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Biomedical subjects

S Ohshima

Publications and source records attributed to S Ohshima.

At least 19 recordsLinked to original sources

Iatrogenic amyloid neuropathy in a Japanese patient after sequential liver transplantation.

A 57-year-old woman in Japan, the first recipient of part of a liver from a 58-year-old man with familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin Val30Met who had had sensorimotor polyneuropathy in the lower limbs for 3 years, started to develop sensory neuropathy 7 years after transplantation. Before the July 1998 sequential transplantation, she had been in a hepatic coma at the terminal stage of primary biliary cirrhosis and waiting for deceased donor liver transplantation. In September 2004, biopsy samples of her duodenum first showed amyloid deposition. Although biopsy materials in 2005 and 2006 showed no changes in amyloid deposition, decreased temperature sensation and pain in fingertips and toes were detected at a neurologic examination in March 2006. Thus, clinical symptoms of FAP appeared about 2 years after amyloid deposition started. Nerve conduction velocity studies revealed mild to moderate axonal sensory polyneuropathy without demyelination. Our findings confirmed iatrogenic sensory neuropathy induced by amyloid deposition 7 years after sequential liver transplantation.

Amyloid Neuropathies, Familial↗

Expression of granulysin in polymyositis and inclusion-body myositis.

BACKGROUND: Granulysin, a recently defined cytolytic molecule, is expressed in cytotoxic T cells and natural killer cells in a similar way to perforin, which is reported to have a major role in the pathogenesis of polymyositis and inclusion-body myositis (IBM). OBJECTIVE: To clarify the role of granulysin in polymyositis and IBM. METHODS: The expression of granulysin and perforin was examined by double staining with CD8, CD4 and CD56 in endomysial infiltrating cells and autoinvasive cells in muscle biopsy specimens of 17 patients with polymyositis (6 steroid resistant and 11 steroid responsive) and of 7 patients with IBM. RESULTS: Similar to perforin, granulysin was expressed in CD8, CD4 or CD56 cells in patients with polymyositis and IBM. The ratio of cells double positive for granulysin and CD8 to all CD8 cells at endomysial sites was notably higher in steroid-resistant polymyositis than in steroid-responsive polymyositis and IBM. CONCLUSION: Granulysin expression in CD8 cells seems to be correlated with steroid resistance in polymyositis.

Antigens, Differentiation, T-Lymphocyte↗

Tension- and afferent input-associated responses of neuromuscular system of rats to hindlimb unloading and/or tenotomy.

Responses of electromyogram (EMG) in soleus muscle and both afferent and efferent neurograms at the fifth lumbar (L(5)) segmental level of spinal cord were investigated during acute and chronic unloading induced by hindlimb suspension and/or tenotomy in adult rats. The soleus EMG and afferent neurogram decreased 88 and 37%, respectively, relative to those at quadrupedal posture on the floor after acute hindlimb suspension that causes passive shortening of soleus due to ankle plantarflexion. However, the afferent neurogram (P < 0.05) and soleus EMG (P > 0.05) recorded on the floor increased after tenotomy of synergists. Furthermore, the afferent input was inhibited when the soleus EMG disappeared after tenotomy of soleus. The afferent neurogram and EMG of the soleus showed correlated responses to a variety of treatments, suggesting that the afferent neurogram recorded at the L(5) segmental level reflects the neural input associated with the activity level of the soleus predominantly. The level of efferent neurogram decreased after acute hindlimb suspension but was not influenced significantly by tenotomy of synergists and/or soleus itself. The EMG and afferent neurograms remained low up to the 4th day but recovered to the preexperimental levels within 14 days, due to reorganization of sarcomere number and length, as well as the shortening of muscle fiber length and recovery of tension development. It is suggested that the levels of EMG and afferent neurogram associated with antigravity muscle are closely related to the tension development of the muscle.

Animals↗

A prospective trial of steroid withdrawal after renal transplantation in children: results obtained 1990 and 2002.

Ten-year graft survival rate was 89% after immunosuppressive therapy with cyclosporine, methylprednisolone, and mizoribine in pediatric renal transplant recipients enrolled in our multicenter study. Adrenocorticosteroids, which cause growth retardation, were reduced by administration on alternate days in 67% and withdrawn in 23% of recipients. Acute rejection episodes occurred in 30% of patients after withdrawal of steroids. Graft function returned to prerejection levels after treatment with high-dose methylprednisolone. Catch-up growth occurred after alternate day administration and steroid withdrawal. Twenty-eight of 94 patients reached the final height of 156 cm in boys and 145 cm in girls, because of the gradually reduced growth rate. Management of growth retardation before transplantation, especially in patients with congenital renal diseases, and early reduction of the steroid dose after transplantation will increase the final height of children with chronic renal failure.

Adolescent↗

Identification and prevalence of an enterotoxin-related gene, se-int, in Staphylococcus intermedius isolates from dogs and pigeons.

AIMS: To determine the prevalence of enterotoxin-producing Staphylococcus intermedius in dogs and pigeons. METHODS AND RESULTS: A total of 106 S. intermedius isolates from 44 dogs and 62 pigeons were tested for the production of enterotoxins A, B, C and D by reverse passive latex agglutination (RPLA) and for sec-canine by PCR. Only one isolate from dog was positive for SEC and sec-canine. Screening of sec-canine-negative strains by nested PCR led to the identification of a novel enterotoxin-related gene, se-int. SE-int showed a significant homology (59-61% identity) with SEC and (56.6% identity) SEB. All 44 isolates from dogs and five isolates (8.1%) from pigeons were se-int positive. CONCLUSIONS: While S. intermedius was isolated more frequently from pigeons than from dogs, se-int was more prevalent among the S. intermedius isolates from dogs, compared with the pigeon isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: Further characterization of the se-int-positive S. intermedius strains should clarify their pathogenic potential including enterotoxigenicity and zoonotic transmissibility to human beings.

Amino Acid Sequence↗

Long time follow up of CD28- CD4+ T cells in living kidney transplant patients.

We previously reported that the CD28(-) CD4(+) T cell subpopulation was expanded in the kidney allograft patients with long graft survival, although these T cells were rarely found in patients with graft survival <5 yr. To understand the CD28(-) CD4(+) T cells in the long-term acceptance of kidney allografts, we examined functions of this population and performed a 4 yr follow up study. Peripheral blood mononuclear cells (PBMC) were obtained from 47 long-term living related kidney allograft recipients. CD28(+) CD4(+) and CD28(-) CD4(+) T cells purified by cell sorting were analyzed for expression of V(beta) repertoire. Donor-specific response was examined in mixed lymphocyte reaction (MLR). A follow up study with long-term kidney allograft patients was performed for 4 yr about the rate of CD28(-) CD4(+) T cells. Eleven patients were examined by MLRs against donors and third party. Four patients with a marked increase of CD28(-) CD4(+) T cells showed the donor-specific responses appeared to be lower when compared with third party-specific responses. Freshly sorted CD28(-) CD4(+) T cells showed a restricted V(beta) repertoire, whereas the V(beta) usage of CD28(+) CD4(+) T cells from the same patients was much diversified. Such difference in V(beta) repertoire was not evident between the two populations from healthy control. A follow up study showed the ratio of CD28(-) CD4(+) T cells appeared to be lower in patients who were suspected of chronic rejection. These unusual CD4(+) T cells might be related to the long-term acceptance of human transplant allografts.

Adult↗

Laparoscopic radical nephrectomy for renal cell carcinoma.

PURPOSE: To estimate the efficacy of the laparoscopic radical nephrectomy we analyzed the clinical data of our series. PATIENTS AND METHODS: One hundred eighty five patients were enrolled in our laparoscopic radical nephrectomy program between July, 1992 and July, 2001. Of the 185 patients, 146 had small renal tumors (smaller than 5 cm in diameter) and 39 had large tumors (equal to or more than, 5 cm in diameter). Under a laparoscope the kidney, adrenal gland, and perirenal fatty tissue were dissected in an en bloc fashion. In case of taking out a small tumor, the specimen was fractionated within the sack to avoid an additional skin incision after entrapping in the laparoscopy sack in the working space. In case of a large tumor, regional lymph nodes dissection was done and the specimen was taken out intact in the sack through an enlarged incision. RESULTS: Our laparoscopic procedure was successful in 171 of the 185 cases; 14 patients required open surgery because of bleeding from an injured vessels or treatment for other injured organs. The mean operative time was 4.7 hours for both small and large tumors. Estimated blood loss was between 237 and 380 ml on average for small and large tumors, respectively. Full convalescence was achieved around 3 weeks after operation in both groups. Only one patient who had large tumor was found to have micrometastasis in 1 of 5 regional lymph nodes. Recurrences were observed in 4 cases of the small tumor group and in 2 cases of the large tumor group during 1 to 108 months of follow-up. CONCLUSION: Laparoscopic radical nephrectomy is a very useful and safe surgical procedure for renal cell carcinoma.

Carcinoma, Renal Cell↗

Multivariate evaluation of factors affecting recurrence, progression, and survival in patients with superficial bladder cancer treated with intravesical bacillus Calmette-Guérin (Tokyo 172 strain) therapy: significance of concomitant carcinoma in situ.

To evaluate the relative importance of clinicopathological factors affecting recurrence, progression, and survival in patients with superficial bladder cancer (pTa and pT1) undergoing bacillus Calmette-Guerin (BCG) therapy (Tokyo 172 strain), we reviewed data for 146 patients treated between 1985 and 1998. The median follow-up period was 64.7 months. Tumour recurrence, progression, and death were evaluated as endpoints using Cox's proportional hazards model. The 5-year recurrence-free rate was 56% for all 146 patients. Those with a past history of bladder cancer (n = 73) had significantly earlier recurrence than those without (n = 73, p = 0.017) and this tended to be the case for concomitant CIS (n = 34) although this did not reach statistical significance. The 5-year progression rate was 15% for all 146 patients and univariate analysis revealed that the presence of concomitant CIS was significantly associated with disease progression (p = 0.002). Multivariate analysis using the proportional hazards model confirmed the finding that only one factor, concomitant CIS, was significantly associated with progression. The 5-year survival rate was 84% for all 146 patients. Furthermore, univariate and multivariate analyses revealed that patient age, history of bladder cancer, and concomitant CIS were variables significantly related to patient survival. The present findings suggest that careful follow-up is mandatory after BCG instillation therapy for patients with superficial bladder cancer and concomitant CIS because of their relatively poor prognosis.

Adjuvants, Immunologic↗

Evaluation of multiple recurrence events in superficial bladder cancer patients treated with intravesical bacillus Calmette-Guérin therapy using the Andersen-Gill's model.

To evaluate factors affecting recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy (Tokyo 172 strain), we reviewed data for 101 patients with superficial bladder cancer (pTa [n = 80] and pT1 [n = 21]) treated between 1985 and 1999. The median follow-up period was 58.9 months. Factors affecting the first tumour recurrence were evaluated using Cox's proportional hazards model and those affecting multiple recurrence with Andersen-Gill's model. The 5-year recurrence-free rate was 63% for all 101 patients. The recurrence frequency, defined as times per 100 patient-months of follow-up, greatly decreased from 7.3 +/- 9.6 (SD) before the instillation to 2.6 +/- 5.6 after the therapy (p < 0.0001). Patients with pT1 tumours tended to have earlier recurrence than those with pTa tumours (p = 0.06). Multivariate analysis using Cox's proportional hazards model revealed that a history of bladder cancer and pathological stage were independent factors affecting the first tumour recurrence after the BCG therapy. When multiple endpoints of recurrence were evaluated using the Andersen-Gill's model, number of tumours as well as a history of bladder cancer and pathological stage demonstrated significant links to tumour recurrence after the BCG therapy. The 5-year progression-free and 5-year survival rates were 89.3% and 85.3% for all the 101 patients, respectively. Because intravesical recurrence may involve multiple events during the clinical course of patients with bladder cancer, the Andersen-Gill's model appears useful for evaluation of risk factors.

Adjuvants, Immunologic↗

Discrete roles of cytokines, TNF-alpha, IL-1, IL-6 in tumor promotion and cell transformation.

Based on our previous results, which pointed to tumor necrosis factor-alpha (TNF-alpha) as the essential cytokine in tumor promotion in mouse skin, we present here three principal findings related to the specific roles of TNF-alpha, interleukin-1 (IL-1) and IL-6 in tumor promotion (using TNF-alpha- and IL-6-deficient mice) and in BALB/3T3 cell transformation: i) The previously reported residual tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in TNF-/- mice was confirmed by experiments with TNF+/+ and TNF-/- 129/Svj mice of the same strain, using two-stage carcinogenesis experiments. TPA produced tumors in 100% of TNF+/+ and 78% of TNF-/- mice at 20 weeks, and the average number of tumors per mouse was 11.1 in the former group and 2.1 in the latter. Judging from the expression of various inflammatory cytokine genes in TNF+/+ and TNF-/- mice, the residual tumor promoting activity of TPA in TNF-/- mice may be dependent on expression of IL-1alpha and IL-1beta genes. ii) Tumor promotion by TPA and okadaic acid in IL-6+/+ and IL-6-/- C57/BL6 mice was studied, with TPA producing tumors in 57.1% of IL-6+/+ and 40.0% of IL-6-/- mice at 20 weeks, and okadaic acid in 40.0% of IL-6+/+ and 53.3% of IL-6-/- mice. Thus, there was no significant difference between TPA or okadaic acid tumor promotion in either group. In addition, expression of IL-6 gene in skin of both types of mice suggested that IL-6 is not the essential cytokine in tumor promotion, since it can be replaced by other cytokines. iii) In transformed clones of BALB/3T3 cells induced by TNF-alpha alone, IL-1alpha gene expression was induced after transformation by TNF-alpha had occurred, which did not occur in parental cells. Expression patterns of TNF-alpha, IL-1beta, IL-6 and IL-10, along with TGF-beta, were similar in both parental and transformed cells. Considering all these results, we conclude that various cytokines have discrete roles in tumor promotion and cell transformation.

9,10-Dimethyl-1,2-benzanthracene↗

Use of marginal organs from non-heart-beating cadaveric kidney donors.

BACKGROUND: The severe shortage of cadaver donor kidneys for transplantation has prompted many centers to utilize older donor kidneys, which have been associated with lower graft survival rates. The aim of the present study was to examine the availability and feasibility of considering kidneys from donors over the age of 60. METHOD: We studied 252 cadaveric renal transplant recipients (156 males, 96 females) who received kidneys from uncontrolled non-heart-beating donors between 1987 and 1997. We performed in situ cooling with especially designed double-balloon catheters to minimize warm ischemic kidney damage. Recipients were classified according to donor age ( age 60), and we examined graft survival rates. All patients were followed for a minimum of 1 year after transplantation. RESULTS: Graft survival rates for recipients of kidneys from the older donor group at 1, 5, and 10 years after transplantation were 77%, 37%, and 30%, respectively. Corresponding values for the younger donor kidney recipients were 87%, 64%, and 47%, respectively (P=0.0011). Improved survival rates were noted when older kidneys were used for lighter weight recipients (<54 kg). No other significant factors impacted on older donor graft survival rates. CONCLUSION: Older donor kidneys are associated with poorer graft survival rates. However, kidney transplants from older donors can be quite effective in lighter weight recipients (<54 kg).

Adult↗

Induction of aneuploidy by nickel sulfate in V79 Chinese hamster cells.

The ability of nickel sulfate (NiSO(4)) to induce chromosome aneuploidy was investigated in vitro using the V79 Chinese hamster cell line. V79 cells were treated with 100-400 microM NiSO(4) for 24h, and monitored up to 72 h following treatment with a chromosome aberration assay, a micronuclei assay using antikinetochore antibodies (CREST assay) and an anaphase/telophase assay. Aneuploid cells were induced in a significant fraction of the cell population 24-48 h following treatment with nickel sulfate. The majority of these cells were hyperdiploid. In addition, nickel sulfate caused increased frequency of cells with kinetochore-positive micronuclei as well as kinetochore-negative micronuclei. Abnormal chromosome segregation such as lagging chromosomes, chromosome bridges and asymmetric segregation were also observed in more than 50% of anaphase or telophase cells following treatment with NiSO(4). The incidences of these abnormalities were dose-dependent in general, although the effects were prominent in a sublethal dose. These results indicate that NiSO(4) has the ability to induce aneuploidy in V79 cells. In addition, the results in anaphase/telophase assay suggest that the compound may have an effect on spindle apparatus, which could result in aneuploidy following abnormal chromosome segregation.

Anaphase↗

Enhancement of T helper2 response in the absence of interleukin (IL-)6; an inhibition of IL-4-mediated T helper2 cell differentiation by IL-6.

Functional roles of interleukin (IL-)6 in T cell response were investigated. Mice deficient in IL-6 and wild mice were immunized with antigens (myelin oligodendrocyte glycoprotein or methylated BSA) and production of IL-4 and interferon (IFN)-gamma by regional lymph nodes was measured. IL-6 deficiency led to an enhancement of IL-4 and an inhibition of IFN-gamma production. Moreover, polyclonal stimulation of spleen T cells from unimmunized IL-6-deficient mice with anti-CD3 plus anti-CD28 antibodies (Abs) demonstrated an enhancement of T helper (Th)(2)responses. The presence of IL-6, however, augmented IL-4 production but it inhibited IFN-gamma expression by spleen T cells in response to polyclonal stimulation and by antigen-primed spleen T cells in response to re-challenge with the antigen. In contrast, the induction of spleen CD4-positive T cells into Th(2)cells in vitro by the anti-CD3 plus IL-4 was completely suppressed by exogenously added IL-6, whereas Th(1)differentiation of T cells by the anti-CD3 plus IL-12 was not inhibited by the presence of IL-6. Thus, these results indicate that IL-6 physiologically could modulate qualitative T cell response and suggest that it augments Th(1)responses partly through its inhibitory capability of IL-4-induced Th(2)differentiation of naive T cells.

Adjuvants, Immunologic↗

Remission of the renal involvement in a patient with primary Sjögren's syndrome (SS) after pulse high-dose corticosteroid infusion therapy.

We report the case of a young female patient with primary Sjögren's syndrome (SS). In addition to sicca symptoms she also suffered from progressive renal insufficiency and renal tubular acidosis (RTA). She was treated with three sets of pulse high-dose corticosteroid infusion and subsequent low-dose corticosteroid oral administration. When the efficacy was evaluated about 6 months after the start of the therapy, dramatic improvements were seen with no adverse effects, not only in laboratory tests but also histopathologically, as indicated by the repeat kidney biopsy. This suggests that renal involvements of SS might be reversible in some cases, and that there might be a clinical benefit of pulse high-dose corticosteroid infusion therapy in SS with progressive renal involvement.

Acidosis, Renal Tubular↗

Characterization of CD28(-)CD4(+) T cells in living kidney transplant patients with long-term allograft acceptance.

CD28(-)CD4(+) T-cell subpopulation is expanded in kidney allograft patients with long graft survival. To seek for the roles of CD28(-)CD4(+) T cells in the long-term acceptance of kidney allografts, we characterized this population by analyzing cell surface molecules, TCR V(beta) repertoire, mixed lymphocyte reaction (MLR), and cytokine production. The number of CD28(-)CD4(+) T cells increased correlatively with time after transplantation in this group of patients. The CD28(-)CD4(+) T cells did not express detectable levels of CD25, CD69, V(alpha)24, or CTLA-4 but expressed heterogeneous amounts of CD45 RA on the surface. Freshly sorted CD28(-)CD4(+) T cells revealed a restricted V(beta) repertoire, whereas the V(beta) usage of CD28(+)CD4(+) T cells from the same patients was much diversified. Expression levels of TGF-beta and IFNgamma gene were significantly higher in the CD28(-) CD4(+) T cells than in the CD28(+)CD4(+) T cells from the kidney allograft patients. These findings suggest that an oligoclonal CD28(-) CD4(+) T-cell population is continuously activated in patients with long allograft survival, which may be linked with the long-term acceptance.

Adult↗

Clinical significance of TT virus in chronic hepatitis C.

BACKGROUND AND AIMS: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A-G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV). METHODS: The 95 subjects studied had chronic hepatitis C (CHC), and underwent interferon (IFN) therapy. TT Virus DNA was detected by using polymerase chain reaction. The nucleotide sequences were determined by using a dideoxy chain termination method. A phylogenetic tree was drawn up by using the neighbor-joining method. RESULTS: TT Virus DNA was detected in 37.9% of patients with the use of an open reading frame 1 (ORF1) primer, and in 88.4% of patients by using a 5' untranslated region (5' UTR) primer. Using both sets of primers, no differences were found between TTV-DNA-positive and -negative subjects with CHC in the clinical findings. Serum TTV DNA was eradicated in 30.6% of patients with the ORF1 primer, and in 19.1% of patients with the 5' UTR primer at 6 months after the cessation of IFN therapy. The levels of TTV DNA before IFN therapy were significantly lower in the viral eradication group than in non-eradication group. The changes in alanine aminotransferase (ALT) concentrations were significantly correlated with changes in HCV-RNA in CHC patients with TTV. Moreover, there was no correlation between the changes in TTV DNA and the course of ALT. CONCLUSION: Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and TTV appears to primarily be caused by HCV and is less attributable to TTV.

Adult↗