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T Tsukamoto

Publications and source records attributed to T Tsukamoto.

At least 325 records · Page 18Linked to original sources

Long-term cultured astrocytes inhibit myelin formation, but not axonal growth in the co-cultured nerve tissue.

The chronic demyelinated plaque of multiple sclerosis (MS) is characterised by a loss of oligodendrocytes, astrogliosis, and incomplete or no remyelination which probably results in part from the suppressive effects of gliotic astrocytes on myelin formation. We explanted mouse cerebella on astrocyte cultures which had been maintained for 2 to 12 weeks and assessed the myelination in the cerebellar tissue at 18 days after explanation. Myelination occurred vigorously in the tissue explanted on 2- to 4-week-old astrocytes, but was poorer in the tissue explanted on astrocytes older than 4 weeks. No myelin sheath was formed on 12-week-old astrocytes, although axons developed equally as well as those in the tissues explanted on 2-week-old astrocytes. As astrocytes were maintained longer, they became fibrous and immunostained more deeply with anti-glial fibrillary acidic protein antibody, being analogous to astrogliosis. These findings imply that astrogliosis in chronic demyelinated lesions of MS may potentially block remyelination.

Animals↗

Correction by gene expression of biochemical abnormalities in fibroblasts from Zellweger patients.

Zellweger syndrome is a prototype of peroxisomal biogenesis disorders and a fatal autosomal recessive disease with no effective therapy. We identified nine genetic complementation groups of these disorders, and mutations in peroxisome assembly factor-1 (PAF-1) and the 70-kD peroxisomal membrane protein (PMP70) genes have been detected by our group F and Roscher's group 1, respectively. We now describe permanent recovery from generalized peroxisomal abnormalities in fibroblasts of a Zellweger patient from group F, such as biochemical defects of peroxisomal beta-oxidation, plasmalogen biosynthesis, and morphologic absence of peroxisomes, by stable transfection of human cDNA encoding PAF-1. In the light of these observations, we designed a gene expression system using fibroblasts from patients with peroxisomal biogenesis disorders. In Zellweger fibroblasts obtained from Roscher's group 1 and transfected with human cDNA encoding PMP70, peroxisomes were not morphologically identifiable, and peroxisomal function did not normalize.

ATP-Binding Cassette Transporters↗

[A clinical study of radial prostatectomy].

BACKGROUND: The objective of this study is to evaluate the efficacy of radical prostatectomy for patients with organ-confined prostate cancer. METHODS: From 1990 to 1994, a total of 50 patients with prostate cancer underwent radical retropubic prostatectomy. RESULTS: Eleven patients were in state A2, 34 in stage B and 5 in stage C according to clinical stage. Extended disease was observed pathologically in 45%, and 59% of patients in clinical stages A2 and B, respectively. Preoperative serum PSA levels were closely correlated with pathological extension of the disease. The disease-free rates for organ-confined disease, extended disease without lymph node metastasis and stage D1 disease were 75% (3 years), 82% (2 years) and 80% (3 years), respectively. Four patients had rectal injuries, and three of these underwent temporary colostomy diversion. Two patients had bladder neck contracture and received internal urethrotomy. Urinary incontinence improved in 60% of patients during the first 6 post-operative and in 90% of patients within 12 post-operative months. Urinary incontinence tended to improve earlier in patients with nerve-sparing than those without it. The erectile capacity in nerve sparing patients recovered good. CONCLUSION: Our results indicate that radical prostatectomy is a safe and temporarily satisfactory treatment for the patient with organ-confined prostate cancer.

Adenocarcinoma↗

[Comparison of symptom degree and frequency to quantity the lower urinary tract symptoms].

(BACKGROUND). To evaluate urinary symptoms, the International Prostate Symptom Score (I-PSS), which queries about frequency of symptoms, has been recently used in a clinical setting. However, there are men who are not satisfied with their voiding conditions in spite of a low symptom score. In such cases, their dissatisfaction may not be appropriately expressed by querying about frequency of the symptoms alone. We investigated whether the degree or the frequency of the obstructive symptoms correlated with the symptom-related problems. (METHODS). We analyzed obstructive symptoms in 739 males 40 years old and older who participated in a field survey for prostatic diseases. (RESULTS). Although not only frequency but degree of "hesitancy", "intermittency during urination", "strain or pushing" or "weak stream" correlated with the trouble, the correlations were higher in frequency than in degree. However, since some participants felt bothered when they expressed some degree of the symptoms alone but not frequency of the symptoms, evaluation of symptom degree may be helpful to identify such participants. Of the participants who answered "none" for frequency of the symptoms, some reported "having a mild symptom" in degree. This indicated that in recognition of symptoms degree may precede frequency. If the obstructive symptoms are very mild, men may express the symptoms as changes in degree, but not as changes in frequency. (CONCLUSIONS). These results suggested that evaluation of symptom degree is necessary for some participants.

Adult↗

[Endobronchial malignant lymphoma of mucosa-associated lymphoid tissue].

A 56-year-old man presented with pulmonary infiltrates. A chest roentgenogram revealed infiltrates in the left upper lobe and a tomogram showed obstruction of the left upper lobe bronchus. Computed tomography of the chest confirmed the presence these infiltrates, and no lymphadenopathy or mediastinal involvement was detected. At bronchoscopic examination, endobronchial masses were found. These masses almost completely obstructed the distal portion of the left upper lobe bronchus and partly obstructed the right upper lobe bronchus. A left upper sleeve lobectomy was done. Macroscopically, the tumor mass looked like a polypoid growth in the bronchial lumen. Microscopic examination showed that the tumor was composed mainly of small cleaved cells. These cells were observed to have infiltrated the epithelium to form lymphoepithelial lesions. Their B-cell origin was shown by the positive CD19 stain. Monoclonality of tumor cells was shown immunohistochemically and by hybridization techniques. Evidence of monoclonal B-cell proliferation was found in the rearrangement of Ig heavy- and light-chain genes, with Bam HI and Hind III digests. The final diagnosis was distinctive B-cell lymphoma (diffuse, small cell type) of mucosa-associated lymphoid tissue.

Bronchial Neoplasms↗

Japanese men have smaller prostate volumes but comparable urinary flow rates relative to American men: results of community based studies in 2 countries.

PURPOSE: We compared prostate volume and peak urinary flow rate in Japanese and American men 40 to 79 years old. MATERIALS AND METHODS: Prostate volume and peak urinary flow rate were measured in eligible Japanese men and results were compared to those of a randomly selected American cohort. RESULTS: Mean prostate volume plus or minus standard deviation averaged 20.3 +/- 10.6 ml. in Japanese and 29.6 +/- 13.4 ml. in American men, while predicted cross-sectional increases with age decade were 1.5 and 5.5 ml., respectively. Peak urinary flow rate was higher but the decrease with increasing age was greater in Japanese men. CONCLUSIONS: Prostate volume is larger and the increase with age is more pronounced in American than in Japanese men. However, Japanese men may have a higher peak urinary flow rate and greater cross-sectional decrease with age.

Adult↗

Non-refluxing ileal ureter replacement using intussuscepted nipple valve--an experimental study in dogs.

Although the vast accumulation of data from the continent urinary reservoir clearly proves that intussusception of the ileum is a reliable procedure for preventing urine reflux, few reports have appeared on the application of this technique to ileal replacement of the ureter. In an effort to determine if the nipple valve created by the intussuscepted ileum can prevent urine reflux in the ileal ureter, an experimental study was done using five dogs. I performed ureteral replacement using a newly developed procedure to secure the nipple valve in place. All dogs were followed for 6 months and evaluated by blood urea nitrogen (BUN), creatinine (Cr), serum electrolyte, urine culture, intravenous urogram (IVU), cystogram, and urodynamic studies. No significant differences were notable between the preoperative and 6-month postoperative values of BUN, Cr, and serum electrolytes in all dogs. Only one of the dogs, which showed extussusception of the nipple valve, demonstrated the reflux. IVUs and Whitaker flow studies did not confirm any urinary outflow obstruction. Furthermore, during the pressure studies, the nipple valve prevented transmission of the increased intravesical pressure to the upper urinary tract. I believe that the intussuscepted ileum can be secured by our procedure and can prevent reflux even though it is incorporated into the urinary system itself.

Animals↗

[Immunohistochemical examination for p53 overexpression in Ta bladder cancer with disease progression].

To evaluate the significance of p53 overexpression on the progression of bladder cancer, seven patients with Ta bladder cancer who eventually progressed to the invasive stage ( > or = stage T1) were immunohistochemically analyzed. The immunohistochemical study was performed using the p53 protein antibody on formalin-fixed, paraffin-embedded tissue sections from all primary and recurrent tumors. In three patients, immunoreactivity was detected only at the time of disease progression, suggesting that p53 mutation may be related to the disease. However, since no staining could not be found in stage Ta bladder cancer, the patient with a risk of progression could not be detected by this immunohistochemical study.

Aged↗

[Combined hormone-chemotherapy for stage D2 prostatic cancer: starting time of chemotherapy in relation to hormone therapy].

We retrospectively analyzed 29 patients with stage D2 prostatic cancer who had been treated with chemotherapy at the urological clinic of Tokyo Medical and Dental University Hospital between 1983 and 1992 to evaluate the efficacy of chemotherapy for advanced prostatic cancer. The patients were divided into three groups according to the starting time of chemotherapy in relation to hormone therapy; 9 patients who received chemotherapy more than four weeks after the initial hormone therapy (group H), 9 patients who received chemotherapy only or in combination with the hormone therapy more than four weeks previously (group C), and 11 patients in whom both therapies were started within four weeks (group HC). Follow-up period ranged from four to 108 months averaging 35. Combination chemotherapy including cisplatin was administered one to 17 times with the median of five. The five-year survival rates estimated by Kaplan-Meier method were 18% in group H, 28% in group C, and 78% in group HC, respectively (HC vs. C: p < 0.05, HC vs. H: p = 0.059). These findings indicate that a combination chemotherapy including cisplatin may improve the prognosis of patients with advanced prostatic cancer when it is started with the initial hormone therapy simultaneously.

Aged↗

Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential.

Normal human mammary epithelial cells express hcx43 and hCx26 proteins, which form functional gap junction channels. Both Cx genes are transcriptionally down-regulated in mammary carcinoma cell lines; consequently, no protein is made and gap junctions are absent. This result suggests that the loss of gap junctional communication may play an important role in carcinogenesis. To address this question, two sets of stable transfectants were produced in a recloned line of human mammary carcinoma cells (MDA-MB-435). One set expressed hCx26, and the other expressed hCx43. Studies of transfectants that contain functional gap junctions showed that they grew more slowly in culture than controls, and that their tumor-forming ability was strongly suppressed. In studies designed to examine their differentiation capacity, these transfectants were found to have regained the capacity to form three-dimensional structures in a matrigel matrix. This property is characteristic of normal mammary epithelial cells, but it is lost in the parental tumor cells and neo-transfectant controls. Thus, junctional communication is shown here to play a decisive role in the morphogenesis of mammary gland structures. The hCx26 and hCx43 genes behave as classical tumor suppressor genes both in culture and in animal tests in restoring growth regulatory properties to metastatic mammary carcinoma cells. Expression of these genes further induces the ability to differentiate as shown by the formation of three-dimensional structures when transfected cells are embedded in a matrigel matrix. These findings suggest that the reexpression of gap junctions may play a vital role in normalizing tumor cell behavior.

Breast Neoplasms↗

[Analysis of site differences in voiding condition of elderly men-- comparison to results of mass screening for prostate diseases between the villages of Shimamaki-mura, Hokkaido and Satomi-Mura, Ibaraki].

We performed mass screening for prostate diseases in the village of Satomi-mura, in Ibaraki Prefecture for males between 40 and 79 years old (participation rate; 21%). The findings were compared to those obtained by mass screening in the village of Shimamaki-mura, in Hokkaido Prefecture, conducted by the same examiners in a consistent manner (participation rate; 47%). When we considered the difference in biopsy rates between the two sites, the detection rate of prostate cancer in Satomi-mura was similar to that in Shimamaki-mura. There were no apparent differences in distribution of prostate volume, the International Prostate Symptom Score (I-PSS) and maximum flow rate between the two sites for each 10-year-age group. Our findings suggested that there was little site difference in the detection rate of prostate cancer and voiding condition between the two villages.

Adult↗

Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans.

Peroxisome-biogenesis disorders (PBD) are genetically heterogeneous and can be classified into at least ten complementation groups. We recently isolated the cDNA for rat peroxisome assembly factor-2 (PAF-2) by functional complementation using the peroxisome-deficient Chinese-hamster-ovary cell mutant, ZP92. To clarify the novel pathogenic gene of PBD, we cloned the full-length human PAF-2 cDNA that morphologically and biochemically restores peroxisomes of group C Zellweger fibroblasts (the same as group 4 in the Kennedy-Krieger Institute) and identified two pathogenic mutations in the PAF-2 gene in two patients with group C Zellweger syndrome. The 2,940-bp open reading frame of the human PAF-2 cDNA encodes a 980-amino-acid protein that shows 87.1% identity with rat PAF-2 and also restored the peroxisome assembly after gene transfer to fibroblasts of group C patients. Direct sequencing of the PAF-2 gene revealed a homozygous 1-bp insertion at nucleotide 511 (511 insT) in one patient with group C Zellweger syndrome (ZS), which introduces a premature termination codon in the PAF-2 gene, and, in the second patient, revealed a splice-site mutation in intron 3 (IVS3+1G-->A), which skipped exon 3, an event that leads to peroxisome deficiency. Chromosome mapping utilizing FISH indicates that PAF-2 is located on chromosome 6p21.1. These results confirm that human PAF-2 cDNA restores peroxisome of group C cells and that defects in the PAF-2 produce peroxisome deficiency of group C PBD.

ATPases Associated with Diverse Cellular Activitie↗

Adenoviral-mediated gene transfer into primary human and mouse mammary epithelial cells in vitro and in vivo.

Primary mammary epithelial cells from both the human and mouse mammary glands can be genetically altered under a variety of situations using the replication-defective adenoviral vector containing a marker gene encoding the E. coli beta-galactosidase. Primary human and mouse mammary epithelial cells in monolayer culture and in three-dimensional collagen gel culture systems were transduced by adenovector at high efficiency. Successful gene transfer was also accomplished in situ and in vivo. In the mouse mammary gland, anatomically restricted gene transfer and expression was demonstrated by micro-injection of adenoviral vector directly into the main duct of the mammary gland. Injection of adenoviral vector directly into the human mammary tissues from reduction mammoplasty specimens, into the mouse mammary gland-free fat pad containing the previously transplanted dissociated human mammary epithelial cells, and intratumorally into the human breast cancer xenografts in nude mice, all resulted in successful gene transfer to human mammary epithelial cells. High efficiency introduction of genetic material into primary mammary epithelial cells is important in the study of mammary carcinogenesis and potentially for gene therapy of human breast cancer.

Adenoviridae↗

Dopamine release in the medial preoptic area during male copulatory behavior in rats.

In vivo microdialysis was employed to measure the extracellular concentrations of dopamine (DA) in the medial preoptic area (MPOA) of rats during male sexual activity to look for a correlation with sexual activity. During copulation, the concentration of DA in the MPOA was significantly increased. A significant difference was detected in changes of DA between copulators and non-copulators. These findings were consistent with the assertion that DA neuron activity in the MPOA facilities male copulatory behavior.

3,4-Dihydroxyphenylacetic Acid↗

[Testicular findings, endocrine features and therapeutic responses of men with idiopathic hypogonadotropic hypogonadism].

The purpose of this study is to clarify the pathological and endocrinological variations of male idiopathic hypogonadotropic hypogonadism (IHH) from the viewpoint of testicular maturation. Twenty-five patients with IHH were classified into 3 groups according to the degree of germ cell maturation. The most mature germ cells in patients with severe IHH, moderate IHH and mild IHH were spermatogonia, primary spermatocytes and postmeiotic germ cells, respectively. All patients were treated with hCG alone or a combination of hMG-hCG for 1 year or more. The therapeutic efficacy of gonadotropin therapy was evaluated by findings of semen analysis, spermatogenesis and sexual maturation. The total GCI, which was expressed as the number of germ cells per Sertoli cell, diameter of the seminiferous tubules and testicular volume in mild IHH were the largest among the 3 IHH groups, and those in severe IHH were the smallest. Even in mild IHH, spermatogonial proliferation and meiotic activity were quantitatively smaller than those of normal pubertal boys. All patients showed extremely low basal testosterone levels. Response of serum testosterone to hCG administration correlated to the maturity of germ cells. Basal serum gonadotropin levels and responses to GnRH administration varied widely among the 3 groups. In particular, the response of serum gonadotropin to GnRH correlated to the maturity of the germ cells. Spermatogenesis could be initiated by hCG alone in IHH patients without cryptorchidism. Normal sperm density was obtained by hCG alone in the case of mild IHH; however, in moderate and severe IHH groups, hMG-hCG therapy was required for sufficient spermiogenesis. Sexual maturation was completely obtained by gonadotropin therapy within 1 year in moderate and mild IHH. However, in severe IHH, satisfactory sexual maturation could not be obtained within 1 year. The therapeutic prognosis for sexual maturation could be made based on the response to the hCG test at 6 months of gonadotropin therapy. In conclusion, the maturity of germ cells before treatment, which varies widely among patients with IHH, is a sensitive parameter for hypothalamo-pituitary-testicular function and the efficacy of gonadotropin therapy for testicular function. In severe IHH groups, to obtain satisfactory sexual maturation, the administration of testosterone should be considered in addition to gonadotropin replacement.

Adolescent↗