Unmasking of proteinuria in the course of genetic dissection of nonproteinuric diabetic nephropathy.

We previously described the development of nonproteinuric diabetic nephropathy (NPDN) in the Cohen diabetic rat (CDs), a model that simulates Type 2 diabetes in humans. Using linkage analysis in an F2 cross, we currently set out to investigate the mechanisms underlying NPDN. We crossbred between CDs and SBN/y, a nondiabetic rat strain, generated F1 and F2 progenies, fed them diabetogenic diet that elicits diabetes and NPDN in CDs but not in SBN/y, and determined metabolic and renal phenotypes.

Ion-channel reconstitution.

In this chapter, a detailed protocol is given for ion-channel reconstitution in the two most used model membranes: planar bilayers and liposomes. In the planar bilayer section, methods are described for the expression of ion channels in Xenopus laevis oocytes, the isolation of their membranes, the insertion of ion channels into the bilayer by vesicle fusion, and the recording of single-ion channel current measurements at a constant applied voltage. The reconstitution of bacterial channels in liposomes is also given.

Effect of lercanidipine on kidney microanatomy in Cohen-Rosenthal diabetic hypertensive rats.

The study was undertaken to determine the effect of treatment with the dihydropyridine-type calcium antagonist lercanidipine on the renal vasculature in Cohen-Rosenthal diabetic hypertensive rats, a genetic model of hypertension associated with type 2 diabetes mellitus. Eight animals were given a daily oral dose of 3 mg/kg lercanidipine in drinking water for 8 weeks, and 6 control animals received no treatment. The effects on blood pressure, glucose level, and kidney microanatomy were evaluated.

Dissection of the components for PIP2 activation and thermosensation in TRP channels.

Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the activation of several transient receptor potential (TRP) channels. The role of PIP2 on temperature gating of thermoTRP channels has not been explored in detail, and the process of temperature activation is largely unexplained. In this work, we have exchanged different segments of the C-terminal region between cold-sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP2 and temperature activation.

A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels.

Temperature transduction in mammals is possible because of the presence of a set of temperature-dependent transient receptor potential (TRP) channels in dorsal root ganglia neurons and skin cells. Six thermo-TRP channels, all characterized by their unusually high temperature sensitivity (Q10 > 10), have been cloned: TRPV1-4 are heat activated, whereas TRPM8 and TRPA1 are activated by cold. Because of the lack of structural information, the molecular basis for regulation by temperature remains unknown.

Menetrier's disease presenting as an acute protein-losing gastroenteropathy in a 27-year-old man with Gaucher disease.

Objectives: To describe a unique case of a young man with Gaucher disease who was diagnosed with Menetrier's disease.

Background: After an acute episode of severe gastritis, the patient developed hypoalbuminemia and protein-losing gastroenteropathy, and became unwell.

Study: Endoscopy revealed an abnormal stomach, with rigid, thickened folds covered with viscous greyish exudates.

Nonproteinuric diabetes-associated nephropathy in the Cohen rat model of type 2 diabetes.

The Cohen diabetic rat is an experimental model reminiscent of human type 2 diabetes. The aim of this study was to characterize the development of end-organ damage in this model. Cohen diabetic sensitive (CDs) and Cohen diabetic resistant (CDr) rats were fed regular diet or a diabetogenic diet.

S3b amino acid residues do not shuttle across the bilayer in voltage-dependent Shaker K+ channels.

In voltage-dependent channels, positive charges contained within the S4 domain are the voltage-sensing elements. The "voltage-sensor paddle" gating mechanism proposed for the KvAP K+ channel has been the subject of intense discussion regarding its general applicability to the family of voltage-gated channels. In this model, the voltage sensor composed of the S3b and the S4 segment shuttles across the lipid bilayer during channel activation.

Latent infective endocarditis: epidemiology and clinical characteristics of patients with unsuspected endocarditis detected after elective valve replacement.

Background: The diagnosis of infective endocarditis is usually made on the basis of clinical and laboratory criteria and may be confirmed by histologic examination or culture of excised valves. We tried to determine the incidence and significance of inflammatory changes in valves excised during operations for reasons other than infective endocarditis.

Methods: The charts and histopathology of all patients undergoing valve replacement during a 10-year period (1993-2002) were reviewed.

Amyloidosis and gastric bleeding in a patient with Gaucher disease.

Goals: To describe the clinical course of a patient with Gaucher disease who subsequently developed amyloidosis.

Background: We present a case of a splenectomized patient with Gaucher disease who developed portal hypertension secondary to an enlarged, cirrhotic-like liver, and recurrent life-threatening upper gastrointestinal bleeding.

Study: Despite repeated diagnostic biopsies, amyloidosis was only ascertained after death.

Osteoporosis in the Cohen diabetic rat: correlation between histomorphometric changes in bone and microangiopathy.

Osteoporosis is well documented in type I diabetes, but its occurrence is controversial in type II diabetes. Microangiopathy is a major complication of type I and type II diabetes. We studied bone and microvascular changes in the Cohen diabetic rat, a unique nonobese model of noninsulin-dependent diabetes mellitus.

Proteinuria and glomerulosclerosis in the Sabra genetic rat model of salt susceptibility.

In search of an experimental model that would simulate the association between proteinuria and salt sensitivity in humans, we studied protein excretion in the Sabra rat model of salt susceptibility. Monthly measurements of urinary protein excretion in animals fed standard rat chow revealed that normotensive salt-sensitive SBH/y developed proteinuria that averaged 65 +/- 7 mg/day (n = 10) at 9 mo, whereas proteinuria in normotensive salt-resistant SBN/y was 39 +/- 4 mg/day (n = 10) (P < 0.01).

The iron-loaded gerbil model revisited: effects of deferoxamine and deferiprone treatment.

Although the beneficial effects of deferoxamine (DFO) on iron-associated morbidity and mortality are well documented, the role of deferiprone (L1) in the management of transfusional iron overload is controversial. This debate involves not only the question of efficacy but also of safety, with particular emphasis on the risk of a paradoxical aggravation of iron toxicity by L1. We used the iron-loaded gerbil model introduced by Carthew et al to compare the chelating efficacy of L1, DFO, or both in two gerbil strains treated by means of weekly iron-dextran injections: Psammomys obesus and pathogen-free Mongolian gerbils (Meriones unguiculatus).

Post-chemotherapy microscopic residual prostate rhabdomyosarcoma: long-term conservative follow-up.

In spite of advances in the treatment of childhood bladder and prostate rhabdomyosarcoma (RMS), the ability to detect minimal residual disease correlates imperfectly with the ultimate outcome. We report the long-term follow-up of a child with microscopic residual RMS after chemotherapy. The correct interpretation of the histologic findings spared the child unnecessary additional therapy and raises enigmatic questions about the biology of minimal residual disease.

Cardioversion-induced fulminant ischaemic hepatitis.

Ischaemic hepatitis, although infrequent, should be considered as a cause of fulminant hepatitis in patients with congestive heart failure. Ischaemic hepatitis is characterized by a marked rise in transaminases occurring within 24-48 h of circulatory failure. Cardioversion of atrial fibrillation to sinus rhythm is associated with an increase in cardiac output in most patients; however, a transient reduction in cardiac output may occur in more than one-third of patients, and may therefore induce ischaemic hepatitis.

Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry.

Anti-DNA autoantibodies are the hallmark of human and murine systemic lupus erythematosus (SLE), an autoimmune rheumatic disease of unknown etiology. Some of these antibodies are believed to be pathogenic for kidney tissue and to initiate immune glomerulonephritis. However, the mechanisms by which anti-DNA antibodies participate in tissue injury remain controversial.

Low serum C3, leukopenia, and thrombocytopenia: unusual features of henoch-schonlein purpura.

Henoch-Schonlein purpura (HSP) affects predominantly the skin, joints, gastrointestinal tract and kidney. Although the pathogenesis is probably of immune origin and complement activation is thought to play a role, laboratory findings including the serum level of the complement components are usually normal. We present a patient with a severe form of HSP nephritis who had unusual laboratory findings of a low level of C3, mild leukopenia and thrombocytopenia.

Prenatal diagnosis of oculocutaneous albinism type I: review and personal experience.

Oculocutaneous albinism type I (OCA I) comprises autosomal recessive syndromes of hypopigmentation and low vision, caused by the lack of tyrosinase activity. Affected families seek genetic counseling and prenatal diagnosis as preventive measures. Until recently, prenatal diagnosis of OCA I was achieved by histologic and electron microscopic examination of fetal skin biopsies.

Pulmonary fibrosarcoma in childhood: fiber-optic bronchoscopic diagnosis and review of the literature.

Primary pulmonary fibrosarcoma is a rare malignant tumor in childhood. In the absence of metastases, complete resection is curative. An 8-year-old boy suffered from unresolving pneumonia due to an obstructing lesion in the left main bronchus.

Systemic lupus erythematosus associated with acute Epstein-Barr virus infection.

Systemic lupus erythematosus (SLE) is a multisystem disease of unknown origin, characterized by a variety of autoimmune phenomena. Viruses have long been postulated to play a role in its pathogenesis. Several observations suggested a link between Epstein-Barr virus (EBV) and SLE.

Lymphocyte subsets in human tonsils: the effect of age and infection.

The aim of the present study was to determine the effect of repeated tonsillitis on the development of lymphocyte subsets in the tonsils and among peripheral blood lymphocytes (PBL) of children. Subsets of T- and B cells were analyzed in the tonsils and in PBL of patients undergoing tonsillectomy for idiopathic tonsillar hypertrophy, recurrent tonsillitis, or tonsillar hypertrophy and tonsillitis. The majority of the CD4+ cells in the tonsils displayed the CD45RO+ phenotype, while the majority of those in the PBL displayed the CD45RA+ phenotype.

End-stage renal interstitial fibrosis in an adult ten years after ifosfamide therapy.

A 33-year-old male presented with end-stage renal failure. Renal biopsy showed severe interstitial fibrosis without glomerulopathy or vasculopathy. More than 10 years previously the patient had been successfully treated for recurrent rhabdomyosarcoma.