A nonsense mutation (R220X) in the alpha-galactosidase A gene causes typical Fabry disease in both genders.

Background: Fabry disease is an X-linked recessive disorder resulting from a deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). Chronic renal failure is an important cause of death in patients with Fabry disease. We report on patients with Fabry disease (a hemizygous male and his mother) due to a nonsense mutation (R220X) in the alpha-Gal A gene.

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

Background: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations.

Determination of a polymeric hindered amine light stabilizer in polypropylene formulated with magnesium hydroxide flame retardant by reactive thermal desorption-gas chromatography.

A polymeric hindered amine light stabilizer (HALS), Tinuvin 622 (MW [symbol: see text] 4000), in PP materials formulated with a magnesium hydroxide flame retardant was determined by reactive thermal desorption (RTD) gas chromatography (GC). Two kinds of the HALS components that were formed through the RTD in the presence of tetramethylammonium hydroxide [(CH3)4NOH, TMAH] were clearly observed in the chromatograms of the PP samples, with negligible interference from the other additives and the PP substrate. Here, the coexisting flame retardant was proved to affect significantly the RTD process of the occluded HALS.

Immune complex-type glomerulonephritis with unusual giant deposits in a patient with active rheumatoid arthritis.

A 61-year-old woman with rheumatoid arthritis (RA) developed small digital ulcers, proteinuria, and hematuria. Serological studies disclosed high titers of antinuclear antibody and rheumatoid factors (RF; IgM-RF and IgG-RF), and an increased level of circulating immune complexes. These findings suggested an active immunological state of RA.

Leiomyosarcoma of the sacral bone in a patient with a past history of resection of uterine leiomyoma.

We report here a case of leiomyosarcoma in the sacrum with a differential diagnosis of metastasizing leimyoma of uterus, since the patient had a past history of resection of uterine leimyoma 19 years ago. The sacral tumor was an osteolytic lesion, 8x6 cm in size on radiological examination. Microscopically, tumor cells consisted of spindle shaped cells with moderate cellular atypia.

73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin.

Although gentamicin (GM) has been used widely as an antibiotic, the specific binding protein of the drug has not yet been understood sufficiently. Here we show that GM specifically associates with the 73-kDa molecular chaperone HSP73 and reduces its chaperone activity in vitro. In the present study, we investigated GM-specific binding proteins using a GM-affinity column and porcine kidney cytosol.

Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy.

Background: Several studies have shown a predominant glomerular deposition of IgG4 in patients with idiopathic membranous nephropathy (MN), whereas significant depositions of other IgG subclasses have been shown in patients with lupus-associated MN and bucillamine-induced MN.

Methods: We examined the distribution patterns of glomerular IgG subclass deposits in 10 patients with malignancy-associated MN (M-MN) and in 15 patients with idiopathic MN by immunofluorescence (IF) microscopy.

Results: The glomerular IF intensities of IgG1 and IgG2 were significantly stronger in the malignancy group than in the idiopathic group (P<0.

Direct analysis of an oligomeric hindered amine light stabilizer in polypropylene materials by MALDI-MS using a solid sampling technique to study its photostabilizing action.

A novel method for the direct analysis of small amounts of an oligomeric hindered amine light stabilizer (HALS) occluded in polypropylene (PP) material was developed to study its photostabilizing action on the basis of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) using a solid sampling technique while avoiding troublesome solvent extraction. In this sampling protocol, the powdered mixture of PP composite sample containing trace amounts of an oligomeric HALS, Adekastab LA-68LD (MW = 1900), and the matrix reagent (dithranol) was spotted on the sample plate, then ion exchanged water was deposited onto the mixture to make a suspension, and finally, the dried mixture adhered on the plate was subjected to MALDI-MS measurement. On the mass spectrum thus obtained by the solid sampling MALDI, the molecular ions of the HALS desorbed from the PP composite were clearly observed as three major series of the HALS components in the range up to about m/z 7000 with little interference by the PP substrate and the other additives.

Decreased phenobarbital absorption with charcoal administration for chronic renal failure.

Objective: To report a case of impaired absorption of orally administered phenobarbital associated with the concomitant administration of activated charcoal, and recovery of the absorption after administration of the 2 drugs was separated by a 1.5-hour interval.

Case Summary: A 78-year-old woman, weighing 50 kg, who had undergone brain surgery was prescribed phenobarbital 120 mg/day for postoperative convulsions.

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis.

Chronic gastritis is frequently associated with infection of Helicobacter pylori and characterized by tissue infiltration of neutrophils, lymphocytes, and plasma cells. To address the mechanism of lymphocyte infiltration in chronic gastritis, we examined the expression of chemokines and their receptors using frozen sections of chronic gastritis, obtained from 23 patients who underwent gastrectomy for gastric cancer. By immunohistochemistry, lymphocytes in inflamed gastric mucosa expressed CCR5 abundantly, CXCR3 less frequently, and CCR4 sparsely.

Reversible posterior leukoencephalopathy in a patient with Wegener granulomatosis.

A 14-year-old girl with rapidly progressive glomerulonephritis was transferred to our hospital because of acute renal failure. A diagnosis of Wegener granulomatosis was made according to the symptom triad of a renal biopsy demonstrating crescentic glomerulonephritis, severe sinusitis, and serological findings of raised proteinase 3 anti-neutrophil cytoplasmic antibody level. In spite of combination therapy with methylprednisolone, cyclophosphamide, and plasma exchange, her renal function gradually deteriorated.

Direct analysis of lipids in single zooplankter individuals by matrix-assisted laser desorption/ionization mass spectrometry.

A highly sensitive method to analyze the intact lipids in a single zooplankter individual at the level of a few tenths of a microgram was developed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) combined with a direct sampling technique. The sampling procedure involved (1) putting a zooplankter individual sample onto the MALDI sample plate, (2) cutting the sample into a few pieces by means of tweezers, (3) depositing aliquots of matrix and cationization reagent solutions on the zooplankter sample, and (4) irradiating with a N2 laser to cause MALDI. By using this technique, the mass spectra of the single zooplankter samples showed a series of ions generated from phospholipids with 34 or 36 carbons in the acyl groups and neutral lipids such as triglycerides and diacylglyceryl ethers with 50-54 carbons in their acyl and alkenyl groups.

Basal membrane localization of MRP1 in human placental trophoblast.

The placental trophoblast is considered to act as a barrier between mother and fetus, mediating the exchange of various materials across the placenta. ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) and multidrug-resistance protein (MRP) are expressed in the placenta and function as efflux transport systems for xenobiotics. In the present study, we aimed to determine the localization of MRP1 in the human placenta in comparison with that of P-gp.

Amyloid A-type renal amyloidosis in a patient with sarcoidosis: report of a case and review of the literature.

A 53-year-old man developed chronic renal failure during a protracted course of sarcoidosis. A renal biopsy showed Congo red-positive homogenous deposits in the subendothelial space of glomerular capillary walls and arterial walls. On electron microscopy, amyloid fibrils were observed in the deposits.

Internalization of antibodies by endothelial cells via fibronectin implicating a novel mechanism in lupus nephritis.

Background: One of the crucial events in lupus nephritis is the glomerular deposition of immunoglobulins (Igs), of which pathogenic properties have been proposed mostly to be either type IIor type III allergic reactions. Some of IgG3-producing hybridoma clones established from an MRL/MpTn-gld/gld (MRL/gld) lupus mouse generate wire loop-like lesions in glomeruli resembling lupus nephritis when injected into SCID mice. These clones are useful for analyzing the mechanisms of glomerular deposition of antibodies in lupus nephritis at the monoclonal level.

Germ cell-specific expression of microphthalmia-associated transcription factor mRNA in mouse testis.

The gene coding for microphthalmia-associated transcription factor (Mitf) contains many promoters that could generate multiple Mitf isoforms with distinct amino-termini, such as ubiquitously expressed Mitf-A and Mitf-H. To gain further insight into Mitf isoform multiplicity and the regulation of the promoter usage of the Mitf gene, we have analyzed the function of the amino-terminal domains of Mitf isoforms and the expression of Mitf mRNA in mouse postnatal testis, which is characterized by spermatogenesis and by a cool temperature because of its unique location. Here we show that the amino-terminal domain of Mitf-A possesses a transactivation activity, as judged by yeast expression analysis.

Betaxolol-induced deterioration of asthma and a pharmacodynamic analysis based on beta-receptor occupancy.

Objective: To report a case of deterioration of asthma associated with continuous use of oral betaxolol, a beta1-selective beta-blocking agent. We also analyzed the pharmacokinetics in this case by applying a receptor occupancy model.

Case Summary: A 68-year-old woman taking 5 mg of betaxolol for hypertension occasionally experienced asthmatic coughing after upper respiratory tract infection.

In vivo delivery of glial cell-derived neurotrophic factor across the blood-brain barrier by gene transfer into brain capillary endothelial cells.

The gene encoding mouse glial cell-derived neurotrophic factor (mGDNF gene) was transfected into brain capillary endothelial cells (BCECs) with the aim of delivering the gene product extensively into the brain parenchyma by making use of the secretory function of BCECs. First, we transfected mGDNF gene into cultured BCECs (MBEC4; mouse brain capillary endothelial cells) in vitro. The amount of mGDNF protein secreted from the transfected cells into the medium was 1500 to 3200 pg/mg of cell protein per day, being about sevenfold higher than that accumulated intracellularly.

Inhibitory effect of erythromycin on potassium currents in rat ventricular myocytes in comparison with disopyramide.

Disopyramide, a class Ia antiarrhythmic agent, has been reported to induce torsades de pointes (TdP) associated with excessive QT prolongation in electrocardiogram (ECG), especially when concomitantly administered with erythromycin, a macrolide antibiotic agent. In this study, we have evaluated the effects of erythromycin on action potential duration (APD) and potassium currents in rat ventricular myocytes in comparison with disopyramide. We have evaluated the relationship between in-vitro potassium current inhibition and in-vivo QT prolongation observed in a previous study.

Dynamics of the fluorescence properties of pyrene residues appended to oligonucleotide hybridization probes.

The dynamic and static properties of the fluorescence of a pyrene-introduced oligonucleotide 16 mer and its hybrid with a target 32 mer. Their fluorescence quantum yields (< 1%) were much weaker than that of unsubstituted pyrene and their fluorescence lifetime of the major decay components were less than 1 ns. The rapid fluorescence quenching was due to the interaction between the fluorophore and bases in the oligonucleotides.

The prototype of sex chromosomes found in Korean populations of Rana rugosa.

The seventh largest chromosome in Japanese populations of the frog Rana rugosa morphologically evolved as a sex chromosome. The sex chromosome is XX/XY type in one geographic form and ZZ/ZW type in another. In contrast, the seventh chromosomes are still homomorphic between the sexes in the other two geographic forms: they are more subtelocentric in the Kanto form and subtelocentric in the western Japanese form.

EPO-producing gastric carcinoma in a hemodialysis patient.

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy.

Infiltrating CD8+ T cells in oral lichen planus predominantly express CCR5 and CXCR3 and carry respective chemokine ligands RANTES/CCL5 and IP-10/CXCL10 in their cytolytic granules: a potential self-recruiting mechanism.

Lichen planus is a chronic inflammatory disease of the skin and oral mucosa in which the cell-mediated cytotoxicity is regarded as a major mechanism of pathogenesis. To understand its pathophysiology further, the present study examined the in situ expression of chemokines and chemokine receptors in oral lichen planus. Immunohistochemical analysis of 15 cases has consistently revealed that infiltrating CD4(+) and CD8(+) T cells in the submucosa predominantly expressed CCR5 and CXCR3.

Change of the heterogametic sex from male to female in the frog.

Two different types of sex chromosomes, XX/XY and ZZ/ZW, exist in the Japanese frog Rana rugosa. They are separated in two local forms that share a common origin in hybridization between the other two forms (West Japan and Kanto) with male heterogametic sex determination and homomorphic sex chromosomes. In this study, to find out how the different types of sex chromosomes differentiated, particularly the evolutionary reason for the heterogametic sex change from male to female, we performed artificial crossings between the West Japan and Kanto forms and mitochondrial 12S rRNA gene sequence analysis.