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Biomedical subjects

S Waga

Publications and source records attributed to S Waga.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of tirilazad mesylate on vasospasm and phospholipid hydroperoxides in a primate model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Tirilazad mesylate has been used in the attempt to prevent cerebral vasospasm after subarachnoid hemorrhage (SAH), although the actual targets of this agent in vivo have thus far been controversial. Chemiluminescence/high-performance liquid chromatography provided a new method for direct measurements of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) in vivo and showed that phosphatidylcholine is the lipid class most susceptible to lipid peroxidation. In the present study we measured those levels in a primate model of SAH for determination of the effects of tirilazad on vasospasm. METHODS: Fourteen Macaca monkeys of both sexes were randomly assigned into 2 groups: a tirilazad group receiving a dosage of 0.3 mg/kg and a placebo group receiving only the vehicle in which tirilazad was delivered. After the induction of experimental SAH around the right middle cerebral artery on day 0, tirilazad or vehicle was administered intravenously every 8 hours for 6 days. On day 7, the animals were killed after angiography and regional cerebral blood flow measurements were performed. The levels of PCOOH and PEOOH were measured in the clots, bilateral parietal cortices, right frontal cortex contact with clots, cerebellar hemispheres, bilateral middle cerebral arteries, and basilar arteries. RESULTS: In the placebo group, a significant vasospasm occurred in the cerebral arteries on both sides, but most prominently on the right side. The degree of vasospasm in the cerebral arteries was significantly attenuated in the tirilazad group (P<0.005). There were no significant differences in regional cerebral blood flow, PCOOH, and PEOOH levels in the clots, cerebral cortices, and cerebellar hemispheres between the 2 groups. In contrast, the levels of PCOOH in the cerebral arteries were significantly higher in the placebo group than in the tirilazad group (P<0.025). It was remarkable that the tirilazad treatments eliminated PCOOH in any vascular territory after SAH. CONCLUSIONS: PCOOH in the artery wall may be an important indicator for vasospasm, and the inhibition of PCOOH may explain the efficacy of tirilazad on vasospasm.

Animals↗
PubMed1999

Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats.

Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) causes cerebral ischemia and infarction. To date, the pathogenesis and gene expression associated with vasospasm remain poorly understood. The present study used fluorescent differential display to identify differentially expressed genes in a rat model of SAH. By using quantitative RT-PCR, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a rat vasospasm model. A significant correlation was observed between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Intracisternal injection of antisense HO-1 oligodeoxynucleotide (ODN) significantly delayed the clearance of oxyhemoglobin and deoxyhemoglobin from the subarachnoid space and aggravated angiographic vasospasm. Antisense HO-1 ODN inhibited HO-1 induction in the basilar arteries but not in the whole brain tissue. This phenomenon was not observed in the nontreated, sense HO-1 ODN-treated, or scrambled ODN-treated arteries. We report the protective effects of HO-1 gene induction in cerebral vasospasm after SAH, a finding that should provide a novel therapeutic approach for cerebral vasospasm.

Animals↗
PubMed1999

Long-term azathioprine therapy in two children with steroid-dependent minimal-change nephrotic syndrome.

Long-term azathioprine therapy as an alternative treatment to cyclophosphamide was done in 2 children with steroid-dependent minimal-change nephrotic syndrome (MCNS). They had already been treated with prednisolone, intravenous methyl-prednisolone pulse therapy, cyclophosphamide and mizoribine. Although cyclophosphamide had been proved to be effective in maintaining their remission, the cumulative dose of the agent limited another course of cyclophosphamide therapy. Since ciclosporine therapy is much expensive, a trial of azathioprine (2 mg/kg per day) was started, and the therapy resulted in inducing sustained remission and reducing prednisolone. The patients were well tolerated the long-term azathioprine therapy over a year. Although the efficacy of azathioprine in the management of childhood MCNS might be restricted, we therefore suggest that this agent should be reconsidered as an alternative treatment to cyclophosphamide.

Azathioprine↗
PubMed1999

Acute tubulointerstitial nephritis following intravenous immunoglobulin therapy in a male infant with minimal-change nephrotic syndrome.

A boy aged 4 years with nephrotic syndrome (NS) was referred to our hospital because of the third relapse of NS. Hypogammaglobulinemia associated with massive proteinuria was observed at the presentation. Residual urinary tract infection required intravenous piperacillin and immunoglobulin therapy (IVIG). Soon after IVIG, he complained of high fever with chills, bilateral knee joint pain, dry cough and chest discomfort. Although he did not develop renal insufficiency, a transient increase in the urinary beta2-microglobulin and decrease in the serum complement hemolytic activity were observed. These clinical manifestations spontaneously ceased. A percutaneous renal biopsy for his NS performed 19 days after the episode of allergic reaction revealed tubulointerstitial nephritis (TIN) with marked eosinophil infiltrates. Glomeruli showed minor glomerular abnormalities. Renal complications associated with IVIG treatment have been reported to date, however, acute TIN has rarely been seen.

Acute Disease↗
PubMed1999

IgA interaction with carboxy-terminal 43-kD fragment of fibronectin in IgA nephropathy.

IgA deposition in the glomerular mesangial matrix is a prerequisite for the diagnosis of IgA nephropathy, and circulating IgA-containing complex has been implicated in this process. Since fibronectin is known to be involved in the assembly of extracellular matrix, this study was conducted to investigate whether fibronectin and its fragments are present in sera of patients and are capable of binding IgA1. Sera from patients with IgA nephropathy were purified by heparin-affinity chromatography, and column eluate were analyzed for the presence of fibronectin using Western blot and a set of anti-fibronectin monoclonal antibodies. Native fibronectin was digested with cathepsin D to obtain fragments similar to those of serum fibronectin. The capacity of fibronectin to bind IgA was examined with a mixture of purified IgA1 and cathepsin D-digested fibronectin fragments. A 43-kD carboxy-terminal fragment of fibronectin was detected in samples derived from sera of patients with IgA nephropathy but not in healthy control subjects. A similar-sized fragment was generated by cathepsin D digestion of the native molecule and was shown to bind to IgA1 in vitro. Since the carboxy-terminal domain is known to be critical in assembling exogenous fibronectin into the extracellular matrix, the affinity to IgA1 to a fragment found in patients may have pathogenic potential to mediate extracellular IgA deposition in IgA nephropathy.

Chromatography, Affinity↗
PubMed1999

[Combined modality therapy for malignant lymphoma of the primary central nervous system: a preliminary report of a new chemotherapeutic regimen with "PEACE"].

Between 1994 and 1998, a total of 5 patients with primary central nervous system malignant lymphoma (PCNSML) were enrolled in this study. There were one man and four women, with a median age of 53 years. These patients were treated with a new systemic chemotherapeutic regimen "PEACE" therapy. After undergoing surgery (biopsy or resection), the patients received radiotherapy followed by adjuvant chemotherapy with combination of procarbazine (P) (100 mg/day, p.o., day 1 to day 5), cyclophosphamide (E) (200 mg/sqm/day, day 4), doxorubicin hydrochloride (A) (20 mg/sqm/day, day 4 and day 5), carboplatin (C) (300 mg/sqm/day, day 1), and etoposide (E) (30 mg/sqm/day, day 1 to day 3). This regimen was repeated for at least three cycles every 4 to 6 weeks. Intrathecal injection of methotrexate was also administrated in conjunction with systemic chemotherapy except in one case. Complete response was seen in one, and partial response in four patients. Toxicity was tolerable. Median survival time was 31.5 months. The results suggest the efficacy of this chemotherapeutic regimen and further emphasize a role for adjuvant chemotherapy in the initial treatment of PCNSML.

Adult↗
PubMed1998

Bilateral intranigral NMDA infusion suppresses neuronal injury without affecting the duration of kainic acid-induced seizures in rats.

The substantia nigra pars reticulata (SNpr) is recognized as an important modulator of seizures within the limbic system. We have investigated the effects of N-methyl-D-aspartate (NMDA) infusion into SNpr upon seizure-related neuronal injury (assessed by expression of the 72-kDa heat shock protein - HSP 72) induced by systemic kainic acid (KA) in rats. Three to four days following implantation of guide cannulae for drug administration into SNpr, KA (7 mg/kg) was injected intravenously to induce seizures. Bilateral intranigral infusion of NMDA (20 nmol) 15 min prior to KA injection, suppressed the expression of HSP 72 in the hippocampal CA1 region without affecting seizure duration. These results support the involvement of NMDA receptors within SNpr in modulating neuronal injury following KA-induced limbic seizures.

Animals↗
PubMed1998

Thoracic spinal angiomyolipoma with extracanal extension to the thoracic cavity. A case report.

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To describe a 72-year-old man with thoracic spinal angiomyolipoma in the ventral aspect of the epidural space and extracanal extension to the posterior mediastinum, to discuss the clinical and radiologic features and unique biologic behavior of this entity, and to review of the literature on angiolipoma and angiomyolipoma. SUMMARY OF BACKGROUND DATA: Spinal angiolipoma and angiomyolipoma are rare tumors, which are localized almost exclusively in the dorsal epidural space of the thoracic spine. Most reported cases have no tendency to involve the surrounding tissue. METHODS: The authors describe the radiologic, surgical, and pathologic findings of this patient and review the findings from other reported cases. RESULTS: Anterior decompression was performed using a right transthoracic incision, and the neurologic symptoms improved immediately. There were no signs of recurrence of the tumor or neurologic deficit within a 2-year follow-up period. CONCLUSION: Results of a literature survey of these tumors support management by prompt and radical surgical intervention for long-term cure, even in cases in which the infiltrating nature is recognized.

Aged↗
PubMed1998

Effects of unilateral intrathecal administrations of low dose tissue-type plasminogen activator on clot lysis, vasospasm and brain phospholipid hydroperoxidation in a primate model of bilateral subarachnoid hemorrhage.

In order to clarify the effect of clot lysis by recombinant tissue-type plasminogen activator (tPA) on the brain lipid peroxidation, we measured phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) levels in a primate model of subarachnoid hemorrhage (SAH). Monkeys were assigned into two groups; a tPA-treated group receiving intrathecal injections of 0.02 mg tPA, and a placebo-treated group receiving saline. The tPA or placebo was injected into the right side of the basal cistern every 8 h for 6 days following bilateral SAH induction. The tPA cleared the right side clots (p < 0.0001), but not the left side clots. The degree of vasospasm in the right middle cerebral artery and the rCBF decrease in the right parietal cortex were significantly attenuated in the tPA group (p < 0.05). In the placebo group, more severe vasospasm and marked rCBF reduction were noted in comparison with those in the tPA group. PCOOH levels in the parietal cortex were significantly higher in the placebo group than in the tPA group (p < 0.05). There were no significant changes in brain PEOOH levels. These results may explain the limitations for clinical application of unilateral intrathecal administration of tPA.

Animals↗
PubMed1998

Bilateral spontaneous dissection of the posteroinferior cerebellar arteries: case report.

OBJECTIVE AND IMPORTANCE: Cervicocerebral arterial dissections occur when blood extrudes into the wall of an artery supplying the brain. The resulting intramural hematoma may compromise the lumen and cause an aneurysmal dilation. Dissecting aneurysms are now recognized with increasing frequency as a cause of strokes. They usually occur spontaneously or are associated with trivial trauma to the artery. A dissecting aneurysm of the posteroinferior cerebellar artery (PICA) is very rare, however. We present a case with ischemic episode and successive subarachnoid hemorrhage caused by bilateral dissection of the PICAs. CLINICAL PRESENTATION: A 47-year-old man experienced sudden onset of cerebellar infarction that rapidly resulted in subarachnoid hemorrhage. Angiography revealed a typical pearl-and-string sign in the right PICA and an irregular stenosis in the left PICA. The patient died shortly after admission. Autopsy demonstrated bilateral dissection of the PICAs not involving the vertebral artery. CONCLUSION: The incidence of intracranial dissecting aneurysms most frequently occurs in the vertebral artery, but the PICA is only rarely involved, especially bilaterally. We are not aware of any other such case in the literature.

Aortic Dissection↗
PubMed1998

An infant case of bilateral small kidneys with both proximal and distal tubular dysfunction.

A male infant with bilateral small kidneys associated with both proximal and distal tubular dysfunction, who showed chronic renal failure soon after birth, is reported. He was also noted to have both proximal and distal type of renal tubular acidosis. The small kidneys were thought to be due to renal hypodysplasia associated with bilateral severe vesicoureteral reflux, by radiological findings. An alkalization therapy with chemoprophylaxis seemed to be of benefit in slowing the progression of renal failure in this case.

Acidosis, Renal Tubular↗
PubMed1998

Subclinical Sjögren's syndrome: a significant 67gallium accumulation in the orbits and parotid glands.

An 8-year-old girl with hypergammaglobulinemia showed an abnormal 67gallium accumulation in the orbits and parotid glands. Although she did not have any subjective siccant complaints, reported typical histopathological and sialographic changes suggesting Sjögren's syndrome (SjS) were observed in the salivary glands. Gallium scintigram might be a valuable and non-invasive diagnostic tool in the diagnosis of children with SjS without sicca symptoms.

Anti-Inflammatory Agents↗
PubMed1998

Cellular proteins required for adeno-associated virus DNA replication in the absence of adenovirus coinfection.

We previously reported the development of an in vitro adeno-associated virus (AAV) DNA replication system. The system required one of the p5 Rep proteins encoded by AAV (either Rep78 or Rep68) and a crude adenovirus (Ad)-infected HeLa cell cytoplasmic extract to catalyze origin of replication-dependent AAV DNA replication. However, in addition to fully permissive DNA replication, which occurs in the presence of Ad, AAV is also capable of partially permissive DNA replication in the absence of the helper virus in cells that have been treated with genotoxic agents. Limited DNA replication also occurs in the absence of Ad during the process of establishing a latent infection. In an attempt to isolate uninfected extracts that would support AAV DNA replication, we discovered that HeLa cell extracts grown to high density can occasionally display as much in vitro replication activity as Ad-infected extracts. This finding confirmed previous genetic analyses which suggested that no Ad-encoded proteins were absolutely essential for AAV DNA replication and that the uninfected extracts should be useful for studying the differences between helper-dependent and helper-independent AAV DNA replication. Using specific chemical inhibitors and monoclonal antibodies, as well as the fractionation of uninfected HeLa extracts, we identified several of the cellular enzymes involved in AAV DNA replication. They were the single-stranded DNA binding protein, replication protein A (RFA), the 3' primer binding complex, replication factor C (RFC), and proliferating cell nuclear antigen (PCNA). Consistent with the current model for AAV DNA replication, which requires only leading-strand DNA synthesis, we found no requirement for DNA polymerase alpha-primase. AAV DNA replication could be reconstituted with purified Rep78, RPA, RFC, and PCNA and a phosphocellulose chromatography fraction (IIA) that contained DNA polymerase activity. As both RFC and PCNA are known to be accessory proteins for polymerase delta and epsilon, we attempted to reconstitute AAV DNA replication by substituting either purified polymerase delta or polymerase epsilon for fraction IIA. These attempts were unsuccessful and suggested that some novel cellular protein or modification was required for AAV DNA replication that had not been previously identified. Finally, we also further characterized the in vitro DNA replication assay and demonstrated by two-dimensional (2D) gel electrophoresis that all of the intermediates commonly seen in vivo are generated in the in vitro system. The only difference was an accumulation of single-stranded DNA in vivo that was not seen in vitro. The 2D data also suggested that although both Rep78 and Rep68 can generate dimeric intermediates in vitro, Rep68 is more efficient in processing dimers to monomer duplex DNA. Regardless of the Rep that was used in vitro, we found evidence of an interaction between the elongation complex and the terminal repeats. Nicking at the terminal repeats of a replicating molecule appeared to be inhibited until after elongation was complete.

Adenoviridae↗
PubMed1998

Cyclin-dependent kinase inhibitor p21 modulates the DNA primer-template recognition complex.

The p21 protein, a cyclin-dependent kinase (CDK) inhibitor, is capable of binding to both cyclin-CDK and the proliferating cell nuclear antigen (PCNA). Through its binding to PCNA, p21 can regulate the function of PCNA differentially in replication and repair. To gain an understanding of the precise mechanism by which p21 affects PCNA function, we have designed a new assay for replication factor C (RFC)-catalyzed loading of PCNA onto DNA, a method that utilizes a primer-template DNA attached to agarose beads via biotin-streptavidin. Using this assay, we showed that RFC remains transiently associated with PCNA on the DNA after the loading reaction. Addition of p21 did not inhibit RFC-dependent PCNA loading; rather, p21 formed a stable complex with PCNA on the DNA. In contrast, the formation of a p21-PCNA complex on the DNA resulted in the displacement of RFC from the DNA. The nonhydrolyzable analogs of ATP, adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS) and adenyl-imidodiphosphate, each stabilized the primer recognition complex containing RFC and PCNA in the absence of p21. RFC in the ATPgammaS-activated complex was no longer displaced from the DNA by p21. We propose that p21 stimulates the dissociation of the RFC from the PCNA-DNA complex in a process that requires ATP hydrolysis and then inhibits subsequent PCNA-dependent events in DNA replication. The data suggest that the conformation of RFC in the primer recognition complex might change on hydrolysis of ATP. We also suggest that the p21-PCNA complex that remains attached to DNA might function to tether cyclin-CDK complexes to specific regions of the genome.

Adenosine Triphosphate↗
PubMed1998

The DNA replication fork in eukaryotic cells.

Replication of the two template strands at eukaryotic cell DNA replication forks is a highly coordinated process that ensures accurate and efficient genome duplication. Biochemical studies, principally of plasmid DNAs containing the Simian Virus 40 origin of DNA replication, and yeast genetic studies have uncovered the fundamental mechanisms of replication fork progression. At least two different DNA polymerases, a single-stranded DNA-binding protein, a clamp-loading complex, and a polymerase clamp combine to replicate DNA. Okazaki fragment synthesis involves a DNA polymerase-switching mechanism, and maturation occurs by the recruitment of specific nucleases, a helicase, and a ligase. The process of DNA replication is also coupled to cell-cycle progression and to DNA repair to maintain genome integrity.

Cell Cycle↗
PubMed1998

Myosin light chain phosphorylation and contractile proteins in a canine two-hemorrhage model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) impairs both contraction and relaxation response in cerebral arteries. We tested the hypothesis that cerebral vasospasm might be ATP-independent contraction, such as latch state, and protein synthesis might be substantially downregulated due to ATP consumption after long-lasting contraction. METHODS: Chronic cerebral vasospasm was induced in the canine 2-hemorrhage model of SAH. The normal and spastic basilar arteries were stabilized in Krebs-Henseleit solution, and contraction was induced by 30 micromol/L prostaglandin F2alpha (PGF2alpha) in vitro and in vivo. Before and at 15 minutes and 1 hour after the treatment with PGF2alpha, the levels of phosphorylated 20-kDa myosin light chain (MLC20) were measured. The time course of expression of contraction proteins actin and MLC20, and contraction-inhibiting proteins h-caldesmon and calponin was determined by immunoblotting techniques. RESULTS: A significant vasospasm occurred in the basilar artery during days 4 to 21, most prominently on days 7 and 14. There were no significant differences in the baseline levels of phosphorylated MLC20 between normal and spastic basilar arteries. The increase in MLC20 phosphorylation by PGF2alpha was significantly attenuated in the spastic basilar artery in vitro and in vivo (P<0.05). The immunoreactivity for actin, h-caldesmon, and calponin in the spastic basilar arteries was progressively decreased until day 14 and returned to the normal level on day 21. In contrast, protein levels of MLC20 did not significantly change during days 0 to 21. CONCLUSIONS: Chronic cerebral vasospasm closely resembles the latch state, and temporary deficiencies of contractile proteins may result from increased destruction and inhibition of protein synthesis.

Animals↗
PubMed1998

Effect of vasospasm on heme oxygenases in a rat model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH)-induced heme oxygenase-1 (HO-1) in glia throughout the rat brain without affecting heme oxygenase-2 (HO-2). However, the relationship between cerebral vasospasm and the expression of heme oxygenases after SAH is thus far unknown. The purpose of the present study was to clarify the effect of vasospasm on the expression of heme oxygenases in a rat model of SAH. METHODS: Endothelin, hemolysate, hemolysate saturated with carbon monoxide (CO-hemolysate), and saline were injected into the cisterna magna of adult rats. Angiography was repeated before each injection and 15 and 60 minutes and 24 hours after each injection. Immunocytochemistry for HO-1, HO-2, and glial fibrillary acidic protein (GFAP) was performed 24 hours after the injection. RESULTS: A significant vasospasm occurred in the basilar artery after the injection of endothelin, hemolysate, and CO-hemolysate. The degree of vasospasm was most prominent 15 minutes after each injection. There was no significant difference in the degree of vasospasm among injections. The HO-1 was induced exclusively in the glial cells throughout the brain after injection of hemolysate and CO-hemolysate; however, it was not induced by endothelin and saline. In the dentate gyrus of the hippocampus and the molecular layer of the cerebellum, the HO-1-positive cells were also stained for GFAP, suggesting astrocytic glial cells. On the other hand, HO-2 immunoreactivity was abundant in neurons and was not affected by endothelin, hemolysate, CO-hemolysate, or saline. CONCLUSIONS: It is suggested that heme per se, rather than ischemia induced by vasospasm, plays a pivotal role in the expression of HO-1 in this rat model.

Animals↗