Search PubMed⌕ Search

Biomedical subjects

B Haag

Publications and source records attributed to B Haag.

At least 19 recordsLinked to original sources
PubMed1998

Tubular antithrombin at transplantation determines subsequent renal allograft function.

BACKGROUND: Antithrombin is found in the microvasculature and tubules of normal and transplanted human kidneys. Although depletion of vascular antithrombin is associated with renal allograft dysfunction, neither the distribution nor clinical significance of tubular antithrombin is known. METHODS: Changes in tubular antithrombin in biopsy specimens (n=41) obtained from donor kidneys at transplantation were studied immunohistochemically. The relationship between these changes and subsequent graft function was analyzed. RESULTS: Granular intracellular antithrombin was found only within the proximal tubular epithelium. Allografts with depleted tubular antithrombin at transplantation (n=20) had significantly greater plasma creatinine concentrations at posttransplant days 3 (P < 0.001) and 5 (P < 0.03) than allografts with normal tubular antithrombin (n=21). Indeed, depletion of tubular antithrombin at transplantation correlated with the degree of graft dysfunction at 3 days after transplantation. CONCLUSIONS: Depleted tubular antithrombin at transplantation is associated with reduced early graft function, and this may identify patients at risk of a complicated follow-up.

Antithrombins↗
PubMed1998

Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes.

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and insulin. RESEARCH DESIGN AND METHODS: A multicenter randomized double-blind placebo-controlled parallel-group comparison study was conducted. The trial was 26 weeks with a 2-week screening period and a 24-week period of treatment with acarbose or placebo, with forced titration from 25 mg t.i.d. to 50 mg t.i.d. after 4 weeks, and titration of 50 mg t.i.d. to 100 mg t.i.d. after 12 weeks based on glucose control. The dosage of insulin was to remain stable. The primary efficacy variable was mean change from baseline in HbA1c, and secondary efficacy variables included mean changes in fasting and postprandial plasma glucose and triglyceride levels. RESULTS: The addition of acarbose to the treatment of patients receiving background insulin and diet therapy resulted in a statistically significant reduction in mean HbA1c of 0.69% compared with placebo. There were statistically significant reductions in postprandial plasma glucose and glucose area under the curve, and in postprandial serum triglyceride levels in the acarbose-treated patients. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. There were no significant differences in hypoglycemic events or liver transaminase elevations between groups. CONCLUSIONS: This study demonstrated that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with insulin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and postprandial glucose levels.

Acarbose↗
PubMed1994

Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene.

The principal substrate for the insulin and insulin-like growth factor-1 (IGF-1) receptors is the cytoplasmic protein insulin-receptor substrate-1 (IRS-1/pp185). After tyrosine phosphorylation at several sites, IRS-1 binds to and activates phosphatidylinositol-3'-OH kinase (PI(3)K) and several other proteins containing SH2 (Src-homology 2) domains. To elucidate the role of IRS-1 in insulin/IGF-1 action, we created IRS-1-deficient mice by targeted gene mutation. These mice had no IRS-1 and showed no evidence of IRS-1 phosphorylation or IRS-1-associated PI(3)K activity. They also had a 50 per cent reduction in intrauterine growth, impaired glucose tolerance, and a decrease in insulin/IGF-1-stimulated glucose uptake in vivo and in vitro. The residual insulin/IGF-1 action correlated with the appearance of a new tyrosine-phosphorylated protein (IRS-2) which binds to PI(3)K, but is slightly larger than and immunologically distinct from IRS-1. Our results provide evidence for IRS-1-dependent and IRS-1-independent pathways of insulin/IGF-1 signalling and for the existence of an alternative substrate of these receptor kinases.

Animals↗
PubMed1992

Implications of a non-lamellar lipid phase for the tight junction stability. Part II: Reversible modulation of transepithelial resistance in high and low resistance MDCK-cells by basic amino acids, Ca2+, protamine and protons.

The transepithelial resistance of confluent epithelial cell monolayers was monitored to investigate the influence of basic amino acids, Ca2+, protamine and protons on tight junction electrical resistance. In an accompanying paper we investigated the effect of these substances on the lamellar/hexagonal II phase transition in reconstituted phospholipid membranes containing phosphatidylserine and phosphatidylethanolamine. We conclude that the permeability of tight junctions may be described by a lipid phase equilibrium where the lamellar phase corresponds to an open state and the hexagonal lipid phase to the closed state of the cell contact. This dynamic lipid model is well suited to describe the morphological as well as functional properties of the tight junctions.

Amino Acids↗
PubMed1992

The endothelial heparan sulfate-antithrombin III natural anticoagulant pathway in normal and transplanted human kidneys.

This is the first study of the antithrombin III-heparan sulfate natural anticoagulant pathway in human kidneys. Immunocytochemical experiments were done to demonstrate the pathway on normal renal endothelial cells. Enzymatic studies were done to show that the antithrombin III was anchored to endothelium by molecules of heparan sulfate. Displacement studies were done with glycosaminoglycans to show that the antithrombin III was bound to its glycosaminoglycan anchor via a heparinlike binding site, and replacement studies showed that antithrombin III could be returned to the same endothelial cells from which it was displaced. Immunocytochemical studies of biopsies showed that normally functioning renal allografts manifested the endothelial antithrombin III-heparan sulfate anticoagulant pathway. The pathway was compromised or absent from the microcirculation of biopsies from rejecting or rejected renal allografts, and the diminishment of endothelial ATIII was associated with the presence of fibrin deposition. It is concluded that compromise of the antithrombin III-heparan sulfate natural anticoagulant pathway results in compromised renal function in transplanted kidneys.

Adolescent↗
PubMed1992

Tissue factor in normal and transplanted human kidneys.

Tissue factor (TF) plays a central role in the initiation of blood coagulation that frequently is enhanced in renal allografts. The identification and localization of TF was studied immunocytochemically in biopsies from normal and transplanted human kidneys and classified according to its distribution. The clinical status of each allograft was then correlated with the TF classifications. From these correlations, four distributional types of TF were identified. In normal kidneys, TF was localized to glomerular epithelium and basement membranes. Glomerular TF expression did not colocalize with mesangial or endothelial HLA-DR reactivity as determined by double antibody techniques. Tissue factor in donor kidneys also was identified in the renal capsule and in the adventitia of large arteries. These structures were not reactive in long-term transplanted grafts. Some cadaver kidneys prepared for transplantation had depleted glomerular TF, and exhibited TF reactivity within stromal tissues. Long-term allografts with progressive loss of renal function and kidneys with advanced rejection exhibited diminished TF reactivity of glomerular epithelium and basement membranes. This was frequently associated with fibrin deposition within the glomeruli and in the intertubular microcirculation. These findings indicate that the evaluation of TF in transplanted kidneys is related to the prognosis of graft survival.

Adult↗
PubMed1992

Novel immunohistochemical markers of human renal allograft dysfunction--antithrombin III, Thy-1, urokinase, and alpha-smooth muscle actin.

We have studied the expression of alpha-smooth muscle actin (alpha sm-1) by mesangial cells, and the expression of Thy-1 glycoprotein, antithrombin III (ATIII), and urokinase by tubular epithelial cells in normal kidneys and dysfunctional renal allografts. Kidney biopsies were studied immunocytochemically for changes in each of these markers and the findings were classified into two groups and compared with creatinine plasma levels at the time the biopsies were taken. In dysfunctional grafts, mesangial alpha sm-1 and tubular epithelial Thy-1 reactivities were greatly diminished, and urokinase and ATIII were missing from proximal renal tubular epithelial cells. Urokinase, which was absent from normal renal glomeruli, appeared in glomeruli of some dysfunctional allografts. The possible usefulness of these markers in patient evaluations was supported by our finding that the distribution of vinculin, fibronectin, myosin, actin B4, desmin, glomerular HLA-DR, and the tubular expression of CD15 remained unchanged. These data prompt us to suggest that the immunocytochemical localization and evaluation of alpha sm-1, Thy-1, ATIII, and urokinase in kidney allografts may be useful adjuncts in the assessment of function in renal allografts.

Actins↗
PubMed1991

Acute small bowel ischemia without transmural infarction.

Two patients with atrial fibrillation had abrupt onset of abdominal pain and massive small bowel distension suggesting mesenterial artery embolism. One patient had dilation of the left atrium and ventricle, the other a mitral value prolapse syndrome with a dilated left atrium. Both patients were treated conservatively and gradually recovered. A small bowel series performed several weeks after the acute episode showed loss of normal mucosa and narrowing of a long segment of the small bowel. A control examination in one patient one year later, still revealed jejunal mucosal abnormalities and stenosis, features similar to those occurring in Crohn's disease. Our observations suggest that analogous to ischemic colitis, an entity of acute ischemic small bowel enteritis exists. Mesenteric ischemia apparently can induce a clinical syndrome of "regional enteritis". The radiologic features should not be confused with those of Crohn's disease.

Aged↗
PubMed1985

[Introduction of a new bandaging technic in CAPD patients].

The protrusion of the peritoneal dialysis catheter from the skin is a technological and biological problem insufficiently solved in CAPD-patients. Infections in this area may demand the removal of the indwelling catheter. A decrease of the infection rate as well as a significant increase of the comfort for the patients is possible by the new bandaging method demonstrated, in which colostomy bags usual in trade are used.

Bandages↗
PubMed1983

Mechanism of plasma catecholamine increases during coronary artery bypass and valve procedures.

Nineteen patients undergoing coronary revascularization (14 patients) or valve replacement (five patients) were studied to monitor the catecholamine levels following operation and for each of three consecutive postoperative days. A significant (p less than 0.01) elevation was observed in both the serum norepinephrine and epinephrine levels immediately following operation, with both responding in a similar fashion (r = 0.804, p = 0.016). While epinephrine returned to control levels within 3 days of operation, the norepinephrine levels remained above control. The elevation in catecholamines associated with cardiac operation is presumed to be secondary to (1) the stress of surgical trauma and (2) the influence of cardiopulmonary bypass, with its attendant hypothermia and hemodynamic alterations. A comparative analysis was performed of (1) the type of operation, (2) the sex of the patient, (3) the presence of postoperative arrhythmia, (4) the history of receiving propranolol, (5) the duration of cardiopulmonary bypass, (6) the duration of operation, and (7) the volume of fluid gradient absorbed during operation. None of these parameters except the sex of the patient was significantly related to the change in either norepinephrine or epinephrine associated with the operation. There was a significantly (p less than 0.05) higher epinephrine level at day 2 and 3 following operation in women than in men. None of the 19 patients had postoperative complications except for arrhythmias, which developed in nine patients and were not associated with the catecholamine responses. It is concluded that peak catecholamine stimulation does not reflect the ease of postoperative recovery. The duration of bypass and operation were also not directly related to the level of stimulation. It is apparent that there are multiple factors which combine to influence catecholamine secretion during cardiopulmonary bypass.

Adult↗
PubMed1980

Antigenic high molecular weight material in penicillin preparations.

Using a radioimmunoassay, RIA, small amounts of high molecular weight antigens have been reproducibly identified in both biosynthetic and semisynthetic brands of penicillin. These impurities were found to be eliminated by simple chemical means. Measures to avoid this type of contaminants in penicillin preparations should be undertaken because of the immunogenic nature of the contaminants resulting in increased risk of sensitization of patients to penicillin.

Antigens↗