Biomedical subjects

K Hosaka

Publications and source records attributed to K Hosaka.

At least 55 records · Page 3Linked to original sources

PubMed1996

[A clinical and pathological study of radical prostatectomy for prostate cancer].

BACKGROUND: Thirty-one patients with prostate cancer underwent radical prostatectomy and simultaneous pelvic lymphadenectomy at Matsumoto National Hospital between 1988 and 1994. Prognostic factors are discussed from their clincopathological findings. METHODS: The patients ranged from 54 to 80-year-old, with an average age of 69.9 years. The median follow-up period was 44 months. The diagnosis was confirmed by needle biopsy or transurethral resection of the prostate. All the patients received short-term endocrine therapy preoperatively, and only noncuratively resected patients underwent adjuvant therapy postoperatively. At initial diagnosis, the tumor grades were well, moderately, and poorly differentiated adenocarcinoma in 9, 12, and 10 patients, respectively. The clinical stage was defined as A2, B, C, D1, and D2 in 12, 4, 6, 3, and 6 patients, respectively. RESULTS: A difference of tumor grade was found between the initial diagnosis and the final diagnosis based on the resected prostate in 8 patients (26%), with 7 of them (88%) showing an increase in grade in the final diagnosis. Also revealed was that 11 of the 25 patients (44%) in stage A2, B, C, or D1 had been understaged preoperatively. The five-year actuarial survival rates were 100%, 92%, and 51% for patients with well, moderately, and poorly differentiated adenocarcinoma, respectively, with a significant difference noted between well and poorly differentiated adenocarcinoma (p = 0.03). Recurrence only developed in patients with pathological stage D tumors. However, the presence or absence of lymph node metastasis did not affect the crude 5-year survival rate. Several stage D patients were successfully treated by radical prostatectomy and adjuvant therapy, achieving long survival. CONCLUSION: These results indicate that patients in clinical stage C have tumors which exhibit differing biological behavior. These patients should be analyzed and classified more precisely so that the most appropriate therapy can be chosen.

Adenocarcinoma↗

PubMed1996

[Clinical analysis of 169 patients with prostate cancer].

At Matsumoto National Hospital, 169 patients with prostate cancer were diagnosed between April 1986 and May 1994. The prostate cancer incidence was the highest in the latter half of the seventies, with an average age of 74.3 years. The clinical stage was defined as A1, A2, B, C, and D2 in 24 (14.2%), 38 (22.5%), 39 (23.1%), 23 (13.6%) and 45 (26.6%) patients, respectively. The clinical stage was not correlated with the patient's age. Incidental carcinoma was discovered in 5.8% of the patients who underwent prostatectomy for benign prostatic hypertrophy (BPH). At initial diagnosis, the tumor was well, moderately, and poorly differentiated adenocarcinoma in 71 (42.0%), 64 (37.9%), and 34 (20.1%) patients, respectively. The median follow-up period was 38.7 months. The over all five-year crude survival rate was 54.8%, while the cause-specific five-year survival rate was 80.0%. The five-year crude survival rate was 58.4, 82.0, 55.2, 42.5 and 37.4%, for patients with cancer at stage A1, A2, B, C, and D. The survival rate was higher for patients with cancer at clinical stage A and shorter for those with cancer at clinical stage D than in other stages. Prognosis was also worse in patients with moderately or poorly differentiated adenocarcinoma than in those with well-differentiated adenocarcinoma. The clinical stage and the pathological grade are important as prognostic factors, although the high incidence of death from other diseases shows that the patients' age should be considered to choose the modality of therapy. These findings indicate that intensive treatment of the patients in clinical stage A2, B and C prostate cancer in combination with screening for the men between 50 and 75 years old for early cancer detection is required.

Adenocarcinoma↗

PubMed1996

[Chronic eosinophilic pneumonia involving eosinophil cationic protein and bone marrow cells].

A 64-year-old women presented with a dry cough. The common cold was diagnosed and she was given medication, but the symptom did not resolve. She came to our hospital, and multiple patchy shadows were seen on a chest X-ray film. Bronchoalveolar lavage fluid contained an abnormally high percentage of eosinophils. Microscopic examination of transbronchial lung biopsy specimens showed infiltration of eosinophils into the alveoli and alveolar septa. Chronic eosinophilic pneumonia was diagnosed. Analysis of bone marrow cells showed high percentages of mature eosinophilic cells, and blood serum had a high concentration of eosinophil cationic protein. An inhalation challenge test with methacholine revealed bronchial hypersensitivity and hyperresponsiveness. Prednisolone (30 mg/day) was given and the symptoms resolved. After steroid treatment, the patient was asymptomatic, although airway hyperresponsiveness remained. The concentration of eosinophil cationic protein in serum and the results of the methacholine inhalation test reflected the degree of chronic eosinophilic pneumonia, and the production of eosinophils in bone marrow was suppressed by steroid medication.

Blood Proteins↗

PubMed1995

Cloning and expression of human cDNA encoding phosphatidylinositol transfer protein beta.

cDNA encoding the beta isoform of human phosphatidylinositol transfer protein was cloned from a human brain cDNA library. The deduced sequence of the protein comprised 271 amino acids with a calculated molecular mass of 31,539 Da, and showed 98.1% identity to that of the beta isoform of rat phosphatidylinositol transfer protein. The cDNA hybridized to a 3.4-kb mRNA, which was widely expressed in various human tissues including brain.

Amino Acid Sequence↗

PubMed1995

Sialyllactose-mediated cell interaction during granulosa cell differentiation. Identification of its binding proteins.

The present study was designed to prove the carbohydrate-binding proteins interacting with cell surface sialyllactosylceramide (GM3, NeuAc alpha 2-->3Gal beta 1-->4Glc beta 1-->1'Cer), which is highly expressed during differentiation of rat ovarian granulosa cells. As a specific ligand for the sialyllactose (SL)-binding proteins on granulosa cells, we used a radioiodinated multivalent SL-linked albumin (Alb-(SL)17). The specific association of the ligand to the putative proteins on the intact cells was competitively inhibited by GM3 more effectively than other gangliosides, sialyllactotetraosylceramide, sialylneolactotetraosylceramide, and several glycoproteins with N-linked oligosaccharides. However, the proteins had no specificity for the side chain (N-acetyl or N-glycolyl forms) of sialic acid in GM3. Scatchard analysis of Alb-(SL)17 binding showed high (Kd = 6.4 x 10(-10)M) and low (Kd = 3.1 x 10(-8)M) affinity population of binding sites. By direct binding of 125I-Alb-(SL)17 to SL-binding proteins on Western blots, the putative proteins with molecular masses of 35, 18, and 14 kDa were detected. The interaction of the multivalent derivative with these binding proteins was differently modulated by Ca2+ and Mn2+. The SL-binding proteins occurred in immature granulosa cells and progressively decreased during differentiation, whereas their endogenous ligand GM3 increased. These results indicate that relatively low molecular weight SL-binding proteins exist on the surface of immature granulosa cells and that they may serve as receptor sites for newly synthesized GM3 during differentiation.

Animals↗

PubMed1995

The SNF2/SWI2/GAM1/TYE3/RIC1 gene is involved in the coordinate regulation of phospholipid synthesis in Saccharomyces cerevisiae.

Genes involved in the phospholipid synthesis of Saccharomyces cerevisiae, such as PEM1, PEM2, PSS, and INO1, are coordinately repressed by myo-inositol and choline. In order to investigate this regulation, we transformed wild-type yeast with a PEM1 promoter-lacZ fusion and isolated two mutants, named ric1 and ric2 (regulation by myo-inositol and choline), exhibiting decreased PEM1 expression. The lowered PEM1 expression in the mutants was monitored in colonies in terms of their failure fully to develop blue color on 5-bromo-4-chloro-3-indolyl-beta-galactopyranoside-containing agar. ric1 mutant was auxotrophic for myo-inositol, indicating that INO1 expression was also affected, whereas ric2 mutant required myo-inositol only in the presence of choline. The RIC1 gene was isolated by complementation of the Ino- phenotype of ric1 mutant and its identity was confirmed by genetic cross between the original ric1 mutant and a gene disruptant. The RIC1 gene was sequenced and found to be identical with the previously identified gene, SNF2/SWI2/GAM1/TYE3, which is known to encode a general transcription factor required for the expression of various genes including INO1. Analysis using various lacZ fusion constructs containing promoters for genes in phospholipid synthesis revealed that the expression of myo-inositol-choline-regulated genes, PEM1, PEM2, PSS, CKI, and INO1, was markedly decreased in the snf2/swi2/gam1/tye3/ric1 background, but the expression of a constitutive gene, PIS, was not. We conclude that SNF2/SWI2/GAM1/TYE3/RIC1 is a positive regulatory gene required for the expression of not only INO1 gene, but also of myo-inositol-choline-regulated genes in general.

Adenosine Triphosphatases↗

PubMed1995

Cloning and sequence of the SCS2 gene, which can suppress the defect of INO1 expression in an inositol auxotrophic mutant of Saccharomyces cerevisiae.

Saccharomyces cerevisiae ire15 mutant has a defect in the expression of INO1, showing the inositol auxotrophic phenotype [Nikawa, J. (1994) Gene 149, 367-372]. We have isolated five yeast genes which suppress the ire15 mutation in multiple copies by genetic complementation. Among them, one gene, designated as SCS2, also suppressed the choline-sensitive dominant mutation, CSE1 [Hosaka, K. et al. (1992) J. Biochem. 111, 352-358]. The CSE1 mutation is not allelic to ire15. Sequencing analysis revealed that the SCS2 gene encodes 244 amino acid residues with a calculated molecular mass of 26,866. INO2/SCS1, which is another suppressor gene for CSE1 and is known to be a positive factor for INO1 expression, also suppressed the growth defect of the ire15 mutant. These results clearly indicate that the ire15 and CSE1 mutations genetically interact and the SCS2 and INO2/SCS1 genes are involved in the regulation of INO1 expression.

Amino Acid Sequence↗

PubMed1995

Isolation and characterization of genes that promote the expression of inositol transporter gene ITR1 in Saccharomyces cerevisiae.

The expression of many genes of Saccharomyces cerevisiae, such as ITR1, is regulated by inositol and choline. In this work, a yeast strain has been constructed in which HIS3 expression is controlled by the ITR1 promoter. Using this strain, three genes were isolated which, when introduced as multicopies, abolish the repression caused by inositol via the ITR1 promoter. Northern blot analysis revealed that two of these three genes, designated as DIE1 and DIE2, clearly increased the expression of ITR1. DIE2 is more effective for ITR1 expression than DIE1. Gene-disruption experiments revealed that DIE1 was essential for the expression of ITR1 but that DIE2 was not. The sequence of the DIE1 gene was shown to be identical to that of INO2 (also called SCS1), which encodes a protein required for the expression of INO1. DIE2 is a new gene and is capable of encoding 525 amino acid residues with a calculated molecular weight of 61,789. Experiments involving lacZ fusion genes showed that multicopy DIE2 resulted in an increase in the expression of both ITR1 and INO1. These results strongly suggest that the DIE1 and DIE2 gene products have an important regulatory function for gene expression of not only ITR1 but also INO1.

Base Sequence↗

PubMed1995

Ofloxacin concentrations in serum, saliva and pleural effusion of patients with pulmonary tuberculosis and lung cancer.

The ofloxacin (OFLX) concentration in serum, saliva and pleural effusion was measured in 12 patients with pleural effusion after oral administration at a dose of 200 mg three times a day (600 mg daily). Three patients had non-small cell lung cancer and the others had pulmonary tuberculosis. The mean OFLX levels in the serum, saliva and pleural effusion at 2 hours after the first administration on day 3 was 3.15 +/- 1.52, 3.36 +/- 2.23 and 2.86 +/- 1.77 micrograms/ml respectively. There was a strong correlation among these concentrations. The OFLX concentration of pleural effusion was predictable from that of saliva. A 3-day oral administration is sufficient to achieve the OFLX level of pleural effusion similar to that of the serum. It is possible that OFLX is effective for pleuritis caused not only by common infectious pathogens but also by Mycobacterium tuberculosis.

Administration, Oral↗

PubMed1995

[In vitro antimicrobial activity of a new quinolone, levofloxacin, against atypical mycobacteria].

We measured th in vitro antimicrobial activity of a new quinolone, levofloxacin (LVFX) against seven clinically isolated species of atypical mycobacteria, including 30 strains of M. avium complex. 8 of M. fortuitum, 4 of M. scrofulaceum, 2 of M. kansasii, 2 of M. gordonae, and 1 of M. chelonae (subsp chelonae). LVFX showed a potent antimicrobial activity against M. kansasii, M. gordonae and M. chelonae (subsp chelonae). In addition, it was suggested that LVFX may be effective for the treatment of infections caused by M. avium complex, since satisfactory antimicrobial activity was displayed against some strains of M. avium complex. Considering the fact that LVFX shows good concentration levers in sputum, this drug could be used in the chemotherapy against the infection with M. avium complex.

Anti-Infective Agents↗

PubMed1995

[Primary varicella pneumonia with respiratory failure].

Varicella pneumonia is a rare but serious and occasionally fatal complication of infection with varicellazoster. A 40-year-old man was admitted to our hospital with fever, eruptions, dyspnea, and severe hypoxemia. A chest X-ray film showed diffuse nodular infiltrative shadows in both lung fields. Transbronchial lung biopsy was done, and examination of the specimen revealed an organizing exudative reaction in the alveolar spaces, as well as interstitial inflammation. Primary varicella pneumonia was diagnosed on the basis of family history, typical eruptions, high titer of antibody against varicellazoster virus, and pathological findings. The patient was treated with methylprednisolone, antibiotics, acyclovir, and immunoglobulin. The skin eruptions and disturbances of gas exchange and diffusion resolved in about one week, but the infiltrative shadows on chest X-ray films remained for more than eight weeks.

Acute Disease↗

PubMed1994

Cloning and characterization of the SCS1 gene required for the expression of genes in yeast phospholipid synthesis.

A dominant mutation of Saccharomyces cerevisiae, CSE1, caused a decrease in the expression of the INO1 gene product, inositol-1-phosphate synthase. The residual activity was completely repressed by the addition of choline to the medium. A mutant carrying this mutation could not grow in the presence of choline unless inositol was added to the medium. Here we report a suppressor gene of the CSE1 mutation, SCS1 (suppressor of CSE1), which was cloned by complementation of CSE1 with a wild-type multicopy yeast genomic library. The cloned SCS1 gene contained an open reading frame which encoded 304 amino acid residues with a calculated molecular mass of 34,234 Da, and the sequence coincided with residues with a calculated molecular mass of 34,234 Da, and the sequence coincided with that of the INO2 gene. An scs1/ino2 null mutant constructed by gene replacement was viable, but auxotrophic for inositol and choline, and used for determination of the mRNA levels of various phospholipid-synthesizing enzymes. In agreement with the reported data for ino2 mutants the disruptant showed decreased expression of the INO1 and PSS genes, which are known to be regulated by inositol and choline. In addition, we newly found that the disruption of SCS1/INO2 also caused a decrease in the expression of the CKI, PEM1, and PEM2 genes, which we previously showed to belong to the inositol-choline-regulated gene family. These results confirm and strengthen the conclusion that the SCS1/INO2 gene is required for expression of inositol-choline-regulated genes in phospholipid synthesis.

Amino Acid Sequence↗

PubMed1994

Cloning of a cDNA encoding a second phosphatidylinositol transfer protein of rat brain by complementation of the yeast sec14 mutation.

A second form (beta isoform) of rat phosphatidylinositol transfer protein cDNA was cloned by complementation of the yeast sec14 mutation from a rat brain cDNA expression library. The deduced sequence of the protein comprised 271 amino acids with a calculated molecular mass of 31,449 Da. The deduced amino acid sequence showed 77% identity to that of the rat phosphatidylinositol transfer protein, recently reported by Dickeson et al. [Dickeson, S.K., Lim, C.N., Schuyler, G.T., Dalton, T.P., Helmkamp, G.M., Jr., & Yarbrough, L.R. (1989) J. Biol. Chem. 264, 16557-16564]. Northern blot analysis revealed that the cDNA probe of the beta isoform hybridized to an approximately 3-kilobase RNA in various rat tissues. The mRNA was expressed abundantly in brain, kidney, liver, and lung, but in a lesser amount in testis.

Amino Acid Sequence↗

PubMed1994

Cloning and sequence of the SCS3 gene which is required for inositol prototrophy in Saccharomyces cerevisiae.

The SCS3 gene of Saccharomyces cerevisiae was cloned by functional complementation, using a conditional mutant exhibiting myo-inositol auxotrophy in the presence of choline, and sequenced. The sequence contained an open reading frame capable of encoding 380 amino acids with a calculated molecular weight of 42,734. Disruption of the SCS3 locus caused myo-inositol auxotrophy. The gene appeared to be involved in the synthesis of inositol phospholipids from inositol but not in the control of inositol synthesis.

Amino Acid Sequence↗

PubMed1994

[Association of antiphospholipid antibodies with valvular heart disease in patients with systemic lupus erythematosus].

The purpose of this study was to evaluate the association of antiphospholipid antibodies with the valvular lesions in patients with systemic lupus erythematosus (SLE). Two-dimensional and color Doppler echocardiographic studies were performed in 65 patients with SLE. Antiphospholipid antibodies were assayed in each patient using two methods: anticardiolipin antibody and lupus anticoagulant. Valvular lesions were observed in 43 patients (66.2%). Mitral or aortic regurgitation (MR or AR) were recognized in 37 patients (56.9%). Moderate or severe MR were significantly associated with antiphospholipid antibodies (20.0%, p < 0.01) compared with patients without antiphospholipid antibodies (2%). Four of nine patients with moderate to severe AR or MR developed cerebral infarctions or digital infarctions. It is suggested that there may be a causal link between antiphospholipid antibodies and moderate to severe valvular lesions in SLE.

Adolescent↗

PubMed1993

Differential regulation of two myo-inositol transporter genes of Saccharomyces cerevisiae.

We previously isolated two distinct Saccharomyces cerevisiae myo-inositol transporter genes, ITR1 and ITR2 (Nikawa et al., 1991). Here, we studied the regulation of their expression by measuring steady-state mRNA levels and beta-galactosidase activities of lacZ fusion genes under different conditions. The results show that the expression of the two ITR genes is differently regulated: ITR1 was repressed by inositol and choline whereas ITR2 was constitutive. Deletion analysis of the ITR1 upstream region and comparison with the upstream regions of other genes involved in phospholipid synthesis indicate that the octamer sequence 5'-TTCACATG-3' is important for the expression and inositol/choline regulation of the ITR1 gene.

Amino Acid Sequence↗

PubMed1992

Cloning of a human choline kinase cDNA by complementation of the yeast cki mutation.

A human choline kinase cDNA was cloned by complementation of the yeast choline kinase mutation, cki, from a human glioblastoma cDNA expression library. The deduced sequence of the human enzyme comprised 456 amino acids with a calculated relative molecular mass of 52,065. The human enzyme resembled the rat liver enzyme over the entire sequence. It also resembled the yeast enzyme in the carboxy-terminal region, but not much in the amino-terminal region.

Amino Acid Sequence↗

PubMed1992

A dominant mutation that alters the regulation of INO1 expression in Saccharomyces cerevisiae.

A dominant, single nuclear gene mutation, CSE1, caused inositol auxotrophy in yeast cells. The inositol requirement was marked when choline was present in the medium. Inositol-1-phosphate synthase, the regulatory enzyme of inositol synthesis, is repressed by inositol, or more profoundly by a combination of inositol and choline in the wild type. In CSE1, the level of inositol-1-phosphate synthase was low and was greatly repressed on the addition of choline alone. In accordance with this, INO1 mRNA encoding the enzyme was low even under the depressed conditions and was profoundly decreased by choline in CSE1. But in the wild type, the addition of choline alone had little effect. An INO1-lacZ fusion was constructed and the control of the INO1 promoter in CSE1 was studied. lacZ expression was repressed not only by inositol, but also by choline in CSE1, whereas it was repressed by inositol, but only slightly by choline in the wild type. CSE1 was unlinked to the INO1 structural gene. Thus CSE1 was thought to be a regulatory mutation. Furthermore, when the CDP-choline pathway was mutationally blocked, choline did not affect INO1 expression, indicating that the metabolism of choline via the CDP-choline pathway is required for INO1 repression.

Carbon Radioisotopes↗