Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 181 records · Page 10Linked to original sources

PubMed1998

Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin.

Osteoclasts are multinucleated cells that resorb bone. Osteoclastogenesis inhibitory factor (OCIF), also called osteoprotegerin (OPG), acts as a naturally occurring decoy receptor for osteoclast differentiation factor, which mediates an essential signal to osteoclast progenitors for their differentiation into osteoclasts. Here we show that the OCIF/OPG knockout mice exhibited severe osteoporosis due to enhanced osteoclastogenesis when they grew to be adults. These mice were viable and fertile. They exhibited marked bone loss accompanied by destruction of growth plate and lack of trabecular bone in their femurs. The strength of their bones dramatically decreased. These results demonstrate that OCIF/OPG is a key factor acting as a negative regulator against osteoclastogenesis. The OCIF/OPG knockout mice provide the first animal model for osteoporosis without other obvious abnormalities.

Animals↗

PubMed1998

Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone.

Osteoclast differentiation factor (ODF), a ligand for osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF), induces osteoclast-like cell formation in vitro. To elucidate the role of ODF in the microenvironment of bone, we examined effects of ODF, OPG/OCIF, and anti-ODF polyclonal antibody on bone resorption using a fetal mouse long bone culture system. A genetically engineered soluble-form ODF (sODF) elicited bone resorption in a concentration-dependent manner and OPG/OCIF blocked the bone resorption. Anti-ODF polyclonal antibody, which neutralizes ODF activity, negated bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, parathyroid hormone, or prostaglandin E2. OPG/OCIF also abolished bone-resorbing activity elicited by these bone-resorbing agents. Interleukin 1 alpha-stimulated bone resorption was also significantly suppressed by anti-ODF polyclonal antibody and OPG/OCIF. Thus, we conclude that ODF plays a critical role in bone resorption in the microenvironment of bone.

Animals↗

PubMed1998

Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL.

Osteoclasts, the multinucleated cells that resorb bone, develop from hematopoietic cells of monocyte/macrophage lineage. Osteoclast-like cells (OCLs) are formed by coculturing spleen cells with osteoblasts or bone marrow stromal cells in the presence of bone-resorbing factors. The cell-to-cell interaction between osteoblasts/stromal cells and osteoclast progenitors is essential for OCL formation. Recently, we purified and molecularly cloned osteoclastogenesis-inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF is a secreted member of the tumor necrosis factor receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction. Here we report the expression cloning of a ligand for OPG/OCIF from a complementary DNA library of mouse stromal cells. The protein was found to be a member of the membrane-associated tumor necrosis factor ligand family and induced OCL formation from osteoclast progenitors. A genetically engineered soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells. OPG/OCIF abolished the OCL formation induced by the protein. Expression of its gene in osteoblasts/stromal cells was up-regulated by bone-resorbing factors. We conclude that the membrane-bound protein is osteoclast differentiation factor (ODF), a long-sought ligand mediating an essential signal to osteoclast progenitors for their differentiation into osteoclasts. ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only osteoclastogenesis but also immune system.

Animals↗

PubMed1998

Central pressor effect of parathyroid hormone-related protein in conscious rats.

Although the parathyroid hormone-related protein gene is widely expressed in the central nervous system, the role of this protein in blood pressure is unknown. This article examines whether parathyroid hormone-related protein is involved in the central regulation of blood pressure. An intraventricularly injected solution of parathyroid hormone-related protein elicited a dose-dependent increase of mean arterial pressure accompanied by a decrease of heart rate in conscious Sprague-Dawley rats. An anti-parathyroid hormone-related protein monoclonal antibody, given in an intraventricularly injected solution, blocked the pressor effect of parathyroid hormone-related protein. Furthermore, this pressor effect of parathyroid hormone-related protein was also abolished after pretreatment by intravenous administration of either hexamethonium bromide or doxazosin mesylate. These results suggest that central parathyroid hormone-related protein is implicated in the regulation of blood pressure, and that this effect may be mediated through sympathetic activation.

Analysis of Variance↗

PubMed1998

DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs.

We report the identification of a transcription elongation factor from HeLa cell nuclear extracts that causes pausing of RNA polymerase II (Pol II) in conjunction with the transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). This factor, termed DRB sensitivity-inducing factor (DSIF), is also required for transcription inhibition by H8. DSIF has been purified and is composed of 160-kD (p160) and 14-kD (p14) subunits. Isolation of a cDNA encoding DSIF p160 shows it to be a homolog of the Saccharomyces cerevisiae transcription factor Spt5. Recombinant Supt4h protein, the human homolog of yeast Spt4, is functionally equivalent to DSIF p14, indicating that DSIF is composed of the human homologs of Spt4 and Spt5. In addition to its negative role in elongation, DSIF is able to stimulate the rate of elongation by RNA Pol II in a reaction containing limiting concentrations of ribonucleoside triphosphates. A role for DSIF in transcription elongation is further supported by the fact that p160 has a region homologous to the bacterial elongation factor NusG. The combination of biochemical studies on DSIF and genetic analysis of Spt4 and Spt5 in yeast, also in this issue, indicates that DSIF associates with RNA Pol II and regulates its processivity in vitro and in vivo.

Amino Acid Sequence↗

PubMed1998

Investigation of the potential active site of a cyanide dihydratase using site-directed mutagenesis.

Cyanide dihydratase has conserved residues in the amino acid sequence with nitrilase, and cyanide hydratase. The conserved amino acid residues in the cyanide dihydratase from Pseudomonas stutzeri AK61 were altered by site-directed mutagenesis. The enzyme completely lost its activity of the cyanide hydrolysis by the replacement of cysteine-163 to serine. The replacement of tyrosine-53 to phenylalanine caused an increase of the K(m) value of the enzyme for cyanide. Substitution of nine other residues seemed to affect the structure of the enzyme.

Amino Acid Sequence↗

PubMed1998

Effects of walking on mortality among nonsmoking retired men.

BACKGROUND: The potential benefit of low-intensity activity in terms of longevity among older men has not been clearly documented. We examined the association between walking and mortality in a cohort of retired men who were nonsmokers and physically capable of participating in low-intensity activities on a daily basis. METHODS: We studied 707 nonsmoking retired men, 61 to 81 years of age, who were enrolled in the Honolulu Heart Program. The distance walked (miles per day) was recorded at a base-line examination, which took place between 1980 and 1982. Data on overall mortality (from any cause) were collected over a 12-year period of follow-up. RESULTS: During the follow-up period, there were 208 deaths. After adjustment for age, the mortality rate among the men who walked less than 1 mile (1.6 km) per day was nearly twice that among those who walked more than 2 miles (3.2 km) per day (40.5 percent vs. 23.8 percent, P=0.001). The cumulative incidence of death after 12 years for the most active walkers was reached in less than 7 years among the men who were least active. The distance walked remained inversely related to mortality after adjustment for overall measures of activity and other risk factors (P=0.01). CONCLUSIONS: Our findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate. Encouraging elderly people to walk may benefit their health.

Aged↗

PubMed1998

Oral mucosal adhesive film containing local anesthetics: in vitro and clinical evaluation.

In vitro and in vivo studies were conducted to gauge the effectiveness of a novel oral mucosa adhesive, moderately water-soluble, pliant polymer artificial dentifrice (AD) film containing dibucaine (DC) for relief of pain due to oral erosion. The film was prepared from a hydroxypropyl cellulose-M (HPC-M) ethanol solution containing varying amounts of DC, as well as polyethylene glycol. In the in vitro experiments, the disintegration of HPC-M showed a lag time of about 50 min, a much lower rate than that of drug release, which more or less leveled off after 50 min. Twenty-five percent of the DC was released from the film (0.113 and 0.225 mg/cm2) after the initial 5 min, which then reached about 80% after 50 min, the time at which the polymer began to break up. In the in vivo study, the local anesthetic effect of the film was evaluated in 23 patients (10 males, 13 females) suffering from the adverse effects of chemotherapy. When applied to the wet surface of the mucosa, the AD film absorbed moisture and showed excellent adhesion. Pain relief in patients lasted 2.2 +/- 0.21 and 4.3 +/- 0.25 h at DC doses of 0.113 and 0.225 mg/cm2, respectively. These results suggest that the AD film may cover mucositis sites of oral mucosa long enough to allow DC release and bring relief from pain arising from chemotherapy and/or radiotherapy.

Adhesives↗

PubMed1998

The value of squamous cell carcinoma antigen as a predictor of nodal metastasis in cervical cancer.

Preoperative serum squamous cell carcinoma antigen (SCC) levels were examined in 148 cases of stage Ib squamous cervical cancer undergoing radical hysterectomy. The effect of the pelvic lymph node status on the marker level was examined by comparing 113 cases with cancer limited to the uterus and 23 cases with cancer confined to the uterus and pelvic lymph nodes using two different multivariate analyses. Ninety-five percent of patients with cancer limited to the uterus showed SCC levels of 4 ng/ml or below. Nearly two-thirds (65%) of patients with serum levels above 4 ng/ml exhibited pelvic lymph node metastasis. The marker values exceeding 4 ng/ml increased the risk of nodal metastasis by eight times, compared with serum levels of 4 ng/ml or below. Multivariate analyses confirmed that the pelvic lymph node metastasis had a larger impact on the marker level than did tumor size or depth of stromal infiltration. SCC levels greater than 4 ng/ml can be considered a high-risk zone for nodal metastasis.

Adolescent↗

PubMed1998

Ovarian metastasis in endometrial carcinoma.

A retrospective study was conducted to investigate the clinical significance of ovarian metastasis in 439 patients with clinical stage I endometrial cancer surgically treated by performing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Histologic examination revealed that 22 patients (5%) had ovarian metastasis. The maximum diameter of the ovarian metastases ranged from 1 to 100 mm. In 18.2% (4/22) of patients with ovarian metastasis, the maximum diameter was less than 2 mm. Patients with metastasis limited to the ovarian surface showed 100% positive peritoneal cytology, 0% lymph node metastases, and 50% recurrence, while patients with metastasis inside the ovary showed 10% positive peritoneal cytology, 36% lymph node metastases, and 53% recurrence. The prognosis of patients with ovarian metastasis alone was situated midway between that of patients with cancer limited to the uterus and that of patients with lymph node metastasis alone. The lymph node status was of importance to determine the prognosis of patients with ovarian metastasis. The series also suggests that there may be two routes for ovarian metastasis; one is a route via the fallopian tube to the ovarian surface and the other is a route via the lymphatics to the inside of the ovary.

Analysis of Variance↗

PubMed1998

Cloning and expression of a gene encoding cyanidase from Pseudomonas stutzeri AK61.

The gene coding for cyanidase, which catalyzes the hydrolysis of cyanide to formate and ammonia, was cloned from chromosomal DNA of Pseudomonas stutzeri AK61 into Escherichia coli. The cyanidase gene consisted of an open reading frame of 1004 bp, and it was predicted that cyanidase was composed of 334 amino acids with a calculated molecular mass of 37,518 Da. The amino acid sequence of cyanidase showed a 35.1% and 26.4% homology to aliphatic nitrilase from Rhodococcus rhodochrous K22 and cyanide hydratase from Fusarium lateritium, respectively. A unique cysteine residue of aliphatic nitrilase, which was suggested to play an essential role in the catalytic activity, was conserved in cyanidase. The active form of cyanidase was successfully expressed by a DNA clone containing the cyanidase gene in E. coli. Its productivity was approximately 230 times larger than that of P. stutzeri AK61. The characteristics of the expressed cyanidase, including optimum pH, optimum temperature. Michaelis constant (K(m)) for cyanide and specific activity, were similar to those of the native enzyme from P. stutzeri AK61.

Amino Acid Sequence↗

PubMed1998

Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome.

To elucidate the role of the KVLQT1 gene in the pathogenesis of long QT syndrome (LQTS), we have established a screening system for detecting KVLQT1 mutations by the polymerase chain reaction-single strand conformation polymorphism technique (PCR-SSCP). We first determined exon/intron boundaries and flanking intronic sequences, and found that the KVLQT1 gene consists of 17 coding exons. Subsequently, we synthesized oligonucleotide primers to cover the coding region and the flanking intronic sequences, and searched for mutations in 31 Japanese LQTS families. When genomic DNA from each proband was examined by PCR-SSCP followed by direct DNA sequencing, mutations were detected in five families; two independent families carried the same mutation and three of the four were novel. Each mutation was present in affected relatives of the respective proband. This work will enable us to search more thoroughly for LQTS mutations associated with KVLQT1, and eventually will help us in finding genotype/phenotype relationships.

DNA Mutational Analysis↗

PubMed1998

Abdominal surgery for patients on maintenance hemodialysis.

Despite the growing number of major surgical procedures being performed for patients on maintenance hemodialysis, few reports focus on the management and outcome of such patients, especially those undergoing major abdominal surgery. We conducted a retrospective review of 30 patients on maintenance hemodialysis who underwent abdominal surgery, 20 of whom underwent an elective operation and 10, an emergency operation. The indications of elective surgery included gastrointestinal cancer, biliary tract disease, and abdominal aortic aneurysm, while those for emergency surgery mainly involved gastrointestinal perforation or bleeding. There were no statistically significant differences between the elective group and the emergency group regarding either the mean time on hemodialysis or the preoperative clinical data. The morbidity and mortality rates were 15% and 10%, respectively, for the patients who underwent elective surgery and 50% and 70%, respectively, for those who underwent emergency surgery (P < 0.01 and P < 0.05, respectively). Those patients with more than a 2-year history of hemodialysis had a significantly higher mortality rate following abdominal surgery than those with less than a 2-year history (P < 0.01). Thus, the morbidity and mortality rates of patients on maintenance hemodialysis who require major abdominal surgery are significantly high, which reinforces the need to further improve the intensive perioperative management of such patients.

Abdomen↗

PubMed1998

ST-segment elevation in right precordial leads implies depressed right ventricular function after acute inferior myocardial infarction.

BACKGROUND: The prognosis of acute inferior myocardial infarction is worse when it is complicated by right ventricular infarction. ST elevation in the right precordial leads is one of the reliable methods for detecting acute right ventricular infarction. The purpose of the study was to examine the relation between ST elevation in the right precordial electrocardiographic leads during acute inferior infarction and the severity of right ventricular systolic dysfunction. METHODS: This study analyzed the relation between ST elevation > or = 0.1 mV in V4R and the severity of right ventricular systolic dysfunction in 43 consecutive patients (men/women: 35/8; average age 62+/-9 years) with acute inferior myocardial infarction with a rapid-response Swan-Ganz catheter to measure the right ventricular ejection fraction (RVEF). RESULTS: RVEF was significantly lower in patients with ST elevation (n = 18) than in those without (n = 25) (33%+/-6% vs 40%+/-9%, p = 0.010). If the infarct-related lesion was located in the proximal right coronary artery, RVEF tended to be lower than if the lesion was located in the distal right coronary artery or the left circumflex coronary artery (33%+/-10% vs 37%+/-9% vs 42%+/-9%, p = 0.101). Logistic regression analysis demonstrated that ST elevation in V4R was the only independent predictor of depressed RVEF (odds ratio = 5.31, 95% confidence interval = 1.28 to 22.1, p = 0.022). CONCLUSION: ST elevation in lead V4R during acute inferior myocardial infarction predicts right ventricular systolic dysfunction.

Adult↗

PubMed1998

Natural hepatocyte growth factor (HGF) from human serum and a bound form of recombinant HGF with heparan sulfate are indistinguishable in their physicochemical properties.

Natural hepatocyte growth factor (nHGF) purified from human serum showed a difference in molecular mass (Mr) between SDS PAGE (76-90 kDa) and gel filtration chromatography on a Sephadex G-200 column (> 200 kDa), whereas nHGF or recombinant HGF (rHGF) from cell culture medium did almost the same Mr (74-100 kDa). A bound form of rHGF with heparan sulfate (or heparin), and an aggregate form of rHGF itself showed a homogeneous band with a Mr of 76-90 kDa on SDS PAGE, but showed a Mr larger than 200 kDa on a Sephadex G-200 column. Both nHGFs, rHGF and the bound form were basic, but the aggregate form was acidic in ionic nature. No significant difference was found in affinity for heparin among these HGF preparations. The bound form treated by the procedures for purification of nHGF from human serum still showed a larger molecular form. The bound form mimicked physicochemical properties of nHGF purified from human serum. These results suggest that a possible form of nHGF in human serum may be a bound form with heparin-like molecules such as heparan sulfate, which are found in the circulation and on cell surface, and purified as the bound form.

Animals↗

PubMed1998

Coffee consumption in hypertensive men in older middle-age and the risk of stroke: the Honolulu Heart Program.

OBJECTIVE: To examine the association between coffee consumption and the development of stroke in men at high risk for cardiovascular disease. METHODS: Coffee intake was observed from 1965 to 1968 in a cohort of men enrolled in the Honolulu Heart Program with follow-up for incident stroke over a 25-year period. Subjects were 499 hypertensive men (having systolic or diastolic blood pressures at or above 140 and 90 mm Hg, respectively) in older middle-age (55 to 68 years) when follow-up began. Past and current cigarette smokers were excluded from follow-up. RESULTS: In the course of follow-up, 76 men developed a stroke. After age-adjustment, risk of thromboembolic stroke increased significantly with increases in coffee consumption (P = 0.002). No relationships were observed with hemorrhagic stroke. When adjusted for other factors, the risk of thromboembolic stroke was more than doubled for men who consumed three cups of coffee per day as compared to nondrinkers of coffee (RR = 2.1; 95% CI = 1.2-3.7). CONCLUSIONS: Although in need of further confirmation, consumption of coffee appears to be positively associated with an increased risk of thromboembolic stroke in hypertensive men in older middle-age. Findings suggest that it may be prudent to advise older middle-aged men with hypertension who consume large amounts of coffee to consider reducing their coffee intake.

Aged↗

PubMed1998

Simultaneous activation of two different receptor systems by enkephalin/neurotensin conjugates having spacer chains of various lengths.

Bivalent ligands composed of enkephalin and neurotensin were prepared and their action in the receptor-receptor interaction was studied with the neuroblastoma cell, NG108-15. Enkephalin was connected via oligosarcosine spacer chain to the N-terminus of neurotensin(8-13). The bivalent ligand stimulated the cGMP production more than plain neurotensin. The affinity of the bivalent ligands for the neurotensin receptor changed with varying lengths of the spacer chain. When the spacer chain was an octamer or a dodecamer of sarcosine, the receptor affinity of those bivalent ligands was higher than neurotensin(1-13), and significantly decreased in the presence of excess amount of enkephalin. These results suggest that the bivalent ligands bind to opioid receptor and neurotensin receptor simultaneously, leading to receptor-receptor interaction. On the other hand, some bivalent ligands, especially that without a spacer chain seemed to bind to the neurotensin receptor by the help of the enkephalin part interacting with a receptor exosite.

Animals↗

PubMed1998

Prolonged QTc interval, impaired pulmonary function, and a very lean body mass jointly predict all-cause mortality in elderly men.

PURPOSE: Assess the joint impact of prolonged QTc interval (QT interval corrected for heart rate), impaired lung function, and low body weight on all-cause mortality. METHODS: This is a population-based, prospective study of the Honolulu Heart Program cohort, performed in Oahu Island, Hawaii, during the 1991-1993 fourth examination of cohort survivors. The participants were 3056 Japanese-American men, 71 to 93 years of age. The measurement consisted of: 1) instrument calculated, heart rate corrected QT interval; 2) one second forced expiratory volume (FEV1) as a percentage of age- and height-predicted FEV1; and 3) body mass index (BMI, kg/m2). Relations of subsequent 3 1/2 year, on average, mortality rates with high risk states of these variables are determined. High risk states are QTc > 440 msec, percent predicted FEV1 < or = 80%, and BMI < or = 21 kg/m2. RESULTS: Mortality rates synergistically increase among groups with one, two, or three high risk states. Men having all three high risk states are seven times more likely to die in the follow-up period than men with no high risk conditions. Very thin men having one other high risk state, pulmonary impairment or prolonged QTc, are four times more likely to die. Excluding diabetics, active smokers, or men taking drugs affecting QT interval does not alter findings. Excluding prevalent coronary heart disease decreases mortality rates among joint high risk groups. CONCLUSION: Results are consistent with clinical studies identifying an autonomic neuropathy associated with wasting chronic lung disease, prolonged QTc, and mortality. Aging populations in developed nations will increase the prevalence of diseases associated with these conditions in decades to come.

Aged↗