Remarkable and persistent shrinkage of uterine leiomyoma associated with interferon alfa treatment for hepatitis.
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Adult↗
Biomedical subjects
A Tsujimura
Publications and source records attributed to A Tsujimura.
Membrane and secretory forms of mouse membrane cofactor protein (CD46) generated from a single gene through alternative splicing.
A cDNA encoding a new secretory form of mouse membrane cofactor protein (MCP, CD46) was identified additionally to the membrane form cDNA. The secretory MCP, predicted from the cDNA sequence, consisted of the conserved four short consensus repeats (SCRs) plus a four amino acid-stretch. Unlike human MCP which comprises many isoforms, mouse MCP cDNA predicted a single isoform of membrane MCP with cytoplasmic tail 1 (CYT1) and serine/ threonine-rich domain C (ST(C)). To clarify the genomic origin and monomorphic alteration of these cDNAs, we cloned and analyzed a mouse genomic DNA harboring the full coding sequence of MCP from a 129/SV mouse genomic library. The mouse Mcp was a single gene approximately 50 kilobases long. Eleven of the 14 coding exons of the human MCP gene and intron-exon boundary sequences were found to be conserved in the mouse gene. The STC homologue but not the STA or STB homologue in the mouse exons was functional: the latter being due to deletions and lack of consensus sequences for splicing. The sequence equivalent to cytoplasmic tail 2 (CYT2) has not been identified in the Mcp genome. Thus, the three exons (ST(A), ST(B), and probably CYT2) responsible for the polymorphism of human MCP by differential splicing were missing in the mouse Mcp gene. Unlike the case in humans, no Mcp-related genes or pseudogenes were observed in the mouse genome. The single mouse Mcp gene was mapped to the R-positive H5 band of mouse Chromosome 1 by FISH. Strikingly, one alternative exon with 73 base pairs (encoding the four new amino acids and a TGA stop codon) was discovered between the SCRIV and the STC exons; alternative splicing causes the generation of the secretory form of mouse MCP. These results on mouse MCP, together with the information concerning other mouse SCR proteins, infer that the regulator of complement activation (RCA) gene cluster is genetically diverged between humans and mice.
Alternative Splicing↗
[A clinical study on renal pelvic and ureteral tumor associated with bladder tumor with special reference to risk factors of subsequently recurrent bladder tumor].
PURPOSE: The purpose of this report is to analyze the clinical feature of renal pelvic and/or ureteral tumor (RUT) associated with bladder tumor (BT) with special reference to risk factors of subsequently recurrent BT. METHODS: Of the 49 patients with RUT who underwent surgery and were diagnosed pathologically as transitional cell carcinoma at the Department of Urology, Osaka National Hospital from April 1986 to October 1996, 20 patients (40.8%) had associated BTs. These patients were categorized to the following 4 groups, Group 1: 5 patients with BT preceding RUT, Group 2: 5 patients with concomitant BT, Group 3: 10 patients with subsequent BT following RUT operation and Group 4: 29 patients without any associated BT. The clinical course of these 4 groups were studied and compared with each other retrospectively. RESULTS: In group 1, the first BTs preceded RUTs by 19 to 81 months (mean 54.6 months). And during this relatively long period, the preceding BTs were treated by TUR for each recurrence, 1 to 9 times (mean 5.2 times). Two of 5 were bilateral RUT cases, which were observed only in this group. In group 2, the prognosis were relatively poor (5-year survival rate: 0%), because all RUTs of this group were high stage. And also the concomitant BTs were showing invasive feature during the observation period, despite they were superficial at first. Thus 3 of 5 underwent radical cystectomy. On the other hand, in group 3, the subsequent BTs, which developed at 2 to 26 month (mean 13.4 month) after RUT operation, were all superficial and resectable by TUR. The 5-year disease specific survival rate was 50% in group 1, 0% in group 2, 63.5% in group 3, 64.9% in group 4. Group 2 had the most poor prognosis. However there was no significant difference in prognosis among the 4 groups. Incidence of preoperative urine positive cytology was significantly higher in group 3, than in group 4 (87.5% vs. 44.8%). CONCLUSIONS: These results indicated that the RUTs with associated BTs have distinct clinical features depending on the sequence of association with the BTs. Especially the RUTs with concomitant BTs should be watched carefully as a high risk group with poor prognosis and possible development of invasive BTs. Positive urine cytology prior to RUT operation may reflect biological activity of tumor cell for dissemination in the lower urinary tract and we suggested preoperative urine cytology was possible predictor of subsequently recurrent BTs after RUT operation in this study.
Adult↗
Molecular cloning of a murine homologue of membrane cofactor protein (CD46): preferential expression in testicular germ cells.
Human membrane cofactor protein (MCP, CD46) has been suggested, although no convincing evidence has been proposed, to be a fertilization-associated protein, in addition to its primary functions as a complement regulator and a measles virus receptor. We have cloned a cDNA encoding the murine homologue of MCP. This cDNA showed 45% identity in deduced protein sequence and 62% identity in nucleotide sequence with human MCP. Its ectodomains were four short consensus repeats and a serine/threonine-rich domain, and it appeared to be a type 1 membrane protein with a 23-amino acid transmembrane domain and a short cytoplasmic tail. The protein expressed on Chinese hamster ovary cell transfectants was 47 kDa on SDS/PAGE immunoblotting, approximately 6 kDa larger than the murine testis MCP. It served as a cofactor for factor I-mediated inactivation of the complement protein C3b in a homologous system and, to a lesser extent, in a human system. Strikingly, the major message of murine MCP was 1.5 kb and was expressed predominantly in the testis. It was not detected in mice defective in spermatogenesis or with immature germ cells (until 23 days old). Thus, murine MCP may be a sperm-dominant protein the message of which is expressed selectively in spermatids during germ-cell differentiation.
Amino Acid Sequence↗
Correlation between the growth of uterine leiomyomata and estrogen and progesterone receptor content in needle biopsy specimens.
OBJECTIVE: To examine the relationship between estrogen receptor (ER) and progesterone receptor (PR) content in needle biopsy specimens and the growth of uterine leiomyomata after biopsy. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PATIENT(S): Thirty-one women with uterine leiomyomata and a normal menstrual cycle. INTERVENTION(S): Transcervical needle biopsy of uterine leiomyomata. MAIN OUTCOME MEASURE(S): The relationships between histologic features (smooth muscle content, immunohistochemical expression of ER and PR) and the percent increase over a 12-month observation period in the volume of the largest myoma nodule measured by magnetic resonance imaging were analyzed. RESULT(S): Both the density and intensity of immunohistochemical staining of PRs in uterine leiomyoma tissue showed significant positive correlation with leiomyoma growth. CONCLUSION(S): The growth of uterine leiomyomata can be determined by histologic and immunohistochemical analysis of needle biopsy specimens from uterine leiomyomata.
Adult↗
Susceptibility to idiopathic azoospermia in Japanese men is linked to HLA class I antigen.
PURPOSE: Approximately 15 to 20% of infertile men have azoospermia. In the Y chromosome a deletion, termed the azoospermic factor, has been found in some cases of idiopathic azoospermia. We investigate the relationship of factors in autosomal chromosomes (HLA class I antigens) to spermatogenesis failure in idiopathic azoospermia. MATERIALS AND METHODS: We evaluated 65 infertile Japanese men with idiopathic azoospermia. The frequency of the HLA allele reported in 1,216 healthy Japanese men was used as a control. HLA class I typing was performed by the National Institutes of Health standard serological method or polymerase chain reaction-sequence specific primer analysis. Allele frequencies were calculated. We determined statistical significance in the frequency of each allele in patients and controls using the chi-square test. The relationship of HLA antigens to idiopathic azoospermia was expressed as relative risk. RESULTS: In Japanese men with idiopathic azoospermia the frequency of HLA-A33, B13 and B44 was significantly increased compared with controls. The relative risk of HLA-B44 was 8.4, an extremely high value compared with that of other diseases and HLA antigens. CONCLUSIONS: We suggest that HLA class I antigens are important genetic markers that represent a risk factor for idiopathic azoospermia.
Alleles↗
Functional involvement of benzodiazepine receptors in ethanol-induced increases of diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.
We have attempted to clarify the mechanisms for alcohol (EtOH)-induced elevation of diazepam binding inhibitor (DBI) mRNA and to investigate whether the increase in DBI mRNA is paralleled with that in DBI using EtOH-treated mice and primary cultured neurons. Both the DBI content and the expression of DBI mRNA were elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice. Simultaneous administration of flunitrazepam (FLN) and Ro15-1788 with EtOH vapor completely abolished the EtOH-induced elevation of DBI mRNA. In addition, the exposure of the neurons for 3 days significantly elevated the expression of DBI mRNA, which was completely inhibited by concomitant exposure of FLN, Ro15-4513 and Ro-15-1788 with EtOH, while muscimol and bicuculline showed no effects on the EtOH-induced increase of DBI mRNA expression. These results indicate that functional interaction between EtOH and benzodiazepine (BDZ) receptors is a critical role in the increased expression of DBI mRNA.
Administration, Inhalation↗
Continuous treatment with nicotine increases diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.
Effect of chronic treatment with nicotine on DBI and its mRNA in mouse cerebral cortex were examined. Continuous treatment of mice with nicotine significantly increased DBI content and its mRNA expression, which was completely abolished by simultaneous administration of mecamylamine (1 mg/kg, i.p.). These results indicate that chronic functional interaction between nicotine and nicotinic acetylcholine receptors has a critical role in increases in DBI content and its mRNA expression.
Animals↗
Management of large placental chorioangioma with Doppler flow velocimetry.
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Adult↗
Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor.
BACKGROUND: The growth and progression of prostate cancer depends on the stromal-epithelial interaction which is under paracrine control. Hepatocyte growth factor (HGF), produced by mesenchymal cells, is a multifunctional growth factor stimulating the movement and growth of epithelial cells including cancer cells. We therefore assessed the relationship between the invasive potential of prostate cancer and HGF in vitro. METHODS: Three human prostate cancer cell lines were used including PC-3 and DU145 (androgen-independent), and LNCaP (androgen-dependent). We studied the expression of the HGF receptor c-met proto-oncogene (c-met) by Western blot analysis, and also determined the effects of HGF on cell scattering, and the mechanisms of invasion and proliferation, by microscopic observation, the matrigel invasion chamber assay, and the MTT assay. RESULTS: c-met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was increased cell motility in the scatter assay and an increased cell invasive potential in the matrigel invasion chamber assay by stimulation with HGF only with DU145 cells. CONCLUSION: HGF plays an important role in the invasion and metastasis of the DU145 cell line through a paracrine mechanism mediated by the c-metreceptor. In the PC-3 cell line, the lack of downstream signal transduction after the c-met receptor is suggested.
Biocompatible Materials↗
[Direct effects of Chinese herbal medicine "hochuekkito" on sperm movement].
BACKGROUND AND PURPOSE: Chinese herbal medicine, "Hochuekkito" is widely used for male infertility in Japan. There have been many reports concerning its clinical usefulness but very few reports of in vitro experiments studying the mechanism of its effects. In addition to stimulating germ cells, we analyzed its direct effects on sperm using computer assisted semen analyzer (CASA). MATERIALS AND METHODS: Motile sperm were prepared using swim up technique from semen collected from ten healthy volunteers. Sperm movements (motility, velocity, linearity) were analyzed by CASA after adding either serum containing anti-sperm antibody (ASA) or normal serum with or without Hochuekkito. RESULTS: Two hours after adding serum with ASA, the decrease of sperm motility was significantly reduced from 25.1% (92.8%-->67.7%) to 12.5% (92.9%-->80.6%) by adding Hochuekkito. No significant difference in velocity and linearity was observed between two groups. By adding normal serum, any of three parameters differed significantly with or without Hochuekkito. CONCLUSION: Protective effects of Hochuekkito on sperm was suggested. Although normal sperm with ASA was used in this report, since the sperm of infertile patients are said to be more fragile, this results imply that direct protective effect is one of the mechanism of Hochuekkito for male infertility.
Adult↗
[A clinical study on renal pelvic and ureteral cancer--with special reference to prognostic factors and adjuvant chemotherapy].
PURPOSE: This report focuses on the prognostic factors of the renal pelvic and ureteral cancer and on the treatment for advanced and/or recurrent cases. METHODS: We reviewed the forty-nine patients with transitional cell carcinoma of the renal pelvis and/or ureter who underwent surgery at the Department of Urology, Osaka National Hospital from April, 1986 to October, 1996. Univariate and multivariate analysis was done on the pathological features from these patients. RESULTS: The patients consisted of 34 males and 15 females and the mean age was 64.9, ranging from 27 to 83. Overall the 1, 3 and 5-year disease specific survival rates were 93.5%, 70.2% and 61.3% respectively by the Kaplan-Meier's method. The prognostic significance of the 6 pathological factors (pT, Grade, INF, pL, pV and pR) were evaluated statistically in terms of generalized Wilcoxon test and/or Cox-Mantel test. All the 6 factors effected on survival rates significantly. However, the grade, INF, pL, pV and pR factors were closely related to the pT factor. Moreover the pT factor was confirmed to be the most important and independent factor according to a multivariate analysis by the Cox's proportional hazard model. And the grade 3 factor with pT2 or higher stage was a high risk factor in recurrences significantly, in spite of curatively operated cases. Thirteen patients with high stage, metastasis or recurrences were treated after operation with the M-VAC or modified M-VAC regimen as preventive, adjuvant and/or salvage chemotherapy. The overall response rate was 72.7% in eleven cases with evaluable lesions, while these regimens could not be expected to improve long-term survival rate. The response rate of combined chemoradiation therapy was 66.7% for six cases with the localized recurrent cancer. CONCLUSIONS: The pT factor was the independent predictor of disease-specific survival. Adjuvant chemotherapy for prevention of cancer recurrence should be considered in the case of pT2 or higher stage plus grade 3 factor, even if curatively operated cases. The M-VAC or modified M-VAC regimen was reconfirmed to be useful as first line chemotherapy of advanced renal pelvic and ureteral cancer. Combined chemoradiation therapy was useful for the localized cancer recurrences, especially as a second line therapy for relapsed cases after M-VAC chemotherapy in this series.
Adult↗
[Study on the duration of pyuria after transurethral resection of prostate].
A retrospective study was conducted on the duration of pyuria after transurethral resection of the prostate (TURP) and the factors affecting the duration in 273 patients, who were diagnosed as having benign prostatic hyperplasia (BPH) with postoperative resolution of pyuria among those who underwent TURP over the last ten years at our clinic. In the 273 patients, the mean (+/- SD) weight of the resected prostate was 13.2 +/- 10.2 g (range : 1-52 g), the mean operating time was 74.3 +/- 29.8 min (25-215 min), the duration of pyuria was 110.6 +/- 38.3 days (23-273 days), and the resected weight to operating time ratio was 0.172 +/- 0.093 g/min (0.018-0.500 g/min). There was a significant correlation between the duration of pyuria and the patient's age, resected weight, operating time, or resected weight/operating time ratio, resected weight being the most important factor. The surgeon, the postoperative antibiotics used, and the preoperative existence of pyuria did not have any significant effect on the duration of postoperative pyuria. Investigation after stratification by the resected weight in 10 g increments suggested that a shorter operating time was important to reduce the duration of postoperative pyuria, particularly in BPH patients with a resected weight of 20-29 g.
Age Factors↗
Molecular cloning of a novel brain-specific serine protease with a kringle-like structure and three scavenger receptor cysteine-rich motifs.
In order to find serine proteases specifically expressed in brain, we designed degenerate mixed primers for consensus sequences of serine protease domains. By PCR utilizing the primers, we have cloned a novel sequence from reverse transcripts of total RNA of mouse brain and used it as a probe to screen a mouse brain cDNA library. Overlapping cDNAs encoding a precursor of a novel brain specific serine protease (BSSP-3) were cloned. DNA insert of the longest clone consisted of 2614-bp with an entire open reading frame encoding a secretory/membrane-anchored precursor protein consisting of 761 amino acids (AA) which may be processed to yield an active enzyme of 245 AA. As found in known serine proteases, BSSP-3 enzyme domain contained a catalytic triad which consists of AA residues essential for the enzyme activity. In the upstream region of the enzyme domain that resides at C-terminus of the precursor protein, there are, from N-terminus to downstream, a sequence similar to a kringle structure and three repetitive ones highly similar to the scavenger receptor cysteine-rich (SRCR) motifs. Northern blot analysis demonstrated that mBSSP-3 mRNA was specifically expressed in the mouse brain, lung and kidney. We concluded that a novel brain serine protease, BSSP-3, is a new member of kringle and SRCR superfamilies.
Amino Acid Sequence↗
Fibroblast growth factor-2 expression is up-regulated after denervation in rat lung tissue.
To understand the role of fibroblast growth factor-2 (FGF-2) during the denervation-reinnervation processes which occur after lung transplantation, we studied FGF-2 gene expression in a rat lung denervation model. The temporal profile of FGF-2 mRNA in denervated rat lungs was quantitatively assessed by competitive reverse transcription polymerase chain reaction (RT-PCR) method. The level of FGF-2 mRNA was consistently higher in denervated lungs, showing a peak value on the 5th post-operative day. Immunohistochemical analysis with an anti-FGF-2 monoclonal antibody disclosed immunoreactivity in Schwann cells at the distal severed end of the nerve fascicle located at the lung hilus, 1 week post-surgery. This study indicates that FGF-2 gene expression is up-regulated following denervation and suggests possible roles of FGF-2 in the reinnervation process of lung tissue.
Animals↗
Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1.
Osteoblast stimulating factor-1 (OSF-1) stimulates in vitro proliferation and differentiation of osteoblastic cells, and its gene is expressed in the bone and brain tissues in mammals and amphibians. To evaluate the in vivo function of OSF-1 in bone metabolism, transgenic mice overexpressing the human osf-1 gene driven by the osteocalcin promoter were generated. Femoral bone mineral content was increased in transgenic mice relative to wild-type controls as estimated by ash assay, depending on the transgene copy number per cell. In ovariectomized mice, bone mass loss due to estrogen deficiency was observed in both transgenic and control mice but bone mass was still higher in transgenic mice than in controls. Bone mass in ovariectomized transgenic mice was comparable to that in wild-type mice without ovariectomy. These observations indicate that OSF-1 may direct in vivo appositional bone formation by increasing osteoblast activity rather than decreasing osteoclast activity, suggesting a new way to treat osteoporosis with OSF-1.
Animals↗
Cloning of human and mouse cDNAs encoding novel zinc finger proteins expressed in cerebellum and hippocampus.
We identified a novel gene, kf-1, highly expressed in the normal cerebellum but not in the cerebral cortex, the expression of which could have been augmented in the cerebral cortex of a sporadic Alzheimer's disease patient. We cloned human and mouse entire kf-1 cDNAs encoding conserved 79 kDa proteins containing a zinc-binding RING-H2 finger motif at the carboxy-terminus as found in acetylcholine receptor-associated protein (RAPsyn). The 3'-untranslated regions are highly conserved between human and mouse as to constitute a common mRNA secondary structure. In situ hybridization analysis of mouse brain sections revealed strong kf-1 expression in the cerebellum and hippocampus. We propose that KF-1 is involved in membranous protein-sorting apparatus similarly to RAPsyn. We mapped the human kf-1 gene to 2p11.2.
Alzheimer Disease↗
Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential expression in oogenesis and embryogenesis.
Human presenilin (ps)-1 and -2 genes have recently been shown to be involved in genesis of early-onset familial Alzheimer's disease. By probing with human (H-) ps-1 cDNA, we isolated two types of cDNA clones, named X-ps-alpha and -beta, from a Xenopus brain cDNA library. The encoded proteins, X-PS-alpha and -beta, may correspond to H-PS-1 and -2 with 89.4 and 85.9% similarity, respectively. The strongest expression of these genes was observed in ovaries and in the early stages of oogenesis, although weak or moderate expression was detected ubiquitously for both X-ps-alpha and -beta genes in multiple tissues. Upon oocyte maturation, the X-ps-beta mRNA level was constant even after fertilization until the midblastula transition. Zygotic expression of these genes became evident only at the tailbud stage. We propose that presenilins may function in preventing cells from undergoing apoptotic degeneration particularly prior to embryonic development and in developmentally matured tissues.
Amino Acid Sequence↗