence of ER-IR cells in the bed nucleus of the stria terminalis, hippocampus, subiculum, lateral septal nuclei, entorhinal and piriform cortex, (b) increased numbers of ER-IR cells in the medial preoptic area and arcuate nucleus of the hypothalamus, and (c) decreased presence of ER-IR cells in the periventricular grey of the midbrain. The data indicate oestrogen receptor modulation in the male brain and suggest that oestrogen binding in distinct brain areas is involved in the regulation of paternal behaviour.

Animals↗
PubMed1993

Enhancement of the acoustic startle response by stimulation of an excitatory pathway from the central amygdala/basal nucleus of Meynert to the pontine reticular formation.

The acoustic startle response (ASR) is a simple motor reaction to intense and sudden acoustic stimuli. The neural pathway underlying the ASR in rats is already fairly well understood. As the ASR is subject to a variety of modulations, this reaction can serve as a model for vertebrate neuroethologists to investigate the neural mechanisms mediating sensorimotor transfer and their extrinsic modulation. We report here on experiments in rats which were undertaken in order to investigate the neural mechanisms underlying the enhancement of the ASR. An increased amplitude of the ASR can be observed during states of conditioned and unconditioned fear. By employing neuroanatomical tract-tracing methods, we describe a pathway from neurons of the medial division of the central amygdaloid nucleus (cA) and the basal nucleus of Meynert (B) to the caudal pontine reticular nucleus (PnC), an important relay station in the acoustic startle pathway. Extracellular recordings from acoustically responsive neurons in the PnC showed that electrical stimulation of the cA/B facilitates the tone-evoked response of these neurons. Behavioural tests following chemical stimulation of the cA/B with NMDA (N-methyl-d-aspartate) in awake rats indicated that activation of this pathway increases the ASR. The lack of sufficient spatial resolution of our stimulation techniques did not allow us to differentiate the relative contributions of the cA and the B to this effect. As the amygdaloid complex has been implicated in emotional behaviour, particularly in the mediation of fear, these findings substantiate the concept that the amygdaloid complex plays a key role for the enhancement of the ASR by conditioned and unconditioned fear.

Amygdala↗
PubMed1993

Cholinergic neurons in the pedunculopontine tegmental nucleus are involved in the mediation of prepulse inhibition of the acoustic startle response in the rat.

The amplitude of the acoustic startle response (ASR) is markedly reduced when the startle eliciting pulse is preceded by a weak, non-startling stimulus at an appropriate lead time, usually about 100 ms. This phenomenon is termed prepulse inhibition (PPI) and has received considerable attention in recent years as a model of sensorimotor gating. We report here on experiments which were undertaken in order to investigate some of the neural mechanisms of PPI. We focused on the characterization of the cholinergic innervation of the pontine reticular nucleus, caudal part (PnC), an obligatory relay station in the primary startle pathway. The combination of retrograde tracing with choline acetyltransferase-immunocytochemistry revealed a cholinergic projection from the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) to the PnC. Extracellular recording from single PnC units, combined with microiontophoretic application of the acetylcholine (ACh) agonists acetyl-beta-methylcholine (AMCH) and carbachol revealed that ACh inhibits the majority of acoustically responsive PnC neurons. Neurotoxic lesions of the cholinergic neurons of the PPTg significantly reduced PPI without affecting the ASR amplitude in the absence of prepulses. No effect on long-term habituation of the ASR was observed. The present data indicate that the pathway mediating PPI impinges upon the primary acoustic startle circuit through an inhibitory cholinergic projection from the PPTg to the PnC.

Acoustic Stimulation↗
PubMed1993

Survival and predictors of death in dialysed diabetic patients.

The objective of this study was to examine diabetic patients at the time of admission to maintenance haemodialysis and to follow them for 36 months in order to define predictors of cardiovascular and non-cardiovascular death. This prospective study comprised all consecutive diabetic patients admitted to 28 German dialysis centres between January 1985 and October 1987; 196 patients were examined, 67 Type 1 (insulin-dependent) diabetic (43 male, 24 female; median age 49 years, range 22-73) and 129 Type 2 (non-insulin-dependent) diabetic patients (54 male, 75 female; 64 years, range 37-82). Outcome measures were death, i.e. myocardial infarction, sudden death, cardiac death of other causes, stroke and non-cardiovascular death. Actuarial survival 36 months after the beginning of dialysis was similar in Type 1 (40%) and Type 2 diabetic patients (43%) despite the age difference. Causes of death were myocardial infarction (18%), sudden death (18%), other cardiac causes (18%); stroke (6%); septicaemia (17%) mostly originating from diabetic foot problems; and interruption of therapy. Survival rates and the proportion dying from cardiac causes were similar in patients with diabetic nephropathy or with other primary chronic renal disease and coincidental diabetes. On dialysis, de novo amaurosis or de novo amputation was not observed in any patient. The strongest predictor of myocardial infarction or sudden death was serum lipids on admission. Duration of hypertension, blood pressure at the time of admission to dialysis, left ventricular hypertrophy or end-diastolic diameter by echocardiography, Sokolow index and average predialysis blood pressure, smoking, interdialytic weight gain and type of dialysis were not predictive of cardiovascular death or death by all causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Insulin autoantibodies and immune response to human insulin therapy in 24 type 1 (insulin-dependent) diabetic children: superiority of radio binding assay over solid phase assay.

To evaluate the immunization pattern against human insulin, 24 newly diagnosed diabetic children (12 females, 12 males; mean age: 7 +/- 4 years) were treated from diagnosis onwards with semisynthetic human insulin (NOVO). Informed consent was obtained from all parents. Blood samples were taken before, 1, 2, 3, 4, 6 and 8 weeks after the start of therapy and, thereafter, at monthly intervals for 2 years. Insulin (auto) antibodies (I(A)A) were measured by radio binding assay (RBA) and by enzyme-linked immunosorbent assay (ELISA). IAA, determined by RBA, were detected in eight children. Using ELISA, IgM IA were not detected after onset of therapy. By contrast, IgG IA were found in 8 children after 2 weeks of treatment and in 12 after 1 month. Using RBA, all children had IA after 2 months of therapy, whereas with ELISA, IA remained undetectable during the study period in 8 out of 24 patients. These results confirm previous observations suggesting that the 2 methods are not interchangeable and yield different estimations of the insulin immune reaction, not only before but also after the start of insulin therapy. In addition, the detection of IA by RBA in all treated patients unambiguously demonstrates that human insulin is immunogenic in man.

Adolescent↗
PubMed1993

Morbidity and mortality due to hypertension in patients with renal failure.

The incidence of, and the mortality from, cardiac disease is strikingly increased in dialysis patients. Coronary disease existing prior to the onset of dialysis is an important determinant of ischemic heart disease (IHD) on dialysis. Death from IHD on dialysis is higher by factor 5-20 than in the general population. In several studies either a marginal or no relation between blood pressure on admission to renal replacement therapy, or average predialysis blood pressure and cardiac death has been noted. In other studies blood pressure was, however, predictive of IHD. Such discrepancies may be explained by a low-risk threshold, a nonlinear relationship, and the necessity to examine large patient cohorts to document the effect. Of great importance may be the potentially increased susceptibility of the heart to hypertensive injury and ischemia. This may be related to factors like left ventricular hypertrophy, cardiac fibrosis and altered cardiac mechanical properties, diminished coronary reserve, and reduced ischemia tolerance, particularly during intradialytic hypotensive episodes due to compromised microcirculation and disturbed insulin-induced glucose uptake and abnormalities of autonomous neural innervation of the heart.

Cardiovascular Diseases↗
PubMed1993

[Magnetic resonance arteriography, duplex sonography and conventional arteriography for the evaluation of peripheral arterial occlusive disease].

A prospective controlled study of 41 peripheral arterial occlusions was carried out, comparing duplex sonography, magnetic resonance arteriography and contrast arteriography. 87.8% of duplex sonography findings and 80.5% of magnetic resonance arteriographies agreed with the appearances of contrast arteriography (gold standard). Duplex sonography tended to overestimate the length of an occluded segment by an average of 2 cm (0.5-5 cm), whereas magnetic resonance arteriography showed less deviation from contrast arteriography (+/- 2 cm). The advantage of duplex sonography lies in its ability to provide morphological and functional information concerning the obliterated segment. Its disadvantage is that it can only demonstrate one segment and that the examination must be carried out in individual segments. Magnetic resonance arteriography provides vascular demonstration in several planes similar to angiography but signal-voids due to limited resolution and flow changes may limit diagnosis of occlusions. Additional phase contrast techniques may provide quantitative information on flow velocities and flow rates. Both duplex sonography and magnetic resonance arteriography are suitable methods for the non-invasive investigation of peripheral arterial occlusive disease.

Aged↗
PubMed1993

Glutamate antagonists in the reticular formation reduce the acoustic startle response.

A previous study has shown that the acoustic responsiveness of reticulospinal neurones in the caudal pontine reticular nucleus (PnC) is reduced by glutamate antagonists. It was postulated that the acoustic startle response is mediated by glutamate receptors on PnC-neurones. In the present study, we tested this hypothesis by local microinjections of different glutamate antagonists into the PnC of unrestrained awake rats. In order to differentiate the drug effects on the head and body startle responses, we measured the head startle response electromyographically, and the body startle response in a ballistic chamber. Both the AMPA/kainate and the NMDA receptor antagonists reduced both components of the startle response dose-dependently. We conclude that both subtypes of ionotropic glutamate receptors in the PnC are relevant for the acoustic startle response in rats.

2-Amino-5-phosphonovalerate↗