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Biomedical subjects

H Nakazato

Publications and source records attributed to H Nakazato.

At least 37 records · Page 2Linked to original sources
PubMed2000

[The result of mass screening of 1997 for prostatic cancer in Isesaki City].

PURPOSE: Screening by only prostate specific antigen (PSA) for prostate cancer was started since PSA had been added to mass screening as one of check lists in 1997 in Isesaki city, Gunma pref. We expected PSA screening to be introduced into other areas. We therefore studied how to perform a screening procedure for prostate cancer as well as discussed our result of the screening conducted lately. MATERIALS AND METHODS: 1,382 out of 1,423 Isesaki citizens who took mass screening aged 40 to 64 were chosen. Regardless of age, men with a serum PSA level equal or larger than 4.1 ng/ml (Tandem R) were selected for second screening since we determined it was a cut-off level for further check-up. Of those men, 38 were requested for second screening and actually only 24 took it. All these men took PSA check-up again, furthermore 23 took transrectal examination (TRE) and/or transrectal ultra sonography (TRUS) except for one of them. The next screening was requested for sixteen of them. Prostate biopsy was conducted for all of them. RESULTS: More old men took screening and were diagnosed prostate cancer. The findings derived from such diagnosis showed one of them aged 50 to 59 and six of them aged 60 to 64 had the cancer. Moreover, four out of twenty with PSA level ranging 4.1 to 10.0 ng/ml and all of three with PSA level over 20.0 ng/ml had the cancer. Five out of sixteen with a positive sign for further PSA check-ups had the cancer. All the three suspect of the cancer by TURS and DRE had prostate cancer. Two of seven with PSA negative showed suspicion of prostate cancer and had the cancer. No neo-adjuvant and total prostatectomy was conducted for four with 4.0 to 10.0ng/ml diagnosed T2N0 M0. One of them with PSA equal or over 20.0 ng/ml was diagnosed T3N0M0. After hormone therapy its PSA decreased to that equal or under 0.5 ng/ml. Total prostatectomy was conducted for it. CONCLUSION: It is not proved that only PSA mass screening for prostatic cancer contributes to detect early cancer and better prognosis cure case. For the proof, it will be nessary that PSA mass screening is examined more people in the wide area. We conclude men aged 65 to 69 also should take PSA check-up based on epidemiological feature of prostatic cancer.

Adult↗
PubMed2000

Membranoproliferative glomerulonephritis in congenital portosystemic shunt without liver cirrhosis.

We report two cases with congenital portosystemic shunt who developed renal lesions without liver cirrhosis. Clinically, both cases showed proteinuria and mild hematuria at 9 and 6 years of age, respectively. In one case, the renal lesion was associated with normal renal function, but nephrotic syndrome followed by chronic renal failure were noted in the other. Renal biopsies showed characteristic histological features of membranoproliferative glomerulonephritis (MPGN) with IgA deposits along the glomerular capillary wall. Our cases strongly suggest the association between congenital portosystemic shunt and renal region. The shunt ratio may be an important predisposing factor for this type of nephropathy since a high shunt ratio (> 90%) was noted in both cases.

Child↗
PubMed2000

[Current status of "low-dose cisplatin-5-FU therapy" for solid tumors (2nd report)--from a nationwide questionnaire on its adverse effects].

A nationwide questionnaire survey was carried out on low-dose cisplatin-5-FU therapy for solid malignant tumors (mostly stomach and colon cancer) regarding its antitumor as well as adverse effects. The regimen was defined as 4 weeks administration of cisplatin 2-5 mg/body, 5 days a week, which was used in 47% of 82 institutions studied. Cases were classified into an Ab regimen (86 cases) with cisplatin 3-5 mg/body, and a Bb regimen (122 cases) with cisplatin 6-30 mg (mostly 10 mg)/body, both of which were given 5-FU 300-500 mg/body daily. The antitumor effect (CR + PR) was shown to be slightly higher in the Bb regimen than in the Ab regimen, and was 35% overall. Very few adverse effects appeared with either regimen for mostly major digestive, hepatic and renal functions, except for myelodepressions (leucopenia and thrombocytopenia), which were more than grade 3 in only a few percent with the Ab regimen, and a little more than 10% with the Bb regimen. The advantages and disadvantages of the A/Bb regimens appeared to be counter-balanced in terms of their antitumor and adverse effects. Most institutions using the Ab regimen favored repeating the regimen cycle as much as possible. Those using more than 6 cycles accounted for about 20% of hospitals.

Antimetabolites, Antineoplastic↗
PubMed1999

Structural organization of the 5'-end and chromosomal assignment of human placental leucine aminopeptidase/insulin-regulated membrane aminopeptidase gene.

Placental leucine aminopeptidase (P-LAP) which is identical with cystine aminopeptidase as oxytocinase was found to be a homologue of rat insulin-regulated membrane aminopeptidase (IRAP) by cDNA cloning. In this study, we confirmed 5'-end cDNA sequence of P-LAP and isolated genomic clones containing the upstream region of human P-LAP gene. The transcription initiation sites determined by primer extension located 478 and 480 bp upstream of the initiation methionine codon, 38 bp downstream of TATA box-like motif. The 5'-flanking region of human P-LAP gene contained DNA-binding motifs for several ubiquitous transcription factors such as SP1 and AP2. Chromosomal localization by fluorescence in situ hybridization showed that the gene was assigned to 5q14.2-q15 of the human chromosome. This study establishes the genetic basis for P-LAP gene research, thereby leading to better understanding of the molecular mechanism underlying the P-LAP gene.

Aminopeptidases↗
PubMed1999

Suppression of murine endotoxic shock by sPLA2 inhibitor, indoxam, through group IIA sPLA2-independent mechanisms.

Endotoxic shock is a systemic inflammatory process, involving a variety of proinflammatory mediators. Two types of secretory phospholipase A2 (sPLA2) have been implicated in this process. Group IB sPLA2 (PLA2-IB) binds to the PLA2 receptor (PLA2R), and PLA2R-deficient mice exhibit resistance to endotoxin-induced lethality with reduced plasma levels of proinflammatory cytokines, such as TNF-alpha. Group IIA sPLA2 (PLA2-IIA) is found in many tissues and cell types, and local and systemic levels are elevated under numerous inflammatory conditions including sepsis. In this study, we investigated the effect of a specific sPLA2 inhibitor, indoxam, on murine endotoxic shock. Indoxam suppressed the elevation of plasma TNF-alpha with a similar potency in PLA2-IIA-expressing and PLA2-IIA-deficient mice after LPS challenge. In PLA2-IIA-deficient mice, indoxam also suppressed the elevation of plasma IL-1beta, IL-6 and NO, and prolonged survival after LPS challenge. Indoxam was found to block the PLA2-IB binding to murine PLA2R with a high potency (Ki=30 nM). The inhibitory effects of indoxam on the LPS-induced elevation of plasma TNF-alpha levels could not be observed in mice deficient in PLA2R. These findings suggest that indoxam blocks the production of proinflammatory cytokines during endotoxemia through PLA2-IIA-independent mechanisms, possibly via blockade of the PLA2R function.

Animals↗
PubMed1999

Impact of splenectomy and immunochemotherapy on survival following gastrectomy for carcinoma: covariate interaction with immunosuppressive acidic protein, a serum marker for the host immune system. Tumor Marker Committee for the Study Group of Immunochemotherapy with PSK for Gastric Cancer.

The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host. To clarify this biphasic effect of the spleen, a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients. The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospective randomized trial (SIP) was analyzed using the Cox's proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein (IAP) level. In patients with high IAP levels (>580 microg/ml) with predicted negative antitumor immune reactions, splenectomy improved the prognosis. In patients with lower IAP values, conversely, the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival. The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient. The effect of immunotherapy is significantly influenced by the activity of spleen cells. The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients.

Aged↗
PubMed1999

A novel form of human neuropsin, a brain-related serine protease, is generated by alternative splicing and is expressed preferentially in human adult brain.

We have cloned cDNAs encoding two isoforms of a human novel serine protease. They encoded sequences of 260 and 305 amino acids, and both showed significant homology to mouse neuropsin. Mouse neuropsin has been reported to be involved in hippocampal plasticity, therefore we designated the proteins as type 1 and type 2 neuropsin, respectively. The amino acid sequences of the two types of human neuropsin were identical, except that type 2 carried an insert of 45 amino acids at the C-terminus of the leader sequence. The essential three amino acids in the active site triad, His, Asp, and Ser, and the single putative N-glycosylation site were conserved in human and mouse neuropsin. Sequence analysis of the 946 bp genomic DNA spanning the region encoding the insertion sequence revealed that two isoforms were generated in human brain by alternative splicing. However, the mouse genomic sequence did not conserve the 3' acceptor consensus sequence at the corresponding position, suggesting that type 2 neuropsin was a species-specific splice variant. When the open reading frames of human neuropsin were expressed in insect cells, both types of neuropsin were detected in the conditioned media by western blot analysis using anti-human neuropsin serum. Northern blot hybridization and reverse transcription-polymerase chain reaction showed predominant expression of type 1 neuropsin in pancreas. Type 2 neuropsin was preferentially expressed in human adult brain and hippocampus, although both types were expressed in fetal brain and placenta in comparable amounts. Dot blot hybridization showed that neuropsin was expressed in various regions of adult brain, including the hippocampus and cerebral cortex, and also in various fetal tissues. These results suggest that human type 2 neuropsin may be important to the adult brain plasticity, although both types may be necessary for the development of the nervous system.

Adult↗
PubMed1999

Chloride channel CLCN5 mutations in Japanese children with familial idiopathic low molecular weight proteinuria.

BACKGROUND: Familial idiopathic low molecular weight proteinuria (FILMWP) is a renal proximal tubulopathy characterized by mild proteinuria consisting of low molecular weight proteinuria and relatively conserved renal function in young patients, but without rickets. Mutations in the renal chloride channel CLCN5 gene have been reported in three disorders of hypercalciuric nephrolithiasis and in FILMWP. METHODS: To assess the relationship between molecular defects and phenotypic variations, we analyzed the CLCN5 gene from three additional Japanese families with FILMWP using single-strand conformation polymorphism and sequencing. RESULTS: We identified three mutations: a single base insertion at codon 514; a single base deletion at codon 116; and a nonsense mutation, R704X. The R704X mutation is identical to that found in X-linked recessive nephrolithiasis, but there was no renal failure in our patient. The first two mutations caused a shift in the reading frame, and all introduced a premature stop codon, resulting in synthesis of truncated CLC-5 proteins that lacked 220 (29%), 610 (82%), and 43 (6%) amino acids, respectively. These mutations were demonstrated to cosegregate with the disease in each of the three families. CONCLUSIONS: We conclude that the CLCN5 gene is responsible for the renal proximal tubulopathy in many Japanese families and suggest that molecular defects, environmental factors, or other modifying genes may account for the different phenotypes.

Amino Acid Sequence↗
PubMed1999

Adjuvant therapy with oral fluoropyrimidines as main chemotherapeutic agents after curative resection for colorectal cancer: individual patient data meta-analysis of randomized trials.

BACKGROUND: Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being studied for adjuvant chemotherapy of curatively resected colorectal cancers. To evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual patient data (IPD) meta-analysis of randomized clinical trials was performed in Japan as an inter-trialist group study. METHODS: Data from the three clinical trials in which postoperative adjuvant therapy with o-FPs was compared with surgery alone in patients with colorectal cancer were sought. IPD from a total of 4960 patients with follow-up periods of at least 5 years were analyzed. RESULTS: The results of the meta-analysis on an 'intention to treat' basis demonstrated a significant benefit of o-FPs in terms of the disease-free survival (DFS) of the total patients [risk ratio (RR) 0.830, 95% confidence interval (CI) 0.742-0.929, P = 0.001]. o-FPs were also demonstrated to be effective for survival in rectal cancer (RR 0.857, 95% CI 0.734-0.999, P = 0.049) and in Dukes'C colorectal cancer (RR 0.828, 95% CI 0.711-0.965, P = 0.016). CONCLUSION: The results suggest the advantage of long term o-FPs, possibly with the injection of mitomycin C, for prognosis for curatively resected colorectal cancer patients.

Administration, Oral↗
PubMed1999

A randomized controlled comparative study of oral medroxyprogesterone acetate 1,200 and 600 mg in patients with advanced or recurrent breast cancer.

A randomized controlled comparative study of oral medroxyprogesterone acetate (MPA) 1,200 mg (arm I) and 600 mg (arm II) was conducted in 80 patients with advanced or recurrent breast cancer. There were no significant differences between arm I and arm II in terms of response rate, duration of response and survival, or in terms of incidence and severity of adverse reactions. The lowest serum MPA concentration in responders tended to be higher than that in nonresponders. In the cohort of this study, the lowest concentration in partial response was 17.4 ng/ml, suggesting that this level may be the required minimum serum concentration.

Antineoplastic Agents, Hormonal↗
PubMed1998

Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked multisystem disorder with major abnormalities of eyes, nervous system, and kidneys. Clinical manifestations include congenital cataract, mental retardation, and renal tubular dysfunction. A gene (OCRL1) responsible for OCRL was identified by positional cloning and its product OCRL-1 protein was shown to be a phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] 5-phosphatase localized to the Golgi apparatus. We describe three mutations in OCRL1, one in a patient with severe phenotype and two in patients with moderate phenotype (degree of mental retardation and musculoskeletal abnormalities). The patient with severe phenotype had a G-to-A transition at nucleotide (nt) 1,739, causing an Arg-to-Gln substitution at amino acid 577, and one patient with moderate phenotype had a C-to-G transversion at nt 1,812, leading to a His-to-Gln substitution at amino acid 601. Both Arg-577 and His-601 are encoded by exon 15 and are probably important for proper function of this protein, since these are conserved in various enzymes catalyzing dephosphorylation of inositol compounds. In the other patient with the moderate phenotype, there was a G-to-A transition at nt 2,797 located at the 3'-end of exon 22. This substitution led to a skip of the same exon as well as conversion of codon-930 from GCT (Ala) to ACT (Thr) in the normal-size transcript. When we measured the enzyme activity in skin fibroblasts from the three patients, the activity was less than 10%, compared to findings in normal controls. Western blot analysis showed absence or severe decrease in OCRL-1 protein in cell lysates derived from these patients.

Adolescent↗
PubMed1998

Oligomerization of N-terminal domain of carcinoembryonic antigen (CEA) expressed in Escherichia coli.

The N-terminal domain of CEA, which is essential for cell adhesion activity and lacks cysteine residue, was expressed in Escherichia coli and purified from the solubilized inclusion bodies by DEAE-Sepharose and gel filtration chromatographies. The purified N-domain migrated in SDS-PAGE as a single 13-kDa band, whereas it migrated in non-SDS-PAGE as five distinct bands. The N-domain, analyzed by two-dimensional PAGE after cross-linking with DSS, migrated in multiple forms ranging from monomer to pentamer, showing unequivocally the presence of multimers in each band. The amount of monomer was distinctively the least among the oligomers in the non-SDS-PAGE. These results suggest that the N-domain of CEA molecule has a strong tendency to self-assemble that may convey the homophilic cell adhesion of CEA.

Carcinoembryonic Antigen↗
PubMed1998

Significance of presence of teratomatous elements in the primary tumour of testicular cancer.

To assess the tumour aggressiveness of teratoma, clinical records of patients with non-seminomatous germ cell testicular cancer were reviewed. Teratomatous elements were found in 57.8% of tumours. The rate of stage I tumours was lower in the teratoma-positive group than in the teratoma-negative group. Lymph node metastasis occurred more frequently than haematogenous metastasis in the teratoma-positive group. Tumour marker response in metastatic stage of teratoma-positive group was very excellent. Even if the radiographic response was not good, most patients were alive without disease after postchemotherapeutic salvage surgery. Furthermore, two patients with pure teratoma, who had tumour recurrence, were successfully treated with the multimodal therapy. Considering the smaller number of stage I patients in the teratoma-positive group than in the teratoma-negative group, the excellent overall response in the teratoma-positive group showed less aggressiveness of the tumour as a whole.

Adult↗
PubMed1998

Noncancerous pulmonary lesions in patients with metastatic testicular germ cell cancer.

By thoracoscopic surgery, we confirmed pulmonary noncancerous lesions in two patients with metastatic nonseminomatous testicular germ cell cancer. The purpose of thoracoscopic surgery was complete resection of postchemotherapeutic residual tumour in one patient or a biopsy for new lesions during chemotherapy. Histological findings were normal lymph node and pulmonary fibrosis. We demonstrated CT findings of these lesions and made some discussion on management of disseminated testicular cancer.

Adolescent↗
PubMed1998

Treatment of stage I seminoma: should beta-HCG positive seminoma be treated aggressively?

To assess the prognostic value of beta-HCG positive stage I seminoma, clinical records of 122 patients with testicular germ cell tumour were reviewed. Fifty-five patients (mean age 38.7 years) of 122 (45.1%) had stage I seminoma. Preorchiectomy beta-HCG level was determined in 54 patients. Twenty-nine patients of 54 (53.7%) had elevated preorchiectomy beta-HCG level. No significant relationship was found in the rate of locally progressive cancer between beta-HCG positive and negative cases. Treatment consisted of radiotherapy after inguinal orchiectomy for beta-HCG negative cases, and chemotherapy or radiotherapy for beta-HCG positive cases. Tumour recurrence was found in one patient with normal beta-HCG level. Our limited series demonstrated that preorchiectomy elevated beta-HCG had no significant relationship to local tumour invasion or prognostic value. Therefore, infradiaphragmatic radiation therapy may be useful for beta-HCG positive stage I seminoma.

Adult↗
PubMed1998

Developmental changes in carbonic anhydrase II in the rat kidney.

We examined the distribution and maturational changes of carbonic anhydrase I (CAI) and carbonic anhydrase II (CAII) in microdissected nephron segments of Sprague-Dawley rats. CAI and CAII proteins were measured by enzyme-linked immunosorbent assay. CAI was not detected in any nephron segment in 7-week-old rats. CAII was present in the collecting ducts, proximal tubules, and thick ascending limbs of loop of Henle in 7-week-old rats. CAII contents were significantly higher in the early proximal tubules (S1) than in second (S2) and late (S3) portions of the proximal tubules, while the contents in S1 were less than in cortical collecting ducts (CCD), outer stripe and inner stripes of the outer medullary collecting ducts (OMCDo and OMCDi). CAII content in each of S1, CCD, and OMCD of 1-week-old rats was only 14% or less of that of adults, but increased steeply during the 2nd and 3rd weeks of life, reaching almost 40% at 3 weeks of age and 97% at 7 weeks. Our results indicate that CAII is present throughout the entire nephron of the rat, and that CAII content in S1, CCD, and OMCD increases exponentially during the first 7 weeks of life. Our data suggest that the immature low levels of CAII may explain, at least in part, the limited capacity of urinary acidification during neonatal life. Further studies are necessary to establish the role of such changes in CAII content in acid-base homeostasis during neonatal life.

Animals↗
PubMed1998

The glycosylphosphatidylinositol-anchored phosphatase from Spirodela oligorrhiza is a purple acid phosphatase.

We recently presented clear evidence that the major low-phosphate-inducible phosphatase of the duckweed Spirodela oligorrhiza is a glycosylphosphatidylinositol (GPI)-anchored protein, and, to our knowledge, is the first described from higher plants (N. Morita, H. Nakazato, H. Okuyama, Y. Kim, G.A. Thompson, Jr. [1996] Biochim Biophys Acta 1290: 53-62). In this report the purified 57-kD phosphatase is shown to be a purple metalloenzyme containing Fe and Mn atoms and having an absorption maximum at 556 nm. The phosphatase activity was only slightly inhibited by tartrate, as expected for a purple acid phosphatase (PAP). Furthermore, the protein cross-reacted with an anti-Arabidopsis PAP antibody on immunoblots. The N-terminal amino acid sequence of the phosphatase was very similar to those of Arabidopsis, red kidney bean (Phaseolus vulgaris), and soybean (Glycine max) PAP. Extracts of S. oligorrhiza plants incubated with the GPI-specific precursor [3H]ethanolamine were treated with antibodies raised against the purified S. oligorrhiza phosphatase. Radioactivity from the resulting immunoprecipitates was specifically associated with a 57-kD band on sodium dodecyl sulfate-polyacrylamide gels. These results, together with previous findings, strongly indicate that the GPI-anchored phosphatase of S. oligorrhiza is a PAP.

Acid Phosphatase↗