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Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 307 records · Page 17Linked to original sources

Exocrine pancreatic function in dogs with denervated pancreas.

There is strong evidence that the vagus nerve plays an important role in exocrine pancreatic secretion. In the present study we examined the effect of total extrinsic denervation of the pancreas on exocrine pancreatic secretion to different stimuli in dogs. In the experiments we used the model of the orthotopic autotransplanted dog pancreas as described by Debas et al. Denervation of the gland did not significantly alter water and bicarbonate response to secretin. The dose-response curve of caerulein showed the denervated pancreas as sensitive as the intact gland. However, autotransplantation of the pancreas caused a significant decrease (p less than 0.05) in protein secretion during intraintestinal L-tryptophan in increasing doses. Furthermore, bicarbonate and protein secretion after food intake was significantly decreased in the denervated pancreas (protein: peak levels 380 mg/15 min and 135 mg/15 min; bicarbonate: 3.2 mEq/15 min and 1.4 mEq/15 min) (p less than 0.02). From our data we conclude that the denervated pancreas is as sensitive as the intact pancreas to stimulation by exogenous secretin and caerulein, whereas denervation of the pancreas causes an important influence in the intestinal phase of pancreatic secretion.

Animals↗

Total denervation of the pancreas does not alter the pancreatic polypeptide response to food intake.

The secretion of pancreatic polypeptide (PP) seems to be controlled by vagal cholinergic mechanisms, since both vagotomy and atropine significantly inhibit the PP response to food intake, sham feeding or insulin hypoglycaemia. In the present study, we examined the PP response to a meal after orthotopic autotransplantation of the pancreas. Completeness of vagal pancreatic denervation was confirmed by the missing response of pancreatic protein and the PP response to insulin hypoglycaemia. Total vagal denervation of the pancreas did not alter the PP response to a meal (peak PP levels 402 +/- 41 pg/ml before transplantation compared to 510 +/- 98 pg/ml after operation). The secretion of PP after food intake seems not to be mediated by direct vagal innervation of the pancreas itself. Since pancreatic autotransplantation results in an interruption of gastropancreatic or enteropancreatic neural reflexes, our results confirm the findings of Debas et al. [Surgery 92:309-313, 1982] and strongly suggest that the PP response to nutrient stimuli is mediated by a humoral mechanism.

Animals↗

Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses.

We investigated impaired cellular immune responses of individuals on chronic hemodialysis by using monoclonal antibodies that trigger differential pathways of T cell activation. Reduced cellular reactivity, which exists in a high proportion of such patients, can be attributed to a failure of the monocyte population to support the process of primary T cell activation in vitro. This defect results in a lack of interleukin 2 production, which is critically dependent on a monocyte-derived signal. In contrast, T lymphocyte function was found to be physiologic. Perhaps more important, the degree of monocyte dysfunction in vitro correlated with the same patients' in vivo responses to hepatitis B vaccination. Addition of recombinant human interleukin 2 fully reconstituted their deficient immune response in vitro.

Adult↗

Perspectives on antigenicity and idiotypy.

The recent crystal determination of a lysozyme-antilysozyme complex provides a three-dimensional prototype of the manner in which contacts in idiotype-anti-idiotype interactions may be realized. Such interactions can be approximated by two complementary "flat" surfaces. Each IDR (autoantigenic locus) location might provide a particular recognition feature between two interacting partners. The combinatorial manner in which IDR domains are recognized by anti-idiotypic antibodies describe the repertoire of private and public (crossreactive) idiotopes of an antibody. Several interesting features emerge from consideration of the Ab contact residues in the crystal structure. First, framework residues are implicated in contacting the antigen: Thr 30 (FR1) of the heavy chain and Tyr 49 (FR2) of the kappa light chain. Both of these residues lie within predicted IDRs. Framework regions have recently been suggested to be involved in several anti-idiotypic systems, although such regions have, in the past, been disregarded based solely upon sequence analysis. The surface variability analysis, which identifies the repertoire of complementary interacting surfaces, depicts the immunoglobulin as having more variability than generally thought. This variability may also extend to T cell receptors since T cell chains express an extensive surface variable repertoire similar to that of the immunoglobulin light chains (Kieber-Emmons and Köhler, unpublished). Second, the D region plays a critical role in the generation of the antilysozyme combining sites. Similarly, the D segment makes up the largest component of an IDR. Third, while the CDR3 of the heavy chain contributes most to the antibody-lysozyme complex it is not the most surface-exposed (see Novotny, this issue). Nevertheless, surface variability analysis indicates that this region is generally immunodominant which is also observed experimentally. Together, these results indicate that perhaps certain IDR regions are intrinsically more antigenic. Idiotypic structures must be accessible for antibody recognition and binding. From a structural viewpoint, a single antibody molecule has a continuum or several different combining sites. Subsequently, a single residue can be contained in several overlapping idiotypic determinants. Surface variability analysis suggests that the hypervariable regions of Igs provide a diverse idiotope repertoire that can be utilized for binding. Monoclonal antibodies have been shown to have multiple specificities and this capacity for multiple binding is also intrinsic to the definitions that have emerged for anti-idiotypic antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

[Improvement in the prognosis of renal cell carcinoma by percutaneous transvascular embolization].

In a retrospective study of 303 patients with renal cell carcinomas the prognostic influence of the percutaneous transvasal embolization of the renal artery was demonstrated. In form of the life-table-method we compared statistically the survival rates of preoperatively or palliatively embolized patients with such ones who were only nephrectomized or treated only symptomatically. In the tumour stages T2 and T3 the preoperative percutaneous transvasal embolization leads to a clearly higher survival rate; in stage T2 statistically significant. After palliative embolization the improvement of the prognosis is evident compared with the inoperable patients who were treated only symptomatically. The prognosis after palliative preoperative percutaneous transvasal embolization and retarded nephrectomy is not worse than after preoperative percutaneous transvasal embolization and immediate nephrectomy. The effect of the preoperative and palliative embolization improving the prognosis should incite all partners who up to now objected to this therapeutic method to reconsider their therapy concept.

Carcinoma, Renal Cell↗

Follow-up studies of three subtypes of acute postinfectious glomerulonephritis ascertained by renal biopsy.

Quantitative correlative investigations by means of light, immunofluorescence and electron microscopy carried out in the early phase of the disease on 58 patients (children and adults) with acute postinfectious glomerulonephritis (APGN) formed the basis of subtyping APGN into a starry sky type, a mesangial type and a garland type [Sorger et al. 1982 and 1983]. The subtypes also showed differences in the clinical picture. The garland type was of special interest since most patients had severe proteinuria. This caused us to follow-up the patients with these three subtypes (up to 10 years and 7 months). Proteinuria proved to be the most reliable follow-up parameter. A comparison of the three groups showed that proteinuria rapidly declined as a rule in the patients with the starry sky and the mesangial patterns. In the garland pattern there were also cases with a complete disappearance of proteinuria, especially in younger patients, but other patients still had a distinct proteinuria after months to years indicating a protracted or chronic course. The morphological findings of the rebiopsies correlated with the clinical courses, especially with the course of proteinuria. The three morphological subtypes are thus significant for estimating the prognosis of APGN, which is favorable as a rule in patients with the starry sky and mesangial types, but much more unfavorable in patients with the garland type. Even if fewer cases with demonstrated streptococcal etiology were found in the garland pattern group, i.e., among patients with the most uncertain prognosis, than in the remaining groups, these differences were not statistically significant. Therefore, our investigations do not provide any indications that different etiological factors are responsible for the three subtypes. The individual immune response of the host body is likely to be very much more decisive.

Acute Disease↗

Identification of Goodpasture target antigens in basement membranes of human glomeruli, lung, and placenta.

Collagenase-digests of human glomerular (GBM), alveolar (ABM), and placenta basement membranes (PBM) were separated by gel filtration columns and the pools rich in Goodpasture antigens (GP) were identified by an antibody inhibition-ELISA. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting on nitrocellulose membranes was performed with each basement membrane preparation. Sera from patients with florid GP-syndrome and antibodies to glomerular basement membrane (anti-GBM antibodies) were incubated with nitrocellulose strips of GBM, ABM, and PBM. Immunoperoxidase staining revealed reactivity with target antigens of 24, 26, 44, and 50 kD in the GBM and of 44 and 50 kD in the ABM and PBM, respectively. No corresponding reactivity was observed using convalescent GP-sera, sera from patients with other immunological diseases or sera from healthy blood donors. The antigens were sensitive to reduction. We conclude, that antigens of similar molecular-weights can be identified by anti-GBM positive sera in human glomerular, alveolar and placenta basement membranes.

Adult↗

[Significance of commemorative meetings on great physicians of the past].

Commemoration-days are particularly significant, when thinking approaches from former times can be related to new hypotheses and working methods and thus can lead to better results. This is generally taken into consideration and here especially applies to great physicians. For the characterization of a great physician 6 points are mentioned: 1. a high measure of creativity, 2. unflinching industry, 3. teachers of their subject, 4. formation of schools, 5. action as an example, 6. setting up a standard for his subject. From the history of medicine 30 great physicians are mentioned with name and lifetime and with short words is thought of their important achievements, continuing effective historically.

History, 15th Century↗

[Physiosclerosis--arteriosclerosis. Progression and regression then and now].

The clinical recognition of the physiosclerosis is still problematic even nowadays. This question seems not to be actual, since the disease arteriosclerosis with all its sequels is the superior epidemiological problem of mankind. Therefore, the inhibition of the progression and the regression of arteriosclerosis is of great interest. Now as ever, however, the coming forth of an atheromatous focus into the blood stream and the later change of the ulcer developed in such a way into fibrous connective tissue is the only regression of the arteriosclerosis in man up to now certainly made evident. A new course is adopted. Three approaches of intervention are represented with own results: favourable effects of multiply unsaturated fatty acid, importance of the trace element balance, particularly of selenium, the use of the classical risk factor concept at all ages.

Arteriosclerosis↗

Relationships between liquid- and solid-phase antibody association characteristics: implications for the use of competitive ELISA techniques to map the spatial location of idiotopes.

A liquid-phase assay system based on small-zone size-exclusion chromatography was used to examine the binding of a monoclonal anti-idiotopic antibody, F6, to its idiotope on the murine plasmacytoma IgA, TEPC-15. Chromatographic behavior revealed a strong association between T-15 and F6, which was previously characterized by solid-phase immunoassay as recognizing a nonbinding site epitope of the T-15. This chromatographic pattern suggests that the inability of the hapten phosphorylcholine to inhibit the anti-idiotope:idiotope relationship in solid-phase immunoassay might be equally explained by the low affinity of the hapten relative to the high affinity of the anti-idiotope antibody. Bivalent interactions between solid-phase IgA and liquid-phase IgG should enhance the binding of the anti-idiotope to an extent that would prevent the hapten from dissociating the complex. Under these solid-phase assay conditions, observation of hapten inhibition may, in some cases, indicate site specificity, but absence of inhibition cannot be interpreted. Computer simulations of solid-phase hapten inhibition scenarios were used to evaluate the qualitative nature of binding inhibition profiles expected under various conditions of liquid- and solid-phase reactant affinities and concentrations. The apparently unusual inhibition curves previously observed in the T-15:anti-T-15 studies in which the degree of binding inhibition by hapten appeared to be independent of anti-idiotope concentration may be predictable in cases of excess solid-phase epitope; the plateau inhibition value is a function of relative affinity constants and concentrations of solid-phase and inhibitor components. The results additionally suggest that the affinity of a liquid-phase antibody may modulate the effective concentration of solid-phase epitope.

Antibody Affinity↗

Impaired cellular immune responses in chronic renal failure: evidence for a T cell defect.

Cellular immune responses in vitro were studied in 24 patients on chronic hemodialysis and 16 healthy volunteers with normal kidney function. Patients on maintenance hemodialysis had lymphopenia with diminished numbers of both T4+ and T8+ T-lymphocytes. The T4/T8 ratios were within the normal range. Peripheral blood lymphocytes (PBL) showed a diminished proliferative response upon stimulation with concanavalin A, phytohemagglutinin and pokeweed mitogen. When cell surface antigens were used for stimulation (mixed lymphocyte culture) uremic lymphocytes also showed a lower proliferation rate. Although without statistical conformation, there was a tendency by uremic PBL to produce less IL-2 as compared to healthy controls. Moreover, in a PWM driven system, peripheral blood lymphocytes from uremics produced significantly less IgG than PBL from normals. These results support the notion that a profound defect in lymphocyte function accounts at least, in part, for the observed immunodeficiency of uremic patients.

Adult↗

[Cattle calcinosis in the Lower Austria Alpine foothills area].

It is reported on cases of calcinosis during winter 1979/80 occurring on 42 farms and leading to 34 forced slaughters and on the control of this disease in a localized region of the Alpine foot-hills. Instruction of the farmers, ploughing up of the meadows with following new sowing of grass without golden oat (Trisetum flavescens) allowed to push back calcinosis in high situated especially endangered farms. The different calcinogenic activity of golden oat in the different stages of growing, pushing back the golden oat by repeated utilisation of the pastures and keeping the cattle in the stable were successful methods. Additionally it was possible to influence the quantity of golden oat in pastures and meadows by methods influencing the growing such as climate, altitude, quality and quantity of fertilizer, age of the meadows. The importance of the Alpine pastures for prevention of calcinosis in cattle is pointed out.

Animals↗