PubMed Health⌕ Search

Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 127 records · Page 7Linked to original sources

Heat-preconditioning confers protection from Ca(2+)-mediated cell toxicity in renal tubular epithelial cells (BSC-1).

A rise in intracellular calcium may mediate ischemic damage by phospholipid hydrolysis and proteolysis. Heat shock proteins have been shown to provide protection from various forms of cell stress, but not from models of Ca(2+)-mediated injury. The effect of heat preconditioning in a model of ionomycin-induced injury in cultured renal tubular epithelial cells (BSC-1) was examined. Hsp70-mRNA expression was induced by hyperthermia (HT) (42 degrees C, 60 min). Hsp70 protein accumulation was maximal after 12-18 h and returned to baseline levels by 96 h. Treatment of BSC-1 cells with ionomycin (7.0 microM) produced lethal cell injury characterized by LDH release. Cells examined at 18 h after HT were significantly less damaged than cells studied at 96 h after HT. Our data are the first to demonstrate that heat preconditioning confers protection from Ca(2+)-mediated cell injury. The state of increased tolerance is transient and closely parallels kinetics of Hsp70 expression.

Amino Acid Transport Systems↗

B cell superantigens in HIV-1 infection.

HIV-I infection affects many of the cellular components vital for the maintenance of immune homeostasis. Similar to the T cell superantigen effect on T cell expansion and depletion in AIDS. HIV components with B cell superantigenic properties could be responsible for the observed B cell activation and skewing of VH family usage. Current data on possible B cell superantigen properties of HIV proteins (gp120) are mostly based on studies describing the clonality and VH family usage of immunoglobulins in HIV infection. Various laboratories reported independently an unusual skewing of the VH-repertoire of antibodies that appears not to be random. According to these observations, an enrichment of VH1 and VH4 family-paralleled a depletion of VH3 family-utilizing anti-HIV-1 gp120 and p24 antibodies in HIV-1 infected individuals and a loss of total VH3+ Ig in patients with late stages of AIDS. Polyclonal and monoclonal (VH1, VH4, and VH5) anti-p24 and gp120 antibodies share a crossreactive idiotype (IF7). IF7 like antibodies were found in the serum of HIV-1 infected individuals, persisting in the course of infection, perhaps contributing to the depletion of VH3 Ig. Furthermore a restriction of clonal heterogeneity of anti-p24 and anti-gp120 antibodies was detected by isoelectric focusing and indicated by skewed kappa/lambda light chain isotype ratios, indicating clonal dominance of certain sets of anti-HIV-1 antibodies during infection. Taken these findings together, a strong case for the involvement of a B cell superantigen can be made, although the mechanism of B cell depletion is not fully understood.

Acquired Immunodeficiency Syndrome↗

[Experimental affecting of pulmonary clearance of Pasteurella multocida induced pneumonia in swine].

The pulmonary clearance of Pasteurella multocida in weaner pigs was not affected by Carrageenan and Silica, two substances which block the function of monocytes/macrophages. Neutropenia, caused by the application of hydroxyurea, however, inhibit the pulmonary clearance markedly and reduced the severity of simultaneously induced pneumonias considerably. This indicates the importance of polymorphonuclear neutrophils for early clearance mechanisms and their inflammation inducing and maintaining effects.

Animals↗

[LPS receptor expression and lps binding capacity of monocytes and macrophages in swine].

The expression of the lipopolysaccharide (LPS) receptor CD14, being of importance for an effective immune response, and the direct measurable binding of LPS molecules by alveolar macrophages (AM), peritoneal macrophages (PM) and peripheral blood mononuclear cells (PBMC) of swine were determined. Additionally, the influence of an experimental intrabronchial infection with Pasteurella multocida on these parameters was investigated. Whereas the AM and the PM differed only negligibly regarding their share of CD14 bearing and LPS binding cells, in contrast to AM the intensity of the LPS-binding of PM was significantly higher. Among the PBMC, two populations could be detected which expressed the CD14 with different intensity, whereas the LPS-binding of both populations was similarly pronounced. Following infection of the animals, AM showed an unchanged percentage of CD14 positive cells and simultaneously an increased CD14 receptor expression. On the other hand, the percentage of the LPS-binding cells rose, while no changes of the intensity of LPS-binding were observable. The studies revealed that intrabronchial infection results in local and systemic alterations of CD14 expression and LPS-binding capacity of different cell populations. However, a direct correlation between the appearance of CD14- and LPS-binding does not seem to inevitably exist, indicating probably CD14-independent LPS-binding.

Animals↗

Analysis of "Ecstasy" by capillary electrophoresis.

Capillary electrophoresis (CE) and it's applications in forensic toxicology are demonstrated by the investigation of amphetamine derivatives in "Ecstasy" tablets. The method is based on capillary zone electrophoresis (CZE) with a phosphate running buffer (pH 2.2). The drugs were dissolved in 0.01 N hydrochloric acid, diluted with distilled water and phenylephrine was added to the samples as an internal standard. A separation of the charged substances is obtained by the different velocities in the electric field. The qualitative determination can be made by the migration times or more accurately by the relative migration times. Other possibilities for identification are the UV-spectra using a diode array detector or the on-column standard addition procedure. By this procedure the sample solution is initially injected followed by the standard solution. Both are concentrated in the column before separation begins. CE shows clear advantages in comparison to high-performance liquid (HPLC) or gas chromatography (GC). The quantitative analysis was carried out using the internal standard phenylephrine. The values obtained for 56 "Ecstasy" tablets and powder containing amphetamine or its derivatives were compared in this study after analysis with CE and HPLC. The results were in very good agreement. Because of it's speed, the high resolving power and the possibility of identification with the on-column standard addition, CE is a powerful alternative to HPLC or GC for the investigation of "Ecstasy" tablets.

Amphetamines↗

A model for respiratory syncytial virus (RSV) infection based on experimental aerosol exposure with bovine RSV in calves.

Five conventionally kept calves aged between 17 and 24 days were experimentally infected with bovine respiratory syncytial virus (BRSV) by aerosol in order to mimic the natural infection route. The calves were killed and autopsies performed 7 days after the first virus challenge. The BRSV isolate used induced tracheitis, bronchitis and atelectasis in infected calves. The only virus which could be isolated from the lungs of the calves was BRSV. In addition, Mycoplasma bovirhinis was isolated from the lungs or/and trachea of two calves. The clinical and histopathological findings, as well as the detection of BRSV antigens by immunofluorescence in the epithelial cells of lung and trachea, and the reisolation of the virus from bronchoalveolar lavage fluids of all inoculated calves, provided confirmation of successful infection with BRSV.

Aerosols↗

Summary of the BIOMOVS A4 scenario: testing models of the air-pasture-cow milk pathway using Chernobyl fallout data.

A unique opportunity to test dose assessment models arose after the Chernobyl reactor accident. During the passage of the contaminated plume, concentrations of 131I and 137Cs in air, pasture, and cow's milk were collected at various sites in the northern hemisphere. Afterwards, contaminated pasture and milk samples were analyzed over time. Under the auspices of the Biospheric Model Validation Study (BIOMOVS), data from 13 sites for 131I and 10 sites for 137Cs were used to test model predictions for the air-pasture-cow milk pathway. Calculations were submitted for 23 models, 10 of which were quasi-steady state. The others were time-dependent. Daily predictions and predictions of time-integrated concentrations of 131I and 137Cs in pasture grass and milk for six months post-accident were calculated and compared with observed data. Testing against data from several locations over time for several steps in the air-to-milk pathway resulted in a better understanding of important processes and how they should be modeled. This model testing exercise showed both the strengths and weaknesses of the models and revealed the importance of testing all parts of dose assessment models whenever possible.

Air Pollutants, Radioactive↗

Etiology and age have only a limited influence on the course of acute pancreatitis.

In a retrospective study of 602 patients with a first attack of acute pancreatitis, it was investigated whether the etiology of the disease and age of the patient are negative factors. There was no significant difference concerning hospital stay, respiratory and renal insufficiency, indication for surgery, or mortality rate among the different etiological groups. However, pancreatic pseudocysts developed significantly more frequently in alcoholics than in patients with other etiologies (p < 0.001 to p = 0.007). There was also no difference concerning hospital stay and respiratory insufficiency among the age groups. The increased incidence of renal insufficiency probably is related to physiological alteration with age, but the indication for dialysis did not increase. Pancreatic pseudocysts were more frequent in patients between 31 and 40 years of age, which was also the peak age group of alcoholics. Indication for surgery was the same for all age subgroups. The increase in mortality rate with age was weakly significant (p = 0.049). For the etiological subgroups, an increase in mortality with age was found only for biliary pancreatitis patients (p = 0.003). It is concluded that etiology and age of the patient have only limited influences on the course of acute pancreatitis.

Acute Disease↗

PECAM-1 expression in human mesothelial cells: an in vitro study.

Mesothelial cells are actively involved in inflammatory processes by expressing a set of cell adhesion molecules (CAMs). Transmigration of leukocytes into inflamed tissues requires a chemotactic stimulus and engagement of platelet-endothelial cell adhesion molecule-1 (PECAM-1). To investigate the kinetics involved in peritonitis, pure cultures of mesothelial cells are necessary. In previous studies, we have found that human mesothelial cells (HOMES) show a weak constitutive expression of PECAM-1, which cannot be further stimulated by cytokines. It is known that all serous cavities and body fluids contain numerous macrophages which strongly express this adhesion molecule. To identify the cells responsible for the expression of PECAM-1, mesothelial cells freshly obtained from omental tissue were isolated using PECAM-1-conjugated magnetic beads by cell sorting. For these studies, the negative as well as the positive fraction of isolated cells were used. As a control, freshly isolated monocytes were studied. Cell cultures were characterized by light and electron microscopy, as well as immunocytochemistry. The negative cell fraction was cultivated and stimulated for different times with tumor necrosis factor-alpha (30 and 300 U/ml), interleukin-1 beta (10 and 100 U/ml) and interferon-gamma (500 U/ml) and PECAM-1 expression was analyzed by a comparative quantitative cell enzyme immunoassay (EIA). The positive cell fraction was treated in the same manner. Both fractions of isolated cells showed strong positivity for cytokeratins 8, 18, 7 and 19, as well as vimentin. CD68, a monocyte marker, was not detected on mesothelial cells. In addition, EIA analysis confirmed the constitutive expression of PECAM-1 obtained from previous studies. This expression on HOMES was not inducible, irrespective of the type and concentration of cytokine studied. These data confirm PECAM-1 expression on mesothelial cells obtained from human omental tissue and suggest a critical role in transmigration of leukocytes during peritoneal inflammation.

Cell Separation↗

Morbidity and mortality in 602 patients with acute pancreatitis seen between the years 1980-1994.

The course of a first attack of acute pancreatitis was evaluated in a retrospective study of 602 patients, who were admitted between 01.01.1980 and 30.09.1993 to the Centers of Internal Medicine and Surgery of the University of Göttingen (n = 417) and from 16.11.1986 to 30.06.1994 to the Municipal Hospital of Lüneburg (n = 185). Etiology was biliary tract disease in 227 (37.7%), alcohol abuse in 177 (29.4%), unknown in 133 (22.1%), and other causes in 65 (10.8%) patients. Mean hospital stay was 27.9 +/- 24 days (x +/- SD), median 23 days. Pancreatic pseudocysts developed in 14.3% of the patients, and surgical treatment was necessary in 11.1%. Within the first 48 hours, respiratory insufficiency was observed in 63.2% of the 204 patients undergoing arterial blood gas analysis while renal impairment occurred in 32.6% of 602 patients. Artificial ventilation was indicated in 12.5%, and dialysis in 7% of the patients. Mortality rate was 6.1%, correlating significantly with respiratory and renal impairment and procedures in connection with these complications and also with transfers from other hospitals.

Acute Disease↗

[Hematuria--diagnostic procedure and therapeutic approaches].

Hematuria is a common clinical problem. It may arise from benign diseases posing minimal risk to the patient to potentially life-threatening conditions. Due to its many causes, the evaluation of hematuria often requires various different diagnostic procedures. To prevent unnecessary diagnostic tests, the workup should begin with noninvasive techniques such as history, urinalysis, laboratory data and ultrasonography. This proceeding allows a simple and rapid differentiation in renal and non-renal causes of hematuria in most cases.

Acanthocytes↗

Induction of human breast cancer-specific antibody responses in cynomolgus monkeys by a murine monoclonal anti-idiotype antibody.

We have generated and characterized a murine monoclonal anti-idiotype (Id) antibody, designated 11D10, which biologically and antigenically mimics a distinct and specific epitope of the high molecular weight human milk fat globule primarily expressed by human breast and some other tumor cells at high density. This epitope is identified by mAb BrE1, which was used as the immunizing antibody or Ab1 to generate the anti-Id (Ab2) 11D10. 11D10 induced antitumor immune responses across species barriers, i.e., in mice and rabbits. In preclinical studies, cynomolgus monkeys were immunized with 2 mg of either 11D10 or the isotype- and allotype-matched control Ab2 3H1 after precipitation with aluminum hydroxide. All monkeys developed high titers of antibodies against the immunizing mouse immunoglobulin. Immunization with 11D10 induced anti-anti-idiotype antibodies (Ab3) which reacted with breast cancer cell lines but not with control T-cell and melanoma cell lines. The Ab3 shared idiotypes with BrE1 (Ab1), as demonstrated by their ability to inhibit 11D10 binding to BrE1. The Ab3 obtained with 11D10 bound specifically to human milk fat globule antigen and competed with BrE1 for binding to breast cancer cell lines, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, Id-specific cellular immune responses were demonstrated in monkeys immunized with 11D10 by T-cell proliferation assays. These results indicate that aluminum hydroxide-precipitated anti-Id 11D10 can induce breast cancer-specific antibodies in nonhuman primates and can serve as a potential network antigen for breast cancer patients.

Animals↗

[Diagnosis of dysfunctions of replanted parathyroid gland tissue by bilateral analysis of intact parathyroid hormones in cubital vein blood. A prospective study].

AIM: In a prospective long-term follow-up study after operative therapy of hyperparathyroidism the value of bilateral determination of parathyroid hormone levels in cubital venous blood after total parathyroidectomy/autologous parathyroid gland reimplantation (musculus brachioradialis) for diagnosis of dysfunctioning grafted tissue is evaluated. PATIENTS AND MATERIAL: From August, 1, 1987 to March, 31, 1994 68 of 243 patients operated on for hyperparathyroidism underwent total parathyroidectomy. Autologous reimplantation of parathyroid gland was carried out simultaneously in 64 patients. Twice delayed reimplantation of cryopreserved tissue was carried out, and there was no reimplantation in two patients up to this day. Three patients were operated on for hyperfunctioning parathyroid autograft after former total parathyroidectomy/reimplantation. RESULTS: During follow-up 5 patients developed dysfunction of (reimplanted) parathyroid gland. Because of low or unprovable levels of intact parathormone the gradients of intact parathyroid hormone between grafted and nongrafted forearm were about 1:1 in postoperative hypoparathyroidism as well as in hypofunction of parathyroid gland. After successful replantation of cryopreserved parathyroid tissue gradients of intact parathyroid hormone increased (> 1:10). In hyperfunction of grafted parathyroid tissue hormone gradients were high (> 1:20 to 1:45,3) because of excessive high levels of intact parathormone in the cubital vein of the graft bearing arm. Successful reduction of parathyroid graft was followed by decrease of parathyroid hormone gradients. CONCLUSION: Regular follow-up of intact parathormone gradients together with intact parathyroid hormone levels and serumcalcium analysis allow the determination of parathyroid graft function. Also differentiation between graft dependent hyperparathyroidism and hyperfunctioning parathyroid tissue in the neck or mediastinum seems to be possible by bilateral determination of intact parathormone. Normal values or a normal range for intact parathyroid hormone gradients can not yet be defined.

Adult↗

Effect of neurotensin on pancreatic growth and pancreatic polyamine metabolism in rats.

The neuropeptide neurotensin is known to play a role in the regulation of exocrine pancreatic secretion, but actually there are conflicting results as to whether or not neurotensin exerts a trophic response on the pancreas and there are no data concerning its effect on pancreatic polyamine metabolism. In the present study, acute and long-term effects of various intraperitoneal dosages of neurotensin that resulted in mildly supraphysiological and even unphysiological high plasma concentrations of neurotensin were studied. Furthermore, neurotensin was simultaneously administered with cholecystokinin (1 microgram CCK-8/kg body wt ip every 8 h) for five days. The administration of neurotensin resulted in an acute significant decrease of pancreatic amylase and trypsinogen concentrations (p < 0.001), which indirectly confirms the potent effect of neurotensin on pancreatic exocrine secretion. In contrast to that, neither during the short-term study (100 micrograms neurotensin/kg body wt ip every 8 h for 2, 4, 6, 8, 16, and 24 h) nor during the long-term study (1 microgram, 100 micrograms, or 200 micrograms neurotensin/kg body wt ip three or eight times daily for 10 d) did neurotensin administration result in any increase of the various parameters of pancreatic growth and polyamine metabolism. Simultaneous administration of neurotensin and CCK failed to alter or further increase the known stimulatory effect of CCK on pancreatic polyamine metabolism and pancreatic growth after 5 d of treatment. These data indicate that neither alone nor in combination with cholecystokinin did various dosages of neurotensin exert any significant stimulation on pancreatic growth or the parameters of pancreatic polyamine metabolism.

Animals↗