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Biomedical subjects

T Onishi

Publications and source records attributed to T Onishi.

At least 19 recordsLinked to original sources

Autoimmune hepatitis following allogeneic PBSCT from an HLA-matched sibling.

A 7-year-old boy with acute lymphoblastic leukemia (ALL) in second remission received an allogeneic PBSCT from his HLA-matched sister. Acute grade II graft-versus-host disease (GVHD) resolved with corticosteroids. Chronic GVHD in the skin and oral mucosa at around day 60 responded to corticosteroids and cyclosporin A. At 6 months after the transplant, he developed hepatic dysfunction with elevated serum transaminases and gamma-globulin. Liver biopsy revealed chronic inflammation with lymphocytes and plasma cells in portal areas without destruction of bile ducts, suggesting autoimmune hepatitis. While rare, autoimmune hepatitis should be considered a potential long-term complication in patients with hepatic dysfunction in the late post-transplant phase.

Biopsy↗

Ixodid tick species recovered from domestic dogs in Japan.

The species of ixodid ticks (Acari: Ixodidae) recovered from domestic dogs in Japan between September to November 2000 and April to June 2001 were identified. A total of 4122 ticks, including 1624 larvae, 1200 nymphs, 1016 females and 282 males were removed from 1221 dogs during these periods. Haemaphysalis longicornis (Neumann) was the most frequently found (40.3% of dogs), followed by H. flava (Neumann) (16.1% of dogs), Rhipicephalus sanguineus (Latreille) (4.8% of dogs) and Ixodes ovatus (Neumann) (4.1% of dogs). Small numbers of H. hystricis (Supino), H. campanulata (Warburton), H. japonica (Warburton), H. ias (Nakamura and Yajima), I. persulcatus (Schulze), I. nipponensis (Kitaoka and Saito) and Amblyomma testudinarium (Koch) were also recovered. In the spring sample, a total of 1408 ticks (78 larvae, 411 nymphs, 792 adult females and 127 adult males) were recovered from 570 dogs. The autumn sample included a larger proportion of larval stage and fewer adult ticks (1546 larvae, 789 nymphs, 224 adult females and 155 adult males). Haemaphysalis longicornis, H. flava and I. ovatus showed a wide geographical distribution from northern to southern Japan, whereas R. sanguineus were mainly distributed in the subtropical Okinawa prefecture with a few exceptions. Dogs in rural areas more frequently carried H. longicornis, H. flava and I. ovatus than dogs in urban or suburban areas, whereas R. sanguineus was more associated with the dogs in urban/suburban areas. Exposure to a garden was significantly associated with R. sanguineus and exposure to woodland was significantly associated with H. flava and I. ovatus. This is the first systematic survey of canine ticks in Japan.

Animals↗

Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency.

Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO (-/-) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26.7+/-1.9 g vs 26.1+/-0.8 g and 28.8+/-1.4 g vs 26.9+/-1.0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P<0.05). The ArKO males showed significantly higher blood glucose levels during an intraperitoneal glucose tolerance test compared with wild-type littermates beginning at 18 weeks of age. By 24 weeks of age, they had higher fasting blood glucose levels compared with wild-type littermates (133.8+/-22.8 mg/dl vs 87.8+/-20.3 mg/dl respectively; P<0.01). An intraperitoneal injection of insulin (0.75 mU insulin/g) caused a continuous decline in blood glucose levels in wild-type mice whereas ArKO males at 18 weeks and older exhibited a rebound increase in glucose levels 30 min after insulin injection. Thus, ArKO male mice appear to develop glucose intolerance and insulin resistance in an age-dependent manner. There was no difference in fasting serum triglyceride and total cholesterol levels between ArKO male mice and wild-type littermates at 13 and 25 weeks of age. However, serum triglyceride and cholesterol levels were significantly elevated following a meal in ArKO mice at 36 weeks of age. Serum testosterone levels in ArKO male mice were continuously higher compared with wild-type littermates. Treatment of ArKO males with 17beta-estradiol improved the glucose response as measured by intraperitoneal glucose and insulin tolerance tests. Treatment with fibrates and thiazolidinediones also led to an improvement in insulin resistance and reduced androgen levels. As complete aromatase deficiency in man is associated with insulin resistance, obesity and hyperlipidemia, the ArKO mouse may be a useful animal model for examining the role of estrogens in the control of glucose and lipid homeostasis.

Aging↗

Molecular cloning and sequencing of feline melanoma antigen 2 (fMAGE-2) obtained from a lymphoma cell line.

Melanoma antigens (MAGE), thought to induce tumor-specific immune responses, are used as potential therapeutical targets for cancer immunotherapy. We hereby report the cloning and sequencing of MAGE cDNA clone, called feline MAGE-2 (fMAGE-2), obtained from a lymphoma cell line. fMAGE-2 cDNA is 1535 base pairs (bp) in length and contains an open reading frame (ORF) of 1131 bp encoding a protein of 376 amino acids. The predicted amino acid sequence shows 45%, 32-42%, 44-47%, and 33% homology with feline MAGE-1, human MAGE-A, human MAGE-B, and human MAGE-C proteins, respectively. mRNA transcripts of fMAGE-2 were detected by RT-PCR in some feline tumors, as well as in testis of adult cat, but not in other normal tissues, indicating that the expression pattern of fMAGE-2 is similar to that of the human MAGE family genes in tumors and normal tissues.

Amino Acid Sequence↗

Identification of feline MAGE-1 gene product by monoclonal antibodies.

Melanoma antigens (MAGE) are thought to induce a tumor-specific immune response and to be potential therapeutical targets for cancer immunotherapy. We have earlier identified the cDNA of feline melanoma antigen 1 (fMAGE-1), but its product was not characterized in detail. We have expressed the recombinant fMAGE-1 protein and have generated monoclonal antibodies (mAbs) against it, to identify the native fMAGE-1 protein in feline lymphoma cell lines and tumor tissues. The fMAGE-1 protein was found to be approximately 39 kDa in molecular mass on sodium dodecyl-sulphate-polycrylamide gel electrophoresis (SDS-PAGE), and it was found to be located in the cytoplasm of the cells by immunofluorescence. Immunoblotting analysis detected the fMAGE-1 gene product in the fMAGE-1-mRNA-positive cells, but not in the fMAGE-1-mRNA-negative cells. An interesting finding of the present study was the distribution of the fMAGE-1 protein, which was found to have a spindle-like distribution, with filaments twining around the nucleus, suggesting that the fMAGE-1 protein may be associated with or form some cytoplasmic filaments. This type of finding is so far the first report of its kind, and to the best of our knowledge it has not been reported in either human or mouse MAGE proteins until now. It most probably implies the major diversity of the MAGE family genes.

Animals↗

Gender as a prognostic factor in patients with renal cell carcinoma.

OBJECTIVE: To evaluate gender as a prognostic factor in patients with renal cell carcinoma (RCC), using a retrospective review of patients with RCC stratified according to gender and analysing factors affecting prognosis. PATIENTS AND METHODS: From January 1957 to December 1995, 768 patients with pathologically defined RCC (all of whom underwent nephrectomy) were classified as having clear cell carcinoma in 662 (follow-up in 648), papillary RCC in 43 (follow-up in 42), chromophobe cell carcinoma in 36 (follow-up in 34) and cyst-associated RCC in 27 (all followed up) according to the criteria proposed by the World Health Organization. The survival rates were compared between men and women, calculated and stratified according to the subtype of RCC. RESULTS: There tended to be a more favourable prognosis in women than in men but the difference was not quite significant (P=0.061). Of those with clear cell carcinoma, women had a more favourable prognosis than men and the difference in survival was significant (P=0.012). No other subtype of RCC was associated with a significant difference in survival between the sexes. There was a smaller proportion of patients with stage IV and a larger proportion with stage I disease in women than in men (P<0.05). Of stage I patients, women had a more favourable prognosis than men (P<0.011). Women had better survival after recurrence than had men, the difference being significant (P=0.007). CONCLUSION: The prognosis is significantly better in women than men with clear cell carcinoma. The factors that contribute to a favourable prognosis in women are the greater proportion of lower stage disease and better survival after recurrence.

Adult↗

Prognostic implications of histological features in patients with chromophobe cell renal carcinoma.

OBJECTIVE: To assess the relationship between the histological features of renal chromophobe cell carcinoma (CCC) and clinical outcome in patients with renal cell carcinoma. PATIENTS AND METHODS: From 1957 to 1996, 41 patients with CCC of the kidney (4.9% of all kidney carcinomas) were treated at our university hospitals. Of these histologically defined cases, four who died from other types of cancer and two who were lost to follow-up were excluded, leaving 35 patients in the study; the carcinoma was classified as the typical variant in 26 and the eosinophilic variant in nine. Based on the differences of the variants, the histological features affecting prognosis were analysed. RESULTS: The overall survival rates at 1, 3, 5, 10, 15 and 20 years were 97%, 82%, 82%, 70%, 62% and 47%, respectively. The prognosis was more favourable in those with the eosinophilic than for the typical variant (there were no cancer-related deaths in the former). Of those with the typical variant, five died within 2 years of surgery; of these, three with high-stage disease had various degrees of sarcomatoid change. Conversely, two patients had a recurrence > 10 years after surgery (late recurrence). Both these patients and the others who later died from cancer had no sarcomatoid change in the tumour areas examined. CONCLUSION: The eosinophilic variant of CCC has a better prognosis; on the contrary, during long-term surveillance, early recurrence was detected especially in those with sarcomatoid change and late recurrence only in two typical variant. These prognostic implications of the histological differences are important for understanding the outcome of renal CCC.

Adult↗

Visual results and complications of temporal incision phacoemulsification performed with the non-dominant left hand by junior ophthalmologists.

AIMS: To assess the results of temporal incision phacoemulsification and aspiration performed with dominant and non-dominant hand of ophthalmology trainees. METHODS: Retrospective analysis were made of 203 surgeries with dominant hand and 207 with non-dominant by five trainees at two institutions. Trainees sat at the patient's head, manipulating instruments with the dominant right hand for the right eye, and the non-dominant left hand for the left eye. RESULTS: Vitreous loss occurred in 12 (5.9%) of 203 dominant operated eyes and seven (3.4%) of 207 non-dominant operated eyes. The rate of endothelial cell loss was 6.1% (9.8%) in dominant and 7.4% (12.4%) in non-dominant. Mean ultrasound time were 1.81 (0.70) minutes in dominant and 1.78 (0.78) minutes in non-dominant. One trainee showed statistically significant excesses in incidence of vitreous loss in dominant operated eyes (8.7%, p=0.0270), and one showed statistically significant prolongation of the operation in nondominant operated eyes (26.3 minutes, p=0.0315). In all other trainees, all parameters had no difference in both sides. CONCLUSIONS: Ophthalmology trainees could successfully learn the technique with both hands. The authors consider that the skill of the non-dominant hand may be knowledge based and that surgeons avoid mistakes by mental efforts.

Adolescent↗

Tunneling mechanism due to chaos in a complex phase space.

We have revealed that the barrier-tunneling process in nonintegrable systems is strongly linked to chaos in complex phase space by investigating a simple scattering map model. The semiclassical wave function reproduces complicated features of tunneling perfectly and it enables us to solve all the reasons why those features appear in spite of absence of chaos on the real plane. Multigeneration structure of manifolds, which is the manifestation of complex-domain homoclinic entanglement created by complexified classical dynamics, allows a symbolic coding and it is used as a guiding principle to extract dominant complex trajectories from all the semiclassical candidates.

Journal Article↗

Mitogen-activated protein kinase pathway is involved in alpha6 integrin gene expression in androgen-independent prostate cancer cells: role of proximal Sp1 consensus sequence.

Metastatic diseases of prostate cancer reveal high expression of alpha6 integrin and the activation of mitogen-activated protein kinases (MAP kinase). Therefore, the present study was conducted to examine whether MAP kinase pathway is involved in the alpha6 integrin gene expression in androgen-independent prostate cancer cell lines. alpha6 integrin mRNA expression, the alpha6 integrin promoter-induced luciferase activities and MAP kinase enzyme activities in androgen-independent LNCaP and PC-3 cell lines were higher than those in androgen-dependent LNCaP. Deletion and mutation analysis showed that Sp1 consensus sequence at -48 to -43 bp from the transcription start site was necessary for basal promoter activity. Binding of Sp1 to its consensus sequence in three cell lines was confirmed by electrophoretic mobility shift assays. Sp1 binding to its consensus sequence, as well as promoter activity and mRNA expression, were found to be inhibited by an inhibitor of MAP kinase kinase 1 and 2, U0126, in the androgen-independent cell lines. Our results indicate that the proximal Sp1 is necessary for basal promoter activity of the alpha6 integrin, suggesting that signal transduction from MAP kinases to activation of Sp1 might be involved in alpha6 integrin gene expression in androgen-independent prostate cancer cell lines.

Consensus Sequence↗

Molecular cloning and sequencing of canine T-cell costimulatory molecule (CD28).

T-cells express CD28 and CTLA-4, and through binding to their shared ligands (CD80/CD86) on antigen presenting cells, provide a potent co-stimulatory signal for T-cell activation and proliferation. To investigate the role of CD28 in canine immune system, we hereby report the molecular cloning and sequencing of the full-length complementary DNA (cDNA) coding for canine CD28, from pokeweed mitogen stimulated canine peripheral blood lymphocytes. The cloned cDNA contains an open reading frame of 663 nucleotides, encoding for a polypeptide of 221 amino acids. The amino acid sequence of the canine CD28 showed 91.9, 80, and 79.6% similarities with those of the cat, cattle, and human counterparts, respectively. Five sequence motifs of TATT or ATTTA involved in the regulation of gene expression by influencing mRNA stability are found in the 3' untranslated region. The hexapeptide motif (MYPPPY), five cysteine residues, a potential N-glycosylation site and a cytoplasmic phosphatidylinositol 3-kinase binding site in canine CD28 molecule are completely conserved in canine CTLA-4. The availability of full length canine CD28 will provide a useful molecule for studying its role in dog immune system.

Abatacept↗

Significance of occipitoaxial angle in subaxial lesion after occipitocervical fusion.

STUDY DESIGN: The significance of occipitoaxial angle in the development of subaxial subluxation after occipitocervical fusion was determined in a minimum 5-year follow-up study performed retrospectively. OBJECTIVE: To clarify the association between the position of the fixed occipital bone and axis and the development of subaxial subluxation. SUMMARY OF BACKGROUND DATA: There have been few reports describing the association between the position of fixation of the occipital bone and axis and subaxial lesion in occipitocervical fusion. MATERIALS AND METHODS: Thirty-eight patients with rheumatoid arthritis who underwent occipitocervical fusion for irreducible atlantoaxial dislocation were reviewed. The angle between the McGregor line and the inferior surface of the axis (O-C2) was measured in healthy volunteers and patients who had undergone occipitocervical fusion. The association between any changes in the alignment of the cervical vertebrae and the development of subaxial subluxation during follow-up periods was studied. RESULTS: The number of the patients in whom postoperative kyphosis and swan neck deformity developed was only five, but in four (80%) of them, retroversion of the occipital bone was used to increase the O-C2 angle. In 14 patients, in whom anteversion of the occipital bone against the axis was excessive, 12 (86%) patients experienced subaxial subluxation after surgery. In the patients in whom fixed O-C2 angles were in normal range, only one patient developed such abnormal changes in the middle and lower cervical vertebrae. CONCLUSION: It is necessary to give attention to the position of the fixed occipital bone and axis during procedures of occipitoaxial fusion for patients with rheumatoid arthritis.

Adult↗

Molecular cloning and expression analysis of feline melanoma antigen (MAGE) obtained from a lymphoma cell line.

Melanoma antigens (MAGE) are regarded as inducing tumor-specific immune response and thought to be potential therapeutical agents for cancer immunotherapy. We hereby report the cloning of feline MAGE cDNA obtained from a lymphoma cell line derived from cat malignant lymphoma, and its expression pattern in tumor and normal tissues. The cDNA encoding the MAGE is 1668 base pairs (bp) in length, and contains an open reading frame (ORF) of 936 bp encoding a protein of 311 amino acids. The predicted amino acid sequence has 29-46% of homology with other MAGE proteins from human and mouse. mRNA transcripts for the feline MAGE were detected in certain tumors, but not in adult cat normal tissues except in testis, by reverse transcription polymerase chain reaction (RT-PCR) analysis. This indicates that the expression pattern of feline MAGE mRNA is similar to those of other MAGE family genes in tumors and normal tissues.

Amino Acid Sequence↗

Biliary excretion of temocapril in zone 1- and zone 3-injured rat.

Temocapril is a prodrug of an angiotensin-converting enzyme inhibitor, temocaprilat, a substrate of multidrug resistance protein 2. Hepatocytes in zone 1 play a role in the uptake and biliary excretion of bile acids under physiological condition, and those in zone 3 may play a role only with their high-dose load. To investigate the pharmacokinetics of temocapril in liver injury, biliary excretion of temocapril was studied in zone 1- and zone 3-injured rats, caused by allyl alcohol and bromobenzene, respectively. Biliary excretion of a tracer dose of radiolabeled temocapril was delayed both in zone 1 and the zone 3 injury, but the extent of inhibition was more prominent in zone 3 injury. Since biliary excretion of organic anions was decreased only in zone 1 injury in our previous study, the present findings indicate that decreased biliary excretion of temocaprilat in zone 3 injury is caused by the inhibition of the metabolism from temocapril to temocaprilat.

Journal Article↗

Intense immunosuppression followed by purified blood CD34+ cell autografting in a patient with refractory juvenile rheumatoid arthritis.

A 15-year-old boy with refractory juvenile rheumatoid arthritis (JRA) underwent intense immunosuppressive therapy followed by purified blood CD34+ cell autografting. He had been taking prednisolone (PDN) daily or every other day combined with methotrexate once a week to control the disease for 7 years. He suffered from psychological complications and a very short stature due to the adverse effects of these drugs. CD34+ cells were purified in bulk from G-CSF-mobilized PBSC using an Isolex 300. After the administration of cyclophosphamide (200 mg/kg) and anti-lymphocyte globulin (45 mg/kg), 3.6 x 10(6)/kg purified CD34+ cells were infused. His post-transplant course was uneventful except for herpes-zoster infection. He is now more than 1 year post transplant and has not taken any immunosuppressive medication. His rate of growth has increased (>10 cm/year) due to the effects of the cessation of PDN and the administration of recombinant human growth hormone (rGH), in contrast to the gain of 2 cm in the preceding 3 years with rGH treatment. Although the durability of this remission is unknown, intense immunosuppressive therapy followed by purified blood CD34+ cell autografting might be acceptable for adolescent patients with refractory JRA to achieve a drug-free period for physical and psychological maturation.

Adolescent↗

Cyst-associated renal cell carcinoma: clinicopathologic characteristics and evaluation of prognosis in 27 cases.

BACKGROUND: No consistent clinicopathologic characteristics of cyst-associated renal cell carcinoma (CRCC) have previously been determined. METHODS: In total, 768 patients with renal cell carcinoma (RCC) underwent radical or partial nephrectomy. Renal cell carcinoma was classified as CRCC in 27 of these patients (3.5%, subdivided into RCC originating in a cyst and cystic RCC), clear-cell RCC in 662 patients (86.2%), chromophobe cell renal carcinoma in 36 patients (4.7%) and papillary RCC in 43 patients (5.6%) according to the criteria of the World Health Organization. RESULTS: The pathologic stage and nuclear grade were usually lower in those with CRCC (low stage/low grade; 89%/96%) or chromophobe cell renal carcinoma (low stage/low grade; 89%/80%) than in those with clear-cell RCC (low stage/low grade; 59%/65%) or papillary RCC (low stage/low grade; 53%/69%). Of the 27 CRCC patients, only 19 (70%) could be diagnosed through preoperative imaging studies. Patients with CRCC showed a favorable prognosis (survival rate: 95% at 1 year, 89.7% at 3 years and 84.4% thereafter) and, especially among the patients with RCC originating in a cyst, no cancer-related death was observed. Comparing the survival among four types of RCC, a favorable outcome was observed in cases of CRCC or chromophobe cell renal carcinoma compared with clear-cell RCC or papillary RCC (clear vs chromophobe: P = 0.002; chromophobe vs papillary: P = 0.019; clear vs cyst-associated: P = 0.001; papillary vs cyst-associated: P = 0.00079). CONCLUSIONS: In cases of CRCC, the disease was usually detected at lower stages and grades and therefore the prognosis was better than in cases of other types of RCC. Preoperative diagnosis of this disease was very difficult, especially in cases of RCC originating in a cyst.

Adenocarcinoma, Clear Cell↗

The prevalence of renal cell carcinoma: a nation-wide survey in Japan in 1997.

BACKGROUND: The present study was conducted to investigate the incidence of renal cell carcinoma by sex, age group and different regions in Japan. METHODS: The survey was conducted from the beginning of January 1997 to the end of December 1997. A total of 1306 Institutions in all 47 prefectures throughout Japan were requested to register cases. RESULTS: There were 6358 persons with renal cell carcinoma, consisting of 4372 men and 1986 women. The age-specific incidence rates showed a peak in the age group of 65-70 years in both men and women. The crude incidence rates per 100 000 population for men and women were 7.1 and 3.1, respectively, and age-standardized incidence rates per 100 000 population for men and women were 4.9 and 1.8, respectively. The incidence rates in the Hokkaido region were significantly higher than in other regions (P < 0.05), among which there was no significant difference in incidence rates. CONCLUSIONS: The present study showed that the incidence rates of renal cell carcinoma in Japan were approximately the same as among Japanese in Los Angeles. The rates were, however, lower than North American and European countries, but higher than China, Central or South American countries and African countries. The reasons for the high incidence of renal cancer in the Hokkaido region are not entirely clear. Further epidemiologic research is required.

Adult↗

Prognostic evaluation of transcatheter arterial embolization for unresectable renal cell carcinoma with distant metastasis.

OBJECTIVE: To evaluate the efficacy of transcatheter arterial embolization (TAE) in patients with unresectable renal cell carcinoma (RCC) and distant metastasis at the time of diagnosis. PATIENTS AND METHODS: The study included 54 patients with histologically defined RCC (by biopsy in 28 and autopsy in 26) who were unable to undergo nephrectomy mainly because their performance status was poor (score > or = 2). The patients were classified into two groups; 24 patients who underwent TAE with ethanol and 30 patients who did not. The two groups were compared for several clinical factors, mainly focusing on the prognosis. RESULTS: There were no significant differences in the clinical factors, including performance status, tumour diameter, vascular invasion, lymph node involvement, adjuvant therapy, metastatic organs or the number of metastases between the groups. However, the proportion of patients with para-neoplastic signs in those undergoing TAE was greater than that in those not, and the difference was significant (chi squared 0.35, P < 0.05). The median survival of the two groups was 229 days (TAE) and 116 days (no TAE). The 1-, 2- and 3-year survival rates in the TAE group were 29%, 15% and 10%, respectively, and in those not undergoing TAE were 13%, 7% and 3%, respectively. Those undergoing TAE had a significantly better prognosis than those who did not (P = 0.019). The adverse effects in patients undergoing TAE with ethanol included fever, back pain on the affected side, nausea and vomiting, but all the patients recovered from these adverse effects. CONCLUSION: TAE with ethanol is a safe and effective treatment for patients with unresectable disseminated RCC and a poor performance status; TAE with ethanol not only induces ablation of the primary tumour, but also prolongs survival.

Aged↗