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Biomedical subjects

T Noda

Publications and source records attributed to T Noda.

At least 253 records · Page 14Linked to original sources

Development and partial characterization of monoclonal antibodies to venom of the parasitoid Microplitis demolitor.

The venom of Microplitis demolitor consists of a mixture of proteins. On native PAGE gels three major proteins designated a, b, and g were detected, while on SDS-PAGE gels two major proteins of M(r) 64.5 and 30.8 kD and several minor proteins were detected. No proteins smaller than M(r) 30.8 kD were present. Murine monoclonal antibodies were generated against different venom components. Analysis by Western blot of venom proteins separated on native and SDS-PAGE gels confirmed that antibodies from seven hybridoma lines recognized venom components. Two of the seven hybridoma lines reacted specifically with protein g on native PAGE gels and the M(r) 30.8 k protein on SDS-PAGE gels, while four other lines cross-reacted with these and other venom proteins. The final hybridoma line reacted with protein a when venom was separated on native PAGE gels and an array of proteins when venom was separated on SDS-PAGE gels. Using an enzyme-immunoassay and specific monoclonal antibodies, M. demolitor females were estimated to inject 0.02-0.05 venom gland reservoir equivalents into its host, Pseudoplusia includens, at oviposition. Venom proteins persisted in host hemolymph for 6-12 h before dropping to undetectable levels.

Animals↗

Establishment and characterization of human cell lines from a serous papillary adenocarcinoma of the endometrium.

Two cell lines, SPAC-1-L and SPAC-1-S, derived from a human serous papillary endometrial adenocarcinoma, have been established and repetitively subcultured as a monolayer culture for over 3 years through 144 passage generations. Each of the two cell lines is a subline derived from one original tumor. They have been independently subcultured from the primary culture dishes without any attempt to clone subpopulations and were further characterized with regard to morphology, growth kinetics, tumor marker production, karyotype, and tumorigenicity. These studies indicated that the SPAC-1-L and -S cell lines are different from each other in some cell properties such as morphological character, growth kinetics, and tumor marker productions. Compared with cell lines from a serous papillary endometrial carcinoma that has been previously reported in the literature, our two cell lines are more tumorigenic on nude mice (100%), which possibly correlates with the unusually aggressive biological behavior of the original tumor. In addition, implanted nude mouse tumors, especially the tumor derived from SPAC-1-S cells, retained many characteristics of the original tumor and histologically closely resembled the original serous papillary adenocarcinoma. Since serous papillary carcinoma is a clinically aggressive histological variant of endometrial adenocarcinoma with a significantly poor prognosis, these SPAC-1-L and -S cell lines should prove useful in future studies of the extremely aggressive biological behavior and unique morphology of this tumor.

Antigens, Tumor-Associated, Carbohydrate↗

Localization of H(+)-ATPase and carbonic anhydrase II in ameloblasts at maturation.

The localization of vacuolar-type H(+)-ATPase and carbonic anhydrase II (CA II) in rat incisor enamel organs at maturation was examined by light and electron microscopy. The immunoreactivity for both vacuolar-type H(+)-ATPase and CA II was intense on the ruffled border of ruffle-ended ameloblasts (RA), but moderate at the distal end of smooth-ended ameloblasts (SA). Immuno-gold particles indicated that CA II was not confined to the ruffled border of RA alone, but also distributed in the cytoplasm of RA and SA. These findings suggest that RA may secrete protons produced by CA II via the ruffled border into enamel by active transport of vacuolar-type H(+)-ATPase. Secreted protons may activate hydrolytic enzymes to degrade the organic components of enamel matrix. Vacuolar-type H(+)-ATPase on vesicles of SA suggests that a specific configuration of ruffled borders in RA may be formed by the fusion of vesicle membranes in the distal end of cytoplasm of SA.

Ameloblasts↗

In vitro and in vivo antifungal activities of liposomal amphotericin B, and amphotericin B lipid complex.

The in vitro and in vivo antifungal activities of liposomal amphotericin B (L-AMPH) and amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, were compared with those of conventional amphotericin B (Fungizone, AMPH). The acute intravenous toxicity was markedly lower in BALB/c mice; 50% lethal doses (LD50s) were 2.75 mg/kg in AMPH, 32.9 mg/kg in L-AMPH and > 75 mg/kg in ABLC. In vitro antifungal activities against Candida albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei were evaluated by the agar plate dilution method. The activities were unchanged against C. albicans, but MICs increased more than four fold in 18 of the 20 strains other than C. albicans in L-AMPH and in 9 of the 20 in ABLC. L-AMPH and ABLC were as efficacious as AMPH in the treatment of mice infected with C. albicans, and at a dose of 0.5 and 1.0 mg/kg of body weight, ABLC was more efficacious on survival A ten-times larger dose (10 mg/kg) of L-AMPH and ABLC was administered to mice with 100% survival, suggesting improved tolerability as compared to amphotericin B.

Amphotericin B↗

Kupffer cell function in chronic liver injury and after partial hepatectomy.

The reticuloendothelial system (RES) plays an important role in the biological defense system. In the liver, Kupffer cells are the main constituent of the RES, and when their function is impaired postoperative complications may more often occur. By using 99mTc-labeled human serum albumin millimicrospheres (99mTc-HSA-MM) combined with assessment of single photon emission computed tomography (SPECT), we have attempted to determine the function of Kupffer cells independently of the hepatic blood flow. First, Kupffer cell function in rats with chronic liver injury caused by CCl4 was studied. The hepatic uptake rate in chronic liver injury was decreased, and a reduced phagocytic activity of the Kupffer cells was noted. The parameter concerning Kupffer cell degradation, the excretion rate (k), was markedly decreased in the early period of chronic liver injury. Changes in Kupffer cell function after 30% and 70% hepatectomy were also studied. After 30% hepatectomy, the excretion rate was decreased on the first postoperative day (POD), and it was increased beyond that found after sham operation on the 3rd POD. In contrast, slower recovery of uptake rate was demonstrated. After 70% hepatectomy, both uptake and excretion rates were markedly reduced, and recovery was prolonged beyond the 5th POD. The hepatic uptake was not parallel with the excretion rate in either experiment. These results suggest that the method that measures the hepatic excretion rate may provide a better assessment of Kupffer cell function than the current uptake measurement with radiolabeled colloid.

Animals↗

Enhanced teratogenic activity of di-n-butyltin diacetate by carbon tetrachloride pretreatment in rats.

Di-n-butyltin diacetate (DBTA) has been shown previously to cause malformations such as cleft mandible, ankyloglossia and fused ribs in rat foetuses after oral treatment of dams on day 8 of gestation. In this study, effects of pretreatment with carbon tetrachloride (CCl4) on the teratogenic activity of DBTA were examined in Wistar rats. Pregnant rats were pretreated sc with CCl4 (0.5 ml/kg) on days 6 and 7 of gestation and were treated orally with DBTA on day 8 of gestation at doses of 0, 4.5, 10 or 22 mg/kg. Caesarean sections were performed on day 20 of gestation, and foetuses were examined for external and skeletal anomalies. Pretreatment with CCl4 enhanced the incidence of external and skeletal malformations caused by DBTA. Concentrations of di-n-butyltin in embryos, maternal liver and maternal blood on day 9 of gestation were increased by CCl4 pretreatment, which inhibited the activity of maternal hepatic microsomal drug-metabolizing enzymes. These results suggest that there is little probability that metabolites of DBTA make a critical contribution to the teratogenicity of DBTA.

Abnormalities, Drug-Induced↗

Effects of TRI-n-butyl phosphate on pregnancy in rats.

A teratological study was carried out on the plasticizer tri-n-butyl phosphate (TBP). Pregnant Wistar rats were treated orally on days 7-17 of gestation with TBP at 0, 100, 200, 400 or 800 mg/kg/day in the dose-finding study and 0, 62.5, 125, 250 or 500 mg/kg/day in the subsequent teratological study. Caesarean sections were performed on day 20 of gestation. In the dose-finding study, all of the pregnant rats were killed by the treatment with TBP at 800 mg/kg/day. In the teratological study, salivation and depression of body weight gain, adjusted body weight gain and food consumption were observed at the higher doses of TBP. There were no significant differences between the groups in the incidence of dead or resorbed foetuses, the number of living foetuses and the body weights of living foetuses of both sexes. The incidence of rudimentary lumbar rib increased significantly at 500 mg/kg/day. There were two cases of malformation: a foetus with deformity of fore- and hind-limbs at 400 mg/kg/day in the dose-finding study and conjoined twins exhibiting three fore-limbs and four hind-limbs at 125 mg/kg/day in the teratological study. These malformations were rare in the background data of teratology, and the incidence of foetuses with malformations was not increased significantly. Therefore, TBP was considered not to be teratogenic in this study.

Administration, Oral↗

Normalization of hair growth in sparse fur-abnormal skin and hair (SPF-ASH) mice by introduction of the rat ornithine transcarbamylase (OTC) gene.

The sparse fur-abnormal skin and hair (SPF-ASH) mouse is a model for the human X-linked hereditary disease, ornithine transcarbamylase (OTC) deficiency. This condition is characterized by abnormal skin and delayed hair growth, hyperammonemia, orotic aciduria and low levels of serum citrulline and arginine. Murakami et al. [1] established a line of transgenic mice, by introducing the recombinant rat OTC (rOTC) gene into fertilized C57BL mouse eggs. We introduced the rOTC gene into SPF-ASH mice by mating SPF-ASH heterozygotes and transgenic mice, which carried this gene. The hemizygous SPF-ASH mice bearing the rOTC gene showed normal hair growth without sparse fur, normal urinary orotic acid excretion and normal serum citrulline and arginine levels. These mice showed OTC activities 2 and 6 times higher in the liver and small intestine, respectively, than the SPF-ASH mice but about 12% and 27% those of the controls [2].

Animals↗

A new approach to the evaluation of broad-spectrum sunscreens against ultraviolet and visible light-induced delayed tanning.

Protection against UV and visible light-induced delayed tanning (DT) and immediate tanning (IT) of two broad-spectrum sunscreens with the same sun protection factor was investigated. Protection factors (PFs) against DT (24 h and 7 days) of the sunscreens differed significantly, but PFs against IT did not. This study indicates that using PF against 24 h DT is more appropriate for an evaluation of broad-spectrum sunscreens against UVA and visible light than IT.

Adult↗

Compound odontomes associated with impacted maxillary primary central incisors: report of two cases.

Odontomes associated with primary teeth are rare. This report describes two cases of compound odontome associated with impacted maxillary primary central incisors in patients aged 1 year 8 months and 1 year 2 months, the latter being the youngest to have been reported with the condition. The odontomes were removed under local anaesthesia. Histological examination revealed immature dental tissues in both cases, but no evidence of root formation. Case 1 revealed 'ghost cells' within the enamel epithelium. The impacted incisors erupted following removal of the odontomes; in Case 2 the crown had an unusual ridge on its labial surface, extending from the gingival margin to a few millimetres from the incisal edge.

Female↗

Complications associated with CDDP intraperitoneal chemotherapy.

As CDDP-ip is known to affect intraperitoneal tumors directly, and reduce CDDP associated adverse reactions, it has been used not only for ovarian cancer but other intraperitoneal tumors. However ip chemotherapy requires catheter placement at the time of laparotomy. We investigated the complications of catheters as an intraperitoneal administration route. The subjects were 84 patients, 39 with temporary catheters and 45 with an implantable port and catheter system. Twenty-seven percent of the temporary catheter patients experienced complications--infection 8%, inflow obstruction 3%, leakage 5%, extrusion 8%, and severe pain 3%. Furthermore, a total of 22% of patients with an implantable port and catheter system experienced complications--inflow obstruction 9%, infection 2%, leakage 4%, and extrusion 7%. Fortunately, no serious complications were observed at our institutions, and the complication incidence seemed lower compared to that of other institutions.

Adolescent↗

A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test.

This paper presents precise sensitization test data of 15 chemicals with a wide spectrum of sensitization potencies, and proposes a new protocol and criteria for quantitative evaluation of sensitization potencies of chemicals. The tests were performed according to the design of Magnusson and Kligman, changing the application concentrations for induction as well as for challenge phases. 3-dimensional relationships between mean response (or sensitization rate), induction and challenge concentrations were found in all chemicals tested. The following 2 values are proposed as a quantitative measure of sensitization potency: (a) the minimum induction concentration that induces a positive response; (b) the challenge concentration that induces a mean response approximately equal to 1.0 among the animals applied with the highest concentration for induction. Both values coincided with each other within the range of 1 order of magnitude in every compound except 2. The values varied by 5 orders or more of magnitude among the compounds, showing a wide variation of sensitization potencies among chemicals. A good correlation was found for every chemical between the value of sensitization potency thus obtained and the residual levels in causative products in human cases of allergic contact dermatitis. A new experimental protocol for obtaining values (a) and (b) is proposed.

Allergens↗

Detection of novel mutations in the gyrA gene of Staphylococcus aureus by nonradioisotopic single-strand conformation polymorphism analysis and direct DNA sequencing.

A total of 36 clinical isolates of Staphylococcus aureus (29 fluoroquinolone-resistant strains and 7 fluoroquinolone-susceptible strains) were studied for the presence of point mutations in the gyrA gene by nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis with silver stain. Direct DNA sequencing analysis of the PCR-amplified DNA fragments confirmed the results obtained by Non-RI SSCP analysis and revealed that fluoroquinolone resistance is closely associated with six types of mutations in the gyrA gene, of which three types of mutations were newly identified: (i) Ser-84-->Leu and Glu-88-->Gly, (ii) Ser-84-->Leu and Glu-88-->Lys, and (iii) Glu-88-->Gly. Furthermore, the novel ATT-->ATC mutation at codon 86 (silent mutation) was seen in only one fluoroquinolone-susceptible strain. All seven mutational types were separated from the wild type in a single electrophoretic step within 3 h after PCR amplification. Thus, we conclude that this new technique is a rapid, simple, and useful screening method for the genotyping of gyrA mutations associated with fluoroquinolone resistance.

Base Sequence↗

Relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs.

BACKGROUND: The relation between left ventricular (LV) oxygen consumption (MVO2) and pressure-volume area (PVA) developed in isolated hearts provides a powerful method to understand cardiac energetics. We investigated application of this relation to the intact circulation, determining its response to steady-state and transient load alterations and enhanced contractility in conscious animals. METHODS AND RESULTS: Eight dogs were instrumented to measure LV pressure (micromanometer), LV volume (three sonomicrometers), and left circumflex and anterior descending coronary artery flows (ultrasonic flowmeter). Data were acquired after recovery from the surgery with the animals awake and unsedated. After administration of hexamethonium and atropine, steady-state loading conditions were changed with phenylephrine or nitroprusside in four to five steps before and during the infusion of dobutamine (6 to 10 micrograms.-1kg.-1min). MVO2 and PVA obtained under steady-state conditions were linearly correlated both before and during dobutamine. The MVO2-PVA relation obtained on a beat-to-beat basis during transient caval occlusion was less linear and not coincident with the steady-state relation. Dobutamine shifted the steady-state MVO2-PVA relation upward in all hearts, increasing the MVO2 axis intercept of the MVO2-PVA relation (P < .01). This intercept correlated with ventricular contractility assessed by the slope (Ees) of the LV end-systolic pressure-volume relation determined by caval occlusion (r = .76, P < .05). The slope of the MVO2-PVA relation increased with dobutamine in seven of eight animals, with the inverse of the slope (representing contractile efficiency) being 31 +/- 6% during control and 24 +/- 6% after dobutamine (P = .06). CONCLUSIONS: MVO2 and PVA are linearly related during steady-state alterations in loading conditions in conscious dogs but not on a beat-by-beat basis during transient caval occlusion. Increase in contractility by dobutamine produces an upward shift of the MVO2-PVA relation.

Animals↗

Effect of exercise on left ventricular mechanical efficiency in conscious dogs.

BACKGROUND: We studied the effect of exercise (7.2 to 8.0 km/h) on the efficiency of the conversion of metabolic energy to external work or stroke work (SW) by the left ventricle (LV). METHODS AND RESULTS: Energy use was calculated from LV myocardial oxygen consumption per beat (MVO2). LV volume was calculated from orthogonal dimensions and coronary flow measured with ultrasonic flow probes. The total mechanical energy of the LV was calculated as the pressure-volume area (PVA). At rest, the MVO2-PVA point fell on the MVO2-PVA relation determined by steady-state changes in arterial pressure produced by graded infusions of phenylephrine. Exercise increased the slope (Ees) of LV end-systolic pressure-volume (PV) relation by 29%. During exercise, the MVO2-PVA point shifted to the right only slightly above the control MVO2-PVA relation by 0.007 +/- 0.005 mL O2.beat-1.100 g LV-1. Despite the increase in ventricular contractility with exercise, the PVA/MVO2 ratio was unchanged because of the marked increase in PVA. During exercise, the transmission of total mechanical energy to external work (SW/PVA) increased from 65 +/- 5% to 72 +/- 4% (P < .01) as the ratio of the arterial end-systolic elastance to Ees decreased from 1.1 +/- 0.2 to 0.8 +/- 0.1 (P < .05). Thus, LV mechanical efficiency (SW/MVO2 = SW/PVA.PVA/MVO2) improved from 12.9 +/- 1.5% to 14.3 +/- 1.1% (P < .05) during exercise. CONCLUSIONS: Exercise increases the efficiency of conversion of metabolic energy to external work by the LV due to alteration in LV arterial coupling resulting in increased production of mechanical energy and enhanced transmission of mechanical energy to external work, which more than offsets any increased metabolic cost of the enhanced contractility.

Animals↗

Usefulness of the pulmonary vein flow velocity-time profile as an estimate of left atrial storage fraction.

During ventricular systole, the left atrium (LA) stores a certain amount of ventricular stroke volume; this is defined as an LA storage volume. From cineangiocardiograms, an LA storage fraction is obtained as the ratio of the LA storage volume to left ventricular stroke volume. From the pulmonary vein (PV) flow velocity-time profile, the LA storage fraction may be estimated as a ratio of the PV flow velocity-time integral during systole (Sa) to a sum of that during systole and diastole (Sa+Da), namely, Sa/(Sa+Da), provided that the PV cross-sectional area remains relatively unchanged during one cardiac cycle and that the PV flow velocity-time profile is similar in any of the PVs draining to the LA. To evaluate usefulness of Doppler echocardiographic method of estimating the LA storage fraction, the authors measured the LA storage fraction from the left upper PV flow velocity-time profile by transesophageal Doppler echocardiography and compared it with the LA storage fraction from conventional cineangiocardiographic volumes. Subjects were 23 patients with a variety of cardiac diseases in normal sinus rhythm, ranging from eighteen to seventy-four years of age. The LA storage fraction was 0.58 +/- 0.12 (mean +/- SD) from cineangiocardiography and 0.64 +/- 0.08 from Doppler echocardiography larger than that from cineangiocardiography (P < 0.01), the correlation was good (r = 0.643). The authors conclude that the left upper PV flow velocity-time profile appears to provide a better correlation with that by cineangiography and may be used as a reliable quantitative estimate of the LA storage fraction.

Adult↗

A study on left atrial transport function. Effect of age or left ventricular ejection fraction on left atrial storage fraction.

Left atrial (LA) storage fraction is defined as the ratio of storage volume of the left atrium (LA) during ventricular systole to left ventricular (LV) stroke volume. To test their hypothesis that left atrial (LA) storage fraction is increased to compensate for impaired LV filling in the heart of aged subjects or with impaired LV ejection fraction, the authors studied 33 "normal" subjects and 25 patients with coronary artery disease. LA volume was measured by LA cineangiocardiography, and LV stroke volume and LV ejection fraction were measured by LV cineangiocardiography. To further evaluate the determinants of changes in LA storage fraction, they measured the ratio of LA active release volume to LV stroke volume, and the ratio of LA passive release volume to LV stroke volume. In "normal" subjects, LA storage fraction was increased with age (r = 0.584, P < 0.01). In patients with coronary artery disease, LA storage fraction was increased as LV ejection fraction was decreased (r = -0.525, P < 0.01). In both cases, LA active release fraction was significantly associated with changes in LA storage fraction rather than in LA passive release fraction. They conclude that LA storage fraction may be an important determinant of LV filling mainly through the LA active release fraction.

Adolescent↗