[Multiple endocrine neoplasia type 2a. Genetic screening in the familial tumor syndrome].
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Drosophila Proteins↗
Biomedical subjects
A Pfützner
Publications and source records attributed to A Pfützner.
Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis.
Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA69 and maltose binding protein. ICA69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA69 antibody titres were 3.4 (+/- 1.4) in 99 patients with acute IDDM compared to 2.8 (+/- 0.9) in 49 healthy blood donors (p < 0.001). A higher mean ICA69 antibody titre of 4.1 (+/- 0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p < 0.01) and healthy control subjects (p < 0.001). The percentage of sera with ICA69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n = 20), inflammatory bowel disease (n = 9) or multiple sclerosis (n = 7) had elevated ICA69 antibodies. In IDDM, presence of ICA69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Gynaecomastia in a patient with a hCG producing giant cell carcinoma of the lung. Case report.
Gynaecomastia, or enlargement of the male breast may result from various endocrine dysfunctions and often reflects ectopic production of substances such as hCG and estradiol. We report on the case of a 30 year old man who presented with gynaecomastia and elevated plasma levels of hCG, estradiol and testosterone. As a result of several diagnostic procedures such as selective venous sampling and magnetic resonance tomography (MRT), a hCG producing tumor of the upper lobe of the left lung was found. This hormonal overproduction induced an enhanced secretion of estradiol and testosterone in the testicular tissue. Histology revealed a giant cell carcinoma with positive immunostaining for hCG. This case report further underlines the necessity of an intensive search for ectopic beta-hCG production due to malignant tumours, in particular in the adult.
Adult↗
Association between diabetic-autonomic-C-fibre-neuropathy and medial wall calcification and the significance in the outcome of trophic foot lesions.
The role of peripheral autonomic nerve failure in the development of medial arterial calcification is discussed controversially in the literature. In addition, the influence of medial wall calcification in the development of trophic foot lesions is still not fully understood. We have compared 28 diabetic patients with cardiac autonomic failure and/or decreased acetylcholine-induced sweat response with 22 diabetic patients without evidence of diabetic neuropathy and 27 healthy control subjects. A strong association was found between medial wall calcification and diminished heart rate variation (p.001) or diminished peripheral sweat response (p < 0.001). Only one subject in the control group exhibited a calcification of the tunica media in the lower limb. Medial calcinosis was accompanied by a significant rise of systolic ankle blood pressure (p < 0.05). In addition, there was a strong relationship between medial wall calcification and trophic foot lesions (p < 0.0001). Our results demonstrate a strong association between sympathetic C-fibre neuropathy and the development of medial wall calcification, as well as between calcification of the tunica media and trophic foot ulceration. Further investigation is necessary to determine whether there is a causal connection between medial arterial sclerosis and diabetic foot ulceration, or whether both are independent consequences of diabetic neuropathy.
Acetylcholine↗
Determination of anti GAD65 autoantibodies with an ELISA before and after standardization with the new international reference serum.
The serum of a stiff-man syndrome patient was declared international GAD reference standard at the "1st GAD Antibody Workshop" held at the "12th International Immunology and Diabetes Workshop" in Orlando, Florida, USA 1993. A comparative study was performed with 123 diabetic and non-diabetic patients to evaluate whether standardization of this reference serum had changed the properties of a commercially available ELISA assay. All samples classified positive with the old test were confirmed with the new assay. Four additional samples with high "normal" values became positive with the new test. One of them was a control person having a family history of diabetes and genetic loci DR4/DR11. These findings might implicate a higher risk for the development of IDDM. The new standardization and adaptation of the ELISA seems to have influenced the sensitivity of the test positively.
Autoantibodies↗
Peripheral osteopenia in adult patients with insulin-dependent diabetes mellitus.
Alterations in bone metabolism in diabetes mellitus is a topic of special interest. Bone blood flow is increased in the distal limb of diabetic patients, which is believed to increase osteoclastic activity. We measure bone mineral density using dual-photon absorptiometry in the distal lower limb, the femoral neck, and the lumbar spine in 41 IDDM patients and in 30 control persons. In the diabetic group there was a 10% reduction of bone mineral density in the femoral neck (p < 0.01) and a 12% reduction in the distal limb (p < 0.001) compared with the control group. No significant difference was found in the lumbar spine (p = 0.22). Our data yield incidence for peripheral osteopenia in IDDM-patients, independent of any systemic bone disease such as osteoporosis. A link between decreased bone mineral density and diabetic neuropathy has been observed for the femoral neck (p < 0.001), but not for the distal limb or axial skeleton. Whether there is a common aetiological link or a casual connection between diabetic neuropathy and bone mineral density has still to be determined.
Absorptiometry, Photon↗
Association between "diabetic thick skin syndrome" and neurological disorders in diabetes mellitus.
Skin thickness on the extremities of patients with diabetes mellitus has been described controversially. Using high resolution ultrasonography, we were able to show a significant increase in skin thickness at the forearm (P < 0.05), thigh (P < 0.001) and lower limb (P < 0.05) of diabetic patients, most prominent at the thigh. No difference in skin thickness was found at the dorsum of the foot. In addition, skin thickness was not related to the duration of diabetes, age or HbA1. A close association was found between diabetic neuropathy and increasing skin thickness. Diabetic patients with neurological disorders had a significant increase in skin thickness versus diabetic patients without neuropathy. The present findings suggest that diabetic neuropathy and abnormalities of connective tissue have a common etiological link in their development or that both are time-dependent processes. Whether changes in capillary blood flow, increase of nonenzymatic glycosylation, polyol accumulation or other metabolic disorders are responsible for these findings remains still to be established.
Adult↗
High proportion of HIV-2 and HIV-1/2 double-reactive sera in two Indian states, Maharashtra and Goa: first appearance of an HIV-2 epidemic along with an HIV-1 epidemic outside of Africa.
The seroprevalence of HIV-1 and HIV-2 infections was determined in selected groups of patients from an STD clinic and in female prostitutes from two different states of India. A total of 809 sera from Maharashtra and of 61 sera from Goa were analyzed. Of the unscreened sera from Bombay, 39% were positive as were 15% of the sera from Goa. Among the HIV-positive sera from Bombay, 79% were positive for HIV-1, 4% were positive for HIV-2 and 17% were positive for HIV-1 and 2. In the Goa group, 67% of the infected sera were HIV-1-positive and 33% were HIV-2 positive. Due to the nearly even distribution of infections between men and women, a mainly heterosexual mode of transmission is evident. HIV-2 infections were first detected in India in 1990 (Rübsamen et al., Lancet, 1991). Before that time, Asia was believed to be free HIV-2. The present study represents the first documentation of a large proportion of these infections, alone and in combination with HIV-1, in the Asian continent. An HIV-2 epidemic running parallel to an HIV-1 epidemic so far has never been observed outside of Africa. This would indicate that a further spread of HIV-2 worldwide is to be expected and that HIV-2 should be included in programs of vaccine development for humans.
Blotting, Western↗
Oligosaccharide profiles of HIV-2 external envelope glycoprotein: dependence on host cells and virus isolates.
The glycosylation pattern of the external envelope glycoprotein of human immunodeficiency virus type 2 (HIV-2) was studied in dependence on host cells and virus isolates. Strains HIV-2ALT, HIV-2ROD and HIV-2D194, differing in their biological properties and in the amino acid sequences of their env genes, were propagated in MOLT4, HUT78 and U937 cells, in human peripheral blood lymphocytes and monocytes/macrophages in the presence of [6-3H]glucosamine. Radiolabelled viral glycoproteins were isolated from the cell-free supernatants and digested with trypsin. Glycans were sequentially liberated by endo-beta-N-acetylglucosaminidase H and peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase F, and fractionated according to charge and size. Comparison of the oligosaccharide profiles revealed that the envelope glycoproteins of different virus isolates, propagated in the same host cells, yielded very similar glycan patterns, whereas cultivation of an isolate in different host cells resulted in markedly divergent oligosaccharide maps. Variations concerned the proportion of high-mannose-, hybrid- and complex-type substituents, as well as the state of charge and structural parameters of the complex-type species. As a characteristic feature, complex-type glycans of macrophage-derived viral glycoprotein were almost exclusively substituted by lactosamine repeats. Hence, glycosylation of the HIV-2 external envelope glycoprotein seems to be primarily governed by host cell-specific factors rather than by the amino acid sequence of the corresponding polypeptide backbone.
Carbohydrate Sequence↗
[Driver's license and diabetes. Legal and social medicine aspects].
The diagnosis of diabetes mellitus is accompanied by a lot of personal and social consequences for the patient himself. One of the most important problems is the influence of the disease on the patients driving skills. This aspect is discussed according to the recommendations of the German ministry of traffic, and advice is given for the diabetic patient taking part at the daily traffic as a car driver.
Accidents, Traffic↗
Architecture in cortical bone and ultrasound transmission velocity.
The square of ultrasound transmission velocity in a material is correlated to the modulus of elasticity, which is an indicator of its mechanical properties. This might make the measurement of ultrasound transmission velocity useful in the noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic material but is architecturally structured. The aim of our study was to investigate and especially to quantify the influence of architecture in cortical bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound transmission velocity was measured parallel and perpendicular to direction of Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/- 29 m/s perpendicular to Haversian channels respectively (p < 0.001). Our results clearly indicate that there is an important influence of architecture in cortical bone on ultrasound transmission velocity which has to be taken into account in its clinical use.
Animals↗
[Effect of antiviral agents].
Due to the closer virus-host interactions viral diseases are more difficult to control by drugs than most of the bacterial infections. Moreover, the search for antiviral compounds against HIV is an exceptional challenge. The enormous genetic and biological variability, the life-long persistence and the invasion of the brain are only some of the aspects which complicate a fast solution. In principal there are three different strategies to develop new chemotherapeutics. Most of the drugs so far tested in clinical trials were identified by routine screening, others were modified by specific chemical synthesis. After the three-dimensional structure of some HIV proteins became known, rational drug design by computer modeling resulted in compounds exhibiting excellent anti-HIV activity in vitro. The reverse transcriptase inhibitor AZT has been used for HIV-infected individuals for several years. However, side effects and the development of AZT-resistant virus strains force to combine AZT with other drugs and to develop additional lead compounds.
Antiviral Agents↗
HIV-1 and HIV-2 infections in a high-risk population in Bombay, India: evidence for the spread of HIV-2 and presence of a divergent HIV-1 subtype.
A high-risk population (patients of a sexually transmitted disease clinic and the GT hospital in Bombay) was tested for antibodies against HIV-1 and HIV-2. Among 405 serum samples, 226 had previously been classified HIV-positive in India using different locally available enzyme-linked immunosorbent assay (ELISA) tests. The serology of 179 samples was unknown. All 405 samples were tested at the Georg-Speyer-Haus (GSH) with the Pasteur HIV-1/2-Combi-ELISA. Positive samples were further analyzed with HIV-1 and HIV-2 Western blot kits from Dupont and Pasteur, respectively. A very high seroprevalence of HIV was found in this population. Among the 179 unscreened samples, 69 (38.5%) were positive in the ELISAs as well as the Western blots for HIV-1 or HIV-2. Among the prescreened samples, only 174 (77%) were confirmed HIV-positive. Altogether, 243 of 405 sera were HIV-positive. Of these, 184 (76%) were reactive with HIV-1, 10 (4%) were reactive with HIV-2, and 49 (20%) had dual reactivity to HIV-1 and HIV-2. Previous data from the Indian Council of Medical Research had already suggested a possible high prevalence of HIV-1 in India. Our results confirm this view. The finding of a substantial spread of HIV-2 infection was, however, totally unexpected in India, but confirms our previous study which had already demonstrated the existence of HIV-2 in this country. Asia can thus no longer be considered free of HIV-2, and testing for HIV-2 appears mandatory, at least in India.(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
Characterization of NAD-dependent 3 alpha- and 3 beta-hydroxysteroid dehydrogenase and of NADP-dependent 7 beta-hydroxysteroid dehydrogenase from Peptostreptococcus productus.
A human fecal isolate, characterized by morphological, physiological and biochemical data as a strain of Peptostreptococcus roductus, was shown to contain NAD-dependent 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and a NADP-dependent 7 beta-hydroxysteroid dehydrogenase. All enzyme activities could be demonstrated in crude extracts and in membrane fractions. The 3 alpha- and 3 beta-hydroxysteroid dehydrogenases were synthesized constitutively. Specific enzymatic activities were significantly reduced when bacteria were grown in the presence of 3-keto bile acids, while other bile acids were ineffective. For the 3 alpha (3 beta)-hydroxysteroid dehydrogenase, a pH optimum of 8.5 (9.5) and a molecular weight of 95,000 (132,000) was estimated. 3 alpha- and 3 beta-hydroxysteroid dehydrogenases were heat-sensitive (about 75% inactivation at 50 degrees C for 10 min). The 7 beta-hydroxysteroid dehydrogenase was already present in uninduced cells, but specific activity could be enhanced up to more than 2.5-fold when bacteria were grown in the presence of 7-keto bile acids. Disubstituted bile acids were more effective than trisubstituted ones, ursodeoxycholic acid was ineffective as an inducer. A pH optimum of 10.0 and a molecular weight of about 82,000 were shown for the 7 beta-hydroxysteroid dehydrogenase. The enzyme preparation reduced the 7-keto group of corresponding bile acids. Again the affinities of disubstituted bile acids for the enzyme were higher than those of the trisubstituted bile acids, but no significant differences between conjugated and free bile acids were observed. The 7 beta-hydroxysteroid dehydrogenase was heat-sensitive (72% inactivation at 50 degrees C for 10 min), but was detectable at 4 degrees C for at least 48 h.
3-Hydroxysteroid Dehydrogenases↗
Characterization of NADP-dependent 12 beta-hydroxysteroid dehydrogenase from Clostridium paraputrificum.
Clostridium paraputrificum D 762-06 was found to contain an NADP-dependent 12 beta-hydroxysteroid dehydrogenase, already present in uninduced cells. Its specific activity could, however, be enhanced up to about 3-fold by the inclusion of bile acids with a 12-keto group or a 12 beta-hydroxy group in the growth medium. 3 alpha-Hydroxy-12-keto-5 beta-cholanoic acid was the most effective inducer. A pH optimum of 10.0 and a molecular weight of 126,000 were estimated by molecular sieve chromatography. The enzyme preparation reduced 12-keto groups in conjugated and unconjugated bile acids and oxidized a 12 beta-hydroxy function, but oxidative activity was only about 25% of the reductive one. Disubstituted bile acids showed lower Km values than the corresponding trisubstituted ones, the lowest Km values being those observed for 3,12- and 7,12-5 beta-cholanoic acids. No measurable activity against 12 alpha-hydroxyl groups could be detected. The enzyme was found to be heat-labile (95% inactivation at 50 degrees C for 10 min), but the activity was maintained for about 4 weeks when lyophilized preparations were stored at -20 degrees C. 12 beta-Hydroxysteroid dehydrogenase activity was also demonstrated in the membrane fraction after solubilization with Triton X-100, suggesting that it was originally a membrane-bound enzyme.
Bile Acids and Salts↗
Synthesis and bioactivity studies of 1-adamantanamine derivatives of peptides.
Small enkephalin-related peptides containing a 1-adamantanamine moiety coupled through an amide linkage at the C-terminus were synthesized. Several of the compounds showed high mu opioid activity and mu receptor selectivity. The new adamantanamine derivatives were also examined for antiviral activity against HIV-1 in a cell culture system. Some of them inhibited syncytia formation even when the antigen assay gave evidence for viral replication.
Adamantane↗
Comparison of the microvascular response to transcutaneous electrical nerve stimulation and postocclusive ischemia in the diabetic foot.
Neurogenic inflammation, mediated by unmyelinated C-nerve fibers, is part of the acute neurovascular response to injury. Laser doppler flowmetry was used to measure the flare response to transcutaneous electrical nerve stimulation (TENS) and to compare this axon reflex vasodilatation with postischemic hyperemia in the skin of the foot in diabetic and nondiabetic subjects. Twenty-one control subjects and 57 diabetic patients (25 type I; 32 type II; 14 without complications; 14 with neuropathy and without retinopathy; 8 with retinopathy and without neuropathy; 21 with neuropathy and retinopathy) were enrolled in the study. Following TENS, an increase in skin blood flow was found at the dorsum of the foot without any significant difference between the different groups. Compared to the control group, axon reflex vasodilatation was significantly reduced in the group of patients with diabetic neuropathy and in the group of patients with diabetic neuropathy and retinopathy at the pulp of the hallux (61 +/- 15 versus -6 +/- 16; versus 23 +/- 5; p < 0.05, respectively). All investigated groups exhibited a significant increase in skin blood flow after arterial occlusion without any significant difference between the groups. A good association was observed between postocclusive and TENS-induced hyperemia at the dorsum of the foot (r = 0.39; p = 0.0002), but only a weak association was found at the pulp of the hallux (r = 0.24; p = 0.03). TENS-induced hyperemia was associated with a diminished sweat response (p = 0.03), but not with pathological cardiovascular function tests (p = 0.07). Electrical axon reflex vasodilatation is diminished in diabetic patients suffering from peripheral autonomic C-fiber injury, especially in skin rich in thermoregulatory blood flow. The diminished neurovascular response is independent of vascular alterations in diabetes mellitus.
Adult↗