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Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

At least 19 recordsLinked to original sources
PubMed1992

A major oligomeric fibroblast proteoglycan identified as a novel large form of type-XII collagen.

Cultured chick embryo skin fibroblasts release a major component with a native molecular mass of about 1 MDa, which resolves into three polypeptide bands of about 300, 350 and 600 kDa upon reduction. We report here the purification of this oligomeric protein and show, by means of polyclonal and monoclonal antibodies, that its three polypeptide constituents are closely related. The 600-kDa polypeptide is likely to be a dimer of two smaller subunits which are cross-linked by non-reducible bonds. By electron microscopy, isolated oligomeric molecules exhibit a novel cruciform structure with a large central globular domain. One arm has the shape of a thin rod about 70 nm in length. The three other arms are thicker, longer (90 nm) and flexible, and carry a prominent double globule at their distal ends. Collagenase treatment of the oligomeric fibroblast protein yields two resistant fragments of about 270 kDa and 320 kDa. The intact 350-kDa and 600-kDa (but not the 300-kDa) polypeptides are chondroitinase sensitive and labeled by metabolic incorporation of [35S]sulfate; collagenase treatment does not remove any [35S] sulfate. Hence, the intact fibroblast protein has glycosaminoglycan chains attached to its non-collagenous domain. Three amino acid sequences obtained from chymotryptic fragments of the fibroblast protein correspond to sequences predicted for chick type-XII collagen from its full-length cDNA [Yamagata, M., Yamada, K. M., Yamada, S. S., Shinomura, T., Tanaka, H., Nishida, Y., Obara, M. & Kimata, K. (1991) J. Cell Biol. 115, 209-221]. However, the novel fibroblast protein described here differs significantly from previously isolated forms of type-XII collagen: its subunits are larger by one third, and it is a proteoglycan.

Amino Acid Sequence↗
PubMed1992

Na(+)-dependent HCO3- transport and Na+/H+ exchange regulate pHi in human ciliary muscle cells.

We investigated intracellular pH (pHi) regulation in cultured human ciliary muscle cells by means of the pH-sensitive absorbance of 5(and 6)-carboxy-4',5'-dimethylfluorescein (CDMF). The steady-state pHi was 7.09 +/- 0.04 (n = 12) in CO2/HCO3(-)-buffered and 6.86 +/- 0.03 (n = 12) in HEPES-buffered solution. Removal of extracellular sodium for 6 min acidified the cells by 1.11 +/- 0.06 pH units (n = 12) in the presence of CO2/HCO3- and by 0.91 +/- 0.05 pH units (n = 8) in its absence. Readdition of external sodium resulted in a rapid pHi recovery, which was almost completely amiloride-sensitive in the absence of CO2/HCO3- but only slightly influenced by amiloride in its presence. Application of DIDS under steady-state conditions significantly acidified the ciliary muscle cells by 0.25 +/- 0.02 (n = 4) in 6 min, while amiloride had no effect. The pHi recovery after an intracellular acid load was completely dependent on extracellular sodium. In HEPES-buffered solution the pHi recovery was almost completely mediated by Na+/H+ exchange, since it was blocked by amiloride (1 mmol/liter). In contrast, a marked amiloride-insensitive pHi recovery was observed in CO2/HCO3(-)-buffered solution which was mediated by chloride-independent and chloride-dependent Na+ HCO3- cotransport. This recovery, inhibited by DIDS (0.2 mmol/liter), was also observed if the cells were preincubated in chloride-free solution for 4 hr. Analysis of the sodium dependence of the pHi recovery after NH4Cl prepulse revealed Vmax = 0.57 pH units/min, Km = 39.7 mmol/liter extracellular sodium for the amiloride-sensitive component and Vmax = 0.19 pH units/min, Km = 14.3 mmol/liter extracellular sodium for the amiloride-insensitive component. We conclude that Na+/H+ exchange and chloride-independent and chloride-dependent Na(+)-HCO3- cotransport are involved in the pHi regulation of cultured human ciliary muscle cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and specific platinum accumulation.

Cisplatin, raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinu m(II) sulfate (compound I), meso-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]-platinum(II) sulfate (compound II), and meso-diaqua[1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]platinum(II) sulfate (compound III) were compared with regard to their effect on the MCF-7 breast cancer cell line in vitro. At equimolar concentrations (5 microM), cisplatin, compound I, and compound II were equiactive after 231 h drug exposure, whereas compound III was ineffective. Although compounds I and II showed markedly greater inactivation than did cisplatin after 6 h incubation with culture medium, compound I (but not compound II) exhibited antitumor activity equivalent to that of cisplatin when cells were exposed to the drugs for 6 h. Platinum measurements by neutron-activation analysis revealed that compound I was selectively and rapidly accumulated by MCF-7 cells, resulting in a high degree of DNA platination within the first few hours of drug exposure. However, when the drug-exposure period was long enough, platinum enrichment was not reflected in an overall difference in the cytotoxicity of compound I vs cisplatin. Nevertheless, compound I should be superior to cisplatin in vivo, provided that effective plasma levels can be maintained for about 6 h.

Breast Neoplasms↗
PubMed1992

Loss of the acoustic startle response following neurotoxic lesions of the caudal pontine reticular formation: possible role of giant neurons.

The effect of the excitotoxic N-methyl-D-aspartate agonist quinolinic acid in the caudal pontine reticular formation on the acoustic startle response was investigated in rats. Bilateral injections of 90 nmol of quinolinic acid led to large lesions in the reticular formation characterized by the loss of all neurons and a marked reduction or even abolition of the acoustic startle response; 18 nmol of quinolinic acid led to smaller lesions characterized by a selective loss of giant neurons within the caudal pontine reticular formation and a reduction of the startle amplitude. The partial correlation analysis revealed that the reduction of the amplitude of the acoustic startle response can be correlated with the loss of the giant neurons (r = 0.575; d.f. = 29; P less than 0.001) but not with the reduction of the number of all neurons (r = 0.207; d.f. = 29; P greater than 0.2) in the caudal pontine reticular formation. These findings were reconciled with electrophysiological and anatomical data indicating that the giant neurons in the caudal pontine reticular formation receive acoustic input and project to motoneurons of the spinal cord. It is concluded that the caudal pontine reticular formation is an important element of the startle pathway and that the giant reticulospinal neurons constitute an important part of the sensorimotor interface mediating this response.

Acoustic Stimulation↗
PubMed1992

Glutamate receptors mediate acoustic input to the reticular brain stem.

Previous studies have shown that many neurons of the pontine reticular brain stem respond to acoustic stimulation. However, it was not clear which neurotransmitter is involved in the mediation of auditory information. As glutamate appears to be a prominent transmitter in the auditory system, we iontophoretically applied antagonists of the AMPA/kainate- and NMDA-receptors to reticular neurons. Both glutamate antagonists reduced the acoustically evoked response, with the AMPA/kainate-receptor antagonist being more efficient. As the neurons showed a short latency and a high intensity threshold to the acoustic stimuli and most of them appeared to project into the spinal cord, we conclude that glutamate receptors on reticulospinal pontine brain stem neurons probably mediate auditory short-latency behaviour, such as the startle response.

2-Amino-5-phosphonovalerate↗
PubMed1992

Microbic superinfection in relapse of inflammatory bowel disease.

To assess the association between symptomatic relapse of inflammatory bowel disease (IBD) and superinfection with enteropathogenic microorganisms, we determined prospectively the incidence of infections with enteropathogenic bacteria, protozoa, and helminths in patients with confirmed longstanding IBD. Sixty-four patients with IBD (49 with Crohn's disease [CD] and 15 with ulcerative colitis [UC]) were consecutively enrolled in the study when relapse occurred. Multiple biopsies for histological and microbiological investigations were taken from all patients who were evaluated by colonoscopy. Parallel stool specimens were investigated for the presence of enteropathogenic bacteria, protozoa, and helminths. In six patients, we detected Clostridium difficile or toxin B (five CD, one UC), in one patient Campylobacter jejuni (CD), and in another patient Salmonella typhimurium (UC). Enteropathogenic Escherichia coli were isolated from three patients. Investigation of biopsies for Mycobacteria, microscopic examination of stool samples for helminths, and immunofluorescence for chlamydia were negative in all patients. In summary, as we found enteropathogenic microorganisms so infrequently in patients with relapse of IBD, despite intensive microbiological screening by tissue sampling for detection of gut adherent bacteria, we believe that microorganisms play only a minor role in the exacerbation of IBD.

Adult↗
PubMed1992

The prevalence of cerebral damage varies with migraine type: a MRI study.

Studies on the prevalence of MRI signal abnormalities in the brains of migraineurs have yielded controversial results. In order to provide further data on this issue we reviewed the MRI scans of 38 migraine patients without current neurologic symptoms (mean age 35.8 +/- 11.9 years). In addition, we compared the findings in those 24 migraineurs under 50 years without major cerebrovascular risk factors (mean age 30.1 +/- 9.0 years) to that in 14 headache and risk factor free volunteers (mean age 37.8 +/- 5.3 years). Overall, focal areas of hyperintense signal were seen in 15 (39%) patients. They were present on both proton density and T2-weighted spin-echo sequences. Lesion prevalence varied according to the type of headache (18% in migraine without aura, 53% in migraine with typical aura, 38% in basilar migraine). The subset of migraine patients under 50 years exhibited MRI signal abnormalities more than twice as often as controls (33% vs. 14%). Punctate white matter hyperintensities were the predominant finding and were seen in 10 of 15 individuals with MRI lesions. More striking signal abnormalities consisted of symmetrical areas of hyperintensity lateral to the posterior horns in two 24 year old patients and of extensive white matter damage with lacunar infarcts in a 59 year old woman. Our findings confirm a higher prevalence of MRI lesions in a mixed group of migraineurs than in headache free individuals. Signal abnormalities are most often non-specific, however their occurrence relates to the type of migraine.

Adolescent↗
PubMed1992

The benefit of graded physical exercise in chronic heart failure.

A new program of rehabilitation is less demanding on cardiac output than standard programs. Twenty-five patients with chronic heart failure (ejection fraction [EF]: 0.26 +/- 0.10) were randomized into 2 groups: a control group with 13 patients and a rehabilitation group of 12 patients. In the control group, 2 did not complete the study (cancer, cardiac transplantation). For the 11 others, the different parameters studied were comparable at day 0 with group R and did not significantly change over 3 months outside of a spontaneous improvement in endurance performance by 22%. In the rehabilitation group (40 sessions over 90 days; specialized equipment) there were no incidents. Tolerance was excellent (heart rate during sessions less than 115 bpm) and all functional parameters improved. Training did not modify the isotopic ejection fraction. The quality of life score increased respectively by 52% (p less than 0.0001 in comparison with the control group) and by 63% (p less than 0.0001); 80% of the patients requested that training be prolonged. The functional improvement obtained by purely peripheral effect had no adverse effect on the heart.

Chronic Disease↗
PubMed1992

[Main anticancer substances of vegetable origin].

During the last thirty years, the systematic screening of thousands of vegetal extracts has led to the isolation of numerous antitumor agents which belong to various chemical series. This paper only deals with some of them which are either of current clinical use or under advanced clinical experimentation, e.g., ellipticine, homoharringtonine, camptothecine, acronycine and their derivatives. The origin, the biological activity and its mechanism, and the toxicity of each of these alkaloids are described. These examples highlight the interest of the Plant Kingdom as source of biologically active new structures and the importance of a good knowledge of the mechanism of the activity and toxicity of active components. This knowledge gives a rational basis to prepare compounds of increased activity or reduced toxicity and to use them at their best in therapeutic.

Acronine↗
PubMed1992

Efficacy of rifaximin on symptoms of uncomplicated diverticular disease of the colon. A pilot multicentre open trial. Diverticular Disease Study Group.

Diverticular disease of the colon is a common health problem in western societies. Most patients with colonic diverticula are asymptomatic; it has been estimated that only 20% of individuals harboring diverticula will develop symptoms and signs of illness and a minority will develop major complications. Although the efficacy of a high fiber diet in the management of symptomatic uncomplicated diverticular disease is still controversial, bran and bulking agents are commonly used. Antibiotics are used to treat major inflammatory complications of diverticular disease but apparently there is no rationale for the use of antibiotics in uncomplicated disease where an inflammatory component is by definition excluded. In a multicenter open trial, 217 patients with symptomatic uncomplicated diverticular disease were treated with glucomannan (110 pts) or with glucomannan plus a poorly absorbable antibiotic (rifaximin 400 mg bid for 7 days each month) (107 pts). Clinical evaluation was performed bimonthly for 12 months using a global score system for 8 clinical variables. After 12 months, patients treated with glucomannan plus rifaximin showed a 63.9% reduction of the score as compared to 47.6% in patients treated with glucomannan only (p < 0.001). Cyclic administration of rifaximin appears to be of some advantage in obtaining symptomatic relief in uncomplicated diverticular disease.

Abdominal Pain↗
PubMed1992

[Relative value of attenuation and negativation of systolic pulmonary venous flow in severe mitral insufficiency. Transesophageal echocardiographic study].

The aim of this study was to analyse the velocity profile of the systolic fraction of the pulmonary venous flow (PVF) in mitral regurgitation (MR). Three velocity profiles were identified in left superior pulmonary vein. Inversion of the systolic fraction of the PVF was specific for angiographic grade 4 MR (specificity 97%, sensitivity 100%). On the other hand, a decrease in this wave is much less specific for mild MR and depends on severe factors such as left atrial pressure, size and ejection fraction and the lack of atrial systole (as in atrial fibrillation or atrioventricular block). Therefore, inversion of PVF has a good positive predictive value for severe MR, but the interpretation of attenuation of this wave should take into consideration not only the MR but also left atrial pressure and compliance.

Blood Flow Velocity↗
PubMed1991

[Does the care of diabetic patients with renal failure in the predialysis phase need improvement?].

The cardiovascular risk profile was assessed in all 208 diabetics accepted for dialysis in 28 German dialysis centres from 1985-1987 (104 men, 104 women, mean age 60 [22-82] years). 71 patients had type 1 and 128 type 2 diabetes, and 9 maturity onset diabetes of the young. Of 169 patients, 164 (97%) had hypertension (median systolic blood pressure at start of dialysis 200 [120-280] mm Hg). Only 74 patients (44%) were on continuing anti-hypertensive medication. Median serum cholesterol was 225 (66-424) mg/dl, LDL-cholesterol 158 (43-335) mg/dl and HDL-cholesterol 32 (10-67) mg/dl. In patients with a history of myocardial infarction (n = 26) the median cholesterol concentration was 269 (126-424) mg/dl, while in those with no history of myocardial infarction (n = 132) it was 221 (66-280) mg/dl (P less than 0.05). Only 5% of the patients had received lipid lowering therapy. Out of 175 patients, 65 (37%) had a history of smoking, and 25 (14%) were still smokers at the start of dialysis. There was a strong association between smoking history and amputations. Only 98 of 208 patients (47%) had had a specialist ophthalmological examination in the 12 months preceding the start of dialysis. Proliferative retinopathy was present in 33 out of 53 (62%) type 1 and 15 out of 98 (15%) type 2 diabetics. Out of 22 patients with unilateral or bilateral blindness, 2 (10%) had received no photocoagulation. - This investigation reveals a need for better medical care of diabetics with pre-end-stage renal failure.

Adult↗
PubMed1991

Ketamine enantiomers and acetylcholinesterase.

(-)-ketamine was found to be more potent than (+)-ketamine in all the studied reactions with acetylcholinesterase. In most cases the difference was small but for two rate constants the (-)-form was unique in having effects. Thus, the stereoselectivity of ketamine in this system is the opposite of most other systems studied.

Acetylcholinesterase↗
PubMed1991

[Transesophageal echocardiography: a new view of the heart].

Transoesophageal echocardiography is a simple technique which is now the object of a growing and well-deserved interest, due to the wealth of information it provides. This examination does not supersede the conventional transthoracic echocardiography, but it completes it by supplying more accurate data, especially in difficult clinical cases, such as mitral valve pathology, cardiac valve prostheses, intracardiac thrombosis, aortic dissection and septal abnormalities.

Echocardiography↗
PubMed1991

Parental behavior in the mouse: effects of lesions in the entorhinal/piriform cortex.

The effects of bilateral radiofrequency lesions in the region of the entorhinal and piriform cortex (ENT/PIR cortex) on pup-retrieving and ultrasound-elicited pup-searching behavior were investigated in ovariectomized estrogen-treated female mice, which were sensitized to pups by co-caring for a litter for 5 days together with the mother (FoEBex), as well as in primiparous lactating females (Flact). A further group of FoEBex were rendered anosmic by an intranasal treatment with zinc sulfate-solution before the sensitization period and tests for parental motivation. Both pup-retrieving and pup-searching behavior were disturbed to the same extent by ENT/PIR lesions and ZnSO4-induced anosmia in FoEBex. In Flact, however, pup-retrieving was not affected by the lesion, while ultrasound-recognition leading to pup-searching was disrupted. The present data suggest sensitization to pups as a case of olfactory learning and thus, the effects of the ENT/PIR lesions are regarded as anterograde olfactory amnesia. From the present data and results reported in the literature, it is suggested to differentiate between the neural substrates processing stimuli relevant for the appetitive component (pup-searching) of parental behavior (among others, the region of the entorhinal and piriform cortex), and the mechanisms regulating the consummatory component (pup-retrieving).

Animals↗
PubMed1991

Influence of affinity of antibodies upon their detection by liquid phase radiobinding assay and solid phase enzyme linked immunosorbent assay. Demonstration using monoclonal antibodies raised against rDNA human proinsulin.

Hybridomas producing proinsulin antibodies were cloned by limiting dilution of cell cultures obtained by fusion of splenocytes of immunized mice with immortal myeloma cells. Some proinsulin monoclonal antibodies crossreacted with labelled insulin but none did with labelled C-peptide indicating that the involved epitopes were at one of the insulin/C-peptide junctions or included in the insulin moiety. Hybridoma supernatants were assayed for IgG concentration by a solid phase assay and for ligand binding by a radiobinding assay and an enzyme linked immunosorbent assay. The half-life of immune complexes formed with radioligand was measured and, as expected, correlated with affinity as measured by the method of Scatchard. Antibody titres determined by enzyme linked immunosorbent assay did not correlate to those measured by radiobinding assay. IgG concentration correlated to enzyme linked immunosorbent assay titres but not to radiobinding assay titres. Finally, a significant correlation was found between radiobinding assay titre and the product of enzyme linked immunosorbent assay titre by the period of immune complexes. It is concluded that, except for very low affinity antibodies, enzyme linked immunosorbent assay is a capacity assay whereas radiobinding assay is influenced by both antibody concentration and affinity. The former assay is thus best suited to detecting low affinity antibodies whereas the latter is more efficient in the presence of low levels of high affinity antibodies.

Animals↗
PubMed1991

Epithelial synthesis of tenascin at tips of growing bronchi and graded accumulation in basement membrane and mesenchyme.

The extracellular matrix protein, tenascin, has been proposed as mediator in epithelial-mesenchymal interactions because of its characteristic distribution during embryogenesis. Here we compared the accumulation of tenascin and laminin in the early chicken lung bud. Laminin is deposited in the basement membrane, starting at the tips and increasing along the shafts of growing primary and secondary bronchi. In contrast, tenascin accumulation is highest in basement membranes and mesenchyme at sites where new bronchial branches are formed. By in situ hybridization, tenascin mRNA was found to be produced exclusively by the epithelium at sites of active growth of bronchial tubes.

Animals↗