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Biomedical subjects

Y Noguchi

Publications and source records attributed to Y Noguchi.

At least 73 records · Page 4Linked to original sources
PubMed2000

[HIV-1 (human immunodeficiency virus type 1) mutant strain associated with zidovudine resistance detected from a Japanese patient with primary HIV-1 infection].

Sequences of HIV-1 pol gene were determined by direct sequencing from a Japanese patient with primary HIV-1 infection. The patient did not receive antiretroviral therapies. However we observed a HIV-1 mutant strain associated with zidovudine (ZDV) resistance. The patient had both the codon 70 and the codon 215 amino acid substitutions in the RT region. Our data indicated that the patient was infected with a HIV-1 mutant strain associated with ZDV resistance and this is the first report in Japan.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Interactions of ofloxacin and erythromycin with the multidrug resistance protein (MRP) in MRP-overexpressing human leukemia cells.

To investigate interactions between the multidrug resistance protein (MRP) and antimicrobial agents, we examined the effects of 12 agents on vincristine sensitivity and efflux of the calcein acetoxy-methyl ester (calcein-AM) of a MRP substrate in MRP-overexpressing cells. Only ofloxacin and erythromycin enhanced sensitivity with increased intracellular vincristine accumulation and inhibited the calcein-AM efflux. Our findings suggest that the two agents are possible MRP substrates and may competitively inhibit MRP function as a drug efflux pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Prediction of the outcome of transtrochanteric rotational osteotomy for osteonecrosis of the femoral head.

We have studied the correlation between the prevention of progressive collapse and the ratio of the intact articular surface of the femoral head, after transtrochanteric rotational osteotomy for osteonecrosis. We used probit analysis on 125 hips in order to assess the ratio necessary to prevent progressive radiological collapse over a ten-year period. The results show that a minimum postoperative intact ratio of 34% was required. This critical ratio may be useful for surgical planning and in assessing the natural history of the condition.

Adult↗
PubMed2000

Long-term outcome of endocrine function in patients with neurohypophyseal germinomas.

Since neurohypophyseal germinomas occur at the pituitary and hypothalamic axis in children and adolescents, the endocrinopathy is one of the common and critical QOL determinants. We carried out a retrospective study on the outcome of endocrine function in patients with neurohypophyseal germinoma, in order to improve or preserve pituitary function after treatment. Sixteen patients (7 men and 9 women), aged 6 to 26 years were admitted and followed up for 95.3 (14-197) months. DI was noted in 12 patients in pretreatment and 16 in posttreatment regardless of tumor size. We carried out the replacement of GH in all 8 patients, presenting the symptoms under 15 years of age. Gonadal or gonadotropic, thyroid and adrenal hormones were replaced in 9, 12 and 15 patients, respectively. Patients with large tumor compressing chiasm or hypothalamus needed hormonal replacement such as gonadal or gonadotropic and thyroid hormones more frequently (<0.01) than those with small one. In addition, two patients with a small tumor at the pituitary stalk and the 3rd ventricle floor showed the improvement of secretion pattern in gonadotropins and ACTH after chemotherapy, although they later needed radiation therapy to control the tumor. Based on our study and review of literature, the endocrinological studies before and after treatment demonstrated that pituitary dysfunction present before treatment persisted or worsened even after tumor remission, except for patients with small and localized ones. The poor endocrine results is considered to be largely radiation-related. Chemotherapy alone seems to be insufficient to obtain complete response (CR). To avoid radiation related pituitary injury, combination of 24 Gy or less dosage of radiation and appropriate chemotherapy is essential. The earlier diagnosis by repeatedly using neuroimaging and serum and CSF tumor markers and earlier initiation of treatment, before irreversible pituitary-hypothalamic damage occurs, contributes to improvement of the outcome of pituitary functions in patients with neurohypophyseal germinomas.

Adolescent↗
PubMed2000

Incidence of malignant tumors in patients with acromegaly.

Neoplasms may be one of the systemic complications to which we attribute high mortality in acromegaly. The present study was designed to investigate the incidence of malignant tumors in patients with acromegaly in the Japanese population. In this report, 44 patients (25 men and 19 women) with biochemically proven acromegaly were studied retrospectively and had a total 670 patient years of the duration of acromegaly. We investigated the incidence of malignant tumors. There were 5 patients with malignant tumors (5 in men) in this study (11%). Male patients with acromegaly had nearly a 3.5 times higher ratio of malignancy than expected and this increased cancer incidence was considered significant (P=0.01). There was no significant increase in cancer incidence of either the total patient population or female patients. The malignant tumors were two thyroid cancers and one colon, one gastric and one bladder cancer. It is of note that the colon cancer of one patient was diagnosed 2 years after transsphenoidal surgery even though the levels of serum GH and insulin-like growth factor (IGF-1) were reduced to normal after operation. This preliminary study has suggested that male patients with acromegaly might have a high risk of malignancy and that careful screening for tumors is needed both before and after surgical and medical treatment, even in patients with normalized serum GH and IGF-1 levels.

Acromegaly↗
PubMed2000

Glucocorticoid-dependency on GH secretion and tumor growth in a GH-producing pituitary adenoma with Cushing's syndrome.

We report a rare case of a 40-year-old woman with Cushing's syndrome and Acromegaly. At the age of 28 she was diagnosed with Cushing's syndrome due to a left adrenal tumor concomitant with a GH-producing pituitary tumor. Before adrenal surgery her basal GH levels were extremely high and CT scanning revealed a high-density mass in the sella turcica. A 28 g left adrenocortical adenoma was removed by adrenalectomy. During the four months after the adrenalectomy, basal GH levels dramatically decreased and the high-density mass detected by CT scanning had disappeared but the basal GH levels and IGF-1 had not been normalized. She gradually became acromegalic in the twelve years after the adrenalectomy. At the age of 40 CT scanning showed reappearance of the pituitary tumor. In order to examine the glucocorticoid dependency on GH secretion, we compared the GH secretion in a series of endocrinological tests before and after oral 8 mg dexamethasone administration for 7 days. There was no difference between before and after dexamethasone administration in the GH secreting pattern, but basal GH levels were apparently increased after dexamethasone treatment. Transsphenoidal surgery was done and pathological examination showed a GH-producing pituitary adenoma. In vitro, dexamethasone increased GH secretion from the cultured GH-producing adenoma cells in a dose-dependent manner. In this case, both GH secretion and pituitary tumor growth seemed to be dependent on glucocorticoid.

Acromegaly↗
PubMed2000

Octreotide improved ventricular arrhythmia in an acromegalic patient.

We saw a remarkable effect of octreotide, the long-acting somatostatin analogue, in reducing the number of ventricular premature complexes (VPCs) in a 59-year-old woman with acromegaly. Her basal GH and IGF-1 levels were up to 22.9 ng/ml and 934.9 ng/ml respectively. MRI revealed a 14 x 12 x 10 mm mass lesion in the pituitary gland. She had hypertension and echocardiography showed an increase in left ventricular wall thickness. Electric cardiography showed the presence of frequent VPCs and 24-h Holter monitoring revealed 24,277 beats of multifocal VPCs/24 h. She was treated with 300 microg/day of octreotide for four weeks before transsphenoidal surgery. After octreotide treatment, GH and IGF-1 were suppressed to 1.8 ng/ml and 145.3 ng/ml respectively, and the tumor size was remarkably reduced. Furthermore, the number of VPCs was also dramatically reduced to 2062 VPCs/24-h (8.5% of pretreatment) with 24-h Holter monitoring. This case shows that VPCs of acromegalic patients can be controlled by suppressing GH and IGF-1 with octreotide, and this agent is useful for reducing both tumor size and frequency of VPCs prior to surgery.

Acromegaly↗
PubMed2000

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Adult↗
PubMed2000

[New protocol for memory-related potential].

A new P300 testing protocol for evaluating memory function is proposed. Four stimuli (S1, S2, S3 and S4) are presented to the subject at 1.5 sec intervals and the subject is instructed to judge whether S4 was the same (80%) or not (20%) as S1, as well as whether S3 was the same (80%) or not (20%) as S2. The S2-S3 comparison acts as an attention shifting mechanism, and by inserting this comparison between S1 and S4, the subject must memorized S1 at the memory site in the brain until S4 is presented. This protocol was performed using both auditory and visual stimulations with 24 college students (age range: 19-28 years old) and a patient (23 years old) with bilateral medial temporal lobe lesions caused by limbic encephalitis. The P300 brain potentials after S3 and S4 were compared. The Wechsler memory scale-revised (WMS-R) test was also assessed in all subjects. The latency of P300 after S4 had a significantly (p < 0.01) longer than that after S3. The latency of P300 after S4 in the patient, who showed the severe auditory as well as the mild visual memory impairment, was longer than the mean + 2 SD in the normal subjects for auditory stimuli, but not for visual stimuli, whereas the latency of P300 after S3 in the patient was longer than the mean + 2 SD in the normal subjects only for visual stimuli. The brain potential after S4 might be more reflective of a degree of memory disorder as compared with that after S3. Furthermore, the latency of P300 after S4 showed a more significant correlation with some WMS-R scores (verbal memory, general memory and verbal delay) than the latency of P300 after S3. These results suggest that measuring the P300 latency after attention shifting in the new protocol is useful for the evaluation of memory functions.

Acoustic Stimulation↗
PubMed2000

Prediction of the nerves of origin of vestibular schwannomas with vestibular evoked myogenic potentials.

OBJECTIVE: To determine whether the nerves of origin of vestibular schwannomas can be predicted using vestibular evoked myogenic potentials (VEMPs). STUDY DESIGN: The study was a retrospective analysis. SETTING: The ear, nose, and throat department of Tokyo Medical and Dental University. PATIENTS: Twenty-eight patients undergoing removal of vestibular schwannomas were included in the study. INTERVENTIONS: Patients underwent pure tone audiometry, VEMP testing, caloric testing, and magnetic resonance imaging preoperatively. Hearing level, caloric weakness, maximum tumor size, and the nerves of origin of tumors were compared with VEMP testing. MAIN OUTCOME MEASURE: Results of VEMP testing. RESULTS: Comparisons between VEMPs and results of the other three examinations revealed no correlations. Complete disappearance of VEMPs was observed only in patients with tumors arising from inferior vestibular nerves. Patients in whom hearing was preserved tended to have preserved VEMPs. Some patients showed damaged hearing and normal VEMP results, although with inferior vestibular schwannomas. A patient with a tumor arising from a cochlear nerve exhibited preservation of VEMP, preserved caloric response, and moderate hearing loss. CONCLUSIONS: Inferior vestibular nerve function and hearing level were reflected in VEMP results. Prediction of the nerve of origin of a tumor was possible only in certain restricted cases.

Adult↗
PubMed2000

["Hetero to homo" allogeneic bone marrow transplantation from a related donor with two HLA loci mismatch].

We describe a 46-year-old HLA-homozygous female patient with CML who received a bone marrow transplant from her son, who had two HLA (A, B) loci mismatch. After conditioning with total body irradiation plus cyclophosphamide, the patient received 4.8 x 10(8) bone marrow cells/kg. Cyclosporin and short-term methotrexate were used for GVHD prophylaxis. She successfully established rapid engraftment with no acute GVHD, and later developed chronic but mild GVHD. Family members with two HLA loci mismatch may be considered as candidate donors for "hetero to homo" bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed2000

Deafness genes.

The pathophysiology of sensorineural hearing impairment, which is a common clinical disorder, remains yet to be determined. For prelingual hearing loss, epidemiological data show that 1 neonate in 1,000 is born with severe to profound hearing loss, and in half of that number the loss is inherited. Some genes responsible for sensorineural hearing impairment have been cloned during the last several years, and the underlying mechanisms causing hearing impairment have begun to be clarified with the advent of recent developments in molecular genetics. Cases of non-syndromic deafness are classified by the mode of inheritance (DFNA, dominant; DFNB, recessive; DFN, X-linked), with the loci being numbered in the order of discovery. To date, 31 autosomal dominant, 28 autosomal recessive, and 6 X-linked non-syndromic sensorineural hearing impairment loci have been mapped, and 17genes have been cloned (Hereditary Hearing Loss Homepage, http://danallab-www.uia.ac.be.dnalab/hhh/). We have identified mutations in four of those 17 deafness genes in Japanese families. Clinical and genetic findings of the above disorders are reviewed.

Adolescent↗
PubMed2000

Metabolic engineering study on the direct fermentation of 2-keto-L-gulonic acid, a key intermediate of L-ascorbic acid in Pseudomonas putida IFO3738.

We have achieved production of 2-keto-L-gulonic acid (2-KLGA) in recombinant Pseudomonas putida IFO3738. Firstly, the genes for sorbose dehydrogenase (SDH)/sorbosone dehydrogenase (SNDH) were introduced into P. putida. The recombinant P. putida/pBBR-SDH produced 0.7 mg/ml of 2-KLGA in a culture broth containing 5% L-sorbose. Replacement of the native SNDH promoter by the Escherichia coli tufB promoter (pBBR-SDH-tufB) improved the productivity of 2-KLGA up to 11.4 mg/ml. Secondly, the sorbitol dehydrogenase (SLDH) gene was also introduced into P. putida. The recombinant P. putida/pUCP19-3DH carrying the genes for SDH, SNDH and SLDH had the ability to produce 2-KLGA (7.5 mg/ml) in a 5% d-sorbitol broth. The productivity of 2-KLGA was improved up to 9.8 mg/ml by changing to an expression system with two plasmids, pBBR-SDH-tufB (for SDH/SNDH) and pUCP19-SLDH (for SLDH), respectively. Moreover, the replacement of the native SLDH promoter by the E. coli tufB promoter (pUCP19-SLDH-tufB) improved the 2-KLGA productivity up to 11.6 mg/ml. Optimization of cultivation conditions increased the conversion yield of 2-KLGA to 32% and that of l-idonate, a metabolite of 2-KLGA, to 40%. These results indicate P. putida IFO3738 is one of the candidate strains for direct fermentation of 2-KLGA.

Journal Article↗
PubMed1999

Tissue inhibitor of matrix metalloproteinase-1 in the plasma of patients with gastric carcinoma. A possible marker for serosal invasion and metastasis.

BACKGROUND: Expression of the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in tumor tissue from patients with gastric carcinoma has been reported to be related to disease progression. However, to the authors' knowledge the clinical significance of plasma TIMP-1 concentrations in these patients has not been clarified. METHODS: Concentrations of TIMP-1 protein were examined by enzyme-linked immunoadsorbent assay in plasma samples from 149 patients who underwent resection of their primary tumors and from 18 patients with nonresected or recurrent disease. RESULTS: In the 149 patients whose primary tumors were resected, plasma TIMP-1 concentration was associated significantly with a variety of pathologic factors including macroscopic type, depth of invasion, lymph node and peritoneal metastases, vessel invasion, pattern of tumor infiltration into surround ing tissue, and disease stage. Plasma TIMP-1 concentration was significantly higher in patients with serosal invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis than in those without these factors. Neither carcinoembryonic antigen (CEA) nor CA 19-9 concentrations appeared to be related to these measures of disease progression. In the 18 patients with nonresected or recurrent disease, TIMP-1, CEA, and CA 19-9 were similarly sensitive in predicting peritoneal, liver, and lymph node metastases. The combination of these three factors was able to detect 73.3% of patients with peritoneal metastasis, 83.3% of patients with liver metastasis, and 88.9% of patients with disease recurrence. CONCLUSIONS: In patients with gastric carcinoma, plasma concentration of TIMP-1 appears to correlate with both serosal invasion and metastasis.

CA-19-9 Antigen↗
PubMed1999

Expression of nitric oxide synthase in gastric cancer.

The expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in samples of normal gastric mucosa and gastric cancer were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-quantitative Western blot. In normal gastric mucosa, eNOS protein was found in all samples examined (mean, 70.2 +/- 60.1), relative to a standard protein. In gastric cancer specimens, eNOS protein was also detected in all samples, but the quantity (86.5 +/- 76.6) was not different from that found in samples of normal mucosa. The quantity of eNOS in gastric cancer tissues was negatively correlated with serosal invasion. iNbS mRNA, detected in nine of 18 cases, was slightly related to massive lymph node metastasis (n1-3 vs. n4). Neither tumor necrosis factor alpha (TNF-alpha) mRNA nor interleukin-6 (IL-6) mRNA was related to the expression of iNOS mRNA. These results suggest that iNOS not eNOS plays a role in gastric cancer tumor extension, but iNOS mRNA appears not to be induced by either TNF-alpha or IL-6.

Blotting, Western↗
PubMed1999

High incidence of synchronous cancer of the oral cavity and the upper gastrointestinal tract.

A high incidence of synchronous esophageal or gastric carcinoma in preoperative patients with carcinoma of the oral cavity was reported. Esophageal carcinoma was found in seven out of 56 patients (12.5%) and gastric cancer in five patients (8.9%) by videoendoscopy aided with lugol staining in the esophagus and indigocarmine solution in the stomach, although all patients were completely asymptomatic for these lesions. All patients were male, regular drinkers and heavy smokers. The depth of invasion of such tumors was limited to either mucosa or submucosa. Those esophageal and gastric lesions beside the primary oral cancers were positive for p53 protein by immunohistochemistry. Careful preoperative evaluation of not only the esophagus but also the stomach should be a routine procedure in patients with carcinoma of the oral cavity.

Aged↗
PubMed1999

Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes.

Adult T-cell leukemia (ATL) is a T-cell malignancy caused by human T-cell-leukemia-virus-I (HTLV-I) infection. ATL comprises 4 clinical forms: acute, chronic, smoldering and lymphoma types. ATL is usually resistant to conventional chemotherapy and has a relatively poor prognosis; however, the resistance mechanisms remain undetermined. To explore the multidrug-resistance (MDR) mechanisms of ATL, we examined the expression and functional activity of MDR-related genes in peripheral-blood mononuclear cells (PBMC) from ATL patients by semi-quantitative RT-PCR and FACScan with calcein-AM. PBMC from ATL patients expressed similar or higher levels of MRP, LRP and cMOAT mRNAs, as compared with normal PBMC. In normal controls and ATL patients, MDR1 mRNA expression was undetectable in this study. PBMC from acute and chronic ATL patients expressed significantly higher levels of MRP and LRP mRNA than did normal PBMC (p < 0.01 and p < 0.05 respectively). In chronic ATL, positive correlations were apparent between levels of MRP and LRP mRNA expression (r = 0.759, p = 0.018), and between each mRNA level and the absolute number of abnormal lymphocytes in peripheral blood. Probenecid, an inhibitor of the MRP pump, significantly increased the accumulation of calcein in PBMC from 3 chronic ATL patients. Our findings suggest that the MRP and LRP genes in ATL are often activated by HTLV-I infection and may confer MDR of ATL cells in vivo. Combined chemotherapy with inhibitors of these MDR genes may be promising in the treatment of ATL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗