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Biomedical subjects

H Okuno

Publications and source records attributed to H Okuno.

At least 55 records · Page 3Linked to original sources
PubMed1998

Myosin light chain phosphorylation and Mn2+ -dependent norepinephrine-induced contractions in guinea-pig vas deferens.

We have reported that norepinephrine but not K+ induced a sustained and dose-dependent contraction without extracellular Ca2+ and Mn2+ in Ca2+-depleted Mn2+-loaded vas deferens from the guinea-pig. In the present study, we determined the phosphorylation of the 20-kDa myosin light chain and examined the effects of inhibitors of calmodulin and myosin light chain kinase on the Mn2+-dependent norepinephrine-induced contraction in order to evaluate the contribution of phosphorylation to this contraction. W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-homopiperazine] and wortmannin inhibited this contraction. However, the Mn2+-dependent norepinephrine-induced contraction developed without a significant increase in the phosphorylation of the 20-kDa myosin light chain. In beta-escin-permeabilized preparations, Mn2+ induced contractions that were inhibited by ML-9. These results suggest that the activation of myosin light chain kinase is essential for the development of Mn2+-dependent norepinephrine-induced contractions and that the phosphorylation of myosin light chain may act as a trigger for these contractions.

Animals↗
PubMed1998

Novel approaches to prodrugs of anticancer diaminodichloroplatinum(II) complexes activated by stereoselective enzymatic ester hydrolysis.

A series of dichloro(ethylenediamine)-type platinum complexes bearing ester-, amide- and ether-bonded alkyl straight chains (C2-C18) was prepared as a model for the prodrug of cis-diamminedichloroplatinum (CDDP). Evaluation of cytotoxic activity of the complexes against the S-180 cell line proved that their enzymatic hydrolysis in the cells lowered the permeability to the cell membranes resulting in an increase of pharmacological activity. Optically active isomers of dichloro(N-2(2-phenylpropanoyloxy)ethyl)-2,3-diaminopropanamide )platinum(II) were prepared. They were re-activated stereoselectively, and a tenfold difference in activity was observed based on the differences in chiral discrimination by enzymes.

Animals↗
PubMed1998

Enhancement of type IV collagenases by highly metastatic variants of HT1080 fibrosarcoma cells established by a transendothelial invasion system in vitro.

A novel in vitro invasion assay system was established in this laboratory, in which the invasion of tumor cells after interaction with endothelial cells could be examined. Two variant cell lines (FP-10, FP-21) were established from parental HT1080 cells using this assay system. FP-10 and FP-21 cells had higher invasive and metastatic potential than the parental cells both in vitro and in vivo. The activity of anchorage-independent proliferation and the adhesion to the HUVEC monolayer of FP-10 and FP-21 was greater than the parental cells. The secretion of type IV collagenase (both MMP-2 and MMP-9) was also increased more significantly by the variant cells than by the parental cells, and the expression of uPA mRNA was higher in FP-10 and FP-21. Treatment of variant cells with human TIMP-2 remarkably suppressed the increment of the in vitro invasion to the same level as parental cells. These results suggest that this in vitro transendothelial invasion system accelerates multiple mechanisms of the metastasis by HT1080, especially the production of type IV collagenases. It can thus provide a useful model of tumor metastasis.

Animals↗
PubMed1998

Decreased expression of cold-inducible RNA-binding protein (CIRP) in male germ cells at elevated temperature.

Physiological scrotal hypothermia is necessary for normal spermatogenesis and fertility in mammals. Cirp is a recently identified cold-inducible RNA-binding protein that is inducible at 32 degrees C in mouse somatic cells in vitro. Cirp is constitutively expressed in the testis of mouse and structurally highly similar to RBM1, a candidate for the human azoospermia factor. To elucidate the role played by Cirp in spermatogenesis, we investigated its expression levels during spermatogenesis and after heat stress. In the mouse testis, cirp mRNA was detected in the germ cells, and the level varied depending on the stage of differentiation. Also, a high level of Cirp protein was detected immunohistochemically in the nucleus of primary spermatocytes. Expression of Cirp was decreased in the GC-2spd(ts) mouse germ cell line when culture temperature was raised from 32 degrees C to 37 degrees C. When mouse testis was exposed to heat stress by experimental cryptorchidism or immersion of the lower abdomen in warm (42 degrees C) water, the expression of Cirp was decreased in the testis within 6 hours after either treatment. In human testis with varicocele analyzed immunohistochemically, germ cells expressed less Cirp protein than those in the testis without varicocele. These results demonstrated that CIRP expression is down-regulated at elevated temperature in male germ cells of mice and humans. Analysis of Cirp expression in the testes will help elucidate the molecular mechanisms leading to male infertility.

Adult↗
PubMed1998

Seminal tract obstruction caused by childhood inguinal herniorrhaphy: results of microsurgical reanastomosis.

PURPOSE: Childhood inguinal herniorrhaphy is a frequent causes of seminal tract obstruction. We investigate the characteristics of this obstruction, surgical techniques for reanastomosis and outcomes in patients with bilateral or unilateral obstruction caused by inguinal herniorrhaphy in childhood. MATERIALS AND METHODS: We treated 22 men an average of 30.5 years old in whom average duration of obstruction was 27.1 years. Obstruction was bilateral in 9 patients and unilateral in 13, and 14 had azoospermia preoperatively. Microsurgical 2 layer vasovasostomy and/or specific tubule epididymovasostomy was performed. RESULTS: Inguinal and crossed vasovasostomy was done in 18 and 4 patients, respectively. The distal end of the vas was found at the internal inguinal ring or in the pelvic cavity in 57.1% of the vasa and more than 3 cm. of the vas had been resected in 37%. Sperm was noted in vasal fluid in 45.2% of the vasa during the operation and the patency rate of inguinal vasovasostomy was 88.9%. Ipsilateral epididymovasostomy performed after patent inguinal vasovasostomy in 5 patients with secondary epididymal obstruction resulted in normal sperm density and 3 pregnancies. In 7 men more than 2 procedures were done. There was sperm in the ejaculate in 12 of the 14 patients who had had azoospermia preoperatively and apparently increased sperm density postoperatively in 4 of the 8 who had not had azoospermia preoperatively. Pregnancy was achieved by 7 of the 21 married men (33.3%). CONCLUSIONS: Microsurgical reanastomosis of the seminal tract resulted in high patency and pregnancy rates in cases of seminal tract obstruction caused by childhood inguinal herniorrhaphy. Patients should elect seminal tract reanastomosis or assisted reproductive technology using epididymal or testicular sperm after receiving sufficient information on each treatment modality.

Adult↗
PubMed1998

[Clinical application of intraoperative ultrasonography for bilateral multilocular cystic renal cell carcinoma: a case report].

A 45-year-old man was referred to our department for further examination of the renal complicated cyst which was found incidentally by ultrasonography. Another complicated cyst in the left kidney was detected by subsequent dynamic CT and ultrasonography, which suggested bilateral cystic renal cell carcinoma. Bilateral partial nephrectomy was performed. Intraoperative ultrasonography was useful for diagnosis of multilocular cystic renal cell carcinoma (MCRCC). It disclosed multiple septa of the right renal complicated cyst which were not revealed by any preoperative examinations. It was also a useful adjunct to partial nephrectomy. It helped to identify the extent of deep intra-parenchymal lesions. The final diagnosis was bilateral synchronous multilocular cystic renal cell carcinoma. This is the second case of bilateral synchronous multilocular cystic renal cell carcinoma reported in Japan. We reviewed the clinical characteristics of 59 cases of MCRCC in the Japanese literature including the present case.

Carcinoma, Renal Cell↗
PubMed1998

[Three cases of the nephrogenic adenoma of the bladder].

Nephrogenic adenoma is a rare, benign tumor of the urinary tract. The origin of this tumor is supposed to be a metaplastic transformation of urothelium in response to stimulation such as recurrent urinary tract infections or surgical trauma. We experienced three cases of nephrogenic adenoma originating in the bladder. The first patient was a 29-year-old man with right vesicoureteral reflux (VUR). When Teflon injection for VUR was performed, a papillary tumor was found on the right wall of the bladder. Transurethral resection of the bladder tumor (TUR-Bt) was performed. The second patient was a 72-year-old woman who was suffering from chronic cystitis. Although she was treated with antibiotics for one year, the symptoms were not improved. Cystoscopy showed multiple papillary tumors at the retrotrigonum of the bladder and TUR-Bt was performed. The third patient was a 75-year-old man who had a history of the left pelvic and bilateral ureteral tumors. Left radical nephroureterectomy and right radical ureterectomy with an ileal graft replacement was performed. Three years later, cystoscopy demonstrated a papillary tumor at the retrotrigonum, which was resected transurethrally. Our cases are the 20th to 22nd cases of the nephrogenic adenoma of the bladder reported in the Japanese literature.

Adenoma↗
PubMed1998

[Synchronous multifocal development of invasive transitional cell carcinoma of the urinary tract in a patient with renal failure receiving long-term hemodialysis: a case report].

We report a case of transitional cell carcinoma in a patient with chronic renal failure receiving hemodialysis for 22 years. A 55-year-old man was admitted to our hospital. Under diagnosis of invasive bladder cancer and left renal pelvic tumor, removal of the whole urinary tract, e.g., bilateral nephroureterectomy and total cystourethrectomy was performed. Transitional cell carcinoma was found in bilateral renal pelvis, left ureter, bladder and prostate in the resected specimen. Thirteen months after the operation, multiple lung metastases and pathologic bone fracture of the 4th lumber vertebra were found. Chemotherapy (3 courses of modified CISCA, consisting of cisplatin, adriamycin and cyclophosphamide) was performed, but the died of systemic metastases of cancer and bleeding due to perforation of multiple gastric ulcers.

Carcinoma, Transitional Cell↗
PubMed1997

Temporal and spatial dissociation of expression patterns between Zif268 and c-Fos in rat inferior olive during vestibular compensation.

We examined the expression of the inducible transcription factors Zif268 and c-Fos in the inferior olive during the behavioural recovery following unilateral labyrinthectomy known as vestibular compensation. These transcription factors were differentially induced in the two subnuclei of the inferior olive. In the beta nucleus, c-Fos induction was restricted to the side contralateral to the lesion whereas Zif268 was induced on both the ipsilateral and contralateral side. In the dorsal cap, both proteins were expressed mostly on the contralateral side. In addition to this spatial difference, the expression of Zif268 attenuated faster than that of c-Fos. The present data suggest a functional difference between these two subnuclei of the inferior olive at the level of gene expression in vestibular compensation.

Animals↗
PubMed1997

Cytotoxicity of platinum (II) dinuclear complexes with 1-alkylthymine ligands against mouse sarcoma 180 cells.

We synthesized five platinum (II) dinuclear complexes containing 1-alkylated thymines. Two of the 1-alkylated thymine, 1-MeThy and 1-EtThy, complexes afforded good crystals. The X-ray structures of these complexes were determined. The 1-MeThy complexes has a head-to-head (H-H) arrangement, while the 1-EtThy complex has a head-to-tail (H-T) arrangement. The 1-MeThy complex (H-H) shows high electrophilicity against chloride anion (CI-) and high cytotoxicity against mouse sarcoma 180 (S-180) cells in vitro. The 1-EtThy complex (H-T) is inactive. The other 1-MeThy complex does not produce CDDP in the reaction with chloride ion and is inactive against the S-180 cell line. This complex is assumed to have an H-T arrangement. Similarly, two different 1-Pr(n)Thy complexes, one with high electrophilicity and cytotoxicity and the other without, must have an H-H and H-T arrangement, respectively. For comparison, we investigated six complexes, 1-methyluracil (1-MeUra) (H-H) dimer, alpha-pyridone (H-T) dimer, alpha-pyridone blue tetramer (PPB), 1-methylcytosine (1-MeCyt) (H-T) dimer, acetate dimer, and 1-MeUra monomer complexes. The alpha-pyridone (H-T), PPB, 1-MeCyt (H-T) dimer, and 1-MeUra monomer complexes are inert to chloride ion and inactive against mouse sarcoma S-180. The 1-MeUra (H-H) dimer and acetate dimer complexes show high electrophilicity and high cytotoxicity. Cellular accumulation of the platinum complexes phenomenally shows that all are incorporated to cancer cells to a lesser extent than CDDP. The relationships between the accumulation, the electrophilicity, and the interaction of these complexes with proteins are discussed.

Alkylation↗
PubMed1997

Association of in vitro growth potential of urinary exfoliated cells with tumor localization and intraluminal recurrence rates of urothelial cancers.

PURPOSE: One problem in the treatment of urothelial cancers, in particular of upper urinary tract cancers, is multifocal synchronous and/or metachronous tumor development in the heterotopic urothelium. We investigated the abilities of exfoliated cells in the urine of patients with urothelial cancers to colonize and proliferate in vitro. MATERIALS AND METHODS: Short-term cultures of 129 urine samples obtained from patients with urothelial cancers and 53 samples from healthy volunteers were compared as to the growth potential of urinary-exfoliated cells and clinico-pathological features, in particular tumor localization and evidence of intraluminal tumor recurrence. RESULTS: Primary cell outgrowth occurred in 112 (86.8%) of the 129 cell cultures from the patients and in 29 (54.7%) of the 53 from the healthy volunteers (p < 0.0001). "Sufficient cell growth" (more than 10(5) cells per flask) was obtained for 77 (59.7%) of the 129 cultures from patients and 7 (13.2%) of the 53 from the healthy volunteers (p < 0.0001). In terms of tumor localization, the rate of sufficient cell growth was significantly higher for patients with upper urinary tract tumor (21/25, 84.0%) than for those with bladder tumor (56/104, 53.8%) (p = 0.0062). Proportional hazard regression analysis showed that only the growth potential of the urinary-exfoliated cells was significantly predictive of intravesical tumor recurrence in patients with superficial bladder tumors (p = 0.011). CONCLUSIONS: The potentials for the colonization and proliferation of urinary-exfoliated cells are associated with intraluminal multifocal tumor recurrence of urothelial cancers.

Adult↗
PubMed1997

Layer-specific differential regulation of transcription factors Zif268 and Jun-D in visual cortex V1 and V2 of macaque monkeys.

To investigate intracellular mechanisms of cortical layer-specific gene regulation, we quantitatively examined the expression of two transcription factors, Zif268 and JunD, and compared their expression levels in each layer of the primary visual cortex (VI) and visual area 2 (V2) of macaque monkeys (Macaca fuscata). The brain sections were immunohistochemically stained for determination of the percentage of Zif268- or JunD-expressing neurons in the total neuronal population. We found area- and layer-specific expression of these transcription factors; Zif268 tended to be expressed at high levels in layers on the parvocellular pathway in V1, whereas JunD did not show such an expression pattern. In V1, many Zif268-immunopositive neurons were observed in layers II/III, IVC beta and VI. The percentage of Zif268-immunopositive neurons was highest in layer IVC beta and lowest in layer IVC alpha. JunD-immunopositive neurons were fewest in layer IVC beta and most abundant in layer VI. In V2, the level of expression of Zif268 was almost the same as that of JunD in layer II/II. However, layer IV of V2 tended to contain more Zif268-immunopositive neurons than JunD-immunopositive neurons, whereas layer VI contained more JunD-immunopositive neurons than Zif268-immunopositive neurons. Although it has been reported that the same extracellular signals induce both Zif268 and JunD, the present results indicate that the expression of these transcription factors is differentially controlled in each layer of the primate visual cortical areas. Furthermore, the present results suggest that these transcription factors contribute to area- and layer-specific gene regulation by mediating transmission of extracellular signals to the nucleus via different intracellular signalling pathways.

Animals↗
PubMed1997

Vestibular schwannoma showing a dural tail on contrast-enhanced magnetic resonance images.

The dural tail on contrast-enhanced magnetic resonance (MR) images, frequently observed in meningiomas, has been used to distinguish between cerebellopontine angle meningiomas and vestibular schwannomas. We report on a 66-year-old female with vestibular schwannoma showing the dural tail on contrast-enhanced MR images. Histological examination revealed that the dural tail corresponded to the thickened dura mater comprising of collagen fibres and scattered hyalinization with no tumoral invasion.

Aged↗
PubMed1997

Strong correlation of basement membrane degradation with p53 inactivation and/or MDM2 overexpression in superficial urothelial carcinomas.

PURPOSES: We investigated the relationships between the degradation of basement membrane underlying superficial urothelial carcinomas, including carcinoma in situ and the functional p53 loss caused by inactivation of p53 and the overexpression of mdm2 oncoprotein. MATERIALS AND METHODS: Nuclear accumulations of p53 and mdm2 were examined immunohistochemically for 60 transitional cell carcinomas (primary lesions) and 13 accompanying (concomitant) carcinoma in situ lesions. Degradation of the basement membrane was defined as the reduction or total loss of type IV collagen expression. Whether there was up-regulation of MMP-1, MMP-2, and MMP-9 was analyzed immunohistochemically. RESULTS: The frequency of the degradation of basement membrane underlying grade 1 pTa tumors was 0%, grade 2-3 pTa tumors 57.1%, and primary CIS lesions 83.3%. Nuclear over-accumulation of p53 was found in 48.3% and of mdm2 in 23.3% of the primary tumors. In pTa-pT1 carcinomas, nuclear staining of p53, mdm2, or both was highly correlated with degradation of the basement membrane underlying carcinomas (p = 0.00002). In the CIS lesions, the association of p53 nuclear staining with the destruction of type IV collagen expression was of borderline significance (p = 0.03). When mdm2 overexpression was considered as a molecular abnormality together with p53 inactivation, the correlation with the degradation of the basement membrane was highly significant (p = 0.00006). Moreover, the functional p53 loss was strongly associated with the up-regulation of matrix metalloproteinases (MMPs) (p = 0.0005). This finding was well correlated with the strong association of basement membrane degradation with up-regulation of MMPs (p = 0.000004). CONCLUSIONS: Degradation of basement membranes underlying superficial carcinomas or CIS of the urothelium was significantly related to p53 inactivation, mdm2 overexpression, or both. The expression status of mdm2 should provide better information about the progression of superficial urothelial carcinomas than the status of p53 alone.

Adult↗
PubMed1997

[A case of uretero-aortic fistula].

We report a case of uretero-aortic fistula. A 69-year-old man with rectal cancer underwent a pelvic exenteration and a double--barreled cutaneous ureterostomy in the right lower abdomen. Stomal stenosis necessitated continuous indwelling of double J stents in the two ureters. Two years postoperatively, massive bleeding occurred during exchange of double J catheters. Occlusive ureterogram demonstrated a uretero-aortic fistula at the crosspoint between the left ureter and the aorta. The surgical repair consisted of closure of the aortic fistula, ligation of the left ureter proximal to the fistula and percutaneous left nephrostomy.

Aged↗
PubMed1996

Feedback signal from medial temporal lobe mediates visual associative mnemonic codes of inferotemporal neurons.

Functional roles of the cortical backward signal in long-term memory formation were studied in monkeys performing a visual pair-association task. Before learning of the task, the anterior commissure of the monkeys was transected, disconnecting the anterior temporal cortex of each hemisphere. After training with 12 pairs of pictures, we injected a grid of ibotenic acid unilaterally into the entorhinal and perirhinal cortex that provide massive backward projections ipsilaterally to the inferotemporal cortex. According to the histological examination, the lesions covered medial and lateral banks of the rhinal sulcus completely and most the entorhinal and perirhinal cortex. After the injections, the monkeys fixated the cue stimulus normally, relearned the preoperatively learned set (set-A) and learned a new set (set-B) of paired associates. Then single units were recorded from the same area as that for the prelesion control. We found that (i) in spite of the lesion, the sampled neurons responded strongly and selectively to both the set-A and set-B patterns, and that (ii) the paired associates elicited significantly correlated responses in the control neurons but not in the cells tested after the lesion either for set-A or set-B stimuli. We conclude that the ability of inferotemporal neurons to represent association between picture pairs was lost after disruption of backward neural signals from the limbic cortex to the inferotemporal neurons, while the ability of the neurons to respond to a particular visual stimulus was left intact.

Analysis of Variance↗
PubMed1996

Immunocytochemical detection of p53 in cultures of exfoliated cells from urine of patients with urothelial cancers.

Early diagnosis of urothelial cancer is critical for successful treatment. Mutation of the p53 gene together with allelic loss of chromosome 17p correlates well with high grade and invasiveness of urothelial cancer. Moreover, this mutation is reported to be an early event for carcinoma in situ of the urothelium. In order to develop a new non-invasive diagnostic method for urothelial cancer, we have established a short-term culture system for urinary exfoliated cells from patients with urothelial cancer. Immunocytochemical detection of p53 in these urine-derived cells was conducted. Short-term cultures of exfoliated cells from 50 ml samples of urine from 52 patients with urothelial cancers were made. Adequate cell growth (> 10(5) cells per flask) was followed by passage onto glass chamber slides for p53 immunocytochemical staining. Successful passage was obtained in 40 of the 52 (76.9%) patients with urothelial cancers studied. The success rate for patients with tumors immunohistochemically positive for p53 nuclear accumulation was 90.5%, and 61.3% for those with tumors negative for p53 (P < 0.05). Results of immunochemical analysis of the p53 in the urine cells and those in the tumor samples were identical in 92.1% of the patients. Culture of exfoliated cells from urine would be a good, non-invasive method for the molecular diagnosis of urothelial cancer that should prove useful for the early detection and follow-up of tumors with p53 mutation.

Adult↗