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Biomedical subjects

J Knolle

Publications and source records attributed to J Knolle.

At least 55 records · Page 3Linked to original sources
PubMed1989

Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis.

The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4-dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C-terminal hexapeptide of secretin are given as examples.

Amides↗
PubMed1989

Potentiation of the effects of atrial natriuretic factor on the cardiovascular system by amiloride.

Amiloride has previously been shown to facilitate receptor binding of atrial natriuretic factor (ANF) to membranes of adrenal cortex and to enhance ANF induced inhibition of steroid secretion in vitro. This interaction of amiloride and ANF also holds true for the cardiovascular system. In precontracted rabbit aortic strips the relaxing effect induced by the combination of ANF (10(-10) mol/l) and amiloride (10(-5) mol/l) was overadditional. The production of cyclic guanosine monophosphate (cGMP), which parallels ANF induced relaxations of vascular strips, was not affected by amiloride alone up to 10(-3) mol/l, but was concentration-dependently increased in the presence of ANF (10(-8) mol/l). In spontaneously hypertensive rats ANF-induced decreases in blood pressure were potentiated by amiloride. Post ischemia reperfusion arrhythmias in isolated rat hearts were reduced by ANF. Amiloride increased this effect. The binding experiments revealed an interaction of amiloride and ANF on the receptor level. Binding of labeled ANF to aortic tissue was concentration-dependently increased by amiloride. Addition of ATP had the opposite effect. Therefore it can be suggested that amiloride and ATP interfere with a mechanism regulating the sensitivity of the vascular ANF-receptor for its ligand regarding binding and signal transforming presumably by a kinase mediated phosphorylation/dephosphorylation process.

Amiloride↗
PubMed1988

Amiloride potentiates the vascular effects of atrial natriuretic factor.

We have demonstrated an interaction between the effects of amiloride and atrial natriuretic factor (ANF) on the vascular system. In precontracted rabbit aortic strips the relaxant effect of a combination of ANF (10(-10) mol/l) and amiloride (10(-5) mol/l) was synergistic. The production of cyclic (c)GMP, which parallels ANF-induced relaxation of the strips, was not affected by amiloride alone up to 10(-3) mol/l, but was concentration-dependently increased in the presence of 10(-8) mol/l ANF. In spontaneously hypertensive rats (SHR) ANF-induced decreases in blood pressure were potentiated by amiloride. Binding experiments revealed an interaction between amiloride and ANF at the receptor level; binding of labelled ANF to aortic tissue was increased by amiloride but decreased by ATP. These data show that amiloride and ATP influence a mechanism that determines the sensitivity of vessels to ANF and this interaction occurs both at receptor level and at the level of transduction.

Adenosine Triphosphate↗
PubMed1988

Atrial natriuretic factor protects the isolated working ischaemic rat heart against the action of angiotensin II.

The interaction between atrial natriuretic factor [synthetic human ANF-(103-126)] and angiotensin II (Ang II) and its influence on reperfusion arrhythmias, cardiodynamics, enzyme loss and metabolic changes were investigated in isolated ischaemic working rat hearts. Acute regional myocardial ischaemia was induced by coronary artery occlusion which was associated with ventricular fibrillation. Perfusion with 1 X 10(-9) mol/l Ang II markedly aggravated these arrhythmias. Perfusion with 1 X 10(-7) mol/l ANF, in contrast, gave protection against ventricular fibrillation and prevented Ang II-induced aggravation of ventricular fibrillation. Atrial natriuretic factor improved cardiodynamics, in particular, during reperfusion, whereas Ang II impaired cardiodynamics and increased the release of creatine kinase and lactate dehydrogenase. These adverse effects of Ang II were absent when ANF was simultaneously perfused. Compared with control hearts, myocardial tissue levels of glycogen, ATP and creatine phosphate were increased in hearts perfused with either ANF or ANF plus Ang II, whereas lactate levels decreased. Perfusion with Ang II alone led to deterioration in these metabolic parameters. These results in isolated working rat hearts suggest that ANF protects against the consequences of ischaemia and reperfusion and that functional antagonism between ANF and Ang II may contribute to this.

Angiotensin II↗
PubMed1988

[Immunohistochemical detection of lysozyme and alpha-1-antichymotrypsin in fibrohistiocytic tumors].

Lysozyme and alpha-1-antichymotrypsin depositions were recorded by means of the PAP technique from benign and malignant fibrohistiocytic tumours. These depositions were seen in relation to lesions with histiocytic reactions. The findings indicate that the detection of these markers support the solution of problems of differential diagnosis. An important role is particularly played by demonstration in fibroblastic elements within the neoplasm proper. The results also suggest the possible existence of an undifferentiated precursor cell.

Diagnosis, Differential↗
PubMed1988

[Immunohistochemical characterization of epithelioid cells].

Focally aggregated epithelioid cells and granulomatous epithelioid cell reactions of different genesis were investigated immunohistochemically by means of PAP method according to Sternberger. We studied the presence of histiocytic markers lysozyme and alpha 1-antichymotrypsin, the content of albumin and of immunoglobulins and the question of immunophagocytosis and the presence of fibronectin. Various forms of activation of epithelioid cells as well as histiocytes and Langhans giant cells were found thereby. In the former, a phagocytosis could never be demonstrated, whereas this was true in histiocytes and giant cells. Fibronectin was not found in epithelioid cells. The findings suggest that epithelioid cells are a specific form of reaction of histiocytic elements. Thus they are a special reaction of MPS in a multiple causal genesis and a morphogenesis according to its own characteristics within a hypersensitivity reaction of a delayed type. Epithelioid cells modulate the immune response and in this way the tissue reaction.

Albumins↗
PubMed1987

Detection of hepatitis B virus markers in sera of asymptomatic hepatitis B surface antigen carriers with special emphasis to pre-S-encoded proteins.

Sera of asymptomatic hepatitis B surface antigen (HBsAg) carriers were analyzed for the presence of pre-S-encoded proteins. Four individuals with biopsy-proven chronic hepatitis uniformly expressed pre-S1- and pre-S2-encoded proteins. Individuals who had histologically normal or largely normal livers were heterogeneous with respect to expression of pre-S-encoded proteins. This heterogeneous expression of pre-S-encoded proteins occurred most likely due to difference in serum HBsAg concentration. Alternatively differences in pre-S gene expression need to be considered. Clinically the study indicates that expression of pre-S domains in serum is unrelated to viremia or chronic liver disease.

Carrier State↗
PubMed1986

Effect of rat atriopeptin III on renal function in dogs during water diuresis and hydropenia.

Experiments have been performed in conscious male beagle dogs under maximal water diuresis or hydropenia to determine the effects of synthetic rat atriopeptin III [r-AP III = r-ANF- (103-126)] (Geller et al. 1984), in an intravenous dose of 50 micrograms/kg body weight, on renal function and plasma renin activity. Intravenous injection of r-AP III resulted in an increase in urine and sodium excretion lasting up to 20 minutes, while the glomerular filtration rate and renal plasma flow were hardly influenced under either of the experimental conditions. r-AP III induced an increase in free water clearance from 7.51 +/- 2.45 ml/min in controls to 12.15 +/- 2.25 ml/min in the first clearance period, whereas the free water reabsorption was only slightly reduced (5.56 +/- 1.22 vs. 5.02 +/- 1.23 ml/min). r-AP III caused a slight increase in plasma renin activity from 0.65 +/- 0.46 in controls to 1.02 +/- 0.47 ng X ml-1 X h-1 in water diuretic dogs and from 3.19 +/- 0.51 in controls to 3.72 +/- 0.81 ng X ml-1 X h-1 in hydropenic dogs. These experiments show that the r-AP III-induced salidiuretic response seems not to be mediated by changes in the glomerular filtration rate and renal plasma flow. Moreover, the increase in free water clearance and the absence of change in free water reabsorption indicate a proximal site of action of r-AP III.

Animals↗
PubMed1981

The significance of serologic, histologic, and immunohistologic findings in the prognosis of 88 asymptomatic carriers of hepatitis B surface antigen.

Eighty-eight asymptomatic carriers of hepatitis B surface antigen (HBsAg) were followed with biochemical, serologic, histologic, and immunohistologic studies over a period of four years. None of the 78 HBsAg carriers with normal or minimally changed liver tissue, antibody to hepatitis B e antigen (HBeAg) in serum, and no intranuclear hepatitis B core antigen (HBcAg) developed a chronic inflammatory liver disease. Four individuals lost circulatory HBsAg, and at least two individuals terminated their HBsAg carrier state. Seven asymptomatic HBsAg carriers with chronic hepatitis were characterized by HBeAg in serum and intranuclear HBcAg. However, three HBsAg carriers with chronic hepatitis and an absence of intrahepatocellular HBcAg were positive for antibody to HBeAg over the observation period. The mechanism that leads to chronic hepatitis in these patients remains to be determined.

Adult↗
PubMed1981

Follow-up of anti-HBc titers in healthy HBsAg carriers and patients with chronic inflammatory liver diseases.

Sera of 85 asymptomatic HBsAg carriers found among blood donors were tested for anti-HBc titers and were retested 4 years later. The results were correlated with the histological findings of first and final biopsy. None of 75 HBsAg carriers with normal or minimally changed liver tissue, 71 of them anti-HBe positive, developed chronic inflammatory liver disease. 4 HBsAg carriers eliminated HBsAg from the serum after a 1-to 3-year HBsAg-carrier state and 2 developed antibody against HBsAg in the sequel. In 65 of 75 cases we found unchanged anti-HBc titers. The geometrical mean titer (GMT) was 1:7,800 in the first and 1:7,000 in the final examination with a range of 1:400 and 1:25,600 in the group of HBsAg carriers with normal liver, and was 1:14,200 and 1:10,300, respectively, with a range of 1:800 and 1:51,200 in HBsAg carriers with minimal changes. In both groups the decrease of anti-HBc concentration within 4 years was not significant. The group of 10 HBsAg carriers with chronic hepatitis did not differ from healthy HBsAg carriers in respect to anti-HBc titers. Anti-HBc titers varied between 1:6,400 and 1:25,600, the GMT was 1:13,700 and 1:12,800, respectively. It is speculated that in healthy HBsAg carriers shedding of serologically undetectable quantities of complete and/or defective HBcAg from liver cell nuclei which contain HBcAg not detectable by immunofluorescence maintain the production of anti-HBc.

Antibodies, Viral↗
PubMed1979

[Spread of hepatitis B virus infection among family contacts of asymptomatic HBsAg carriers (author's transl)].

Family members of 34 asymptomatic HBsAg carriers were tested for different hepatitis B virus (HBV) markers. Among 67 family members tested 24 (36%) presented signs of a past or ongoing HBV-infection. Spread of HBV-infection was particularly high in those families in which the HBsAg carrier was positive for HBeAg and Dane particle-associated DNA polymerase activity. Non-parenteral "horizontal" transmission of HBV among spouses and brothers and sisters and probably parenteral vertical transmission of HBV from carrier mothers to their infants occurred in approximately the same frequency. Fathers transmitted HBV unfrequently to their offsprings. The results show that the risk to acquire a HBV-infection from an asymptomatic HBsAg carrier is closely linked to the serological findings in the HBe/anti-HBe-system of the index HBsAg carrier and not to the family relationship to the HBsAg carrier.

Adolescent↗
PubMed1979

Hepatitis B virus markers among family contacts of asymptomatic HBsAg carriers.

A study was undertaken to establish the risk of family contacts of HBsAg carriers acquiring a hepatitis B virus (HBV) infection. About one-third of all household contacts of asymptomatic HBsAg carriers had signs of past or ongoing HBV infection. Family contacts of HBsAg carriers with high numbers of circulating Dane particles were shown to have a higher risk of developing HBV infection than family contacts of HBsAg carriers without serological evidence of HBV synthesis. The probability of acquiring HBV infection was not different between spouses, parents, children, and brothers and sisters, respectively of asymptomatic HBsAg carriers.

Adult↗
PubMed1979

[Radioimmunological determination of HBeAg/anti-HBe in HBsAg-positive liver diseases and in "healthy" HBsAg carriers].

This paper describes a "solid-phase"-radioimmunoassay for the demonstration of HBeAg and anti-HBe. The investigations revealed the following results: 1. HBeAg is positive in all patients with acute type B-hepatitis during the acute phase of illness. During the normal course of the disease HBeAg turns to negative followed by an anti-HBe lasting for several months. 2. Cases with a persistent virus B-replication as HBsAg-positive CPH, CAH or patients on hemodialysis are positive for HBeAg in their serum. By means of the fluorescent antibody technique these patients have demonstrable HBcAg and HBeAg in their liver biopsies. 3. Healthy HBsAg carriers are anti-HBe-positive in their serum. In their liver biopsies there are no signs of an on-going virus B-replication (HBsAg and HBeAg negative). 4. The radioimmunological determination of HBeAg and anti-HBe enables us to differentiate between the groups with HBsAg positive acute or chronic hepatitis and the group of healthy HBsAg-carriers.

Antibodies, Viral↗
PubMed1978

[Exceptional clinical courses of granulomatous colitis in children and adolescents (author's transl)].

Acute complications are known in chronic ulcerative colitis as well as in Crohn's colitis. They can rarely be seen also in childhood and adolescence. Massive rectal bleeding, particularly acute toxic dilatation of the large bowel should be treated surgically after a short-term medical therapy. The procedure of choice is the one stage proctocolectomy. Alternatively the method described by TURNBULL performing a loop ileostomy and several colostomies can be used. Besides the clinical symptoms and signs more than 8 stools and a temperature of more than 38 degrees C in the first 24 hours of hospitalisation can predict a severe clinical course.

Adolescent↗
PubMed1977

[Severe toxic liver injury after overdosage of parenteral administered carbohydrates: a case report (author's transl)].

A 31-year old female patient with anorexia nervosa developed a severe toxic liver injury after parenteral hyperalimentation. Over a period of five days she received a total amount of carbohydrates of 0.47-1.07 g/kg/hr consisting of glucose, fructose and the polyalcohols sorbitol and xylitol. A steep rise in SGOT, SGPT, and GLDH were noted as well as prolongation of the prothrombin time and decrease of the clotting factors; uric acid and lactate increased, serum phosphate decreased. After termination of parenteral hyperalimentation a laparoscopy and liver biopsy were performed. The liver biopsy revealed by light- and electronmicroscopy signs of a severe toxic liver injury. After reduction of total carbohydrates and later oral feeding a complete remission occurred. The cause of the toxic liver lesions was believed to be due to an overdosage of fructose and sorbitol.

Adult↗