Minimal change variants: IgM nephropathy.
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Child↗
Biomedical subjects
H Matsukura
Publications and source records attributed to H Matsukura.
Persisting mesonephric duct in a neonate with ipsilateral renal agenesis.
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Abnormalities, Multiple↗
Immunoglobulin A nephropathy associated with cyclic neutropenia.
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Adolescent↗
Discordant phenotypic expression of Alport syndrome in monozygotic twins.
BACKGROUND: Alport syndrome is a genetically heterogeneous disorder, but most patients showed the X-linked form resulting from mutations in the COL4A5 gene. A few cases of mosaicism in Alport syndrome have been reported. METHODS: We describe the case of an 8-year-old boy with mosaicism in Alport syndrome. Punch skin biopsies were obtained from the patient's mother and monozygotic twin brother. Five biopsy specimens from non-Alport patients were used as controls. Immunohistochemical analysis was performed using rat monoclonal antibodies towards individual collagen IV(NC) domains. RESULTS: Kidney tissue of the patient showed: mosaic expression of alpha3(IV), alpha4(IV) and alpha5(IV) in the glomerular basement membrane (GBM), distal tubular basement membrane (TBM) and Bowman's capsule; mosaic alpha6(IV) expression in the Bowman's capsule and distal TBM; and well-preserved expression of alpha1(IV) and alpha2(IV). The patient's skin exhibited mosaic alpha5(IV) expression. His mother and monozygotic twin brother disclosed a normal linear staining of alpha5(IV) in their epidermal basement membranes. This unusual mosaicism of alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) is consistent with a pattern of female heterozygotes of Alport syndrome. CONCLUSION: This discordant phenotypic expression of Alport syndrome in monozygotic twins with unaffected parents suggests possible somatic mosaicism in the COL4A5 gene.
Child↗
Secondary erythrocytosis associated with distal renal tubular acidosis.
AIMS: Diagnosis and classification of renal tubular acidosis (RTA) have traditionally been made on the basis of functional studies. Despite recent expanding knowledge about the molecular abnormalities involved in renal bicarbonate (HCO3-) and H+ transport, the pathophysiology of secondary erythrocytosis in association with distal RTA remains obscure. CASE HISTORY: A 2-month-old boy with severe hyperchloremic metabolic acidosis with positive urine anion gap was diagnosed with distal RTA. Replacement therapy with sodium bicarbonate and potassium citrate succeeded in improving his metabolic acidosis and growth. His renal function remained normal. He had persistent erythrocytosis. CONCLUSION: Secondary erythrocytosis is a rarely reported association of distal RTA. It may increase the risk of thromboembolism.
Acidosis, Renal Tubular↗
Acute poststreptococcal glomerulonephritis mimicking Henoch-Schönlein purpura.
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Acute Disease↗
Stereoselective syntheses of the C'D'E'F'-ring system of maitotoxin and the FG-ring system of gambierol.
[structure: see text]. The stereoselective syntheses of the C'D'E'F'-ring system of maitotoxin and the FG-ring system of gambierol were accomplished. The key steps involve 6-endo-cyclization of methylepoxide, SmI2-induced reductive cyclization, 6-endo-cyclization of vinylepoxide, and formation of the lactone ring.
Ciguatoxins↗
SH2D1A mutations in Japanese males with severe Epstein-Barr virus--associated illnesses.
X-linked lymphoproliferative disease (XLP), a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection, has been linked to mutations in the SH2D1A gene. To search for the occurrence of SH2D1A mutations in Japan, we performed genetic analysis of the SH2D1A gene in 40 males presenting with severe EBV-associated illnesses, including fulminant infectious mononucleosis, EBV-positive lymphoma, and severe chronic active EBV infection. SH2D1A mutations were detected in 10 of these 40 patients. Five of these 10 cases were sporadic. Patients with SH2D1A mutations displayed severe acute infectious mononucleosis with hyperimmunoglobulin M, hypogammaglobulinemia, and B-cell malignant lymphoma. By contrast, chronic active EBV infection was not associated with SH2D1A mutations. XLP survivors exhibited normal levels of circulating EBV-DNA during convalescence, suggesting that SH2D1A protein is not directly responsible for control of EBV replication. Thus, genetic analysis of the SH2D1A gene is particularly useful in the diagnosis of sporadic cases and carriers of XLP. (Blood. 2001;98:1268-1270)
Adolescent↗
Clinical and mutational characteristics of X-linked agammaglobulinemia and its carrier identified by flow cytometric assessment combined with genetic analysis.
BACKGROUND: X-linked agammaglobulinemia (XLA), caused by mutations in Bruton's tyrosine kinase (BTK ), is the most common form of inherited antibody deficiency. We previously reported that a flow cytometric evaluation of BTK expression in monocytes could easily detect XLA as well as its carrier. OBJECTIVE: Our purpose was to perform further flow cytometric analysis in additional XLA families in Japan. METHODS: In all, 106 hypogammaglobulinemic males (from 91 families) of various ages with a lack of mature B cells (<1%) were investigated. RESULTS: Flow cytometric assessment revealed the deficient BTK expression status in 78 families (93 patients), and mutations in BTK were identified in 76 of 78 families with presumed XLA. Of the patients with normal BTK expression, 2 showed missense mutations in which the normal amount of altered BTK transcript would cause the XLA phenotype. As many as 30% of these patients with XLA were clinically or genetically recognized beyond 5 years of age. Higher concentrations (>300 mg/dL) of serum IgG were evident in the cases diagnosed among adults, seemingly preventing severe infections. Fifty-seven of 70 mothers of patients with BTK deficiency were diagnosed as obligate carriers on the basis of a bimodal BTK expression pattern. Nine of the remaining 13 mothers showing nonmosaic BTK expression had no mutations in 2 alleles; surprisingly, the other 4 mothers had the mutated alleles. CONCLUSIONS: A diagnostic approach based on flow cytometric assessment for XLA should be initially considered in genetic investigation of antibody deficiencies, regardless of the patient's age.
Adolescent↗
Clinicopathological characteristics of the focal and segmental form of idiopathic membranous nephropathy: comparison with the typical form of this disease.
Although idiopathic membranous nephropathy (IMN) is thought to represent a diffuse glomerulopathy, it was found that three of 31 children histologically diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG) and C3 on the glomerular capillary walls. The present study attempted to comparatively investigate clinical and pathological features of the diffuse group and the focal segmental group in 31 IMN children. Immunofluorescence study revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along glomerular capillary walls. In contrast, focal and segmental deposition of IgG and C3 was noted in three children with IMN. In addition, focal and segmental electron-dense deposits were identified in these cases. In two children of the focal segmental group, immunofluorescent patterns of IgG deposition were unchanged even at the second biopsy. The focal segmental form of IMN tended to occur in younger children than diffuse IMN. However, other clinical parameters such as the range of proteinuria, hematuria, serum albumin and prognosis did not show any significant differences between both groups. Electrophoretic profiles of urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were not different between both groups. It is proposed that the focal segmental form of IMN may have a distinctive glomerulopathy from the typical form of IMN.
Child, Preschool↗
Photodegradation products of a new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.
A new antibacterial fluoroquinolone derivative, orbifloxacin (ORFX), is decomposed photochemically in aqueous solution. When ORFX solution was irradiated with a chemical lamp or sunlight, three major photodegradation products were isolated by preparative HPLC. These degradation products were identified by electron-impact mass spectrometry, liquid-secondary-ion mass spectrometry and 1-H-NMR spectroscopy. Moreover, the photodegradation pathway was investigated by a similar study using several fluoroquinolone derivatives which were presumed to be the intermediates of the photoreaction of the ORFX. Consequently, it was found that two main photochemical reactions, the decomposition of the dimethylpiperazinyl moiety and the elimination of the cyclopropyl group, take place in ORFX. The detected structures of photodegradation products and the photodegradation studies of the postulated intermediates suggested that the photodecomposition of the dimethylpiperazinyl ring at the 7-position and the elimination of the cyclopropyl group at the 1-position occurred concurrently with the release of fluorine at the 8-position.
Anti-Infective Agents↗
Serum tumor necrosis factor in mesangial IgA glomerulonephritis with macroscopic hematuria in children.
Tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma levels were measured in the sera obtained from 29 patients with IgA glomerulonephritis (IgA GN), 8 patients with minimal change nephrotic syndrome (MCNS) and 12 patients with upper respiratory tract infection (URI) without renal diseases in children. The serum TNF-alpha level of IgA GN was 123.0 +/- 175.4 pg/ml, MCNS was 4.9 +/- 4.0 pg/ml and URI was 10.5 +/- 4.5 pg/ml respectively. The serum TNF-alpha level of IgA GN was significantly higher than those of MCNS and URI. The serum TNF-alpha level of URI was on the high trend compared with that of MCNS, but was not statistically significant. Although the TNF-alpha level was related to mesangial cell proliferation in patients with IgA GN, it was unrelated to the grade of mesangial matrix expansion and magnitude of proteinuria. In 17 patients with IgA GN having macroscopic hematuria, the serum TNF-alpha level was 190.5 +/- 201.6 pg/ml, and in other IgA GN patients with microscopic hematuria it was 37.4 +/- 75.7 pg/ml. The serum TNF-alpha level of IgA GN with macroscopic hematuria was significantly higher than that with microscopic hematuria. In 6 patients with IgA GN with macroscopic hematuria, the serum TNF-alpha level was significantly decreased after macroscopic hematuria disappeared. The mean serum IFN-gamma level of IgA GN was 0.3 +/- 0.6 IU/ml, and MCNS was not detectable. Although the serum IFN-gamma level was related to mesangial cell proliferation in patients with IgA GN, it was unrelated to magnitude of proteinuria, the grade of mesangial matrix expansion and also the presence or absence of macroscopic hematuria. We suggest that macroscopic hematuria of IgA GN was closely related to the serum TNF-alpha level.
Adolescent↗
Decrease of mesangial matrix after immunosuppressive therapy in children with reversible membranoproliferative glomerulonephritis type I.
We followed the course of membranoproliferative glomerulonephritis (MPGN) type I after immunosuppressive therapy in 10 children. At diagnosis all patients had abnormal urinary findings. After a mean follow-up of 14 years all but one patient showed normal urinalysis and renal function. Glomerular morphometry revealed an increase in the ratio of mesangial matrix area to glomerular area (M/G%) in all patients. After immunosuppressive treatment, a second biopsy was performed, which showed a significantly decreased M/G% in 4 patients. In 3 of the remaining 6, the mean M/G% was significantly lower in a third biopsy when compared with the first. In addition, there was a negative correlation between M/G% and duration from onset disease to biopsy (r = -0.46, p <0.05). Fifteen biopsies (6 initial and 9 repeat biopsies) were examined for the staining of various extracellular matrices. In the initial biopsy type IV collagen, type V collagen and fibronectin were increased in expanded mesangial areas. Type III collagen was found segmentally in a few biopsies only. M/G% correlated with the grade of type IV collagen, type V collagen and fibronectin staining. These findings suggest that a reversible clinical course of MPGN type I in children is paralleled by a decrease of mesangial matrix expansion.
Adolescent↗
Photodegradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.
The photodegradation kinetics of orbifloxacin (1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid) was investigated in aqueous solution at various pH values (1.2-12.5) and at an ionic strength of 0.5. The photodegradation experiments were performed using a fluorescent or a chemical lamp as a light source and the cumulative number of photons during exposure was determined by a ferrioxalate actinometer. It was found that the photodegradation of orbifloxacin followed apparent first-order kinetics under both types of artificial light. The photodegradation rates of orbifloxacin in a neutral medium were higher than those in acidic and alkaline media. Orbifloxacin was most unstable in solution at pH 7.4, and its degradation half-life was 0.9 h. Also, the log k-pH profile indicated that the photodegradation rate of orbifloxacin was related to the dissociation of the carboxylic and dimethylpiperazinyl groups and the main photo-labile species was the zwitterionic form. In addition, the photodegradation kinetics of the decarboxylated derivative of orbifloxacin in aqueous solution was investigated to determine the effect of the functional groups on the photodegradation of orbifloxacin.
Anti-Infective Agents↗
Degradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.
The degradation kinetics of orbifloxacin [1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid] was investigated as a function of pH (1.5-10.5), temperature (100-120 degrees C) and buffer concentration (0.05-0.2 M) by means of high-performance liquid chromatography. The degradation of orbifloxacin in aqueous solution followed apparent first-order kinetics under all experimental conditions. No appreciable effect of buffer on the degradation of orbifloxacin was observed for any of the buffer species used in this study. The log k-pH profiles indicated specific-acid and specific-base catalyses and there were inflection points near pH 6 and 9 corresponding to the pKa1 and pKa2 values. From the Arrhenius plots, the activation energies for k'H, k'H2O, kH2O, k"H2O and k"OH were found to be 31.9, 36.9, 23.5, 26.5 and 19.0 kcal/mol, respectively. Arrhenius data obtained from this study showed that the degradation of orbifloxacin at room temperature was negligible at all pH values studied conditions (pH 1.5-10.5).
Anti-Infective Agents↗
[Studies on the inhibitory action of leminoprazole against rabbit gastric H+,K(+)-ATPase].
Inhibitory action of leminoprazole ((+/-)-2-[[2-(isobutylmethylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, LEM) against the H+,K(+)-ATPase activity in rabbit gastric vesicles was investigated. LEM inhibited the H+,K(+)-ATPase activity in leaky vesicles in a concentration- and time-dependent manner. When preincubated with gastric vesicles (20 micrograms protein/ml) for 30 min at 37 degrees C in medium (pH 6.1 or 7.4), the IC50 values were 5.3 microM and 19 microM, respectively. The inhibitory action of LEM was not competitive with respect to K+ and was not reversed by dilution, suggesting that the inhibitory action is irreversible. Inhibition of the enzyme activity by LEM was not found when beta-mercaptoethanol (0.1 mM) was premixed with enzyme before addition of LEM, and it was partially recovered by addition of beta-mercaptoethanol or dithiothreitol (50 mM) after LEM treatment. These results suggest that LEM reacts with essential SH groups of H+,K(+)-ATPase and inactivates the enzyme by forming a covalent disulfide bond. The inhibitory activity of LEM was more potent at pH 6.1 than at pH 7.4, and the rate of the reaction of LEM with GSH was enhanced by lowering the pH of the medium. The inhibition of proton transport by LEM (30 microM) was found after the intact vesicles were fully acidified. LEM also strongly inhibited the valinomycin-stimulated H+,K(+)-ATPase activity. Therefore, it is considered that LEM inhibits H+,K(+)-ATPase activity by an unknown activated reaction under the acidic condition. Alternatively, the possibility was also suggested that an acidic condition is not always necessary for the inhibition of H+,K(+)-ATPase activity by LEM, since LEM, at higher concentration, inhibited the initial rate of acidification and inhibited nigericin-stimulated H+,K(+)-ATPase activity in intact vesicles.
Animals↗
[Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+,K(+)-ATPase activity in rats].
The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+,K(+)-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+,K(+)-ATPase activity, and their IC50 values were 31 microM and 24 microM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+,K(+)-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+,K(+)-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+,K(+)-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+,K(+)-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+,K(+)-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+,K(+)-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+,K(+)-ATPase activity to the same degree as the single administration.
Animals↗
Effects of NC-1300-O-3 on gastric mucus secretion and prostaglandin release in rats.
We investigated the effect of NC-1300-O-3 on gastric mucus secretion and prostaglandin release into the gastric lumen in rats. NC-1300-O-3 following single or repeated administration for up to 4 weeks significantly increased the hexose content in the gastric lumen at 10 to 100 mg/kg, p.o. Omeprazole and cimetidine at doses that strongly inhibited gastric acid secretion had no effect on the hexose content following single or repeated administration for 8 days. When administered repeatedly for 8 days, NC-1300-O-3, omeprazole and cimetidine significantly decreased the hexosamine content in gastric surface mucosa, but significantly increased gastric mucus secretion was observed at the same time only with NC-1300-O-3, indicating that this agent has a profile of action on gastric mucus metabolism different from those of omeprazole and cimetidine. NC-1300-O-3 at 10 and 30 mg/kg, p.o. and omeprazole at 30 mg/kg, p.o. increased the release of prostaglandins into the gastric lumen, and this was markedly inhibited by pretreatment with indomethacin, suggesting that these agents may enhance prostaglandin biosynthesis in the gastric mucosa. From these results, it seems that the enhancement of NC-1300-O-3 on gastric mucus secretion and prostaglandin biosynthesis in the gastric mucosa contribute to the antiulcer effect of NC-1300-O-3.
Animals↗