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Biomedical subjects

S Waga

Publications and source records attributed to S Waga.

At least 73 records · Page 4Linked to original sources

Age-related histologic alterations after prednisolone therapy in children with IgA nephropathy.

To examine whether the age of onset of clinical symptoms in childhood IgA nephropathy may affect changes of histologic alterations after receiving prednisolone therapy, an evaluation of glomerular lesions seen in biopsy specimen was done. Eighteen children with IgA nephropathy met study criteria. They received alternate-day prednisolone therapy within a month after the first renal biopsy. Renal biopsies were done at presentation and repeated at a mean interval of 23 months. The patients were grouped as follows: Group A, 8 cases which showed clinical symptoms at the age of 9 or under; Group B, 10 cases which showed the symptoms at the age of 10 or over. At the initial presentation, histologic indices including a percentage of mesangial area occupying glomeruli (the M/G ratio) in the 2 groups did not show a significant difference. The activity score and the M/G ratio in the group A decreased significantly at the second biopsies (4.6+/-0.9 vs. 1.8+/-1.0 and 25.7+/-6.1% vs. 21.4+/-2.7%, respectively), while in the group B did not. These observations may indicate the age of onset of clinical symptoms in childhood IgA nephropathy affects changes of histologic alterations after receiving prednisolone therapy.

Adolescent↗

Efficacy of long-term sulfamethoxazole-trimethoprim therapy in a boy with hyperimmunoglobulin E syndrome.

A boy with hyperimmunoglobulin E syndrome (HIE syndrome), who was successfully treated with long-term sulfamethoxazole-trimethoprim (SMX-TMP) is reported. He had been suffering from recurrent pruritic dermatitis soon after birth and had a significant high level of serum immunoglobulin E. Although an initiation of SMX-TMP therapy resulted in resolution of his clinical manifestations, cessation of the treatment exacerbated the symptoms. Chemoprophylaxis of other oral antibiotics, which were suitable for Staphylococcus aureus isolated from lesions of the patient were unsuccessful. Another trial of low-dose SMX-TMP therapy resulted in gradual subsidence of the clinical manifestations. From these observations, efficacy of SMX-TMP therapy to prevent bacterial infection in the patient is clinically apparent. Although precise mechanism of the therapy remains speculative, long-term SMX-TMP therapy might be of benefit and low clinical toxicity in HIE syndrome.

Anti-Bacterial Agents↗

Transcranial Doppler pattern after intracarotid papaverine and prostaglandin E1 incorporated in lipid microsphere in patients with vasospasm.

We studied the effects of intracarotid papaverine and prostaglandin E1 incorporated in lipid microsphere (Lipo-PGE1) in relation with transcranial Doppler parameters such as mean flow velocity (MFV) and pulsatile index (PI) of the proximal segment of the middle cerebral artery. Eighty patients with subarachnoid hemorrhage (SAH) were included in this study. In the case of angiographic vasospasm, papaverine at 7 mg/min with total dose below 300 mg per artery and 10-20 micrograms of Lipo-PGE1 were injected in the supraclinoid portion of the internal carotid artery. Vasospasm was improved in 24 patients (63%), however, it was unchanged in 14 patients (37%). The former patients had more favorable outcomes than the latter patients (p < 0.005). After intracarotid injection therapy, the correlation between MFV and PI was classified into three types: type 1, both MFV and PI decreased; type 2, MFV decreased but PI increased; and type 3, both MFV and PI fluctuated. The Glasgow Outcome Scale 3 months after SAH was as follows: type 1 (n = 15), good in 14 (93%) and moderate disability in one (7%); type 2 (n = 9), good in eight (89%) and vegetative state in one (11%); and type 3 (n = 14), moderate disability in five (36%), severe disability in seven (50%), and death in two (14%). Chi-square analysis showed significant differences between type 1 and type 3 (p < 0.005), and type 2 and type 3 (p < 0.005). In conclusion, intracarotid papaverine combined with Lipo-PGE1 was effective for vasospasm but type 3 patients require a different treatment protocol.

Alprostadil↗

[Clinical studies of tazobactam/piperacillin (TAZ/PIPC) in pediatric patients].

Tazobactam/Piperacillin (TAZ/PIPC) is a newly developed intravenous antibiotics, in which TAZ, a new potent inhibitor of beta-lactamases, is combined with PIPC, a well-established beta-lactam antibiotics, at the ratio of 1:4. In this study, we clinically evaluated efficacy of the drug in 14 pediatric patients with various infections, and pharmacokinetic study was applied to 3 patients. Range of age was from 1-month to 15 1/4-year. Patients consisted of 9 cases of pneumonia, 3 urinary tract infection, 1 acute otitis media, and 1 left sacroiliitis with sepsis. Standard dose of TAZ/PIPC was 50 mg/kg/dose and administered 2-4 times per day with intravenous injection or drip infusion. Two cases of pneumonia were excluded because of non-bacterial infection. Nine causative pathogens including 3 Gram-positive cocci and 6 Gram-negative bacilli were detected in 7 patients, of which 5 Gram-negative strains produced bete-lactamase. All of cases showed 100% of efficacy rate and bacteriological eradication rate. It was noted that beta-lactamase-producing E. coli and B. catarrhalis were eradicated efficiently by TAZ/PIPC, which should be resistant to PIPC alone according to MIC data. Non-serious diarrhea and discomfort of back with nausea were observed in one each patients as side effects. Both of side effects were transient, and improved with anti-diarrheic agent or cessation of the drug, respectively. As abnormal laboratory test results, moderate increases of the eosinophils and platelets counts as well as moderate elevation of the transaminases were observed in 2 separate patients. Pharmacokinetics study showed that Cmax, T1/2, and AUC were similar to the data reported in adult patients. Urinary recovery rate in the first 6 hours also resemble the data from adult patients. Based on above results, TAZ/PIPC is a useful agents pediatric infections by beta-lactamase producing strains also.

Adolescent↗

[A child case of idiopathic membranous glomerulonephritis associated with isolated anti-nuclear antibody detected by urine mass-screening of school children].

A 12-year-old boy was referred to our hospital because of persistent hematuria with proteinuria. He was found to have urine abnormalities by a school mass-screening and visited a hospital, where a routine examination revealed proteinuria of 190 mg/d/, hematuria of 2+ and anti-nuclear antibody (ANA) of 1: 320 with a speckled pattern. The other laboratory findings, including anti-DNA antibody were unremarkable. Hypocomplementemia was not seen. Although he had no disabilities and manifestations suggesting systemic lupus erythematosus, urine abnormalities persisted. Percutaneous renal biopsy findings demonstrated stage II diffuse membranous glomerulonephritis (MGN). Neither anti-hepatitis B virus antigens and antibodies nor hepatitis C virus antibody were detected in his sera. Thus, the diagnosis of idiopathic MGN was made. Initiation of a 6-month course of alternate-day prednisolone (an initial dosage at 30 mg) combined with an anti-thrombocyte agent resulted in gradual subsidence of the urine abnormalities and ANA titer. Although pathogenesis of his MGN remains speculative, possible activation of autoimmunities, which led to ANA positivity, might be responsible.

Antibodies, Antinuclear↗

Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein.

p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control.

Binding Sites↗

Plasma levels of protein C, protein S, and antithrombin III in patients with subarachnoid haemorrhage.

This study was designed to evaluate the clinical value of consecutive measurements of the levels of the anticoagulation factors protein C. protein S and antithrombin III in the plasma of patients with subarachnoid haemorrhage (SAH). Sequential samples of plasma were obtained from 34 patients at days 0 to 3, 5, 8, 14, and 20 days after SAH. Their levels of protein C, protein S and antithrombin III were measured by specific immuno-assays, and the symptomatic vasospasm and clinical states of the patients were monitored. Based on the retrospective comparisons between the measured levels of the three factors and the levels in pooled plasma from normal volunteers, the time course of changes in the levels allowed the classification of the patients into five groups as follows: A, the levels of the three factors decreased suddenly at 5 days after SAH, then increased again (n = 6); B, the three factors increased continuously (n = 13); C, the three factors remained below the normal range (n = 3); D, the three factors remained within the normal range (n = 6); and E, the three factors decreased continuously (n = 6). In group A patients, temporary deficiencies in the three factors occurred that coincided with the occurrence of delayed neurological deficit (DND). Twelve patients (92%) in group B had a favourable outcome (good and moderate disability) without DND. The patients in group C had low levels of anticoagulation factors and mild DND followed by a favourable outcome. Five patients (83%) in group D had a favourable outcome. In group E, five patients (83%) had a poor outcome (severe disability and death) due to DND. When clinical outcomes were compared by patient group, the patients in group E had significantly more unfavourable outcomes than did the other groups (P < 0.01). Although the mechanism responsible for the decrease in anticoagulation factor levels remained unclear, the results suggested that the decrease in anticoagulation factors may indicate hypercoagulability and cerebral ischaemia after SAH.

Adult↗

Differential expression of tenascin-C and tenascin-X in human astrocytomas.

Tenascins (TNs) are a family of extracellular matrix glycoproteins. The first member of this family to be recognized, tenascin-C (TN-C), is known to be expressed in various tumors including human astrocytomas. Tenascin-X (TN-X) is the latest member of the TN family to be reported, and its expression in tumor tissues has not yet been examined. In this study, we found expression of TN-X in glioma cell lines and human astrocytomas by immunoblot analysis using anti-mouse TN-X antibodies. We also examined the expression of TN-C and TN-X immunohistochemically in a series of 32 human astrocytomas and tissue from 5 normal brains. Expression of TN-X was up-regulated to a higher degree in low-grade astrocytomas than in high-grade astrocytomas. TN-X was mainly localized in the perivascular stroma around tumor vessels, and weakly expressed in the intercellular spaces among tumor cells. In contrast, TN-C was more strongly expressed in the intercellular spaces and in tumor vessels in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas) than in low-grade astrocytomas. In the tissues expressing both TNs, the distribution of TN-X was often reciprocal to that of TN-C. These findings indicate that the expression of TN-C and TN-X in astrocytomas is different, and that these glycoproteins could be involved in neovascularization in different manners.

Animals↗

Role of endothelium in regulation of smooth muscle membrane potential and tone in the rabbit middle cerebral artery.

1. The characteristic features of the endothelium-mediated regulation of the electrical and mechanical activity of the smooth muscle cells of cerebral arteries were studied by measuring membrane potential and isometric force in endothelium-intact and -denuded strips taken from the rabbit middle cerebral artery (MCA). 2. In endothelium-intact strips, histamine (His, 3-10 microM) and high K+ (20-80 mM) concentration-dependently produced a transient contraction followed by a sustained contraction. Noradrenaline (10 microM), 5-hydroxytryptamine (10 microM) and 9,11-epithio-11, 12-methano-thromboxane A2 (10 nM) each produced only a small contraction (less than 5% of the maximum K+-induced contraction). 3. N(G)-nitro-L-arginine (L-NOARG, 100 microM), but not indomethacin (10 microM), greatly enhanced the phasic and the tonic contractions induced by His (1-10 microM) in endothelium-intact, but not in endothelium-denuded strips, suggesting that spontaneous or basal release of nitric oxide (NO) from endothelial cells potently attenuates the His-induced contractions. Acetylcholine (ACh, 0.3-3 microM) caused concentration-dependent relaxation (maximum relaxation by 89.7 +/- 7.5%, n=4, P<0.05) when applied to endothelium-intact strips precontracted with His. L-NOARG had little effect on this ACh-induced relaxation (n=4; P<0.05). Apamin (0.1 microM), but not glibenclamide (3 microM), abolished the relaxation induced by ACh (0.3-3 microM) in L-NOARG-treated strips (n=4, P<0.05). 4. In endothelium-intact tissues, His (3 microM) depolarized the smooth muscle membrane potential (by 4.4 +/- 1.8 mV, n = 12, P < 0.05) whereas ACh (3 microM) caused membrane hyperpolarization (-20.9 +/- 3.0 mV, n = 25, P< 0.05). The ACh-induced membrane hypepolarization persisted after application of L-NOARG (-23.5 +/- 5.9 mV, n=8, P<0.05) or glibenclamide (-20.6 +/- 5.4 mV, n=5, P<0.05) but was greatly diminished by apamin (reduced to - 5.8 +/- 3.2 mV, n = 3, P< 0.05). 5. Sodium nitroprusside (0.1-10 microM) did not hyperpolarize the smooth muscle cell membrane potential (0.2 +/- 0.3 mV, n=4, P>0.05) but it greatly attenuated the His-induced contraction in endothelium-denuded strips (n-4, P<0.05). 6. These results suggest that, under the present experimental conditions: (i) spontaneous or basal release of NO from endothelial cells exerts a significant negative effect on agonist-induced contractions in rabbit MCA, and (ii) ACh primarily activates the release of endothelium-derived hyperpolarizing factor (EDHF) in rabbit MCA.

Animals↗

Chronic urticaria associated with aseptic meningitis: an atypical urticarial vasculitis?

The patient was a 7-year-old girl with early onset urticarial cutaneous lesions and was later complicated with aseptic meningitis. Her skin lesions occurred in the infantile period and were diagnosed as urticaria, but did not disappear with antihistamines and were recurrent and persistent. In addition, she had experienced an episode of headache about once a month since 1991, when she was 4 years old, and was diagnosed as aseptic meningitis. All studies including skin biopsy for urticarial vasculitis (UV) and systemic lupus erythematosus (SLE) were negative except for the data from non-specific inflammations. A systemic corticosteroid therapy dramatically reduced her symptoms. An unusual clinical course for this patient is described. It might suggest that this case is a presentation of the disease entity of UV, chronic urticaria and possibly SLE. To our knowledge, a similar case has not been previously reported.

Child↗

Acute tubulointerstitial nephritis associated with piperacillin therapy in a boy with glomerulonephritis.

An 11-year-old boy with glomerulonephritis developed acute renal failure 4 days after beginning piperacillin (PIPC) treatment. Renal biopsy revealed acute tubulointerstitial nephritis (ATIN) with marked eosinophils. A lymphocyte stimulation test (LST) for PIPC demonstrated an extremely high LST index of 626%. The serum levels of immunoglobulin E and eosinophil cationic protein also showed a significant increase at 9021 IU/mL and greater than 150 micrograms/L, respectively. These observations suggest that a hypersensitivity reaction might play a role in the pathogenesis of ATIN. This is the first report to describe PIPC-induced ATIN in a child.

Acute Disease↗

p53-induced p21 controls DNA replication.

The p21 protein, a regulator of cyclin-dependent kinases (CDKs), has been thought to be one of the key proteins to function in cell proliferation suppression upon DNA damage. In normal cells but not in many tumor cells, p21 forms a quaternary complex with a cyclin, a CDK and the proliferating cell nuclear antigen (PCNA), one of the DNA replication and repair factors, suggesting that this complex might play an important role in maintaining the integrity of the genome. Here, we have focused on the p21-PCNA interaction in the context of DNA replication or DNA repair, presenting the data from both in vitro and in vivo studies of the p21 function.

Antigens, Viral, Tumor↗

Effects of nitroglycerin on vasospasm and cyclic nucleotides in a primate model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Nitroglycerin, as well as nitric oxide, causes hyperpolarization and cGMP elevation in vascular smooth muscle cells. It is unknown whether nitroglycerin ameliorates vasospasm by an increase in cGMP levels after subarachnoid hemorrhage (SAH). The purpose of the present study was to measure the levels of both cGMP and cAMP in the cerebral arteries and parietal cerebral cortices in a primate model and to determine the effect of nitroglycerin on vasospasm after SAH. METHODS: Chronic vasospasm was induced by clot placement around the right middle cerebral artery (MCA). Seven days after the surgery, angiography was repeated and either nitroglycerin (3 micrograms/kg per hour) or saline was administered intravenously. Angiography and regional cerebral blood flow (rCBF) measurements in the bilateral parietal cortices were performed before and after each treatment. Both cGMP and cAMP levels were measured in the cerebral arteries and bilateral parietal cortices. RESULTS: A significant vasospasm occurred in the cerebral arteries on both sides, more prominently on the right side. Concomitantly, rCBF on the right side was significantly decreased (P < .05). In the right MCA, cGMP levels were significantly lower than in the normal MCA (P < .05). After the administration of nitroglycerin for 3 hours, the cerebral vessels were significantly dilated on both sides (P < .05), and rCBF was significantly increased on the right side (P < .05) but not on the left side. Although depressed cGMP levels in the right MCA were not recovered by nitroglycerin, a significant increase in cGMP levels was observed in the basilar artery (P < .05). In both parietal cortices, cGMP levels were significantly decreased after SAH (P < .05) and unchanged after nitroglycerin treatment. There were no significant changes in cAMP levels in SAH and after nitroglycerin treatment. CONCLUSIONS: The vasodilator effect of nitroglycerin in spastic MCA may not be mediated by an increase in cGMP levels, suggesting an involvement of hyperpolarization of the smooth muscle cells. Given the increase in rCBF, nitroglycerin may be therapeutic for the treatment of vasospasm.

Animals↗

Capacity of H2O2 release from monocytes in steroid-sensitive nephrotic syndrome.

The pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) is poorly defined. We previously demonstrated that monocytes from SSNS patients with proteinuria were activated to display exaggerated phagocytosis of opsonized particles and paradoxically reduced chemotaxis. In this study, we evaluated the capacity of hydrogen peroxide (H2O2) release from monocytes in 19 patients with SSNS and 13 healthy controls, by exposure to phorbol myristate acetate (PMA), using scopoletin method. Of 19 patients of SSNS, 7 were proteinuric and 12 in remission. The H2O2 release was significantly higher in SSNS patients with proteinuria than those in remission or normal controls [177.49 +/- 94.75 (mean +/- S.D.) vs. 60.67 +/- 58.89 (p < 0.02) or 85.02 +/- 48.62 nmol/90 min/mg cell protein (p < 0.05)]. Follow-up measurements in two SSNS patients showed that H2O2 release was reduced when proteinuric condition was improved to be in remission. Our data suggest that monocytes in SSNS with proteinuria were activated and were prepared to receive some extracellular signaling leading to protein kinase-C activation for releasing H2O2.

Adult↗

An adolescent case of anti-neutrophil cytoplasmic autoantibodies-associated crescentic glomerulonephritis complicated with subclinical autoimmune thyroiditis.

We report here a 15-year-old girl with myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated crescentic glomerulonephritis (CreGN) and subclinical autoimmune thyroiditis. She was found to have proteinuria and hematuria by a school mass-screening a year before the first visit to the hospital, where a routine examination revealed blood urea nitrogen (BUN) 36.8 mg/dl and serum creatinine concentration of 1.63 mg/dl, although she had no apparent disabilities. On admission, the additional laboratory findings showed proteinuria of 1.06 g/day, hematuria of 3+, and a creatinine clearance of 30.1 ml/min. Hypocomplementemia was not observed. A renal biopsy revealed pauci-immune CreGN with 95% fibrocellular crescents, 84% sclerosis and/or hyalinosis and a massive cellular infiltration in the interstitium. She had MPO-ANCA of 865 EU/ml and an anti-thyroid microsome antibody titer of 1:1,600 without the detection of anti-glomerular basement membrane antibodies. Laboratory tests and scintigraphies for the thyroid gland did not show any abnormalities. Under the diagnosis of MPO-ANCA-associated CreGN, cocktail therapy consisting of prednisolone, cyclophosphamide, dilazep hydrochloride and warfarin was started. Improvement of urinary abnormalities and suppression of further deterioration of renal function were observed. Serial renal biopsy 6 months after the initiation of therapy showed decrement of interstitial cell infiltration and no generation of other crescentic glomeruli. The patient's serum titer of anti-thyroid microsome antibody was not affected by the adsorption of MPO-reacted IgG, suggesting that MPO-ANCA was not cross-reactive to thyroid microsome antigen.

Adolescent↗

Production of a chimeric fibroin light-chain polypeptide in a fibroin secretion-deficient naked pupa mutant of the silkworm Bombyx mori.

The allelic Nd-s and Nd-sD mutations of the silkworm Bombyx mori are mapped to the same locus as that of the fibroin light (L)-chain gene (Fib-L). The silkworm carrying the homozygous Nd-s or Nd-sD mutation secretes less than 0.3% of the normal level of fibroin and produces a thin cocoon (naked pupa). In this study, cDNA sequences of the Nd-s and Nd-sD L-chains were compared with the cDNA and genomic sequences of the L-chain of the B. mori J-139 strain, a normal-level producer of fibroin. The two mutant cDNA sequences are almost identical except for one base change in the coding region. The N-terminal half of the L-chain encoded by exons I to III is identical between the mutants and J-139, but the rest of the molecule is completely different. The C-terminal half of the Nd-sD mutant L-chain is encoded by two exons, IV' and V', which are brought into proximity with the exon III by recombination between sequences in the third intron and in the far downstream region with concomitant loss of a region containing exons IV to VII. Sequences corresponding to exons IV' and V' are present about 10 kb downstream of the L-chain gene in the J-139 genome. Their homologous sequences have not been found in the DNA and protein databases. The chimeric L-chain molecule of about 27 kDa is present in posterior silk glands of Nd-s and Nd-sD strains without disulfide-bonding to the fibroin heavy (H-) chain, as revealed by Western blotting with the antibody specific to the C-terminal half of the mutant L-chain.

Amino Acid Sequence↗