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Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed1996

Insulin-like growth factor-I serum concentrations and patterns of insulin-like growth factor binding proteins in patients with chronic liver disease.

BACKGROUND/AIMS: Serum concentrations of insulin-like growth factor-I are decreased in liver cirrhosis. However, this growth factor is bound for the most part to specific binding proteins that are known to modulate biological actions. Plasma insulin-like growth factor binding proteins are predominantly synthesized in the liver. METHODS: The effect of liver disease on basal and on growth hormone-stimulated serum concentrations of total and "free" insulin-like growth factor-I and on insulin-like growth factor binding protein patterns is reported. Sera were obtained from 20 patients with non-cirrhotic chronic liver diseases and from 20 patients with cirrhosis before and 24 h after a single subcutaneous dose of growth hormone. Samples were analyzed using radioimmunoassays, gel chromatography, ligand blotting and immunoblotting. RESULTS: In cirrhosis, serum concentrations of total and "free" insulin-like growth factor-I were decreased, the binding protein pattern was changed profoundly showing a reduction in the 150 kD complex and an increase in the 30-40 kD complexes. Concentrations of binding protein-1 and -2 were increased, while that of binding protein-3 was decreased in cirrhosis. The response to growth hormone was blunted. These changes were related to the degree of liver dysfunction as assessed by the Child-Pugh classification. CONCLUSIONS: A pathogenetic link of altered bio-availability of insulin-like growth factor-I to clinical characteristics of advanced liver disease, e.g. insulin resistance or skeletal muscle wasting, may be suggested by the present data.

Adult↗
PubMed1996

Reform, not rhetoric: a critique of welfare policy and charting of new directions.

Current changes in welfare policy are examined, and the likelihood that they will be unworkable or counterproductive is discussed. Based on knowledge and data from the articles in this special section, as well as other relevant research, policy and program recommendations are offered for welfare reform that would most effectively help poor women support themselves and their families.

Aid to Families with Dependent Children↗
PubMed1996

Synthesis of insulinlike growth factor binding proteins and of the acid-labile subunit in primary cultures of rat hepatocytes, of Kupffer cells, and in cocultures: regulation by insulin, insulinlike growth factor, and growth hormone.

The adult liver is the main source of circulating insulinlike growth factors (IGFs) and their serum binding proteins (IGFBPs) including the acid-labile subunit (ALS), a component of the ternary binding protein complex. Within the liver, the biosynthesis of individual proteins has been attributed to different cell populations, e.g., that of ALS to hepatocytes and that of IGFBP-3 to nonparenchymal cells. Ligand and immunoblotting as well as Northern blotting analyses were used to study synthesis of IGFBPs and their hormonal regulation in cultured adult rat hepatocytes, Kupffer cells (KCs), and cocultures. In hepatocytes, synthesis of IGFBP-1, -2, and -4 was observed; insulin and IGF-I decreased that of IGFBP-1, and -2 while increasing that of IGFBP-4. KCs synthesized IGFBP-2, and -3, insulin and IGF-I showing no effect. In cocultures, however, synthesis of IGFBP-3 was stimulated by insulin and IGF-I. By immunocytochemistry IGFBP-3 biosynthesis was localized to KCs exclusively. When pore membranes were used for separation of hepatocytes and KCs in coculture, this insulin-stimulatory action on IGFBP-3 synthesis was preserved. Growth hormone (GH) did not affect biosynthesis of IGFBPs. Expression of ALS was localized in hepatocytes only. Insulin, IGF-I, and GH increased ALS expression. It can be concluded that biosynthesis of individual IGFBPs and of ALS are compartmentalized in adult rat liver and are distinctly regulated by insulin, IGF-I, and GH. The insulin-dependent stimulation of IGFBP-3 synthesis in KCs appears to require a diffusable mediator derived from hepatocytes.

Animals↗
PubMed1996

Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG).

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.

Adult↗
PubMed1996

[The calcium hypothesis of brain aging].

The "calcium hypothesis of brain aging" assumes that a small increase in free intra-cellular calcium concentration ([Ca2+]i) over years or decades finally leads to brain lesions similar to the short [Ca2+]i overload following one acute event (e.g., stroke). Recent data are reviewed that disprove the hypothesis in this rather simple form. Studies on brain cells of experimental animals as well as on animal and human blood cells suggest that [Ca2+]i is reduced rather than elevated in brain aging. However, probably as compensation, aging seems to lead to enhanced sensitivity of the brain (or of calcium-dependent mechanisms in the brain) to changes in [Ca2+]i. Under normal conditions, both alterations seem to compensate each other. However, under situations of additional stress leading to elevated [Ca2+]i (hypoxia, hypoglycemia), aged brain cells might be more vulnerable because of a reduced ability to down-regulate [Ca2+]i. In contrast to these typical changes in the aging, very little evidence exists that [Ca2+]i is also changed in Alzheimer's disease. On the other hand, recent evidence suggests that the modulation of [Ca2+]i by beta-amyloid is specifically altered in this disease, but the pathogenetic significance of this observation is not yet finally understood.

Aged↗
PubMed1995

The amplifying effect of beta-amyloid on cellular calcium signalling is reduced in Alzheimer's disease.

The amplifying effect of beta-amyloid fragment 25-35 (beta A25-35) on the mitogen-induced rise of free intracellular calcium in circulating lymphocytes was strongly reduced in 24 patients with Alzheimer's disease when compared with elderly, non-demented controls. Low beta-amyloid responses were significantly correlated with the presence of the apolipoprotein E epsilon 4 allele, suggesting a dose effect.

Adult↗
PubMed1995

beta-Amyloid peptide decreases membrane fluidity.

The beta-amyloid peptide-25-35 (beta A25-35) decreases the fluidity of mouse brain membranes in a concentration-depending fashion. First effects were already seen at a beta A25-35 concentration of 100 nmol/1. beta-Amyloid peptide(1-40) was similarly active. beta A25-35 also decreases the fluidity of human lymphocyte membranes and of membranes from the cortex, hippocampus, striatum, and cerebellum of the rat, although the effects in the rat cerebellum are only weak. Scrambled beta A25-35 when investigated under similar conditions showed no effects on membrane fluidity. It is suggest that the effect on cellular calcium-signalling but also the neurotoxic properties of beta-amyloid might be the result of its concentration depending effects on membrane properties.

Amino Acid Sequence↗
PubMed1995

Recurrent episodes of acute hepatitis associated with LKM-1 (cytochrome P450 2D6) antibodies in identical twin brothers.

BACKGROUND/AIMS: Liver/kidney microsomal antibodies have been noted in liver disease of different etiology, e.g. in autoimmune hepatitis, chronic hepatitis C and D virus infection and in drug-induced liver disease. Unlike these, acute hepatitis of unknown etiology associated with high-titer liver/kidney microsomal-1 antibodies (cytochrome P450 2D6) is reported in identical twin brothers. METHODS: Patients were studied using clinical, biochemical, serological and immunological methods, as well as liver biopsy. RESULTS: The acute icteric episodes were followed by spontaneous remission with complete normalization of liver function tests and liver histology. During the acute phase, serum titer for liver/kidney microsomal-1 antibodies (detected by indirect immunofluorescence, ELISA and Western blot analysis) was exceedingly high and decreased gradually thereafter. Hepatitis C and D virus infection were excluded by repeated serological testing; exposure to drugs or chemicals was not evident. Concomitant autoimmune disease was not detectable. HLA typing for class 1 and 2 antigens was positive for the HLA haplotype DQ2, but negative for HLA B4, B8, DR3 and DR4. CONCLUSIONS: The present observations might suggest a hitherto unreported form of acute hepatitis of unknown etiology, distinct from other liver diseases in which liver/kidney microsomal antibodies have been described so far.

Acute Disease↗
PubMed1995

Synthesis of insulin-like growth factor binding proteins and of the acid-labile subunit of the insulin-like growth factor ternary binding protein complex in primary cultures of human hepatocytes.

BACKGROUND/AIMS: The liver is the main source of circulating insulin-like growth factor binding proteins. In man, the cellular origin of insulin-like growth factor binding proteins has remained obscure. METHODS: Human hepatocytes isolated from surgical specimens were purified and cultured using a collagen gel immobilization technique. Gene expression of individual insulin-like growth factor binding proteins and of the acid-labile subunit of the insulin-like growth factor binding proteins by Western ligand blotting and immunoblot analysis. Neutral size chromatography of medium samples was used to detect insulin-like growth factors binding protein complexes. RESULTS: In cultured hepatocytes transcripts for insulin-like growth factor binding protein-1, -2, -3, -4 and for acid labile subunit could be demonstrated. Ligand blotting revealed the secretion of insulin-like growth factor binding proteins of molecular weights of 24 kD, 30 kD, 34 kD, 43 kD and 46 kD, respectively. Using polyclonal antisera, these proteins were identified as insulin-like growth factor binding protein-1, -2 and the insulin-like growth factor binding protein-3 doublet. Neural size chromatography of culture supernatants showed the presence of an insulin-like growth factor binding protein complex of approximately 40 kD, but absence of the high molecular weight ternary complex of 150 kD. CONCLUSIONS: It is concluded that in man parenchymal liver cells have to be regarded as a source of acid-labile subunit and of circulating insulin-like growth factor binding proteins including insulin-like growth factor binding protein-3.

Blotting, Northern↗
PubMed1995

Effect of insulin-like growth factor II on uptake of arylsulfatase A by cultured rat hepatocytes and Kupffer cells.

Mannose 6-phosphate/insulin-like growth factor II receptors have been characterized in hepatocytes and Kupffer cells isolated from adult rat liver. Affinity labeling with [125I]insulin-like growth factor II revealed a protein of Mr 250,000 in both cell types. Labeling was inhibited by an antiserum against the mannose 6-phosphate/insulin-like growth factor II receptor. In Kupffer cells, [125I]insulin-like growth factor II was also cross-linked to a second protein of Mr 130,000. In both cell types, insulin-like growth factor II was 10 times more potent than insulin-like growth factor I in displacing [125I]insulin-like growth factor II from its receptor. The mannose 6-phosphate-specific uptake of [125I]arylsulfatase A via the mannose 6-phosphate/insulin-like growth factor II receptor was inhibited by insulin-like growth factor II and antibodies against the receptor, but was not affected by insulin-like growth factor I, insulin or transforming growth factor beta 1. Cell surface iodination followed by immunoprecipitation of the mannose 6-phosphate/insulin-like growth factor II receptor showed that expression of the mannose 6-phosphate/insulin-like growth factor II receptors at the plasma membrane was increased two-fold by insulin-like growth factor II. These results suggest that binding of insulin-like growth factor II to the mannose 6-phosphate/insulin-like growth factor II receptor blocks the binding and uptake of mannose 6-phosphate-containing lysosomal enzymes and may be directly involved in a co-ordinate regulation of ligand uptake from plasma into hepatocytes and Kupffer cells.

Animals↗
PubMed1995

Cellular localization and hormonal regulation of biosynthesis of insulin-like growth factor binding proteins and of the acid-labile subunit within rat liver.

In the circulation, most of the IGFs are bound to a high molecular weight binding protein complex of 150 kDa that consists of IGF-I (or IGF-II), IGFBP-3 and the acid-labile subunit (ALS). Within rat liver, individual components of the 150 kDa complex are synthesized in different cellular compartments. ALS expression is localized in hepatocytes, but not in non-parenchymal cells. IGFBP-3 mRNA, however, is exclusively expressed in non-parenchymal and among them in endothelial and Kupffer cells. Co-cultures of hepatocytes and Kupffer cells were used as a model to study the hormonal regulation of biosynthesis of the components of the 150 kDa complex. Although expressed in different liver cell populations IGFBP-3 and ALS were regulated synergistically. Insulin stimulated both the expression of ALS and IGFBP-3 in co-cultures in a dose-dependent manner, while expression of IGFBP-I was decreased. Regulation of IGFBP-3 synthesis of Kupffer cells required a mediator that is secreted by hepatocytes, since IGFBP-3 expression in cultures of pure Kupffer cells did not respond to the stimulating effect of insulin.

Animals↗
PubMed1995

Glucose metabolism and liver cirrhosis.

Chronic liver disease is characterized by numerous metabolic alterations, predominantly catabolic, resulting in the clinical picture of malnutrition and even cachexia in some patients. The following review focuses on disturbances of glucose metabolism and of hormonal interactions that could contribute to the clinical picture of malnutrition seen in chronic liver disease. Body composition is altered in a characteristic manner with an increase in fat mass and a significant loss of muscle tissue. Furthermore, defective glucose storage due to reduced insulin sensitivity predominantly of muscle tissue has been observed. The pathogenesis of insulin resistance leading to an impaired glucose tolerance or a manifest diabetes mellitus is as yet unknown. A receptor/postreceptor dysfunction probably exists in chronic liver disease that might be explained by the following factors: 1. Altered membrane lipid composition and increased levels of free fatty acids; 2. long-lasting hyperinsulinemia; 3. increased plasma levels of insulin counteracting hormones such as growth hormone, glucagon, catecholamines and possibly cytokines; 4. a lack of liver-derived humoral factors with insulin-like activity, i.e. insulin-like growth factors I and II.

Catecholamines↗
PubMed1995

[Initial clinical experiences with TIPS (transjugular intrahepatic portasystemic stent-shunt)].

15 patients with predominantly alcoholtoxic liver cirrhosis (mean age 50 years; 8 men and 7 women) were treated by the technically successful implantation of a transjugular portosystemic stent-shunt (TIPS) within a period of 1 year. The indications for TIPS implantation were the following: gastroesophageal bleedings in 12 cases (10 patients with recurrent variceal bleeding including 2 emergency cases with severe bleeding resistant to conventional therapy and 2 patients with exclusively gastral bleeding due to severe hypertensive gastropathy) and ascites resistant to conventional therapy in 3 cases. Portovenous pressure could be effectively reduced by mean of 37%. Within a mean observation period of 8 months 13 patients including the emergency cases remained without recurrent bleeding. Duplexsonography showed patent stents. 1 patient suffered from an early recurrent bleeding due to occlusion of the stent-shunt. The estimation of liver function according to the Child-Pugh-classification showed only minor changes. Before TIPS 9 patients were in class A, 4 in B, 2 in C; after TIPS 8 patients in A, 5 in B and 2 in C. Ascites resolved completely. Following TIPS all patients appeared to abstain from alcohol. After TIPS 5 from 14 surviving patients (36%) developed clinically manifest encephalopathy within the first 4-8 weeks (2 patients with previous episodes of encephalopathy, 2 other patients after withdrawal of lactulose). By enhanced conservative treatment (lactulose, paromomycine and protein restriction) encephalopathy could be overcome. 8 from 11 surviving patients investigated displayed characteristic MRI changes with an increased signal intensity in the basal ganglia (T1 weighted images). According to our preliminary results TIPS represents a new successful interventional regimen for the treatment of portal hypertension in selected cases.

Adult↗
PubMed1995

[Effects of dehydration on functional parameters of fluid balance as well as effectiveness of rehydration using crystalline or colloidal infusion drips in calves].

Studies were conducted on 57 calves (aged 3-23 d) to elucidate the effects of diarrhoeal and experimentally induced dehydration upon functional parameters of the fluid balance and of renal functionality. Aggravating intensity and length of diarrhoea was found to be accompanied by decline in intravasal and extracellular fluid compartments. Ante mortem dehydration of the animals with diarrhoea was close to 20% relative to body weight. This was paralleled by life-threatening drop of glomerular filtration rates to < 10% of original physiological values. Administration of a diuretic, associated with reduction by 50% of daily liquid uptake, proved helpful in generating dehydration of 5 to 6% relative to body weight. Evidence was provided to the effect that isooncotic colloid-electrolyte solution was superior to pure isotonic electrolyte solution for rehydration of calves dehydrated in the first place in the way described. Colloidal infusion, in particular, produced favourable therapeutic effects in terms of optimization of blood plasma volume and renal ultrafiltration.

Animals↗
PubMed1995

[Evaluation of hypoxic conditions in calves using the erythrocyte density test (EDT)].

The erythrocyte density separation test (EDT) divides the red blood cells into two groups: younger (less dense) and older (more dense) erythrocytes. Using this test enables veterinarians to assess the erythropoiesis in calves on the basis of the percentage of less dense (younger) red blood cells. Anemic calves, as well as those with pneumonic infections show higher proportions of less dense red blood cells in the EDT than healthy ones. This testing procedure makes it possible to estimate the effects of an oxygen deficiency condition, such as hypoxemia, anemia, shock etc. on the peripheral tissues. So the EDT represents a valuable complement to existing hematological laboratory methods. Carrying out the EDT is very simple and suitable in routine clinical testing.

Anemia↗
PubMed1995

[Diagnostic and pathophysiological aspects of the determination of kidney function in animals].

Early diagnosis of loss in renal function (< 60-70%) is not possible either by resorting to the parameters of plasma urea and creatinine concentrations (responsive to functional loss by > 75% or by reference to urine concentration capacity (urine density: sensitive to concentrations > 60%). However, clearance techniques for determination of the glomerular filtration rate (GFR) have proved suitable for quantitative assessment of renal function. Endogenous creatinine clearance is one of the most common clinical approaches in GFR determination. Criticism of results obtainable from endogenous creatinine clearance appears to be justified by pharmacokinetic aspects of creatinine as an indicator, as well as by some of its analytical peculiarities. The tediousness of the procedure is another counterproductive aspect pertaining to large-scale use of endogenous creatinine clearance in veterinary medicine. Total blood-plasma clearance of exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate (diagnostic validity) and practical method for carrying out clinical kidney-function diagnostics. However, more research on a number of related issues will be required before the general introduction of the procedure.

Animal Diseases↗
PubMed1995

Cryoglobulinemia in chronic hepatitis C virus infection: prevalence, clinical manifestations, response to interferon treatment and analysis of cryoprecipitates.

Chronic hepatitis C virus infection can be associated with mixed cryoglobulinemia and systemic vasculitis. The pathogenesis remains poorly understood. 55 consecutive patients with chronic HCI infection (anti-HCV- and serum HCV RNA-positive) were studies prospectively. Cryoglobulinemia was detected in 28 patients (51%) with a mean cryocrit level of 2.2%. Clinical symptoms of vasculitis were encountered in six patients. Compared to those HCV-infected patients without cryoglobulinemia the following distinctive features were observed in the presence of cryoglobulinemia: increased age (p<0.02), female preponderance (p<0.002), longer-lasting HCV infection (mean of 10.7 vs. 4.7 yrs), higher prevalence of cirrhosis (42.8 vs. 0%), increased serum concentration of IgM and increased rheumatoid factor activity, decreased concentration of serum C4 (each p<0.05). The response to interferon treatment was similar in patients with and without cryoglobulinemia. When cryoprecipitates were analyzed by immunofixation, type II cryoglobulinemia was present in 1/3 and type III in 2/3 of patients. By SDS-PAGE four different proteins were demonstrable in cryoprecipitates each identified by immunoblotting as IgG and IgM heavy or light chains respectively. Cryoprecipitate IgGs were shown to react with HCV structural as well a non-structural proteins in a recombinant immunoblotting assay (RIBA). In contrast, cryoprecipitate IgMs reacted only to the HCV core protein c22-3. HCV RNA was detected in cryoprecipitates without a significant enrichment when compared to the corresponding serum or supernatant HCV RNA content. Given the monoclonality of some cryoprecipitate IgM and their reactivity to HCV core, a cross-reactivity to IgG was postulated. In fact, when performing a computer-assisted search for sequence homology, a motif within the core protein (EGLGWAGWL, conserved in HCV genotypes) was identified homologous to a sequence of IgG heavy chains. Thus, temperature-dependent affinity changes of IgM anti-HCV core (nonapeptide) and ensuing complex formation with IgG via binding to the homologous IgG sequence could be a mechanism of cryoprecipitate formation.

Adult↗