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Biomedical subjects

K Horiuchi

Publications and source records attributed to K Horiuchi.

At least 73 records · Page 4Linked to original sources

[Trend of aging on the number of teeth investigated through a survey of dental health representation in a simple equation by using a kinetic method and its application].

A survey of dental health was conducted on 6,933 residents (aged 61.8 +/- 11.1) in 4 villages Nara Prefectural Uchiyoshino Health Center administers. Examinees were divided into 7 ages groups. The mean value of present teeth at each age group was calculated. Age dependency of number of teeth was investigated with a kinetic model based on the following premise. 1. Changes between age groups can be treated as a time series occurrence. 2. Number of missing teeth can be estimated as 29 - that of present teeth. Results show that the rate of decrease of the number of present teeth is of a first order in itself and the number of missing teeth. It can be mathematically expressed as follows: -dX/dt = k.X.(29 - X).......eq. (1). in which X = number of present teeth, 29 - x = number of missing teeth k = rate constant, t = time. From this simple relationship the following are suggested 1. Tooth loss is caused by the interaction of present teeth and sites where teeth are lost. 2. Integration of eq. (1) yields ln¿(29 - X)/X¿ = 29.k.t + a.......eq. (2). in which 0 < X < 29, t = time from the youngest age group (20-29), a = constant. It appears that, from eq. (2), the dental health of a community is determined by two coefficients, 29.k and a. 3. Helping a person realize his present and future dental state and to motivate action for prevention of tooth loss by showing him his rate of decrease, "tooth age" and the predicted number of teeth a certain years later calculated from eq. (1) and eq. (2), can be of great value. 4. Eq. (2) is transformed to X = 29/¿exp(29.k.t + a) + 1¿, which represents the reverse S-shaped curve of the age dependency of the number of teeth. 5. Applying this method to cohort analysis will enable forecast of the trend of the number of teeth.

Adult↗

A tumor preventive effect of dietary restriction is antagonized by a high housing temperature through deprivation of torpor.

Energy restriction (ER) has proven to be the only effective means of retarding aging in mice. The mechanisms of multiplicity of effects of ER on aging remain, however, fragmentary. ER induces daily torpor, the induction of which is reduced by increasing the ambient temperature to 30 degrees C. The effects of preventing hypothermia in ER animals were studied in terms of the expected consequences of ER on survival, disease pattern and a number of physiological parameters in autoimmune prone MRL/lpr mice and lymphoma prone C57BL, 6 mice. The results demonstrate that torpor plays a crucial role in the prevention of lymphoma development but does not have an affect on other aspects of ER, such as prevention of autoimmune diseases.

Aging↗

Lack of vasodilatory response in skeletal muscle blood vessels of aged spontaneously hypertensive rats.

Regional hemodynamic responses to the vasodilators, hydralazine (1 mg/kg, i.v.) and verapamil (0.1 mg/kg/min, i.v.), were examined in conscious Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), 15 and 50 weeks of age, using the radioactive microsphere method. The flow rates of heart and skeletal muscle in SHR were higher than those in WKY, and the flow rates of liver, kidney, intestines, and skin in SHR were lower than those in WKY. These differences between the regional blood flow in WKY and SHR were observed in both aged and young rats. The changes in organ blood flow induced by hydralazine and verapamil were similar for WKY and SHR in most organs. Both drugs increased the skeletal muscle blood flow in WKY and young SHR, but not in aged SHR, that is, the skeletal muscle blood vessels in aged SHR lost their vasodilatory response. These results suggest that, although a lack of vasodilatory responses in the skeletal muscle vasculature of aged SHR may be triggered by persistent hypertension, the vital organ vasculature maintains its normal vasodilating capacity.

Age Factors↗

Applicability of short-lived radiometallic nuclide for high sensitivity two-site "sandwich" immunoradiometric assay: human growth hormone assay.

The sensitivity of the IRMA method is limited by the specific activity (SA) of the conventionally employed radioisotropic label and high sensitivity radioimmunoassay should theoretically be attained by the use of short-lived radiometallic nuclides. Our group have achieved radiolabeling of high SA IgG by using the radiometal, gallium-67 (67Ga) with a short half-life (T1/2 = 78 h) and deferoxamine (DF), a bifunctional chelating agent bound through a multispacer (dialdehyde starch, DAS) as the linker (J Nucl Med 32:825, 1991). In the present work, the application of the approach is attempted by employing a two-site IRMA for human growth hormone (hGH); the monoclonal antibody to hGH (MAB2) is bound to DF via DAS and the coupled DF-DAS-MAB2 is radiolabeled with 67Ga. The 67Ga-DF-DAS-MAB2 of high SA (4,884 MBq/mg versus 370-518 MBq/mg calculated for radioiodinated MAB2) was thus used for the two site 'sandwich' 67Ga-IRMA. Excellent correlation with the 125I-IRMA was registered, and higher detection capability obtained by using 67Ga over the 125I in the hGH IRMA offered a good basis for the exploitation of short-lived radio-nuclides in the IRMA system.

Antibodies, Monoclonal↗

The effect of tamoxifen on bone metabolism and skeletal growth is different in ovariectomized and intact rats.

The effects of tamoxifen (TAM) treatment on bone metabolism and skeletal growth were studied in sexually mature intact or ovariectomized (OVX) rats. Experiment 1 was designed to observe the effects of TAM on bone metabolism and skeletal growth in intact rats and included two groups: (1) intact plus vehicle and (2) intact plus TAM. Experiment 2 was designed to investigate the effects of TAM on OVX rats and included the other two groups: (3) OVX plus vehicle and (4) OVX plus TAM. Serum calcium osteocalcin and urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured serially before and after TAM treatment for 6 weeks in order to monitor bone turnover. Bone mineral density (BMD) and bone mineral content (BMC) of excised right femora and lumbar vertebrae were determined by dual energy X-ray absorptiometry (DXA). To examine the effect of TAM on skeletal growth, the conventional parameters of femora and the histology of right tibiae were also measured. TAM did not induce significant change in the biochemical markers in intact rats during the 6-week experiment. Bone mass and skeletal growth were not changed by TAM treatment in intact rats. However, TAM treatment reduced the increase in serum osteocalcin and urinary pyridinium cross-links from 1 week to 6 weeks postovariectomy in the OVX rats. TAM inhibited the skeletal growth in OVX rats, because TAM treatment shortened femoral length and decreased the cell number in the growth plate in OVX rats in this study. Our findings indicate that TAM exerts an effect of estrogen agonist on bone metabolism and skeletal growth in OVX rats, however, it does not affect them in intact rats.

Animals↗

Cryptogenic localization-related epilepsy of neonatal onset.

We report three patients with localization-related epilepsy of neonatal onset. They exhibited favourable psychomotor development and had no cerebral lesions on neuroimaging studies despite the presence of intractable partial seizures of neonatal onset. Although rare, some cases of epilepsy of neonatal onset may be cryptogenic, i.e. they belong to neither the symptomatic nor the idiopathic group.

Blood Glucose↗

Recognition mechanisms of the minus-strand origin of phage f1 by Escherichia coli RNA polymerase.

BACKGROUND: The primer RNA for the synthesis of the minus strand of filamentous coliphages is produced by host RNA polymerase at a specific site on the plus strand template. The mechanism used by the enzyme in recognizing the origin is unknown, but minus strand replication requires the holoenzyme form of RNA polymerase. The origin contains two inverted repeats which can form hairpins. RESULTS: When the origin sequence is drawn arranging the two hairpins horizontally, it resembles a stretch of a mostly double-stranded molecule. The nucleotides protected from nucleases by the holoenzyme were found to be located in two regions on this drawing: one around the 35th nucleotide upstream of the RNA start site, and the other ranging from the 10th nucleotide upstream to the 10th downstream, of the start site. The core enzyme did not show any protection. Mutational analyses of the origin indicated that the base-paired structure in the former region was important for origin activity. In the region around the 10th nucleotide upstream of the start site, specific base(s) in the non-template strand were required for origin activity, while the base sequence of the template strand was irrelevant. CONCLUSIONS: It is likely that the recognition mechanism of the origin by RNA polymerase shares common features with that of transcriptional promoters.

Base Sequence↗

Overproduction of penicillin-binding protein 7 suppresses thermosensitive growth defect at low osmolarity due to an spr mutation of Escherichia coli.

Escherichia coli delta prc mutants lacking periplasmic protease Prc, which was originally found involved in the C-terminal processing of penicillin-binding protein (PBP) 3, show thermosensitive growth at low osmolarity. We isolated thermoresistant revertants containing extragenic suppressor (spr) mutations. In the prc+ background the mutations also caused thermosensitivity at low osmolarity. They were all mapped at about 48 min on the chromosome and most probably allelic to one another. From this chromosomal region we cloned a gene that could correct the thermosensitive defect of an spr mutant, which turned out to be a multicopy suppressor of spr. Analysis of the nucleotide sequence predicted that the gene would code for a low-molecular-weight PBP, and penicillin-binding experiments revealed the product to be PBP 7. Disruption of the gene on the chromosome caused no apparent growth defect. PBP 7 seemed to be degraded by protease Prc. Overproduction of mutant PBP 7 that had the active site serine residue replaced with alanine did not correct the spr thermosensitivity, suggesting importance of the DD-endopeptidase activity in the multicopy suppression.

Alleles↗

Modulating effects of propofol on metabolic and cardiopulmonary responses to stressful intensive care unit procedures.

OBJECTIVE: Patients in the intensive care unit (ICU) undergo acute increases in metabolic and cardiopulmonary demands in response to routine care interventions, such as chest physical therapy. This study examined whether the short-acting drug, propofol, could blunt the responses to chest physical therapy. DESIGN: Prospective, randomized, crossover (placebo vs. drug) study. SETTING: University hospital surgical ICU. PATIENTS: Postoperative ICU patients being ventilated in the synchronized intermittent mandatory ventilation mode. INTERVENTIONS: Two groups of 16 patients were studied. Each patient received two successive sessions of chest physical therapy. In random fashion, one was preceded by the administration of placebo and the other by an intravenous bolus of propofol (0.75 mg/kg in one group and 0.35 mg/kg in the other group). Each session was preceded and followed by a period of rest. MEASUREMENTS AND MAIN RESULTS: The increases in oxygen uptake, CO2 elimination, oxygen delivery, heart rate, and systolic blood pressure associated with chest physical therapy were attenuated with the low dose and suppressed with the high dose of propofol. The Paco2 concentration was slightly increased during both placebo and drug administration. CONCLUSIONS: Propofol, in the doses administered in this study, significantly reduced the hemodynamic and metabolic stresses caused by chest physical therapy.

Adult↗

Identification of F-reticulocytes by two-stage fluorescence image cytometry.

Precise determination of reticulocytes (young red blood cells) containing fetal hemoglobin (Hb F), F-reticulocytes, is important for assessment of the efficacy of drugs such as hydroxyurea and butyrate in elevating the levels of Hb F in patients with sickle cell disease (SCD) and beta-thalassemia. We developed a reliable and easily applicable method for determining F-reticulocytes using fluorescence image cytometry. Reticulocytes were first identified by preparing a monolayer smear of blood stained by acridine orange. Images of reticulocytes and of all cells were obtained for a selected area on the smear. After removing the acridine orange, cells containing Hb F (F-cells) in the same area were then identified by immunofluorescence. Using images of F-cells, reticulocytes, and all cells for the same fields it was possible to identify F-reticulocytes. To assess the validity of our two-stage staining method, we compared our results with those obtained by traditional methods. There was significant correlation of our method with the conventional immunofluorescence staining method for F-cells (r2 = 0.99; slope = 0.99) and with the accepted brilliant cresyl blue method for reticulocytes (r2 = 0.97; slope = 0.96). Heretofore, the ability to determine F-reticulocyte levels has been limited to a small number of laboratories possessing special equipment and techniques. The method presented here should be of great interest to many basic science and clinical investigators involved in studies evaluating synthesis of Hb F.

Acridine Orange↗

Sickling in vitro of reticulocytes from patients with sickle cell disease at venous oxygen tension.

Changes in the degree of sickling in vitro of reticulocytes and nonreticulocytes from patients with sickle cell disease were studied under complete deoxygenation (PO2 = 0 mm Hg) and partial deoxygenation (PO2 = 30 mm Hg, the average PO2 in the venous circulation) conditions at pH 7.4. Degree of sickling was quantitated by image analysis after identification of reticulocytes by acridine orange staining. Sickling in vitro of reticulocytes and nonreticulocytes under complete deoxygenation was similar and relatively unchanged during a 2-hour incubation. In contrast, under partially deoxygenated conditions, at least two populations of reticulocytes were apparent, one more susceptible to sickling than the other; nonreticulocytes were generally less susceptible to sickling. Many of the severely deformed reticulocytes showed formation of long spicules during incubation. These data suggest that a subset of reticulocytes are more susceptible to sickling than nonreticulocytes, and that the degree of reticulocyte sickling in vitro increases dramatically with time even at constant partial oxygen pressures observed in the venous circulation. Since dehydration in sickled reticulocytes seemed to be proceeding, mechanisms of inhibition were also examined. We found that quinine, an inhibitor of the Ca(++)-activated K+ efflux, inhibited part of the reticulocyte sickling while okadaic acid, a K(+)-Cl- co-transport inhibitor, did not inhibit sickling under our experimental conditions. These phenomena observed at pH and oxygen tension similar to physiological venous conditions may be important in understanding the clinical course and pathophysiology of sickle cell disease.

Anemia, Sickle Cell↗

[Characteristic and effective usage of adriamycin].

The utility of adriamycin (doxorubicin), an anti-cancer antibiotic, for the treatment of transitional cell carcinoma of the bladder has been appreciated. Adriamycin is still used intravesically for superficial bladder cancer to avoid implantation of floating cancer cells after transurethral resection, to decrease the incidence of recurrence and treat an unresected part of the tumor. On the other hand, cisplatin-based multi-drug chemotherapies including adriamycin have proven effective in treating locally and systemically advanced bladder cancer.

Administration, Intravesical↗

Survival of F-reticulocytes in sickle cell disease.

Fetal hemoglobin, Hb F, is known to be an important factor for clinical course of sickle cell disease, as it suppresses polymerization of sickle hemoglobin. To investigate the effect of Hb F on the survival of sickle reticulocytes (young red cells) in circulation, Hb F levels in individual reticulocytes and mature erythrocytes were quantified via fluorescence image cytometry. We first examined unfractionated SS cells from 3 patients with different Hb F levels, and found that Hb F levels in reticulocyte populations were always lower than those in erythrocyte populations. This suggests that subsets of reticulocytes with lower Hb F levels are removed during maturation while those with higher Hb F levels tend to survive to become erythrocytes. The distribution of Hb F in reticulocytes was different among these patients and seems to strongly affect the survival of F-reticulocytes. We also analyzed density-separated fractions, and found that Hb F levels in reticulocytes found in the densest fraction were lower than those in lighter fractions. This suggests that reticulocytes with lower Hb F levels are susceptible to quick dehydration within their maturation period (1-2 days) in circulation.

Anemia, Sickle Cell↗

Estimation of fetal hemoglobin levels in individual red cells via fluorescence image cytometry.

A method for estimating fetal hemoglobin (Hb F) levels in individual red blood cells was developed. Cell smears were prepared using a slide maker to ensure uniform thickness and were then stained with immunofluorescence. An antifading gel was applied to preserve a stable fluorescence. The total fluorescence intensities from the same number of red cells in different slide specimens correlated with their hemolysate Hb F levels, which were determined via column chromatography (R = 0.95). Hb F level in individual cells was estimated from fluorescence intensity and cell area, which were determined via image analysis techniques and the hemolysate Hb F level. Blood from a normal subject, a subject with hereditary persistence of fetal hemoglobin, and from sickle cell patients with varying Hb F levels was analyzed. Our analyses showed a wide distribution of Hb F among cells for the normal subject and a gaussian distribution with a peak at the hemolysate Hb F level for the subject with hereditary persistence of fetal hemoglobin. The Hb F distributions were unique to the patients with sickle cell disease. Because Hb F level in individual sickle cells is crucial to the inhibition of cell sickling, the unique hb F distribution may be important in determining the clinical course of this disease.

Anemia, Sickle Cell↗

Sickling in vitro at venous and arterial oxygen tensions of reticulocytes from patients with sickle cell disease.

Sickling of reticulocytes and mature erythrocytes from patients with sickle cell disease was compared at venous and arterial oxygen tensions (PO2 = 30 and 90 mm Hg). Reticulocyte-rich fractions (d < 1.06) were partially deoxygenated in two ways after incubation at PO2 = 180 mm Hg: (1) PO2 of 30 mm Hg for 1 hour, and reoxygenation to 90 mm Hg for 2 hours and (2) PO2 of 90 mm Hg and kept for 2 hours. Percentages of sickled cells were always higher (3-5 times) in reticulocytes than in mature erythrocytes. Percentage of sickled reticulocytes measured at PO2 = 90 mm Hg after partial deoxygenation to PO2 = 30 mm Hg was 2 times higher than that obtained directly at PO2 = 90 mm Hg. In contrast, there was no difference in percentage of sickled cells in the mature erythrocyte population under the two experimental conditions. These results suggest that reticulocytes are more susceptible to sickling under venous oxygen tension and less likely than mature erythrocytes to resume discoidal shape even at arterial oxygen tension.

Anemia, Sickle Cell↗

A cell division inhibitor SulA of Escherichia coli directly interacts with FtsZ through GTP hydrolysis.

E. coli SulA is an SOS-inducible protein that inhibits cell division. FtsZ is a protein that plays a central role in bacterial cell division. Using purified SulA protein that was fused to the maltose binding protein, we demonstrate in vitro that SulA interacts with FtsZ to form a stable complex. The reaction requires GTP and Mg ion. GDP and GTP gamma S cannot substitute for GTP, which suggests that hydrolysis of GTP is required for the reaction. The complex is formed in a molar ratio of approximately one to one of the two proteins. It is likely that the complex formation represents the in vivo mechanism by which SulA inhibits cell division.

ATP-Binding Cassette Transporters↗

Effects of a synthetic rat adrenomedullin on regional hemodynamics in rats.

The effects of rat adrenomedullin, a novel vasorelaxant peptide, on systemic and regional hemodynamics were examined in conscious Sprague Dawley (SD) rats and spontaneously hypertensive rats (SHR). The intravenous infusion of adrenomedullin at rates of 1.67 and 5 micrograms/kg per min decreased the mean arterial pressure in a dose-dependent fashion in both types of rats. Adrenomedullin at a rate of 5 micrograms/kg per min increased the heart rate and cardiac output. As a result, the total peripheral resistance significantly decreased. With regards to the regional hemodynamics, adrenomedullin significantly increased the flow rates in the lungs, heart, spleen, kidneys, adrenal glands and small intestine of SHR. The flow rates in the brain and skin did not change and the flow rates in the skeletal muscle and testis were decreased. These regional hemodynamic changes were also observed in SD rats and there was no qualitative difference in the regional responses to adrenomedullin between SHR and SD rats. Thus, adrenomedullin predominantly increased the flow rates in organs in which adrenomedullin gene was highly expressed. It therefore seems that adrenomedullin may act as a local vasodilatory hormone rather than as a circulatory hormone.

Adrenomedullin↗

Mandibular reconstruction using the double barrel fibular graft.

Five patients underwent mandibular reconstruction using the double barrel fibular graft from 1989 to 1994. Bony defects ranged from 7 to 14 cm. In three patients, two skin flaps were taken with the fibular graft for composite reconstruction. In order to overcome the main disadvantage of the fibular graft, i.e., small circumference of the bone, a harvested fibula was osteotomized into several portions, folded into two parallel lengths, and fixed along the inferior border of the mandible and the alveolar ridge. The double barrel fibular graft provided more than 4-cm alveolar height without damaging bone viability. In Orientals, a fibula is approximately 1.5 cm thick, and using a single fibular strut for mandibular reconstruction may result in subsequent difficulty in wearing conventional dentures or osseointegrated implants. All patients acquired good mandibular contour and enough thickness of the alveolar ridge, and could wear a conventional denture and eat a solid diet. This procedure seems to be superior to the iliac bone graft for major mandibular reconstruction because of its length, the possibility of three-dimensional composite reconstruction, increased bone thickness, and minimal donor-site morbidity.

Adolescent↗