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Biomedical subjects

N Shinohara

Publications and source records attributed to N Shinohara.

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

Near-normal linear growth in the setting of markedly reduced growth hormone and IGF-1. A case report.

A 14.2-year-old prepubertal boy diagnosed with complete-type growth hormone deficiency and tertiary hypothyroidism, keeps growing in the height range between -1 and -2 SD. He has been treated with levothyroxine only. To understand the growth mechanism of this boy, we analyzed the serum growth hormone (GH) with a radioimmunoassay (RIA), serum GH bioactivity with Nb2 and erythroid progenitor cell bioassays, and growth hormone-binding protein (GHBP) with a ligand-mediated immunofunctional assay (LIFA). In addition, IGF-1 and free IGF-1 were analyzed by immunoradiometric assay (IRMA) and insulin-like growth factor-binding protein-3 (IGFBP-3) by Western immunoblot. Peak GH-RIA responses to insulin, arginine and GH-releasing factor, and nocturnal GH secretion, were low (0.5-2.3 ng/ml); bioactive GH was low (0.313 ng/ml), and GHBP was elevated (84 ng/ml). The serum levels of IGF-1 and free IGF-1 were continuously low, 17.1-39.3 and 0.17-0.26 ng/ml, respectively. Moreover, serum IGFBP-3 levels were low (1.68- 1.39 mg/l) and IGFBP-3 protease activity was negative. Prolactin and insulin were in the normal range. The result of the assay for growth-promoting activity showed that the patient's serum stimulated normal erythroid progenitor cells twice as potently as did healthy thin adult control serum. These results suggest that GH and IGF-1 are not indispensable for maintaining physical growth in this boy. Thus, it appears that circulating GH and IGF-1 are not mandatory requirements for maintaining normal physical growth, and other, as yet uncharacterized, pathways or growth factors might be sufficiently compensatory under certain conditions.

Adolescent↗
PubMed1999

[An autopsy case of pulmonary embolism due to renal angiomyolipoma in an elderly woman].

An 86-year-old woman with a 13-year history of hypertension was admitted because of consciousness disturbance, hypotension, tachycardia, and cyanosis at her extremities. Enhanced computed tomography showed a thrombus in the truncus pulmonalis and right pulmonary artery, and also showed a left renal mass and a right renal cyst. Under a diagnosis of pulmonary embolism we started anticoagulant therapy, but the patient died five days after admission. At autopsy, a saddle-like thrombus was found in the truncus pulmonalis and bilateral trunks of pulmonary arteries. Microscopic examination showed smooth muscle cells in the thrombus. We could not find any other thrombus in the inferior vena cava, intrapelvic veins, nor in veins of lower extremities by milking. We also found tumors in both kidneys. Microscopically all tumors were diagnosed as angiomyolipoma. There were many fibrin thrombi in the sinuses of the tumors but there was no evidence of malignancy. We finally diagnosed pulmonary embolism due to renal angiomyolipoma because there was no other thrombus origin and microscopically the same smooth muscle cells were found both in the renal tumor and the pulmonary thrombus. There is only one case report concerning pulmonary embolism due to renal angiomyolipoma which happened during operative treatment. The treatment method of renal angiomyolipoma is determined by tumor size and symptoms, and usually intensive treatment is not performed in cases without symptoms. Our patient had no symptoms until the onset of severe complication of pulmonary embolism, suggesting that radical treatment is necessary for renal angiomyolipoma with a thrombus even when there are no symptoms.

Aged↗
PubMed1999

[Assessment of QOL and survival for patients undergoing radical cystectomy or bladder preservation for invasive bladder cancer].

PURPOSE: In this study, we have retrospectively compared patient backgrounds, prognosis and QOL (quality of life) in patients with invasive bladder cancer treated by radical cystectomy or by bladder preservation. PATIENTS AND METHODS: This study enrolled recent 30 cases from each institutions, totally 120 cases from four institutions. All patients were diagnosed with invasive bladder cancer in stage T 2 or T 3, N 0, M 0. The patients planned for preserving the bladder were treated with a combination of intra-arterial chemotherapy and radiation as an induction therapy. The questionnaire used to assess QOL was the EORTC QLQ-C 30 (Japanese-language edition). RESULTS: Radical cystectomy was selected as the initial treatment in 60 cases (the planned radical cystectomy group). Bladder preservation was planned but the presence of residual tumors after induction therapy underwent radical cystectomy in 18 cases (the preservation-radical cystectomy group). Bladder preservation was achieved in 42 cases (the preservation group). In a comparison of background factors, histologically grade 3 tumor and cases with histology other than transitional cell carcinoma, were significantly common in the planned radical cystectomy group. Because this study is not an randomized test, it is difficult to compare the outcomes between the patients treated by radical cystectomy or by bladder preservation. However, it is indicated that the candidates for bladder preservation therapy exist among the patients with T 2 or T 3, N 0, M 0 bladder cancer. Quality of life, as evaluated from global QL and from physical, cognitive, and emotional function, tended to be better in the patients with their bladder, although no difference was noted among the groups with regard to life role or social function. Symptoms such as sleep disturbance and diarrhea were common in the radical cystectomy groups, and financial impact, constipation, appetite loss, and dyspnea also tended to more frequently affect patients in these groups. CONCLUSION: Our results indicate that bladder preservation treatment using an induction therapy is one of option of the treatment for clinically T 2 or T 3, N 0, M 0 bladder cancer. We need a prospective randomized study with a long-term follow-up to elucidate true candidates for this treatment.

Aged↗
PubMed1999

[A case of localized fibrous tumor of the pleura after four years follow up and evaluate the doubling time with computed tomography].

Thirty-five-year female had taken video assisted thoraco-surgery (VATS) and resected her localized fibrous tumor of parietal pleura. She suspected chest tumor with annual X-ray survey for lung disease four years ago. She complained of left side back pain recently. Her chest CT revealed that the tumor enlarged than before. She was performed video assisted thoraco-surgery. The tumor was solid hard and connected to the parietal pleura with pedicle, which was resected easily from her pleural cavity. Histrogical examination detected that her tumor was localized fibrous tumor of parietal pleura. CD 34 and Vimentin were positive and cytokeratin was negative in this case. Four year and two examinations of the chest CT later, we could determine the doubling time (800.7 days) of localized fibrous tumor in this case.

Adult↗
PubMed1998

5-fluorouracil and low-dose recombinant interferon-alpha-2a in patients with hormone-refractory adenocarcinoma of the prostate.

BACKGROUND: The effectiveness of a chemotherapy regimen including 5-fluorouracil (5-FU) and recombinant interferon-alpha-2a (rIFN-alpha-2a) was evaluated in hormone-refractory prostate cancer patients. METHODS: Patients received a continuous intravenous infusion of 5-FU at 600 mg/m2/day for 5 days (D1-D5), followed by a bolus injection of 5-FU on D15 and D22. Patients received intramuscular injection of rIFN-alpha-2a at 3 million IU on D1, D3, D5, D15, and D22. This schedule was repeated every 4 weeks. RESULTS: Between 1993 and 1995, 23 patients with hormone refractory prostate cancer were enrolled in this study. Two of five patients with nodal disease exhibited partial responses according to the NPCP criteria. Fourteen of 17 patients with bone disease showed stable disease. Of 21 patients assessible for response, 9 patients had a decrease in the PSA level greater than 50% of baseline. Bone pain disappeared partially or completely in 8 of 14 patients with this symptom at entry. The median overall survival was 18 months. The associate toxicity was well tolerable. CONCLUSIONS: Combination chemotherapy of 5-FU and low dose rIFN-alpha-2a in patients with hormone-refractory prostate cancer proved feasible, and with acceptable toxicity.

Adenocarcinoma↗
PubMed1998

Supernumerary ring chromosomes and nuclear blebs in some low-grade malignant soft tissue tumours: atypical lipomatous tumours and dermatofibrosarcoma protuberans.

We investigated the diagnostic significance of supernumerary ring chromosomes in low-grade soft-tissue neoplasms. Chromosome slides were prepared from 123 samples of soft-tissue tumours using the standard trypsin-Giemsa banding technique. Supernumerary ring chromosomes were found in 6 cases of soft tissue tumours: 5 cases of atypical lipomatous tumour (ALT) and 1 case of dermatofibrosarcoma protuberans (DFSP). By chromosome painting with fluorescence in situ hybridization (FISH), the ring chromosome in 1 ALT was painted over its entire length with the chromosome 12 probe. Nuclear blebs and micronuclei, which were observed in each case of ALT, also contained chromosome 12 material; and these structures may represent a topological distribution of ring or giant marker chromosomes in the interphase nuclei. Our findings suggest that supernumerary ring chromosomes are characteristic of some low-grade soft tissue neoplasms including ALT and DFSP.

Adult↗
PubMed1998

Ossifying renal tumor of infancy: the first Japanese case with long-term follow-up.

Presented is the first Japanese case of ossifying renal tumor of infancy (ORTI), which is an extremely rare tumor and of which only nine cases have been reported in the literature. The patient was a four-month-old Japanese boy presenting as hematuria. A small nodular tumor (approximately 1 cm in size) protruded into the right pelvis from the superior caliceal region. Histologically the tumor originated from the tip of one medullary papilla and consisted of small rounded cells with a dense arrangement and several foci of minimally calcified osteoid lesions, including fewer but larger cells. Transition from the small to larger cells was suggested. The small cell only expressed vimentin, but the larger coexpressed vimentin, desmin, and epithelial membrane antigen. These findings suggested that the small cells differentiated to the larger cells with an epithelial nature associated somehow with osteoid formation. Embryonal metaplasia was assumed to occur in the collecting ducts entrapped by the tumor. The patient has been well without recurrence for more than 23 years. This is the longest survival period compared with other reported cases and confirms the benign nature of ORTI. It is absolutely crucial to make an accurate diagnosis of ORTI to avoid unnecessary treatment.

Follow-Up Studies↗
PubMed1998

Treatment of metastatic nonseminomatous germ cell tumors of the testis: significance of the international consensus prognostic classification as a prognostic factor-based staging system.

BACKGROUND: We reviewed treatment results in patients with metastatic nonseminomatous germ cell tumors of the testis and examined the significance of the International Consensus Prognostic Classification to make appropriate risk-based decisions concerning induction chemotherapy. METHODS: We divided 37 patients treated with platinum-based combination chemotherapy into good, intermediate, and poor prognostic groups utilizing the International Consensus Prognostic Classification. The data was analyzed for both overall survival and progression-free survival among the 3 prognostic groups. RESULTS: Among the 37 patients, 10 died (8 of progressive disease, 1 of pneumonia during induction chemotherapy and 1 of cyclophosphamide-induced hemorrhagic cardiomyolitis during salvage chemotherapy). The survivors were followed for 6 to 1 84 months from the beginning of induction chemotherapy (median, 80 months). Five of the 37 patients (14%) were classified as having a good prognosis, 1 8 (48%) as intermediate, and 14 (38%) as having a poor prognosis. The patients in the poor prognostic group had a 5-year overall survival of only 40%, while those in the good and intermediate groups had 5-year overall survivals of 100% and 94%, respectively. When we applied the International Consensus Prognostic Classification to patients with advanced disease classified by the Indiana University Staging System, these patients could be clearly divided into good-risk and poor-risk groups. CONCLUSIONS: The International Consensus Prognostic Classification is easily applicable and accurate for risk assessment in patients with metastatic nonseminomatous germ cell tumors of the testis. This classification will now be widely used in general oncology practices and for clinical trials in these patients.

Adolescent↗
PubMed1998

Long-term effect of recombinant human insulin-like growth factor I on metabolic and growth control in a patient with leprechaunism.

Leprechaunism is the most severe form of insulin resistance, manifesting with abnormal glucose metabolism and retarded growth. In the present study, we investigated the biological actions of recombinant human insulin-like growth factor I (rhIGF-I) in fibroblasts derived from a patient with leprechaunism. In the same patient, we also investigated the pharmacokinetics of IGF-I and the long-term effect of rhIGF-I treatment on metabolic control and physical growth. The patient's fibroblasts showed normal binding of IGF-I, normal phosphorylation of the beta-subunit of the IGF-I receptor, and normal [3H]thymidine incorporation in response to IGF-I. The fibroblast studies suggested that the patient would respond to IGF-I therapy, but certainly did not exclude the possibility of IGF-I resistance in vivo. Administration of recombinant human GH at the dose of 2.0 IU/kg for 3 consecutive days induced a minimal response of serum total IGF-I and IGF-binding protein-3 (IGFBP-3), suggesting partial GH resistance. To increase the serum total IGF-I level, we administered rhIGF-I with combination therapy of intermittent and continuous s.c. injection. This sustained the serum total IGF-I level, but not the serum IGFBP-3 level, within the normal range. The patient was treated with combination therapy of rhIGF-I by both s.c. injection and continuous s.c. infusion for 6 yr and 10 months. Administration of rhIGF-I at total daily dose of 1.6 mg/kg maintained her growth rate and hemoglobin A1c level nearly within the normal range. These findings suggest 1) that this leprechaun patient has an IGF-I-deficient state and partial GH resistance, as reflected by impaired production of IGF-I and IGFBP-3; 2) that rhIGF-I treatment works effectively for preventing postnatal growth retardation and normalizing glucose metabolism in patients with extreme insulin resistance; 3) that this treatment requires relatively higher dose of rhIGF-I; and 4) that treatment appears to be safe and devoid of adverse effects.

Blood Glucose↗
PubMed1998

Obesity induced by neonatal monosodium glutamate treatment in spontaneously hypertensive rats: an animal model of multiple risk factors.

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases.

Animals↗
PubMed1998

[Complicated form of spastic paraplegia with congenital cataract: a case report].

We report a 33-year-old man who manifested spastic paraplegia with congenital cataract, dementia, deformity of the foot (pes cavus, high arch and hammer toes), ataxia, and peripheral neuropathy. Magnetic resonance imaging showed mild deformity of the trunk of the corpus callosum and atrophy of superior cerebellar vermis. Metabolic diseases were ruled out by the clinical course and special examinations. Other patients, including 2 of ours, with spastic paraplegia and thin corpus callosum have been reported, but the present case is different because of congenital cataract and the form of the corpus callosum. We consider that there may be a variety of complicated forms of spastic paraplegia. To assess the etiology of complicated forms of spastic paraplegia, further case accumulation is very important.

Adult↗
PubMed1998

[A case of bow hunter's stroke caused by bilateral vertebral artery occlusive change on head rotation to the right].

We report a case of bow hunter's stroke caused by simultaneous bilateral vertebral artery occlusive changes at the right C3-4 and the left C1-2 level on head rotation to the right side. The pathogenesis and surgical treatment for this particular case are discussed. A 61-year-old male with cervical spondylosis repeatedly experienced vertebrobasilar insufficiency when he rotated his head over 60 degree from the mid-position to the right side. Bilateral vertebral angiography demonstrated severe compression of the right vertebral artery by a lateral osteophyte and instability at the C3-4 level accompanied with the mechanical stenosis of the left vertebral artery at the C1-2 level only at the time of turning his head to the right. As the surgical treatment we performed osteophytectomy of the right uncovertebral joint at the C3-4 level in addition to anterior decompression with fusion using hydroxyapatite spacer and titanium plate at that level. Postoperatively, the patient had no ischemic episodes and there was angiographical resolution of the rotational stenosis at the C3-4 level. For the clinical manifestation of bow hunter's stroke on head rotation, it is indispensable that simultaneous severe occlusive changes present on bilateral vertebral arteries. In case of a vertebral occlusive change caused by lateral osteophyte at the unstable vertebral joint, anterior decompression and fusion with osteophytectomy may be a wiser approach than arterial decompression or posterior fusion at the C1-2 level to another vertebral artery occlusive lesion.

Cerebrovascular Disorders↗
PubMed1998

Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Application and limitation of neoadjuvant hormonal therapy for prostate cancer].

Of 156 patients, 111 (clinical stage T1a-b; 21, T1c; 17, T2a-b; 36, T2c; 27, T3; 10) immediately underwent radical prostatectomy (surgery group), and 45 (clinical stage T1a-b; 8, T1c; 4, T2a-b; 10, T2c; 9, T3; 14) received neoadjuvant hormonal therapy (NHT group). NHT offered probability of increasing organ-confined cancer(OCC; pathological stage pT2 or lower N0M0) in the following group, which contains (a) patients who had moderately differentiated adenocarcinoma in the biopsy specimen and T2b or lower diseases, and (b) those who had well differentiated adenocarcinoma, T2c diseases and PSA levels of 10 ng/ml or higher, referred to as "OCC suitable criteria". Of 156 patients, 51 (33%) met OCC suitable criteria. In those cases, the proportion of OCC in NHT group was significantly higher than that in surgery group (11/12 (92%) vs. 16/39 (41%), p = 0.002). NHT is useful for increasing OCC in patients who meet OCC suitable criteria.

Adenocarcinoma↗
PubMed1998

[Surgical analysis for metastatic lung tumor from renal cell carcinoma].

Metastatic lung tumor from renal cell carcinoma were studied in 29 cases. Eighteen patients were treated surgically, 11 were treated non-surgically. The overall 5-year survival rate with the patients of pulmonary resection was 53.5%, and that with those of conservative therapy was 0%, and this difference is statistically significant (p < 0.05). There was no significant difference in any characteristics such as sex, age, stage, grade, disease free interval, metastatic pattern and combination with or without interferon therapy. There was no significant difference in surgically treated patients with pulmonary metastasis in terms of any factors such as age, sex, stage, grade, disease free interval, pulmonary metastasis pattern, metastatic number, surgical procedure, combination with or without interferon therapy statistically. Analysis for the surgically treated patients with pulmonary metastasis from renal cell carcinoma shows no significant difference in prognosis with any characteristics. This result shows efficacy of surgery even if for the patients with synchronous bilateral multiple pulmonary metastasis from renal cell carcinoma.

Adult↗
PubMed1997

Lck-independent triggering of T-cell antigen receptor signal transduction by staphylococcal enterotoxins.

Superantigens (SAgs) activate T-cells in a manner specific to the Vbeta region of the T-cell antigen receptor. Stimulations by SAgs provoke drastic T-cell activation that leads to programmed cell death or the anergic state of responding cells. To characterize the signal transduction pathway initiated by SAgs, mutant lines derived from the human leukemic T-cell line Jurkat were tested for their reactivities against prototypic SAgs, staphylococcal enterotoxins. The J.CaM1.6 cell line, which lacks Lck expression and lost reactivity against T-cell antigen receptor-mediated stimulation, was activated by staphylococcal enterotoxins in a manner indistinguishable from the Jurkat cell line. In contrast, the J.45. 01 cell line, which lacks expression of functional CD45, showed severely impaired reactivity. The role of Lck appears to be replaced by another Src family protein-tyrosine kinase, Fyn. In J.CaM1.6 cells, Fyn was rapidly phosphorylated and activated after staphylococcal enterotoxin treatment. The kinase-inactive mutant of Fyn significantly suppressed the reactivity against staphylococcal enterotoxin E in J.CaM1.6 cells, and the expression of the active form of Fyn reconstituted reactivity against staphylococcal enterotoxin E in J.45.01 cells. These results demonstrate that SAgs activate T-cells in an Lck-independent pathway and that Fyn plays a critical role in the process.

Antigens, CD↗
PubMed1997

Comparative analysis of the gp120-binding area of murine and human CD4 molecules.

The structural basis for the difference between human and murine CD4 molecules in binding to HIV envelope protein gp120 has been intensively studied. Eighteen mutant human CD4 molecules were produced by segmental replacement of beta strands and loops in the gp120-binding area of the molecule with corresponding murine sequences or by single amino acid substitutions. Examination of these mutant CD4 molecules for gp120 binding indicated that murine CD4 molecule does not bind gp120 for the following three reasons: (a) The loops flanking the C" strand are longer than their human counterparts, causing significant difference in local tertiary structure; (b) valin, rather than phenylalanine, which is the key amino acid for the binding occupies position 43; (c) amino acids at positions 45 and 46 are different, causing further decrease in binding affinity. Furthermore, the present study indicated that the aromatic ring of Phe43 and the negative charge of Arg59 play key roles in gp120 binding.

Amino Acid Sequence↗