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Biomedical subjects

K Kohri

Publications and source records attributed to K Kohri.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of eicosapentaenoic acid on urinary calcium excretion in calcium stone formers.

OBJECTIVES: The low incidence of atherosclerosis and other degenerative disease, including urolithiasis, in the Greenland Eskimo has been attributed to their high consumption of oily fish with its high concentration of eicosapentaenoic acid (EPA). With a westernized diet, the oxygenated products of renal prostaglandin synthesis are metabolites of the n-6 series and these are known to play important roles in several pathophysiological processes involved in calcium stone formation. Buck's group presented a hypothesis that the initiating factor for lithiasis triggers prostaglandin synthesis, and showed that this influenced by EPA treatment. METHOD: In order to ascertain the effects of EPA on plasma lipids and urinary parameters, we undertook a clinical study whereby a highly purified preparation was administrated (1,800 mg/day) to 88 patients with urinary stones for 3 months (short term) and 18 months (long term). RESULTS: Hyperlipemia improved the affected individuals and urinary calcium was significantly reduced in the hypercalciuric but not in the normocalciuric group. CONCLUSION: The results suggest that EPA by reducing urinary calcium might favorably affect urine composition in a way that possibly reduces the risk of calcium stone formation.

Adult↗
PubMed2001

[A study on the mechanism of the spermatogenic damage after vasectomy in rats].

PURPOSE: Vasectomy may result in damage to spermatogenesis. There are several explanations for this damage, including an increase of pressure in the seminiferous tubules and an autoimmune reaction. Recently, vasectomy has been reported to induce germ cell death by apoptosis. However, the exact mechanism of this vasectomy-induced germ cell apoptosis is unclear. To elucidate this mechanism, we designed a vasectomized rat model and examined the testiscular alterations and apoptotic degeneration biochemically and microhistopathologically. Particularly, we analyzed the expression of nitric oxide synthase (NOS) and nuclear factor kappa B (NF kappa B), which plays a critical role in the induction of the iNOS gene, in the testis after vasectomy to gain insight into the association between germ cell apoptosis and these factors. MATERIALS AND METHODS: The testes of 40 Wistar rats (10-weeks old) were studied at 1, 2, 5 and 10 weeks after unilateral (left) vasectomy. Wistar rats weighting 290 to 310 g were divided into 2 groups and subjected to underwent either unilateral vasectomy or sham surgery under ether anesthesia. Bilateral testes were carefully observed biochemically and histopathologically. Apoptosis was detected by an in situ end-labeling technique (detection of cellular DNA fragmentation) and electron microscopy. Neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) protein was detected by Western blotting and immunohistochemical studies using each NOS monoclonal antibody. To confirm the co-localization of cellular DNA fragmentation in germ cells and each NOS, each set of consecutive testis sections (one stained for cellular DNA fragmentation and the others for each NOS) were examined. Expression of NF kappa B proteins was examined immunohistochemically using a NF kappa B p65 polyclonal antibody. RESULTS: At 5 and 10 weeks after vasectomy, the vasectomized left testis was significantly lighter than the unvasectomized right testis and sham-operated testis. At that time, the seminiferous tubules of vasectomized testes were highly damaged, presenting narrow tubular diameter, disorder of cellular arrangement, depletion of the germ cells, and local interstitial fibrosis. Vasectomized testes demonstrated a significantly increased number of apoptotic germ cells per cross-sectional area compared with sham-operated testes at 5 and 10 weeks after operation (p < 0.01). Electron microscopy revealed apoptotic germ cells each with a darkly stained nucleus. Western blotting and immunohistochemical studies demonstrated that iNOS proteins were more strongly expressed on vasectomized testes as time passed after vasectomy. Examination of consecutive sections from the vasectomized testis revealed that visibly apoptotic germ cells that exhibited positive staining for cellular DNA fragmentation were also intensely stained for eNOS and iNOS. NF kappa B p65 proteins were more strongly expressed in the nucleus of germ cells in the vasectomized testis than in the sham-operated testis. CONCLUSIONS: We found that vasectomy results in damage to spermatogenesis in adult rats, that may induce germ cell apoptosis, and that iNOS and NF kappa B may play a critical role in the germ cell apoptosis after vasectomy.

Animals↗
PubMed2001

Effects of isoproterenol on spontaneous excitations in detrusor smooth muscle cells of the guinea pig.

PURPOSE: Because beta-adrenoceptor agonists would be a useful tool for the pharmacological treatment of unstable bladder, we investigated the cellular mechanisms underlying beta-adrenoceptor mediated inhibition on spontaneous excitation in detrusor smooth muscle. MATERIALS AND METHODS: Detrusor smooth muscle bundles were isolated from guinea pig bladders. Changes in membrane potential were recorded using an intracellular recording technique. In preparations loaded with the calcium indicator fura-PE3 changes in the concentration of intracellular calcium ions were measured simultaneously with membrane potential. Effects of isoproterenol on spontaneous changes in the membrane potential and intracellular Ca(2+) were examined RESULTS: Detrusor smooth muscle cells exhibited spontaneous action potentials that were associated with transient increases in intracellular Ca(2+) (calcium transients). Isoproterenol, which hyperpolarized the membrane, prevented action potentials and calcium transients. This induced inhibition of calcium transients was not affected by cyclopiazonic acid. Isoproterenol induced hyperpolarization was inhibited by inhibitors of protein kinase A, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride and Rp-adenosine-3',5'-cyclic phosphorothioate. Hyperpolarization was blocked by a solution containing 30 mM. potassium but not by a range of potassium channel blockers. Ouabain and a solution of 0.5 mM. potassium also inhibited hyperpolarization. CONCLUSIONS: Our results suggest that isoproterenol prevented spontaneous action potential discharges and associated calcium transients through the activation of protein kinase A. The isoproterenol induced inhibition of intracellular Ca(2+) largely depends on the prevention of spontaneous action potentials since the contribution of the intracellular calcium store was small. Isoproterenol hyperpolarizes the membrane, probably by stimulating sodium pump activity.

Action Potentials↗
PubMed2001

[Critical role for cell cycle regulators in androgen receptor function].

Androgen plays an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute persistent activation of AR function, even during androgen ablation therapy.

Antineoplastic Agents, Hormonal↗
PubMed2000

Cyclin E as a coactivator of the androgen receptor.

Androgens play an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the COOH terminus portion of the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute to persistent activation of AR function, even during androgen ablation therapy.

Cell Line↗
PubMed2000

Induction of KAI-1 expression in metastatic cancer cells by phorbol esters.

KAI-1 is a tumor suppressor gene whose down-regulation has been shown to be associated with the development of metastases of cancer cells. Here, we demonstrated that KAI-1 expression was induced by activating protein kinase C even in metastatic prostate cancer cell lines in which its expression was significantly down-regulated. KAI-1 expression was enhanced in a dose-dependent manner by PMA, and its induction is at least in part due to transcriptional activation. Pretreatment with calphostin C abrogated its induction by PMA. Our findings may provide useful information for developing a novel drug capable of inducing KAI-1 expression and thereby inhibiting metastasis.

Antigens, CD↗
PubMed2000

N-Glycan structures of an osteopontin from human bone.

N-Glycan structures of osteopontin (a bone matrix protein) from human bone (lumbar vertabrate) are reported in detail. Asn-linked glycan portion was released from 100 microg of osteopontin by digestion with glycoamidase A (from sweet almond), and the reducing ends of the N-glycans were reductively aminated with 2-aminopyridine. The derivatized N-glycans were separated and structurally identified by a multidimensional mapping technique on HPLC columns. Two major N-glycan structures were also confirmed by mass spectrometry. The proposed structures are shown below. The result should permit future comparison with the N-glycan structures of osteopontins obtained from other sources (kidney tissues, macrophages, urinary stones, human milk, etc.).

Aminopyridines↗
PubMed2000

Analysis of osteopontin DNA in patients with urolithiasis.

We previously reported the importance of osteopontin (OPN) in the formation of urinary calculus. Since OPN protein is present in normal kidneys, we investigated the difference in OPN at the DNA level between normal subjects and urolithiasis patients. There has not been any genetic investigation of OPN in familial urolithiasis previously reported worldwide. To confirm hereditary predisposing factors for urolithiasis, changes in OPN DNA within a family were investigated in relation to the presence or absence of urinary calculus. Leukocyte OPN DNA from two normal subjects and five patients with urinary calculus was investigated by SSCP analysis: OPN DNA nucleotide sequence was determined, based on the result of SSCP analysis. As a result, a mutation of GCC to GCT, encoding amino acid position 250 (Ala-250) was found. To confirm the frequency of mutation at this site, OPN DNA was extracted from peripheral blood in 36 normal subjects (Con group), 25 patients with familial urolithiasis (FSF), and 40 patients with recurrent urinary calculus and who had had two or more previous episodes (RSF). The degree of mutation at Ala-250 was then examined by restriction fragment length polymorphism (RFLP) method. As described above, the nucleotide codon encoding the amino acid sequence position 250, Ala-250, was GCC in two normal subjects. This is the original codon. In five patients with urolithiasis it was GCT, showing a substitution of C with T. On examining the frequency of this mutation, the ratio of normal homozygous GCC was 11/36 in the Con group, 1/25 in FSF and 1/40 in RSF. The ratio of heterozygous GCC/GCT was 16/36 in the Con group, 15/25 in FSF and 26/40 in RSF, and the ratio of homozygous GCT was 9/36 in the Con group, 9/25 in FSF and 13/40 in RSF. Furthermore, the gene frequency of the normal codon GCC was 0.528 in the Con group, 0.3 in FSF and 0.35 in RSF, showing a significantly higher incidence in the Con group (P < 0.05). The gene frequency of mutated GCT was 0.472 in Con group, 0.7 in FSF and 0.65 in RSF, showing a significantly higher incidence in urolithiasis patients (P < 0.05). On investigating the inheritance of Ala-250 in five families in which both parent and offspring demonstrated urolithiasis, the nucleotide substitution in Ala-250 in parents with urolithiasis was inherited by their offspring. In all five families the offspring developed urinary calculus. This study showed that there is no difference in OPN structure between the Con group and urolithiasis patients. However, it was predicted that due to the frequency of normally coded GCC being high in the Con group a difference in the amount of OPN might be caused by a difference in transcription velocity between the two groups. Furthermore, it was suggested that examining the inheritance of Ala-250 within a family is a diagnostic method for identifying the predisposing hereditary factors for urolithiasis patients.

Base Sequence↗
PubMed2000

Aberration of chromosomes 8 and 11 in bladder cancer as detected by fluorescence in situ hybridization.

Although a bladder cancer-specific abnormality in chromosomes or genes has not been reported, chromosomal regions that tend to become abnormal have been recognized. In this study, we investigated abnormalities in chromosomes 8 and 11. There were 27 patients with bladder cancer, 16 males and 11 females, who participated in this study. Abnormalities in chromosomes 8 and 11 were investigated by the fluorescence in situ hybridization (FISH) method. Probes used in this study were chromosome 8 alpha-satellite and chromosome 11 alpha-satellite (Oncor Co.). Of 27 cases, 15 cases were positive for chromosome 8 (55.6%) and ten cases were positive for chromosome 11 (37.0%). Since the FISH method detects chromosomal abnormality by the number of signals generated in cancer cells, this method is objective and simple and thus may be applicable in clinical practice.

Adult↗
PubMed2000

Effects of simulated microgravity on mammalian fertilization and preimplantation embryonic development in vitro.

OBJECTIVE: To study the effects of simulated microgravity on mammalian fertilization and preimplantation embryonic development in vitro with the use of a horizontal clinostat device. DESIGN: Controlled animal study. SETTING: Research laboratory at a university medical school. ANIMAL(S): B6D2F1 (C57BL/6 x DBA/2) and ICR mice between 8 and 10 weeks old. INTERVENTION(S): The first experiment was performed to investigate whether gravity is required for fertilization in vitro under three conditions: clinostat rotation, rotational control, and stationary control. In the second experiment, one-cell embryos were cultured under each condition and their morphology and viability were assessed at 96 hours. MAIN OUTCOME MEASURE(S): The fertilized numbers and embryonic numbers at the morula and blastocyst stages were recorded in each condition. RESULT(S): In the first experiment, there were no statistically significant differences in the efficiency of achieving normal fertilization in vitro among the conditions. In the second experiment, there was a statistically significant decrease in the number of embryos reaching the morula and blastocyst stages after 96 hours in culture under clinostat rotation. CONCLUSION(S): These results suggest that the process of fertilization in vitro is not sensitive to the gravitational vector. However, the possibility exists that the frequency of early embryonic lethality is increased by microgravity.

Animals↗
PubMed2000

Clinical features of primary hyperparathyroidism: preoperative localization and parathyroidectory.

The introduction of the multichannel autoanalyser made measurement of serum calcium concentrations easier, and led to a dramatic change in clinical presentations. The reliable methods such as computed tomography (CT), ultrasonography (US) and magnetic resonance imaging (MRI) for preoperative localization of abnormal parathyroid glands has long been sought to increase the cure rate of surgical treatment. We report the clinical feature of primary hyperparathyroidism (PHPT). Patients were classified into four stages in chronological order. The early patients (the first stage, 1970-1979) were mainly diagnosed in the treatment of urolithiasis. Approximately 20% of patients in the second stage (1980-1986) were symptom-free, and hypercalcemia was detected by autoanalyzer. Patients in the third stage (1987-1993) underwent preoperative localization studies including CT. scintigraphy, ultrasonography and MRI. The recent patients (the fourth stage, 1993-1999) were mostly treated in the present hospital. In the first stage, PHPT was an uncommon metabolic disorder hat was typically associated with nephrolithiasis and was two to three times more common in men than in women. In the second, third and fourth stages, PHPT is a common and often symptomless endocrine disorder. The ratio of male to female is decreasing, because men are dominant in stone-formers. Four parathyroid glands were searched carefully in the first and second stages, and unilateral cervical exploration was performed in some preoperatively localized parathyroid glands in the third and fourth stages.

Aged↗
PubMed2000

Congenital urethrocutaneous fistula.

BACKGROUND: A 3-year-old boy visited our hospital for aberrance of urination. He had a fistula on his ventral penile shaft. Our diagnosis was congenital urethrocutaneous fistula. METHODS/RESULTS: We performed one-stage repair transverse preputial onlay island flap urethroplasty. Postoperatively, the patient was voiding comfortably with no recurrence of fistula. CONCLUSIONS: Congenital urethrocutaneous fistula is rare. Eighteen cases of congenital urethrocutaneous fistula have been reported previously. We consider the etiology of congenital urethrocutaneous fistula as a deficiency of the urethral plate and fusion of urethral folds.

Child, Preschool↗
PubMed2000

Immunohistochemical detection of carcinogen-DNA adducts in normal human prostate tissues transplanted into the subcutis of athymic nude mice: results with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 3,2'-dimethyl-4-aminobiphenyl (DMAB) and relation to cytochrome P450s and N-acetyltransferase activity.

Human prostate tissue transplanted into nude mice was examined immunohistochemically for DNA adducts formed after administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Positive staining for DMAB- or PhIP-DNA adducts was evident in 70-95% of both epithelial and stromal cells in human prostate xenografts. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a normal human prostate epithelial cell line (PrEC) to express both cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) mRNA, while a normal human prostate fibroblast cell line (NHPF) expressed NAT2, but not CYP1A2 mRNA. In addition, NAT2 and to a lesser extent CYP1A2 mRNAs were also found in four cases of normal human prostate tissues. The results suggest that initial activation of chemicals by liver CYP1A2 and subsequent metabolism by prostate NAT2 is a major pathway of DNA adduct formation in human prostate cells. Thus, the data suggest that human prostate has the potential to be targeted by environmental carcinogens.

Aged↗
PubMed2000

Cystic lymphangioma of retroperitoneum and groin.

We report a case of cystic lymphangioma of the retroperitoneum and groin. A 38-year-old male was referred to our hospital due to a right inguinal mass without tenderness. CT, MRI revealed retroperitoneal mass and inguinal mass. Biopsy of the inguinal mass was performed. The lesion was multicystic, and adherent to the surrounding tissue. Pathological examination revealed lymphangioma.

Adult↗
PubMed2000

Solitary fibrous tumor of the peritoneum found in the prevesical space.

Solitary fibrous tumors (SFT) are well recognized in the pleura, but their rare occurrence at other sites has become appreciated only in recent years. We experienced a 68-year-old male patient who presented with frequency of urination and difficulty in voiding. Computed tomographic scan revealed a solid and cystic mass which measured 12 x 10 cm in the prevesical space. This tumor showed typical histopathologic features of SFT, and was immunostained positive for vimentin, CD34 and CD99. This is an extremely rare case of SFT arising from the parietal peritoneum found in the prevesical space.

Aged↗
PubMed2000

Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages.

There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other than their antibacterial properties. In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro. The release of NO was assessed by direct measurement with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determined by Northern blotting. Incubation of PAMs with lipopolysaccharide from Escherichia coli and recombinant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA. The release of NO was reduced by coincubation of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 73+/-10, 81+/-6 and 84+/-9%, respectively, but was not altered by amoxycillin or cefaclor. These macrolides likewise inhibited the induction of type II NOS mRNA, whereas no inhibitory effects were observed with amoxycillin or cefaclor. These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airway inflammation.

Amoxicillin↗