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Biomedical subjects

S Nabeshima

Publications and source records attributed to S Nabeshima.

At least 19 recordsLinked to original sources

Liver transplantation from an identical twin without immunosuppression, with early recurrence of hepatitis C.

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon alpha and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.

Adult↗

2'-,5'-Oligoadenylate synthetase response ratio predicting virological response to PEG-interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C.

OBJECTIVE: Although all the mechanisms of elimination of hepatitis C virus (HCV) by Interferon (IFN) have not been fully elucidated, the 2'-5'-oligoadenylate (2-5A) system is one of the mechanisms of the antiviral effect of IFN. Consequently, the measurement of 2'-5'-oligoadenylate synthetase (2-5AS) activity could be useful for the evaluation of IFN treatment. This retrospective study was aimed at assessing whether 2-5AS activity functions as a clinical marker of virological response to PEG-interferon-alpha2b (PEG-IFN) plus ribavirin therapy of chronic hepatitis C. METHODS: The 32 patients included in this study had high viral loads of serum HCV-RNA of genotype 1b with chronic hepatitis C. All the patients received a regimen of PEG-IFN plus ribavirin for 48 weeks, and were then divided into two groups: one group (effective group) with undetectable serum HCV-RNA levels at 24 weeks (n = 22) of therapy, the other group (ineffective group) with persistent presence of HCV-RNA in serum at 24 weeks (n = 10). The 2-5AS activity in serum was measured 2, 8 and 12 weeks before initial administration. RESULTS: The 2-5AS response ratio (measured value/measured value of baseline 2-5AS) at 2, 8 and 12 weeks after the administration in the effective group was significantly higher than that in the ineffective group. CONCLUSIONS: These results suggest that the ratio of 2-5AS is closely related to the antiviral effect, and that the measurement of 2-5AS response ratio may be a useful clinical parameter of virological response to PEG-IFN plus ribavirin therapy of chronic hepatitis C.

2',5'-Oligoadenylate Synthetase↗

Interferon-beta induction/interferon-alpha2b plus ribavirin therapy in patients with chronic hepatitis C.

Treatment of chronic hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin improves the rate of eradication of the virus by less than 20% in patients with genotype 1b and a high viral load. In this study we assessed whether IFN-beta induction/IFN-alpha2b plus ribavirin enhances the efficacy of the therapy in patients with chronic hepatitis C. The efficacy of IFN-beta induction/IFN-alpha2b plus ribavirin therapy (group A, n=7) was compared with that of IFN-alpha2b plus ribavirin (group B, n=7) in 14 patients with high levels of HCV-RNA (> 100 K/U/ml). No significant differences were observed in the clearance of HCV-RNA between the two groups (A and B, respectively) 2 weeks after the start of the treatment (0% and 14.3%), at the end of the treatment (71.4% and 100%) and 6 months after the end of the treatment (28.6% and 14.3%). Recovery was complete in 28.6% and 14.3%, transient in 42.9% and 85.7% and absent in 28.6% and 0% in groups A and B, respectively. Early log changes in the viral load from the baseline after 2 weeks of treatment were 2.41 +/- 0.91 and 2.77 +/- 0.20 in groups A and B, respectively, with no significant difference between the two groups. In the present study, we were not able to demonstrate that IFN-beta induction/IFN-alpha2b plus ribavirin therapy was superior to IFN-alpha2b plus ribavirin therapy in patients with genotype 1b and high viral loads.

Adult↗

A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of influenza.

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-gamma production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.

Acute Disease↗

TI-201 SPECT compared with histopathologic grade in the prognostic assessment of cerebral gliomas.

PURPOSE: Although TI-201 SPECT has been used to evaluate the malignant grade of cerebral gliomas, the gold standard continues to be histopathologic examination. The authors assessed and compared the prognostic abilities of the two studies using survival analysis. MATERIALS AND METHODS: Twenty-nine patients underwent 34 sessions of TI-201 SPECT plus surgery for primary or recurrent cerebral gliomas 12 to 78 months before this analysis. Using conventional survival analyses, such as the log-rank test, Cox regression, and the Akaike cross-tab method, the authors evaluated the prognostic significance of 10 variables: histopathologic grade, TI-201 SPECT, Tc-99m HMPAO SPECT, tumor cell viability, radionecrosis, neurologic defects, clinical improvement, surgery, chemotherapy, and external beam radiotherapy. RESULTS: TI-201 SPECT was most strongly related to prognosis, followed by histopathologic grade. The other variables had little prognostic value. The Cox stepwise selection procedure indicated that TI-201 SPECT was the only independent predictor of outcome, whereas histopathologic analysis was eliminated from the prognostic model. However, the Kaplan-Meier survival curve and the Akaike method indicated that histopathologically low-grade tumors were more closely associated with longer-term survival than were TI-201 low uptake tumors. CONCLUSIONS: TI-201 SPECT is not only closely correlated with the histopathologic grade of tumor but is a significantly better predictor of outcome than histopathologic grade. However, histopathologic examination may provide additional information on longer-term survival. TI-201 SPECT is a valuable procedure, especially in patients in whom a histologic diagnosis of possible glioma cannot be made.

Adolescent↗

[A case of severe adult measles pneumonia--efficacy of combination of steroid pulse therapy, high-dose vitamin A and gamma globulins].

A 33 year-old female was admitted with facial, trunk and limb eruptions, conjunctiva intrahemorrhage, Koplik's spots in the pharynx and severe hypoxemia after fever and upper respiratory tract symptom. Infiltrative shadow of the whole right lung was seen on chest radiography. Fine crackles were seen in the lower left lung and in the whole right lung. Severe inflammation and liver dysfunction were indicated by blood test. Measles antibody IgM was high. The abnormal interstitial shadows were confirmed in greater detail by chest computed tomography. Her condition was diagnosed as measles pneumonia. A combination therapy with steroid pulse, high dose vitamin A, and gamma globulin was started, after which the patient gradually improved, indicating the effectiveness of this combination therapy for severe adult measles pneumonia.

Adult↗

Migration of a lumboperitoneal shunt catheter into the spinal canal--case report.

A 50-year-old female suffered upward migration of a lumboperitoneal (LP) shunt catheter into the spinal canal, manifesting as disturbance of short-term memory. Revision of the shunt confirmed that the tube had migrated into the spinal canal. The tube was pulled back into the peritoneal cavity and attached firmly to the fascia with a new anchoring device. LP shunts have the advantages of technical simplicity and extracranial procedure, but firm fixation is recommended since movements of the spine may cause proximal tube migration.

Female↗

[Surgical treatment for symptomatic arachnoid cysts].

During the period from 1983 to 1999, 12 patients with symptomatic arachnoid cyst were treated. The mean patient age was 20.6 years. The most common location was the middle fossa (10 cases). Initial CT scan revealed associated subdural hygroma in 7 patients and hydrocephalus in one. Clinical symptoms were related to increased intracranial pressure, cranio-megaly and seizure. One infant with a huge arachnoid cyst was treated, using a cystoperitoneal (CP) shunt. Four patients underwent membraectomy. Combination CP shunt and membraectomy was performed in 5 patients. The remaining 2 arachnoid cysts were complicated with subdural hygroma and, initially, they were observed conservatively, but hygroma gradually changed to hematoma. One was treated by irrigation and the other hematoma was spontaneously absorbed. Significant complications included extensive subdural effusion in one patient, contralateral chronic subdural hematoma in two, intracranial hypotension in two, and shunt dependency in one. There were no recurrences during the follow-up period (mean 3.6 years).

Adolescent↗

The efficacy of conventional radiation therapy in the management of pituitary adenoma.

PURPOSE: To evaluate the efficacy of conventional radiotherapy for reducing tumor size and endocrine hypersecretion of pituitary adenomas. METHODS AND MATERIALS: We reviewed the records of 91 patients with pituitary adenoma, who were first treated between 1969 and 1994 and had been followed for more than 2 years (median, 8.2 years.) Of these patients, 86 had received postoperative radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51 Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were assessed. The efficacy of radiotherapy was evaluated before treatment and during the follow-up period (1-14 years; median, 3 years) by estimating tumor size on computed tomography or magnetic resonance imaging in 56 patients, as well as by endocrine testing in the 22 patients who had secreting adenomas. Local control rate, prognostic factors, and side effects were analyzed. RESULTS: Mass-effect symptoms improved in 72% and 79% of patients who had such symptoms due to nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone levels normalized in 74% of patients who showed endocrine hypersecretions. The greatest size reduction was seen 3 years after the completion of radiotherapy (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR, 27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas (2 with prolactinoma and 1 with Cushing's disease) showed a mismatch between reduction in tumor size and normalization of endocrine hypersecretion. The 10-year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma, growth-hormone-secreting adenoma, prolactinoma, and Cushing's disease, respectively. Univariate analyses showed that disease type and radiation field size were significant prognostic factors. Brain necrosis occurred in 1 patient who received a 60-Gy dose of irradiation. CONCLUSION: We conclude that conventional external radiotherapy with 50 Gy is safe and sufficient to control pituitary adenoma. Careful observation is required in the management of secreting adenomas because the effects on tumor size and endocrine hypersecretion may be mismatched in some secreting adenomas.

Adenoma↗

Increased frequency of interferon-gamma-producing peripheral blood CD4+ T cells in chronic hepatitis C virus infection.

OBJECTIVES: To determine the profile of cytokine secretion by CD4+ T helper (Th) cells in chronic hepatitis C virus (HCV) infection, we used flow cytometry to determine the percentage of interferon (IFN)-gamma and interleukin (IL)-4 producing cells from CD4+ T lymphocytes in peripheral blood obtained from patients chronically infected with HCV. METHODS: Peripheral blood mononuclear cells isolated from 89 HCV infected subjects (22 asymptomatic carriers, 56 patients with chronic hepatitis, and 11 patients with liver cirrhosis) and 24 healthy controls were stained with surface CD4 and intracellular IFN-gamma and IL-4. Serum soluble IL-2 receptor (sIL-2R) levels were analyzed by ELISA. RESULTS: The frequency of IFN-gamma producing CD4+ cells in asymptomatic HCV carriers, patients with chronic hepatitis, and patients with liver cirrhosis were significantly higher than those of healthy controls (p<0.01, respectively). In contrast, the percentages of IL-4-producing CD4+ cells were very low, and there were no significant correlations with disease progression. A significant elevation in serum sIL-2R levels was found in chronic HCV infection compared to healthy controls, and serum sIL-2R levels significantly correlated with the frequency of IFN-gamma-producing cells. CONCLUSIONS: In HCV infected subjects, both serum sIL-2R and IFN-gamma are increased in chronic HCV infection no matter the stage of disease, meaning they are no different in asymptomatic carriers, patients with chronic hepatitis, and patients with liver cirrhosis, and that Th1 cytokine or Th1 cells may participate in the pathogenesis of liver damage in chronic HCV infection.

Aged↗

Influenza in three patients with human immunodeficiency virus infection.

Three Japanese outpatients with human immunodeficiency virus (HIV) infection on anti-retroviral therapy showed evidence of influenza in January 1999. CD4+ T cell counts of these patients prior to the diagnosis of influenza were 72, 248, and 152/mm3, and HIV RNA levels were 19,953, 1,259, and 1,585 copies/ml, respectively. Fever continued 4 to 5 days with no severe complications. One patient showed post-influenzal bronchitis which was effectively treated by antibiotics. None of these patients showed increased serum HIV RNA levels during and after influenza, however, in one patient, a transient reduction of CD4+ and CD8+ cells was seen during the active phase of influenza. Although symptoms of influenza in HIV carriers are generally mild and similar to those in healthy adults, careful follow-up is needed as symptoms of influenza in some HIV-infected patients can be prolonged and serious.

AIDS-Related Opportunistic Infections↗

Magnetic resonance imaging of calvarial eosinophilic granuloma with pericranial soft tissue reaction--case report.

A 4-year-old girl presented with an eosinophilic granuloma in the cranial vault. Magnetic resonance (MR) imaging showed the mass as slightly low intensity on T1- and high intensity on T2-weighted images. The pericranial soft tissue was densely enhanced after gadolinium-diethylenetriaminepenta-acetic acid infusion. The mass was soft and successfully removed. Histological examination disclosed Langerhans' cell histiocytosis. MR imaging is useful for the diagnosis of calvarial eosinophilic granuloma with soft tissue involvement.

Acute-Phase Reaction↗

[Clinical problems in the treatment of primary central nervous system malignant lymphoma].

While the treatment of extracerebral lymphomas with the combination of chemotherapy and radiotherapy has drastically improved outcomes, the treatment of primary central nervous system malignant lymphoma(PCNSML) has been disappointing. Because of the variety of clinical presentations, progression of disease, and treatment modalities, careful inspection of factors which influence survival may suggest possible approaches for a more effective management in each case. In this report, clinical problems in the treatment of PCNSML was discussed with presenting cases experienced at Tenri hospital since 1983. There were twenty-one cases of histologically proven PCNSML. Surgical resection was undertaken in 11 patients. The remaining patients underwent biopsy only. All patients received radiation therapy. Various modality of chemotherapy was performed in 14 cases. Tumor recurrence was occurred at one or more CNS sites, including 3 patients who had meningeal relapse and one patient who also relapsed outside the CNS. The median survival time was estimated to be 15 months. Among the 9 patients alive at last contact the median length of follow up was 31.5 months(range 4 to 56 months). The following problems were presented and discussed; 1) varieties of initial clinical presentations, 2) variable recurrence patterns, metastases including CSF dissemination and extracranial metastases, 3) treatment-related leukoencephalopathy.

Adult↗

[A case of psoriatic arthropathy complicated with spinal fracture and epidural hematoma].

A 78-year-old man with psoriatic arthropathy complicated with traumatic spinal fracture and epidural hematoma is reported. He had fallen down the stairs. On admission one hour after injury, he developed an incomplete C6 quadriparesis. CT revealed a C6-7 fracture and dislocation on sagittal reconstruction. MR imaging disclosed the compression of the spinal cord between the posterior margin of the vertebral body and an epidural hematoma. The patient had had the skin lesion, psoriasis vulgaris, for about 20 years and been previously treated for uveitis. Serological tests for rheumatoid factor and HLA B-27 were negative. Emergent laminectomy and evacuation of the epidural hematoma were carried out because of progressive neurological deterioration. Osteoporotic laminar bone and ossified yellow ligament were observed to have been fractured. Conservative therapy was selected for spinal instability. Although a respiratory complication occurred postoperatively, he was transferred to the rehabilitation facility in an improved neurological condition.

Accidental Falls↗

[A case of intravascular malignant lymphomatosis presenting as cerebral infarction].

A case of intravascular malignant lymphomatosis (IML) presenting as progressive cerebral infarction is reported. A 62-year-old previously healthy male developed progressive dementia. MRI of the brain at the nearest hospital revealed multiple infarcts with unknown etiology. His level of consciousness deteriorated rapidly, and then he was transferred to our hospital for further evaluation. High grade fever, raised serum C reactive protein (CRP), and raised lymphoma markers (serum LDH and soluble IL-2 receptor (sIL-2R)) were observed. Repeated brain MRI disclosed progression of multifocal cerebral infarctions. We considered IML most likely, and we performed muscle biopsy. However muscle biopsy didn't demonstrate any proliferation of neoplastic cells of lymphoid origin within small vessels. Thereafter IML was diagnosed by brain biopsy. The patient underwent chemotherapy, but died of pneumonia due to severe myelosuppression. IML is a rare disease but most commonly shows neurological symptomatology as its clinical manifestation. Dementia is the most common neurological symptom, and progressive multiple infarction is the most common of the MRI findings. Rapidly progressive dementia associated with multiple infarction, when elevated CRP, LDH and sIL-2R are observed in the laboratory data, is suggestive of IML.

Biomarkers, Tumor↗

Synthesis of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with N-acetylneuraminic acid.

In order to develop glycosylated cytokine, recombinant human IL-1alpha was chemically modified with N-acetylneuraminic acid (NANA). NANA with C9 spacer, 8-(hydrazinocarbonyl)octyl 5-acetamido-3, 5-dideoxy-D-glycero-alpha-D-galacto-2-nonulo-pyranosidonic acid potassium salt (6), was synthesized by glycosylation of C9 spacer, 8-[2-N-(benzyloxycarbonyl)hydrazinocarbonyl]octanol, with methylthio glycoside derivatives of NANA in the presence of molecular sieves 3A and methyl (methylthio)sulfonium trifrate in propionitrile, followed by separation of a and beta anomers with a column chromatography and deprotection. Compound 6 was coupled to IL-1alpha by the acyl azide method. The glycosylated IL-1 was purified by anion-exchange chromatography, and NANA coupled to IL-1 was confirmed by oxidation with NaIO4. Based on the molecular weight average number of carbohydrate molecules introduced per molecule of IL-1alpha was estimated to be 2.9.

Chromatography, High Pressure Liquid↗

In vitro biological activities of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with N-acetylneuraminic acid.

In the previous study, N-acetylneuraminic acid (NANA) with C9 spacer was chemically coupled to human recombinant (rh) IL-1alpha in order to study the effect of glycosylation on its biological activities, and to develop IL-1 with less deleterious effects. In this study we examined a variety of IL-1 activities in vitro, including proliferative effect on T cells, antiproliferative effect on myeloid leukemic cells and melanoma cells, stimulatory effects on IL-6 synthesis by melanoma cells and PGE2 synthesis by fibroblast cells. NANA-introduced IL-1alpha (NANA-IL-1alpha) exhibited reduced activities about ten times compared with original IL-1alpha in all the activities performed in vitro. The competitive binding of 125I-IL-1alpha to mouse T cells and pre-B cells with unlabeled IL-1alphas suggests the decrease in binding affinities of NANA-IL-1alpha to both type I and type II IL-1 receptors. Therefore, reduced activities of NANA-IL-1alpha well correlated with the decrease in its receptor binding affinities.

Animals↗

[Evaluation of a rapid enzyme immunoassay for detection of influenza A virus among adult and elderly patients].

Directigen Flu A, an enzyme immunoassay membrane test for the detection of influenza A virus, was compared with serum hemagglutinine inhibition assay in adult and elderly patients. Throat specimens were collected by vigorous swabbing from febrile patients who were suspect for influenza by clinical symptoms and tested with Directigen Flu A. Serum samples were collected from the patients at onset of illness and two to eleven weeks later and tested for antibody titer to influenza A/H1N1, A/H3N2, and B. A total of 57 patients were involved in this study; 32 under 59 years of age and 25 over 60 years of age. Influenza was diagnosed in 42 patients by HI titer elevation (73.7%). Directigen Flu A was positive in 25 patients. Results of Directigen Flu A and HI test agreed in 40 patients. Sensitivity and specificity of Directigen Flu A were 59.5% (25/42) and 100% (15/15), respectively. There was no significant difference in sensitivity between the two age groups. These results indicate the potential usefulness of Directigen Flu A in the surveillance of influenza A infection in the geriatric population. Directigen Flu A gives results within 15 minutes without expensive equipment. Use of Directigen Flu permits the timely administration of antiviral therapy and infection control among hospitalized and institutionalized geriatric patients.

Adult↗