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Biomedical subjects

H Kitamura

Publications and source records attributed to H Kitamura.

At least 415 records · Page 23Linked to original sources

Production of bronchial papilloma with calcitonin-like immunoreactivity in rats exposed to urban ambient air.

In order to assess the effect of prolonged inhalation of polluted ambient air on the respiratory tract, 30 Sprague-Dawley rats were kept in facilities built close to a street with heavy traffic in the City of Yokohama for 18 months in an atmosphere of either filtered (filtered group) or non-filtered polluted ambient air (exposed group), and the histology of the lung was examined. Scattered areas of chronic inflammation were seen from the nasal to bronchiolar mucosae in both the groups. Rats which inhaled the urban ambient air showed deposition of dust particles in the alveolar space and the peribronchiolar tissue, but no deposition was recognized in the filtered group. In both the filtered and exposed groups, papillary hyperplasia showing a positive immunoreaction to calcitonin was noted in the bronchobronchiolar epithelium. The hyperplasia was thus shown to have endocrine differentiation and this was considered to be pulmonary endocrine cell hyperplasia. In the exposed group, 2 bronchial papillomas were induced, and were shown to contain cells giving a positive immunoreaction to calcitonin. A histogenetical sequence was suggested in these 2 lesions because of their histological and immunohistochemical similarities.

Air Pollutants↗

Hypersensitivity of human tumor xenografts lacking O6-alkylguanine-DNA alkyltransferase to the anti-tumor agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea.

Human tumor cell strains having different activities of O6-alkylguanine-DNA alkyltransferase (ATR) were transplanted into nude mice and chemotherapeutic responses of tumor xenografts were compared after intraperitoneal injection of the anti-tumor drug 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). The tumor strains used were four Mer+ strains possessing high ATR activity and three Mer- strains lacking this activity. Included in these Mer+ strains was a clone 5'dD which expresses the Escherichia coli ATR in Mer- HeLa cells and thus shows the Mer+ phenotype. All the Mer- tumor xenografts were much more sensitive than tumors of Mer+ strains, including the clone 5'dD; after the highest ACNU dose (three injections of 50 mg/kg), some Mer- tumors disappeared completely and the growth of other tumors was severely retarded, whereas all Mer+ tumors continued to grow. These results demonstrate that ATR activity in tumor cells is a major determinant of tumor response to ACNU, and further suggest that measurement of ATR activity in biopsy specimens may provide a useful guide to predict the response to chemotherapy.

Animals↗

Characterization of the bacterial population structure in an anaerobic-aerobic activated sludge system on the basis of respiratory quinone profiles.

Bacterial respiratory quinones were used as biomarkers for studying the bacterial population structure, especially the content of Acinetobacter species, in a laboratory-scale anaerobic-aerobic activated sludge system and in the standard aerobic system. All tested sludges contained both ubiquinone and menaquinone, with a molar ratio of about 1:0.5. High-performance liquid chromatography showed that ubiquinone with eight isoprene units (Q-8) was present as the predominant ubiquinone, Q-10 was the second most common type, and Q-9 and other homologs were minor components in the anaerobic-aerobic sludge and the standard aerobic sludge. Bacteriological examination indicated that, in both sludge systems, Q-8-containing bacteria constituted a large proportion of the aerobic heterotrophic bacterial flora, but only a few strains with Q-9 were found. These findings demonstrate that the population of Acinetobacter species, which contain Q-9 as the major quinone, is negligible in those environments. The present results suggest that the introduction of anaerobic conditions into the aerobic batch process has little influence on the bacterial community structure.

Aerobiosis↗

Morphology of lymphatics of the mammalian heart with special reference to the architecture and distribution of the subepicardial lymphatic system.

The subepicardial lymphatic system in the rat and dog heart has been investigated by means of scanning electron microscopy. Following application of hydrogen peroxide, the epicardium was removed with a forceps under a dissecting microscope. The subepicardial region contained a well-developed lymphatic system which consisted of the main lymphatic trunks and lymphatic capillaries. The lymphatic trunks of large diameters ran from the apex of the heart to its base. The subepicardial lymphatic capillaries were ramified and anastomosed with each other to form a relatively dense network which extended over the entire surface of both ventricles. These networks joined the main lymphatic trunks. Further, some similar networks were connected with the underlying myocardial lymphatic capillaries.

Animals↗

Bromocriptine-induced morphological changes in cultured growth hormone-producing pituitary adenoma cells.

Tumor tissues obtained from two patients with growth hormone-producing pituitary adenomas were cultured and treated with bromocriptine, then examined for morphological changes. Untreated tumor cells (controls) were morphologically well preserved and in terms of growth hormone secretion. Tumor cells exposed to bromocriptine for 7 days contained many vacuoles, which, after 14 days of exposure, grew larger and more numerous. These vacuoles appeared to be extensions of endoplasmic reticulum: some were connected to rough or smooth endoplasmic reticulum or, occasionally, to Golgi apparatus, and there were ribosomes on their surfaces. Bromocriptine apparently has cytocidal effects on growth hormone-producing pituitary adenoma in vitro.

Adenoma↗

Spontaneous colon cancer and its spontaneous regression in highly inbred Wistar Furth rats: genetic analysis.

The incidence of spontaneously occurring colon cancer and its spontaneous regression in the highly inbred Wistar Furth (WF) rat was studied using 1346 rats from the 19th to the 21st inbreeding generation. A statistical analysis revealed a positive phenotypical correlation between parents and offspring concerning the incidence of colon cancer and its spontaneous regression. The incidences of cancer-bearing offspring born from the crosses of cancer-free dams and cancer-bearing, spontaneous regression and cancer-free sires were 21%, 14.1% and 22.7%, respectively, and these results manifested a statistically significant difference. The incidences of spontaneous regression in the male offspring born from the same crosses mentioned above were 35%, 46.8% and 23.5%, respectively; they also represented a significant difference. Based on the analysis, two independent genetic factors, one carcinogenic and the another regressive, were suggested to determine the phenotypes of offspring. The cancer-bearing offspring have the carcinogenic factor but not the regressive factor, while the spontaneous regression ones have both factors. The frequencies of the carcinogenic and the regressive factors in male rats were estimated to be 54.1% and 59.8%, respectively, on average from the 19th to the 21st generation. A genetic pool of the carcinogenic and the regressive factors was established in the WF rat.

Animals↗

[Pineal metastatic tumor from lung cancer initially caused by neurological abnormalities of pineal body tumor].

A rare case is reported of pineal metastasis from lung cancer initially caused by neurological abnormalities of pineal tumor. A 70-year-old female suffering from headache and deterioration of consciousness for 1 week was admitted. She also had a tumor on both sides of her neck. On admission, neurological examination revealed disturbance of upward gaze, and CT scans showed hydrocephalus and pineal tumor. The tumor was seen as a slightly high density mass on non-contrast CT, and was homogeneously enhanced after administration of contrast material. Right V-P shunt and excision of the left neck tumor were performed at the same time. Pathological diagnosis of neck tumor was undifferentiated carcinoma metastasized to cervical lymph nodes. Extensive study was made, by bronchial fiberscope and biopsy, in order to find the origin of the malignancy and disclosed a small cell lung cancer of left lower lobe. The patient took radiation therapy for both the whole brain (60 Gy) and for the bilateral cervical regions (45 Gy). Two courses of chemotherapy using CDDP, ADR, VCR and CY were administered. Both the neck and the pineal tumors were markedly reduced in size at the termination of radiation therapy. However, she was readmitted 3 months later because of dyspnea. Chest X-P revealed enlargement of the left-lung tumor. She died on April 22, 1987. General autopsy disclosed invasive enlargement of left lung cancer, however, no remote metastasis was found. Examination of pineal region showed only necrotic pineal tissue, and no tumor cell was seen in either macroscopic or microscopic study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Intraventricular flow dynamics in hypertrophic cardiomyopathy with midventricular obstruction investigated by Doppler echocardiography].

Seven patients with hypertrophic cardiomyopathy having midventricular obstruction (MVO) were examined using two-dimensional, conventional Doppler and color Doppler echocardiography to investigate intraventricular flow conditions. The controls were 35 patients with hypertrophic cardiomyopathy without MVO. All MVO patients had "hour-glass" LV cavities during systole, resulting from either hypertrophy at the midventricular level or hypertrophied papillary muscles, where systolic mosaic signals originated. Systolic peak flow velocities at the midventricle ranged from 2.5 to 4.2 m/s, proving the presence of a pressure gradient between the apex and the base of the LV. In fact, a pressure drop of 15-30 mmHg was demonstrated in four patients who underwent cardiac catheterization. These high velocity jet flows were not detectable at the midventricle in the control subjects. Peak ejection velocities in the outflow tracts were significantly lower in patients with MVO compared to those with hypertrophic cardiomyopathy and subaortic stenosis (129 +/- 29 vs 384 +/- 111 cm/s; p less than 0.001). As midventricular obliteration became severe, systolic jets at the midventricle increased in velocity. Waveforms changed from single- to double-peaked, and lasted until the isovolumic relaxation or the rapid filling phase beyond the second heart sound. Consequently, isovolumic relaxation waveforms at the midventricle using the apical approach changed the direction; from "the base to apex" to "the apex to base". An isovolumic signal away from the transducer was only observed in two patients without MVO. Diastolic color reversal and mosaic signals at the midventricle were also seen in five of the seven patients with MVO. Peak flow velocities in the rapid filling phase were significantly higher at the papillary muscle level than at the mitral valve level, indicating that MVO continues up to early diastole. It was suggested that MVO disturbs intraventricular flow dynamics during both systole and diastole. Color Doppler echocardiography is particularly useful in determining the site of obstruction and allows further evaluation by pulsed and continuous wave Doppler techniques to precisely measure pressure gradients. With routine, careful use of Doppler echocardiography, MVO may prove to be a more common entity than was previously believed.

Adult↗

Evaluation of the peri-implant membrane induced around ceramic dental implants in dogs: a transmission electron microscopic study.

A description of the supporting tissues of single-crystal sapphire implants which had functioned for twelve months is reported. The tissue was recovered at autopsy. The peri-implant membrane was formed by the action of mastication forces on the implants and consisted of three non-mineralized connective tissue layers. Layer I was composed of collagen fibers. These fibers were oriented parallel to the implant surface. Layer II lacked collagen fibers. This layer was composed of connective tissue materials. Layer III was covered by osteoclasts or osteoblasts. This layer was composed of collagen fibers which radiated to the bone surface. The collagen fiber bundles did not run from the implant fibers to the bone fibers. This peri-implant membrane formed only a hammock-like supporting mechanism. These findings suggest that the implant had been encapsulated by the peri-implant membrane, which failed to distribute masticulation stress to the peripheral tissues. One year after implantation of single-crystal implants, the tissue-implants interface was observed. Non-mineralized connective tissue layers (a "peri-implant membrane") existed at all implant interfaces. The origin of this structure and the role of a peri-implant membrane are discussed.

Aluminum Oxide↗

[Nuclear cardiological examination for evaluation of hypertrophic cardiomyopathy with midventricular obstruction and apical aneurysm: a case report].

Midventricular hypertrophy (MVO) is a rare and complicated myocardial disease. Its pathophysiology and prognosis remain unknown, and few nuclear cardiological findings for MVO were reported. On a 44-year old man with MVO, thallium-201 (Tl) myocardial scintigraphy and gated blood pool scintigraphy (GPS) were performed to evaluate their usefulness. GPS revealed a characteristic hour-glass deformity of the left ventricular cavity, apical aneurysm and asynchrony due to obliteration of the midventricle. Anteroseptal hypertrophy in midventricle and myocardial damage in apico-inferior region were detected by Tl. Thus, nuclear cardiological studies are proved to be useful and essential in not only diagnosis but also evaluating pathophysiology and observing natural history noninvasively.

Adult↗

Inhibition of immune haemolysis by a serum factor found in C3-deficient subjects.

A serum factor, which inhibits haemolysis of the buffer control used in a C3 haemolytic assay, was found in a C3-deficient subject (C3D). Since the buffer control consisted of EAC142, C5 and C6-9 reagent (C6-9R, prepared by treatment of guinea-pig serum with KSCN and hydrazine hydrate), the factor seems to be an inhibitor of C3-independent immune haemolysis. Gel filtration and CM cellulose column chromatography of C3D serum suggested that the inhibitor may be C8. The inhibition was not observed in C8-depleted C3D serum. Furthermore, isolated C8 was found to inhibit haemolysis of EAC142 by C5 and C6-9R in a dose-dependent fashion. Thus, C8 was found to be an inhibitor of C3-independent immune haemolysis in the assay. Further studies revealed that C8 also inhibits haemolysis of EAC142 by C3, C5 and C6-9R (C3 assay system) or that of EAC1423 by C5 and C6-9R (C5 assay system), indicating that C3 or C5 haemolytic activity can be underestimated by the presence of C8 in a sample. C8 did not inhibit haemolysis in the assay system when isolated C6-C9 of human origin were used, but did inhibit haemolysis when isolated C6-C9 of guinea-pig origin was used instead of C6-9R. Thus, it was suggested that the incompatibility of human C8 with guinea-pig C6-C9 might be responsible for this phenomenon. Additional experiments for the mechanism clearly showed that human C8 inhibits the haemolysis of EAC1-7 (EA bearing human C1-C5 and guinea-pig C6 and C7) by guinea-pig C8 and C9 by binding to EAC1-7 prior to guinea-pig C8.

Animals↗

Cytogenetic changes in rat tracheal epithelial cells during early stages of carcinogen-induced neoplastic progression.

The cytogenetic changes in enhanced growth (EG) variants of rat tracheal epithelial cells in culture were examined. These variants which are detectable at 35 days after carcinogen exposure are the first phenotypic alteration in the multistep neoplastic process studied in this model system. Karyotypic analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced EG variants at Day 35 was made possible by the development of an in situ method of cytogenetic analysis on intact colonies containing too few cells for conventional chromosome preparation methods. Of the transformed EG variant colonies in both control and N-methyl-N'-nitro-N-nitrosoguanidine-treated groups, 62-78% had abnormal karyotypes which included numerical and structural changes. There were no specific chromosome changes, although aberrations of chromosomes 3 and 4 were recurrently observed. However, some colonies of even the most morphologically transformed EG variants were composed of only diploid cells. To confirm this finding 10 EG variant colonies were bisected and half of the clone was prepared for chromosome analysis and the other half was subcultured to measure the clonogenicity and karyotypes of the cells. Cells from 3 colonies plated very poorly on 3T3 feeders and therefore no karyotypic analysis of the colony-forming cells was possible; the cells of the 3 parental colonies were diploid. Three other parental colonies were predominantly diploid (80-90%) but upon replating the resultant daughter colonies had progressively smaller fractions of diploid cells indicating a selection for cells with abnormal karyotypes. When more selective conditions were used (i.e., growth after removal of the feeder cells), the percentage of abnormal cells increased even further. In one case the parental cells had a karyotypic alteration in the long arm of chromosome 4 and this karyotypic alteration was accentuated in the daughter colonies. Thus, selection of cells with increased growth ability upon subculturing or growth in the absence of feeder cells (properties associated with the acquisition of immortality) resulted in concomitant selection for cells with abnormal karyotypes. Since some of the carcinogen-induced rat tracheal epithelial cells expressing the EG variant phenotype were diploid, it is possible that the first step in this transformation process is an epigenetic change. However, most of the diploid cells became terminal. The aneuploid subpopulations present in these colonies have a selective growth advantage and comprise the cell compartment that expresses continued growth, immortality, and ultimately tumorigenicity.

Aneuploidy↗

Structure and distribution of lymphatic capillaries and fenestrated blood capillaries in the conduction system of the rabbit heart.

The distribution and structure of lymphatic and blood capillaries in the rabbit heart conduction system were investigated by transmission electron microscopy. The sinuatrial node, atrioventricular node, and atrioventricular bundle possessed a rich network of lymphatic capillaries, which were situated not only at the periphery but also in the interior of the conduction system. The fine structure of these lymphatic capillaries was essentially similar to those within the atria and the ventricles. Although blood capillaries within working myocardium were nonfenestrated, the heart conduction system was often supplied by fenestrated blood capillaries. In the atrioventricular node and bundle especially, fenestrated blood capillaries and lymphatic capillaries were topographically associated, forming an extensive microcirculatory system. The presence of fenestrated capillaries suggests that a fast transcapillary passage of metabolites occurs in these regions, while the lymphatic capillaries may play an important role in the removal of macromolecules and excess intercellular fluid.

Animals↗

Immunohistochemical and immunoelectron microscopic study of an amylase-producing, CA19-9 positive ovarian mucinous cystadenocarcinoma.

A 75-year-old woman with a right ovarian tumor revealed high levels of serum amylase and CA19-9 which decreased to within normal limits after the operation. A histopathological study of surgically excised tumor tissue revealed a mucinous cystadenocarcinoma. The tumor was composed of three elements: adenoma, adenoma with low potential malignancy, and adenocarcinoma. Using the light microscopic indirect immunoperoxidase technique for amylase and CEA, and the Avidin-Biotin affinity technique for CA19-9 and CA12-5, the amylase and CA19-9 were stained in the cytoplasm of the adenoma and adenocarcinoma although CEA was stained only in the cytoplasm of the adenocarcinoma. An ultrastructural study using the immunoperoxidase method revealed that CA19-9 was positive in the apical portion of the tumor cells and amylase was positive in the entire secretory vesicles of the tumor cells. Furthermore, ciliated tumor cells derived from fallopian tube epithelium were not observed in the light and electron microscopic specimens.

Aged↗

The mechanism of discordant xenograft rejection.

The mechanism of discordant xenograft rejection using the guinea pig-to-rat heart graft model was studied. In this model, we found that (A) Rejection occurred rapidly, in 17.5 +/- 8.3 min (mean +/- SD) (n = 8). (B) The graft survived longer when the recipient rat was pretreated with cobra venom facter (CVF). (C) Complement hemolytic titers in serum showed significant reduction of C3 in rejection without consumption of C4 and C2, suggesting complement activation through the alternative pathway. (D) No natural antibodies were detected in this combination. Complement-dependent cytotoxicity (CDC) titer, and hemagglutination (HA) titer were lower than x1. (E) Histological examination of the rejected heart xenograft revealed a large area of myocytolysis without interstitial cellular infiltration. (F) In vitro experiments showed that rat complement attacked guinea pig erythrocytes (Egp) via the alternative pathway. These findings indicate that rejection in this discordant xenograft model of guinea pig-to-rat was caused by primary activation of complement via the alternative pathway.

Animals↗

Pulmonary adenoma and endocrine cell hyperplasia in Syrian golden hamster treated with 4-nitroquinoline 1-oxide.

Chronic effects of 4-nitroquinoline 1-oxide (4 NQO) on the lungs of Syrian golden hamsters were studied. 4 NQO was subcutaneously injected weekly for 3 weeks at a dose of 20 mg/kg body weight. The animals were sacrificed at the 65th and 80th experimental weeks. Two cases of pulmonary adenomas were demonstrated in the 10 4 NQO-treated animals at the 80th week, and the tumor cells contained cytoplasmic lamellar inclusion bodies. In a previous study, we reported 4 NQO- induced pulmonary endocrine cell hyperplasias in the 4 NQO-treated hamster after the 20th experimental week (Jpn. J. Cancer Res., 77, 1986). In the present study, 12 pulmonary endocrine cell hyperplasias were recognized in serial sections of the 24 treated animals. The hyperplastic lesions showed positive immunoreactivity to calcitonin. The hyperplastic lesion did not develop to pulmonary endocrine cell neoplasm.

4-Nitroquinoline-1-oxide↗

Chronotropic effect of nizofenone fumarate in rabbit sino-atrial node in vitro.

1. The effects of nizofenone fumarate were studied on the membrane potentials and currents of rabbit sino-atrial node preparations by means of the double-microelectrode voltage clamp method. 2. In spontaneously firing pacemaker cells, nizofenone (above 1 microM) decreased the heart rate. Above 3 microM, nizofenone reduced the maximum upstroke velocity, the amplitude of the action potential and the slope of the phase 4 depolarization, and prolonged the action potential duration at 50% repolarization. 3. Under voltage clamp conditions, nizofenone decreased the slow inward current and the time-dependent potassium outward current in a dose-dependent manner. 4. These findings suggest that nizofenone exerts an inhibitory action on the automaticity of sinoatrial node preparations via effects on both inward and outward currents.

Action Potentials↗