Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1995

[Nitric oxide in therapy of pulmonary hypertension after correction of congenital single atrium].

We report on a 19-month-old boy with congenital single atrium. Cardiac catheterization preceding the surgical repair revealed an elevated pulmonary artery pressure of 60/15 mmHg (mean pressure 40 mmHg). Pulmonary flow was 8.4 l/min.m2 and systemic flow was 5.5 l/min.m2. Pulmonary arteriolar resistance was elevated to 4.2 U.m2 with 64% left-right shunt and 25% right-left shunt. Arterial O2-saturation varied around 90%. After surgical repair (insertion of a Goretex patch), the patient required mechanical ventilation with 100% oxygen for adequate oxygenation. Cardiac catheterization was repeated on the first postoperative day. No residual shunts were found. The pulmonary artery pressure was 66/40 mmHg (mean pressure 50 mmHg), systemic arterial pressure was 85/62 mmHg (mean pressure 68 mmHg). Cardiac index was 2.8 l/min.m2, pulmonary vascular resistance was 12 U.m2. After administration of prostacyclin a significant decrease of pulmonary artery pressure was observed, but without changing the ratio between pulmonary and systemic pressure. The AaDO2 varied between 400 and 580 mmHg and the oxygenation-index (PaO2/FiO2) was less than 1.0. In this situation, an attempt with inhaled nitric oxide (NO) was performed. After adding 20 ppm NO to the inspired gas, the AaDO2 decreased significantly from 580 to 270 mmHg and the oxygenation-index (OI) rose from 0.9 to 1.5. The inspired fraction of oxygen could be reduced quickly to 60%. During the next days, the concentration of NO was reduced stepwise to 1 ppm. Finally, the AaDO2 was within the normal range (25-65 mmHg) and the OI rose to a level about 4.0. The FiO2 could be reduced to 30% and nitric oxide therapy could be stopped and the child could be extubated.

Administration, Inhalation↗

PubMed1994

Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity.

Besides the neurotoxic properties of beta-amyloid (beta A4), apolipoprotein E polymorphism seems to play an important role in the pathogenesis of sporadic Alzheimer's disease (AD). The calcium amplifying effect of beta A25-35 (the neurotoxic sequence of beta A4) in dissociated mouse brain neurons and human lymphocytes was nearly abolished by cholesterol (100-500 mumol/l). This effect may be related to the membrane stabilizing properties of cholesterol which could be confirmed by measurements of membrane fluidity. ApoE did not affect the Ca2+ amplifying effect of beta A25-35, but amplified the neuronal Ca2+ response significantly in a very low concentration (100nmol/l). The findings suggest a possible link between AD pathology and ApoE polymorphism by the calcium amplifying effect of ApoE itself as well as by the modulation of beta A4 neurotoxicity by cholesterol.

Amyloid beta-Peptides↗

PubMed1994

Similar age-related changes of free intracellular calcium in lymphocytes and central neurons: effects of Alzheimer's disease.

Several studies suggest that alterations of cytosolic free calcium concentration ([Ca2+]i) are involved in the pathophysiology of aging and Alzheimer's disease (AD). However, only few data are presently available giving detailed information about specific characteristics of age-related or AD-specific changes in cellular Ca(2+)-homeostasis. To allow a comprehensive evaluation of age-related changes in [Ca2+]i we performed parallel investigations in central mouse brain cells and mouse spleen lymphocytes of young and aged animals and also in human lymphocytes and granulocytes of young and aged donors and additionally of AD patients. In aged animals, basal [Ca2+]i was decreased in brain cells but increased in spleen lymphocytes. No age-related alterations in baseline [Ca2+]i was found in human lymphocytes or granulocytes. However, comparison of activation-induced rise in [Ca2+]i revealed parallel age-related changes in the different cell-types investigated. The increase in [Ca2+]i after depolarization of mouse brain cells with KCl and after stimulation of mouse lymphocytes with phytohaemagglutinin (PHA) was significantly impaired in aged animals. Moreover, activation of human lymphocytes with PHA also revealed a reduced increase in [Ca2+]i in cells of aged donors. In lymphocytes of AD-patients there was a tendency to higher basal [Ca2+]i compared to their aged matched controls, but no specific alterations in [Ca2+]i could be found after stimulation with PHA. Also no age-related or AD-specific changes were found in granulocytes after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Disturbances of the neuronal calcium homeostasis in the aging nervous system.

Maintenance of the cellular calcium homeostasis plays an important role for neuronal cell function and interneuronal cell to cell communication. Therefore, alterations of the neuronal Ca2+ homeostasis may play a crucial role for brain aging in general and for age-related deficits in cognitive functions particularly. Numerous studies indicate various disturbances of the Ca2+ homeostasis on different levels like Ca2+ channel properties, 45Ca2+ uptake, or Ca2+ binding proteins. Investigations on alterations of the free intracellular calcium concentration ([Ca2+]i) in presynaptic synaptosomal preparations led to inconsistent results reporting increased or unchanged [Ca2+]i in aged animals. Postsynaptic alterations of [Ca2+]i have been investigated mainly indirectly by electrophysiological methods and revealed prolonged Ca(2+)-dependent afterhyperpolarization or prolonged Ca2+ spike duration. By using acutely dissociated mouse brain cells it was possible for the first time to evaluate age-dependent alterations of postsynaptic [Ca2+]i directly. In neurons of aged mice basal [Ca2+]i was reduced and depolarization-induced rise in [Ca2+]i was also reduced, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca(2+)-influx. Depolarization-induced, Ca(2+)-mediated inositolphosphate accumulation was also increased in aged animals. This leads to the conclusion that Ca(2+)-dependent intracellular processes become more sensitive during aging. Investigations about the effect of beta-amyloid on the Ca2+ homeostasis in the same system revealed a small but consistent destabilizating effect of this peptide on K(+)-induced rise in [Ca2+]i which may result in chronically increased neuronal vulnerability. Together with increased Ca2+ sensitivity during aging this might be one of the reasons for the increasing prevalence of Alzheimer's disease (AD) with aging.

Aging↗

PubMed1994

Alterations of intracellular calcium regulation during aging and Alzheimer's disease in nonneuronal cells.

Because of its function as an intracellular messenger in many cells, calcium plays an important role in signal transduction. Changes in intracellular free calcium concentration occur in central neurons during aging and Alzheimer's disease (AD). It is possible that similar changes in peripheral cells could mirror or, at least parallel, similar abnormalities in the brain. Assuming that manifestations of the aging process and AD are also present outside the central nervous system, nonneuronal tissues like lymphocytes could be used to search directly for abnormalities in cellular calcium regulation in man. Consistent with observations of reduced depolarization-induced Ca2+ rises in dissociated neurons of aged mice, corresponding age-related changes of reduced mitogen-induced Ca2+ responses were observed both in mouse lymphocytes and, more importantly, in circulating human lymphocytes. With respect to AD, Ca2+ responses after stimulation were unaltered (compared to normal controls). In addition, freshly prepared human lymphocytes showed elevated mitogen-induced Ca2+ responses after exposure to beta-amyloid, the main component of senile plaques in AD. These findings again parallel our observations that this peptide amplifies the K(+)-induced Ca2+ rise in acutely dissociated mouse brain cells. Thus, the lymphocyte seems to be a valuable model to study the effects of beta-amyloid in man. In a preliminary study with AD-patients, sensitivity of the lymphocytes to beta-amyloid's effects on Ca2+ rise was reduced, an observation which was entirely unexpected. Nevertheless, such studies indicate lymphocytes may represent a promising candidate for a peripheral marker of AD and can contribute to the understanding of the disease process.

Aging↗

PubMed1994

Influence of gender on the monoethylglycinexylidide test in normal subjects and liver donors.

The objective of this study was to investigate the effect of gender on monoethylglycinexylidide (MEGX) formation in normal subjects and cadaveric liver donors. The study included 92 male and female healthy volunteers < 45 years of age and 98 age- and sex-matched liver donors from a previous study, whose livers were used for transplantation. Women < 45 years not taking contraceptives showed significantly lower MEGX concentrations 30 min after lidocaine administration than men [median (16-84th percentile)]: 59 micrograms/L (41-70 micrograms/L) versus 81 micrograms/L (58-98 micrograms/L)]. The lowest MEGX 30 min values were observed in women taking contraceptives: 39 micrograms/L (25-48 micrograms/L). Intraindividual variability of serial MEGX tests was moderate (median: 17.8%, n = 8) when measured in female subjects taking no contraceptives and males. Cadaveric liver donors showed significantly higher MEGX 15 and 30 min values compared with normal subjects (p < or = 0.0001). There was no statistically significant difference between MEGX values obtained in male and female cadaveric donors. The urinary excretion of MEGX was similar in male and female normal subjects. Our results suggest that sex-related differences in MEGX formation as well as the influence of contraceptives have to be taken into account when test results from living related liver donors and patients with less advanced chronic liver disease are evaluated. In cadaveric liver donors, however, sex-related differences do not affect MEGX formation.

Adult↗

PubMed1994

Negative extrathoracic pressure ventilation in central hypoventilation syndrome.

Nine patients with central hypoventilation syndrome (CHS) were treated with negative extrathoracic pressure ventilation (VNEP). Treatment with VNEP was started between 20 days and 57 months of age, which was two days to 47 months after diagnosis. The equipment to provide VNEP utilised a new system with a latex neck seal and Perspex chamber allowing easy access to the child. Seven patients are managed with VNEP at home by their parents. They did not have a tracheostomy when VNEP was started at ages of 22, 24, 31, 38, and 75 days, 5 and 57 months. They have continued to be successfully managed with VNEP and without tracheostomy. Short periods of intubation and positive pressure ventilation were required on 10 occasions (median duration 7 days, range 4 to 21 days) in four subjects during respiratory tract infections. Three patients required periods of continuous positive airway pressure (CPAP) via a nasal mask or a nasopharyngeal airway during sleep to overcome upper airway obstruction. In three patients the hypoventilation improved and two of these do not require regular ventilatory support at 1.3 and 3.4 years of age. Six of these seven patients are developing normally. In two patients with long term tracheostomies, VNEP could not be established at an age of 29 and 52 months because of tracheal obstruction after temporary removal of their tracheostomy cannula. VNEP is an effective, non-invasive, treatment in infants with CHS if initiated before tracheostomy. It may improve the children's quality of life during the daytime. If upper airway obstruction is a problem in the first year of life, it may be combined with nasal mask CPAP.

Child Development↗

PubMed1994

Essential mixed cryoglobulinemia (EMC) in a case of chronic hepatitis C--successful treatment with interferon alpha.

Chronic hepatitis C virus infection has previously been shown to be associated in some cases with an immunologic disorder called "Essential Mixed Cryoglobulinemia" (EMC). In this report a case of transfusion-associated chronic hepatitis C will be demonstrated. During patient's follow-up over a period of fifteen years the woman developed symptoms consistent with the clinical triad of EMC: general weakness, polyarthralgias and purpura. Laboratory chemical values support the presence of mixed cryoglobulins. Application of different therapeutic strategies revealed an improvement of both clinical and biochemical findings during interferon-alpha treatment. Results suggest that during chronic hepatitis C virus infection interferon-alpha therapy may represent the elective choice of treatment for typical symptoms of EMC.

Biopsy↗

PubMed1994

Hereditary pancreatitis--a case report.

A female patient with hereditary chronic pancreatitis is described. She presented initially at the age of 18 years with abdominal pain due to acute pancreatitis. Predisposing etiological factors were not recognized. During the ensuing years she had recurrent episodes of abdominal pain and chronic pancreatitis with extensive pancreatic calcifications was finally demonstrated. Six other family members within three generations were affected by chronic pancreatitis suggesting an autosomal dominant mode of transmission. None of the affected patients showed signs of diabetes mellitus, aminoaciduria or hyperparathyroidism.

Adult↗

PubMed1994

[Current therapeutic strategies in hepatocellular carcinoma, Part 1].

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver, most prevalent in Asia and Africa but also showing a rising incidence worldwide. Chronic hepatitis B and C virus infection is the most important risk factor for HCC. More than half of the patients suffer from underlying liver cirrhosis. The prognosis is determined by tumor stage and residual capacity of the liver, the median survival being 0.9 to 12.8 months for patients receiving no specific treatment. In the East, early detection has been improved by screening programs which seem to be less valuable in the Western world.

Carcinoma, Hepatocellular↗