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Biomedical subjects

J Kohler

Publications and source records attributed to J Kohler.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Ambulatory/partial inpatient neurologic-neuropsychologic rehabilitation. I: Results of a demand analysis in South Germany].

This study presents a survey on the demand for out-patient neurological-neuropsychological rehabilitation. Neurologists working in acute care and in in-patient rehabilitation settings as well as neurologists and neuropsychologists with out-patient practice were asked to rate the demand for and the present means to realize out-patient neuropsychological rehabilitation. The results show a great demand for out-patient rehabilitation. The preferred concept and model of out-patient rehabilitation depends on the setting where the participants of the study work with a tendency to favour flexible programs close to patients' habitation.

Ambulatory Care↗
PubMed1997

[Ambulatory/partial inpatient neurologic-neuropsychologic rehabilitation. II: Results of an analysis of patient management characteristics in South Germany].

Neurological-neuropsychological out-patient rehabilitation in Southern Germany is realized mostly by neurologists and neuropsychologists in out-patient practice. However, profile and quantity of treatment as well as the structure of the health system fail to meet the requirements of out-patient rehabilitation as described in the first part of the study.

Ambulatory Care↗
PubMed1996

T cell immune responses to haptens. Structural models for allergic and autoimmune reactions.

Protein-reactive chemicals, metal salts and drugs, commonly classified as immunological haptens, are major environmental noxes targeted at the immune system of vertebrates. They may not only interfere with this defense system by toxicity alone, but more often by evoking hapten-specific immune responses resulting in allergic and eventually autoimmune responses. Here, we review recent developments in the analysis of the structural basis of hapten recognition, particularly by T lymphocytes, which represent central elements in cell-mediated, as well as in IgE dependent, allergies. A break-through in this field was the finding that T cells detect haptens as structural entities, attached covalently or by complexation to self-peptides anchored in binding grooves of major histocompatibility antigens (MHC-proteins). Synthetic hapten-peptide conjugates were shown to induce hapten-specific contact sensitivity in mice, opening new routes for studying hapten-induced immune disorders.

Amino Acid Sequence↗
PubMed1995

Characterization of the pre-mRNA binding site for yeast ribosomal protein L32: the importance of a purine-rich internal loop.

The structure of the RNA binding target for Saccharomyces cerevisiae ribosomal protein L32 was examined using chemical and enzymatic probes as well as thermodynamic methods. In vivo, the production of yeast RPL32 is regulated by a feedback mechanism whereby RPL32 binds to the 5' end of its transcript and inhibits splicing. The binding site of ribosomal protein L32 on the L32 RNA transcript can be reduced to fewer than 30 nucleotides which compromise a stem-internal loop-stem structural motif. The internal loop is closed by a potential G-U pair, is asymmetric and contains mostly purines. The existence of the two helical regions was confirmed by chemical and enzymatic probing. The reactivity of the loop region suggests a structure intermediate between that of single and double-stranded RNA. Base stacking continues into the loop, but two loop bases are extremely reactive to chemical agents. The interaction between the model RNA and the protein is specific and has a dissociation constant of approximately 10 nM. Several of the loop bases are critical for protein binding, as demonstrated by mutational data and chemical protection and modification interference studies. The internal loop destabilizes the RNA, and allows the RNA to melt in an all-or-none fashion.

Aniline Compounds↗
PubMed1995

Endothelin-1 expression in myenteric neurons cultured from rat small intestine.

Endothelin is a potent vasoactive peptide. More recently, endothelin-1 (ET-1) has been found in neural tissues such as spinal cord, brain and peripheral ganglion cells. Inagaki (Gastroenterology 101 (1991) 47) reported evidence of ET-1-like immunoreactivity in enteric neurons, but there are no reports of ET-1 peptide or mRNA expression specifically in myenteric neurons. Using a primary culture of myenteric neurons, we set out to evaluate ET-1 peptide and mRNA expression. Myenteric neurons were cultured using a dissection and enzyme dispersion technique. ET-1 reactivity was localized to neurons and ET-1 levels from cells and media were assayed by radioimmunoassay under a variety of media conditions or with depolarizing buffer or veratridine (75 microM). Prepro ET-1 mRNA expression was determined by Northern analysis of total RNA utilizing a rat ET-1 cDNA. ET-1 immunoreactivity was observed almost exclusively in myenteric neurons. Cells contained 0.78 pg/micrograms protein and did not vary with variations in media conditions. Basal release/secretion into media occurred but was not enhanced by depolarizing media or veratridine. High levels of ET-1 mRNA expression were identified. These results of high level constitutive expression of ET-1 linked with previous reports of ET-1 modulation of cholinergic intestinal smooth muscle contraction suggest a neuromodulatory role.

Animals↗
PubMed1995

Cross-reactive trinitrophenylated peptides as antigens for class II major histocompatibility complex-restricted T cells and inducers of contact sensitivity in mice. Limited T cell receptor repertoire.

The induction of contact sensitivity in mice by hapten reagents such as trinitrochlorobenzene (TNCB) involves the activation of class II major histocompatibility complex (MHC)-restricted, hapten-specific, CD4+ T cells. Reports from different laboratories have indicated that the relevant antigenic epitopes in such reactions might include hapten-conjugated, MHC class II-associated peptides. This study for the first time directly demonstrates that hapten-peptides account for the majority of determinants recognized by trinitrophenyl (TNP)-specific CD4+ T lymphocytes. The sequences of those TNP carrier peptides do not have to be related to mouse proteins. Thus, we show that TNP-modified peptides derived from mouse IgG, pigeon cytochrome c or staphylococcal nuclease known to bind to I-Ab or from lambda repressor with specificity to I-Ad as well as TNP-proteins such as bovine serum albumin, ovalbumin or keyhole limpet hemocyanin all create class II-restricted hapten determinants for a number of TNP-specific T cell clones and hybridomas. All of these cells were induced with cells modified by trinitrobenzene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP-specific helper T cells may cross-react with different TNP-peptides bound to identical class II molecules. Chemical treatment of antigen-presenting cells with TNCB or TNBS may thus result in a limited number of particularly repetitive immunodominant hapten epitopes. Immunodominant epitopes were also indicated by an overrepresentation of the TCR elements V beta 2 and V alpha 10 in I-Ab/TNP-specific T cells. Most importantly, however, we demonstrate that TNP attached to lysine 97 in the staphylococcal nuclease peptide 93-105 (i.e. a clearly "non-self" sequence) is able to prime mice for subsequent elicitation of contact sensitivity by TNCB in the absence of foreign protein. We take this to indicate that those TNP-peptide determinants defined by us as immuno-dominant are responsible for the induction of contact sensitivity to haptens.

Amino Acid Sequence↗
PubMed1995

Glyceroltrioleate/glyceroltrierucate therapy in 16 patients with X-chromosomal adrenoleukodystrophy/adrenomyeloneuropathy: effect on clinical, biochemical and neurophysiological parameters.

UNLABELLED: We have investigated the effect of glyceroltrioleate/glyceroltrierucate (GTO/GTE) therapy on X-chromosomal adrenoleukodystrophy in 16 patients with adrenoleukodystrophy (n = 6), adrenomyeloneuropathy (n = 3), Addison disease without neurological involvement (n = 2), and neurologically and endocrinologically asymptomatic patients (n = 5). Therapy was carried out for 19.4 +/- 10 months. All patients showed a normalization of C 26:0 plasma fatty acid concentrations. None of the seven neurologically asymptomatic patients developed neurological symptoms. Somatosensory evoked potentials of the tibialis nerve was the most sensitive electrophysiological parameter, showing a slight improvement in neurologically asymptomatic patients during therapy. In none of the patients with normal cranial MRI at start of therapy (n = 6) has MRI deterioration been observed whilst on therapy. Follow up of the neurologically asymptomatic children supports the hypothesis that GTO/GTE therapy might prevent the development of neurological symptoms. Six of the nine neurologically symptomatic patients deteriorated to varying degrees whilst on therapy. MRI alterations have worsened in all patients with clinical deterioration. CONCLUSION: GTO/GTE treatment should be initiated in all neurological asymptomatic boys before first neurological symptoms develop. To discover these patients very long-chain fatty acid determination should be performed in all family members at risk when adrenoleukodystrophy or adrenomyeloneuropathy is diagnosed.

Adolescent↗
PubMed1995

Gentle Touch, a lens material resistant to protein deposition.

We investigated the ability of the Gentle Touch, a non-ionic contact lens material containing 35% netrafilcon A and 65% water, to repel protein deposits. Studies were conducted in vivo (lenses worn by patients) and in vitro (lenses coated by artificial tears). Acuvue soft contact lenses, an ionic lens material containing 42% etafilcon A and 58% water, were used as controls. After 1 to 2 weeks of wear, protein deposits on Gentle Touch lenses averaged 1.5-2.8 micrograms per lens versus 338-444 micrograms per lens for Acuvue. Gentle Touch lenses that were heat-coated with an FDA tear solution recommended for testing protein deposition averaged 6.5 micrograms of protein deposits per lens, whereas almost 100 micrograms of protein was deposited on each Acuvue lens. Lenses treated with an artificial tear solution deposited a non-detectable amount of protein on each Gentle Touch lens versus more than 358 micrograms on each Acuvue lens. These studies demonstrated that Gentle Touch lenses are highly resistant to protein deposits.

Biocompatible Materials↗
PubMed1993

IFN-gamma involvement in the severity of gram-negative infections in mice.

The role of IFN-gamma in the regulation of inflammation leading to gram-negative septic shock is still poorly understood. IFN-gamma blockade has been shown to improve the survival of animals challenged with i.v. bolus injections of LPS and gram-negative bacteria. We have investigated a model of focal Escherichia coli infection leading to peritonitis and septic shock. Mice were challenged i.p. with an inoculum near the LD50. The addition of rIFN-gamma together with bacteria increased the mortality and the level of blood TNF-alpha and IL-6. Conversely blockade of IFN-gamma with a neutralizing mAb significantly improved the survival of the mice. This beneficial effect was not associated with a stringent decrease in blood bacterial counts and TNF-alpha and IL-6 levels in survivors. In this model, the protective effect of anti-IFN-gamma mAb contrasted with the ineffectiveness of a neutralizing anti-TNF-alpha mAb. These findings suggest that overproduction of IFN-gamma might have a more detrimental role than overproduction of TNF-alpha during focal gram-negative infections.

Animals↗
PubMed1993

[Unilateral blindness in neurosyphilis].

A 55 year-old patient developed loss of vision in his right eye over a period of a few weeks with the clinical finding of uveitis and papillaedema. Subsequently, also the left eye was affected by a marked deterioration of vision. The neurological findings were normal. The laboratory findings showed a marked elevation of the ESR (> 100 mm within the first hour) and protein electrophoreses showed changes suggestive of chronic inflammation. Analysis of the cerebrospinal fluid revealed a lymphocytic meningitis with 180/3 cells; the positive serological and liquor findings for TPHA and FTA led to the definite diagnosis of neurosyphilis. Treatment intravenously with 3 x 4 million units penicillin G daily for a fortnight proved curative. Vision of the left eye recovered fully, but the ophthalmological changes in the right eye were irreversible. This case shows that even today the differential diagnosis of syphilis must be considered with loss of vision of doubtful aetiology and uveitis.

Blindness↗
PubMed1992

Cytokine production after intravenous or peritoneal gram-negative bacterial challenge in mice. Comparative protective efficacy of antibodies to tumor necrosis factor-alpha and to lipopolysaccharide.

The production of TNF-alpha, IL-1, and IL-6 was measured in mice after bolus i.v. Escherichia coli O111 LPS injections and during bacteremia induced either by bolus i.v. or by i.p. challenges of live E. coli O111. High but transient TNF-alpha peaks were observed after bolus i.v. LPS or bacterial challenges. In contrast, the levels during lethal peritonitis increased progressively to values 50- to 100-fold lower than the peak values observed after i.v. injections, and remained sustained until death. Whereas after i.v. challenge with 1000 LD50 of LPS, anti-TNF-alpha antibody fully protected mice from death and reduced serum IL-1 and IL-6 levels, anti-TNF-alpha antibody did not improve the survival of mice nor reduced serum IL-1 and IL-6 levels after i.p. bacterial challenge. In contrast to anti-TNF-alpha antibodies, anti-LPS antibodies were protective in the peritonitis model. Protection was accompanied by a striking reduction of bacterial numbers and of TNF-alpha, IL-1, and IL-6 levels in the serum, but the levels of these cytokines were only marginally affected in the peritoneal lavage fluid. This latter observation demonstrates that the local peritoneal cytokines did not diffuse readily into the circulation, thus suggesting that at least part of the circulating cytokines are produced systemically. In conclusion, the striking differences between cytokine profiles as well as the divergent efficacy of anti-TNF-alpha antibody after i.v. bolus and after i.p. challenges suggest that TNF-alpha may not be as important in the pathogenesis of lethal peritonitis than after lethal acute bacteremia.

Animals↗
PubMed1992

[Neurologic complications of Q-fever (Coxiella burnetii)].

We report on fifteen patients with a typical syndrome of Q-fever. Four patients (= 27%) showed signs of nervous system involvement. One patient developed a meningitic syndrome, another patient had a passing psychosis. In two patients, severe cerebellar deficits were predominant. It is pointed out that these two patients were under lithium therapy because of manic-depressive illness. A synergetic neurotoxic effect of cociella burneti infection and lithium is discussed as a possible cause of the severe cerebellar pattern of symptoms.

Adult↗
PubMed1990

Induction and activity of NO synthase in bone-marrow-derived macrophages are independent of Ca2+.

The aim of the present study was to analyse whether an increase in the intracellular free Ca2+ concentration ([Ca2+]i) plays a role as a signal mediating synthesis of nitric oxide (NO) in bone-marrow-derived macrophages, either by stimulating induction of NO synthase or by regulating the activity of the enzyme. Therefore we compared the effects of various synthetic analogues of bacterial lipopeptide and of lipopolysaccharide (LPS) on NO production (assessed as nitrite formation during an incubation for 24 h) and on [Ca2+]i [measured with the fluorescent probe indo-1 (1-[2-amino-5-(6-carboxyindol-2-yl)phenoxy]-2- 2-(2'-amino-5'-methylphenoxy)ethane-NNN'N'-tetra-acetic acid)]. Strongly dissociating effects were evoked on nitrite formation and on [Ca2+]i by the stimuli. LPS was preferentially effective on nitrite formation, whereas the Ca2+ ionophore ionomycin and AlF3 induced increases only in [Ca2+]i. The lipopeptides N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)-(2RS)- propyl]-(R)-cysteinylalanylglycine, N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)- (2RS)-propyl]-(R)-cysteinylseryl-lysyl-lysyl-lysine and (S)-(1,2- dicarboxyhexadecyl)ethyl-N-palmitoylcysteinylseryl-lysyl-lys yl-lysine stimulated both parameters, but the maximal effects on nitrite formation and the shape of the dose-response curves did not parallel the effects on [Ca2+]i. Reduction of extracellular Ca2+ with EGTA significantly inhibited increases in [Ca2+]i, but did not change nitrite formation. Furthermore, NO synthesis in the cytosolic fraction of stimulated macrophages was not affected by Ca2+ over the concentration range 10 nM-2 microM. We conclude that increases in [Ca2+]i are not required for NO production in bone-marrow-derived macrophages. Thus the cellular regulation of NO production strikingly differs from that in the vascular endothelium, brain and adrenal gland.

Aluminum↗
PubMed1990

[Lyme borreliosis in neurology and psychiatry].

Neurological manifestations of Lyme disease are as multifarious as the entire spectrum of this common infection. In stage I, fibromyalgia and, more rarely, painful muscular fasciculation, dominate the clinical picture. In the individual case, mild psychic abnormalities may already be observed. Characteristic of the 2nd stage is lymphocytic meningopolyneuritis. Involvements of the CNS are expressed not so much in focal deficits, as in diffuse psychopathological disorders. In stage 3, CNS manifestations are characterized by chronic, in part multifocal, encephalitides and encephalomyelitides, isolated transverse myelitides and cerebral vasculitic disorders. The clinical symptomatology may be dominated by severe psychiatric syndromes. Connatal and subclinical latent infections of the nervous system with Borrelia represent special forms.

Diagnosis, Differential↗
PubMed1990

A magnetic measurement device for the kinematic analysis of unrestrained human hand movements.

A magnetic measurement device is described which was constructed to study human hand- and finger-movements. The system overcomes some problems frequently arising in the study of finger grip movements. It allows the simultaneous recording of several positions which cannot be observed with optical devices because they are hidden by other parts of the limb. Trajectories are recorded using small receiver coils moving in an alternating magnetic field of 3 transmitter coils. The performance of subject's movements is not significantly disturbed. A high sampling rate and a lack of mechanical damping permit a high temporal resolution which can analyze rapid movements. Subjects are not exposed to any biological risk or discomfort. Thus, a recording session can be repeated numerous times. The results obtained from this type of apparatus may allow quantification of the course of progressing diseases and to study the effects of remediation.

Electromagnetic Fields↗
PubMed1990

Ischemic stroke due to protein C deficiency.

Plasma protein C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis has been only rarely observed. We describe a young patient with heterozygous protein C deficiency who experienced a severe stroke due to thrombotic occlusion of the left middle cerebral artery.

Adult↗
PubMed1989

The role of short-term visuo-spatial memory in control of rapid multi-joint prehensive movements.

How memorized visuo-spatial information influences motor control and whether this information is able to replace the feedback processing in cases of visual deprivation was studied using an unrestrained finger- and hand-movement paradigm. Nineteen right-handed subjects were asked to grasp and lift a small block with the index finger and thumb of the right hand, as quickly as possible. The efficiency of motor performance was analysed by measuring the grasping time derived from tangential velocity profiles of the fingertips. The data revealed significantly shorter grasping times under continuous visual guidance than during blind grasping. Grasping times increased under conditions with stepwise prolongation of visual deprivation time prior to the movement onset. The results support the general concept that within the first seconds of visual deprivation, stored visuo-spatial information can partly compensate for the lack of continuous visual feedback.

Adult↗