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Biomedical subjects

H Hofmann

Publications and source records attributed to H Hofmann.

At least 109 records · Page 6Linked to original sources

Isolation of (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine, the characteristic structural element of cyclosporins, from a blocked mutant of Tolypocladium inflatum.

By mutagenic treatment of a strain of Tolypocladium inflatum, a cyclosporin non-producing mutant was obtained which accumulated the characteristic building unit of cyclosporins, (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (abbreviation Bmt; systematic name: (2S,3R,4R,6E)-2-amino-3-hydroxy-4-methyl-6-octenoic acid) in free form. The isolation from a culture filtrate was performed by extraction, chromatographic separation and final crystallization from methanol - water. The structure and stereochemistry of this amino acid was determined by chemical transformation and correlation to dihydro-MeBmt, with known chirality [(2S,3R,4R)-3-hydroxy-4-methyl-2-methylamino-octanoic acid], obtained by hydrolysis of dihydrocyclosporin A.

Chemical Phenomena↗

[Diagnosis and epidemiology of hepatitis C].

After years of unsuccessful attempts to isolate the causative agent of hepatitis non-A-non-B this has recently been accomplished. The nucleic acid of a virus, now called hepatitis C, was cloned which formed the basis of a diagnostic ELISA. In this test antibodies against a non-structural protein of the virus can be detected. These antibodies are not actually protective but rather indicate virus activity. The first generation test is hampered by some unspecificity but mostly by the fact that seroconversions are detected very late, sometimes up to 6 months after infection. However by including some more antigens in the ELISA of the second generation this problem will hopefully be overcome. Hepatitis C virus (HCV) antibodies could be found in up to 90% of patients with posttransfusion hepatitis. But also about 75% of patients with sporadic (cryptogenetic) hepatitis, were positive for HCV. Beside multiple blood transfusions (0.7% of blood donors in Austria are infected) other risk factors for HCV are needle sharing by i.v. drug users and treatment for hemophilia, because of HCV is not inactivated during the preparation of antihemophilic plasma. A virus inactivating procedure is therefore carried out in modern preparations. A high percentage of hemodialysis patients are also infected. However, important differences (0 to 30%) were found between different dialysis units. Other investigations revealed that the HCV risk for medical personnel is not extremely high, perhaps only twice that of the normal population. Sexual transmission of the virus seems to be possible but not of practical importance. Although the majority of hepatitis cases which earlier were classified as non-A-non-B, can now be diagnosed as hepatitis C, the possible existence of one more hepatitis virus cannot be excluded.

Blood Transfusion↗

[Quantitative two-dimensional echocardiography. Study results in patients with cystic fibrosis].

15 patients with cystic fibrosis aged 8-19 years were graduated into 3 stages of the cor pulmonale dependent on results of an examination with the microcatheter: stage 0:6, stage I: 4 and stage II: 5 patients. These patients were studied in the period from April 1987 to January 1988 echocardiographically. With this size and contractility of the right ventricle were especially considered. The end-diastolic and end-systolic area of the right ventricle could be measured in the apical 4-chamber-view in 14 of the altogether 15 patients and out of this the fractional area-shortening could be calculated. The end-diastolic area of the right ventricle in the patients with stage 0 was on an average 11.4 cm2/m2 body surface bs (8.7-13.5), in stage I 11.2 cm2/m2 bs (9.2-13.5), and in stage II 9.7 cm2/m2 bs (9.0-10.8). The end-systolic area of the right ventricle in stage 0: 7.2 cm2/m2 bs (6.8-8.4), stage I: 7.1 cm2/m2 bs (6.0-8.5), and stage II: 8.02 cm2/m2 bs (6.4-10.1). The results we found don't differ significantly in the 3 groups. Contrary to this fractional area-shortening of the right ventricle shows a falling tendency: stage 0.35.2% (22-49), stage I 32% (7-56), stage II 17.2% (4-38) with an increasing part of patients with a value under 28% (stage 0:1 patients, stage I 2 patients, stage II 3 patients). Contractility and pump-efficiency of the left ventricle were calculated in the apical 4-chamber-view according of the area-length-method. The findings don't show an increasing size of the right ventricle in the sense of a cor pulmonale but a decreasing contractility and pump-efficiency of the right ventricle as expressions of a cardial manifestation of the basic illness in the sense fo a symptomatic cardiomyopathy. A disturbance of the contractility of the left ventricle could be seen in 7 of the 15 patients (47%).

Adolescent↗

[Serodiagnosis in dermatological diseases in Borrelia burgdorferi infections].

185 patients with dermatological symptoms of Borrelia burgdorferi infection (erythema migrans, lymphadenosis cutis benigna, acrodermatitis chronica atrophicans) and morphea were examined for Borrelia burgdorferi antibodies; in addition, sera from 173 patients were tested for exclusion of Borrelia infection. Commercially available immunofluorescence tests and enzyme immunoassays supplied by four different companies were evaluated. To investigate the specificity of these assays, sera of 34 patients with syphilis in different stages and sera from 98 control persons were examined. None of the assays evaluated was suitable for the diagnosis of early infection (sensitivity 4-35%). However, they are more reliable for the diagnosis of late infection (sensitivity 56-100%). The variation in specificity between the different assays was 82-100%. Crossreactions with Borrelia burgdorferi antibodies occurred frequently in patients with syphilis (3-47%). The reliability of serological assays should be improved by antigen purification and combination of screening and confirmatory assays. After treatment the decline in IgG and IgM antibodies is very slow.

Acrodermatitis↗

[Excessive morbidity in kindergarten children--assessment in an industrial region].

Based on 3638 cases of illness over one year, the constant high morbidity of nursery school children in an industrial region were analyzed and compared. Extremely high is the number of illnesses of the upper respiratory tract with otitis media, conjunctivitis and with enteritis from October to March. In an industrial conglomerate combined effects of harmful substances are possible. Present measurements of industrial waste are insufficient. The morbidity of nursery school children demands a much higher intensification of ecological hygienic effort.

Child Day Care Centers↗

[HIV infection in stage IV C-2 (CDC). Increase in the p24 antigen value before critical decrease in CD4+ lymphocytes].

The Center for Disease Control proposed a classification system of HIV-infection including a symptomatic stage IV C-2 with secondary infections like thrush, oral hairy leukoplakia and herpes zoster. Because the prognostic value of these symptoms for the development of AIDS has been proven and the CDC-classification does not include any immunological parameters we analyzed the numbers of CD4+-lymphocytes and the frequency of HIV-antigen in 65 HIV-infected individuals. When entering stage IV C-2, the incidence of HIV-antigenemia was as high as in full blown AIDS (53% and 60%, respectively). However, we observed no decrease of CD4+-lymphocytes as compared to earlier CDC-stages.--We conclude that in stage IV C-2 the increase of viral protein production proceeds independently from CD4+-status.

CD4 Antigens↗

[Results of rubella prevention in Austria (1988 status)].

The aim of any rubella eradication programme is the prevention of rubella embryopathy. In Austria, every girl aged 13 years is vaccinated without prior antibody testing. In addition, all pregnant women are tested for antibodies and vaccinated post partum, if necessary. As in other European countries, this policy has not (yet) led to the elimination of rubella embryopathies. In 1987 and 1988, 3 embryopathies as well as 16 and 17, respectively, rubella infections in pregnant women were diagnosed. In order to monitor the effectiveness of the vaccination in 13 years old girls, we tested 325 sera from student nurses (mean age 15.6 years) as well as 895 sera from pregnant women (mean age 23.1 years). In the 1st group, only 2.2% had a titer of less than or equal to 16 in hemagglutination inhibition test and therefore were not unequivocally protected. In the pregnant women, this ratio was 6.1%. We therefore draw the conclusion that in some cases the protection afforded by the vaccination begins to decrease after 10 years. At the same time, we also tested the sera of 4186 pregnant women who claimed they never had been vaccinated. Their mean age was higher (26 years) and 11.1% were not unequivocally protected. In addition, we tested 28 women who had been vaccinated 3 to 6 months previously due to negative serology. Of these, 6 (21.4%) did not produce antibodies with a titer of at least 32. Many European countries had the same experience and therefore began vaccinations of all children in the 2nd year, using the trivalent vaccine (mumps, measles, rubella) instead of the bivalent one (without rubella).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The Intersalt study: results and perspectives].

The recently published Intersalt Study comprising 10,079 participants from 52 study centers in 32 countries demonstrated that the simple linear relationship so far postulated for the association between electrolytes and hypertension is history. In addition overweight and alcohol consumption make an independent contribution to the level of individual blood pressures. The study results have to be interpreted carefully in the framework of a differentiated epidemiologic analysis.

Adult↗

[Severe fetopathy--toxoplasma despite serologic screening. A case report].

Toxoplasmosis is a special prenatal infection because it is susceptible to medication. Serologic screening and early diagnosis of a new infection is a prerequisite for successful treatment, which protects the fetus from infection. A case of a twenty-two year old gravida-II shows, that infection is possible despite negative initial screening. A new infection was diagnosed because of seroconversion at a routine screening at the end of the second trimester. An ultrasound scan showed severe hydrocephalus, hepatomegaly, and ascites. Labor was induced in the 33rd gestational week. Conatal toxoplasmosis was confirmed by histologic and microbiologic studies of the placenta and membranes. We discuss the difficulties resulting from negative primary serology.

Adult↗

[Ulrich oculo-oscillodynamography in carotid artery stenosis and temporal arteritis].

Oculo-oscillodynamography (OODG) after Ulrich was performed on 21 patients suffering from unilateral hemodynamically relevant carotid stenosis. In ten patients the perfusion pressure was low on the affected side. In the other eleven patients there was no difference between the two sides and these patients were thought to have well-developed collateral anastomoses. In nine patients with temporal arteriitis low perfusion pressure was found by OODG on the side with the lower visual acuity. After systemic therapy with corticosteroids the perfusion pressure normalized on both sides.

Aged↗

[Oculo-oscillodynamography findings in glaucoma without hypertension].

Oculo-oscillodynamography after Ulrich was performed in 27 patients suffering from glaucoma without hypertension (so-called low-tension glaucoma). Patients who had severe systemic disease or were receiving systemic medication which might influence IOP, and patients with narrow angle and an IOP higher than 22 mm Hg were excluded. In 85% of the patients a severe decrease in systolic ciliary perfusion pressure was found, whereas the systolic retinal and diastolic ocular perfusion pressures were significantly lower in almost 30% of the cases. Glaucoma without hypertension appears to be caused by the vascular change at the disk.

Aged↗

Cyclosporins--new analogues by precursor directed biosynthesis.

Cyclosporin A (ciclosporin), a potent and clinically important immunosuppressive drug (Sandimmun), represents the main component of a group of over 25 closely related, cyclic undecapeptides produced by the fungus Tolypocladium inflatum. By feeding experiments using DL-alpha-allylglycine as precursor, specific incorporation in position 2 was attained leading to [Allylgly2]cyclosporin A. Exogenously supplied L-beta-cyclohexylalanine results in the almost exclusive production of [MeCyclohexylala1]cyclosporin A (replacement of methylbutenyl-methylthreonine-1). D-Alanine in position 8 can be successfully substituted by D-serine. The new [D-Ser8] analogues of the cyclosporins A, C, D and G as well as [Allylgly2]cyclosporin A exhibit high immunosuppressive effects.

Amino Acids↗

[What hides behind the diagnoses angina follicularis and lacunaris? A contribution to the differentiation of tonsillitis].

An one-year examination of 315 children shows that under the diagnosis of follicular tonsillitis or lacunar tonsillitis many aetiological different diseases are summarized. More frequently than previously assumed adeno-, respiratory syncytial-, influenza A-, entero-, herpes simplex- and probably other viruses are the cause. It is shown to what extent the critical general evaluation also of discrete clinical data enables a differentiation. The usual general penicillin therapy of the patients with tonsillitis can be dispensed with.

Adolescent↗

[Viral nucleic acids in the serum of hepatitis B patients].

Detection of hepatitis B viral DNA (HBV-DNA) is the most reliable test for infectivity of a patient's serum. HBV-DNA was detected by spot hybridization on nylon membrane. HBV-DNA was detected during the first or second week of jaundice in 22/133 (16.5%) sera from patients with acute hepatitis who did not develop chronic disease later on. However, in patients with acute hepatitis who later on developed the chronic form, HBV-DNA was found in 12/12 (100%) cases in the first or second week after onset. In other patients who had chronic hepatitis for longer than one year HBV-DNA was detected in 92/113 (81.4%) sera when HBe antigen was also detectable and in 11/104 (10.6%) when HBe antibodies were found. HBV-DNA was present in 32/38 (84.2%) sera from healthy antigen carriers when HBe antigen was detected and only in 2/173 (1.2%) sera of HBe antibody positive HBs antigen carriers. The highest levels of HBV-DNA were found in patients with chronic hepatitis B infection who were found in patients with chronic hepatitis B infection who were on haemodialysis therapy. Almost all had HBe antigen and HBV-DNA was also detectable in 82/84 (97%) sera. 11/28 (39.3%) sera from patients with chronic hepatitis B as well as HIV infection showed HBV-DNA. Detection of HBV-DNA has significantly improved the accuracy of diagnosis of hepatitis B viral infection.

DNA, Viral↗

Biosynthesis, secretion and extracellular localization of anchorin CII, a collagen-binding protein of the calpactin family.

The amino acid sequence of anchorin CII, a collagen-binding protein isolated originally from chondrocyte membranes, was previously determined by sequencing of cDNA and proteolytic fragments of the protein. Computer analysis of the protein sequence revealed four internal repeats of approximately 70-80 residues, each containing a highly conserved consensus sequence of 17 residues. These repeats show considerable homology with sequences in human and bovine calpactin, lipocortin, endonexin and protein II, which are members of a family of Ca2+- and phospholipid-binding proteins, as well as major substrates of tyrosine kinases. While these proteins have been located at the inner side of the plasma membrane of fibroblasts and epithelial cells, here we present experimental evidence that anchorin CII is at least partially released from cells and binds to the outer cell surface. Biosynthesis studies in cell-free systems and in cell culture indicate that anchorin CII is not processed, which is consistent with the absence of signal sequences from the protein. Yet, pulse-chase experiments show that anchorin is released into the culture medium of fibroblasts after 30 min, and in chondrocyte cultures after 20 h. Anchorin CII was located to the outer cell surface of chondrocytes by lactoperoxidase-catalyzed cell surface iodination as well as by antibody labeling both at light- and electron-microscopical level. The pericellular localization of anchorin CII is consistent with the notion that this protein is involved in the interaction of chondrocytes and fibroblasts with extracellular collagen.

Amino Acid Sequence↗