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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 793 records · Page 44Linked to original sources

Vestibular pathology in a new-mutant mouse.

The histological characteristics of the vestibule in a strain of new-mutant mice were studied under light microscopy. These new-mutant mice, manifesting drawing back, circling, head-tossing and hyperactive behavior arose as a spontaneous mutation in the C3H/He stock. For our study, 36 of these mice ranging in age from 10 days to 18 months were used. At 10 to 15 days after birth, the vestibular gross anatomy was well-developed and all three cristae and two maculae were morphologically normal. Age-dependent degeneration of the saccular maculae was found to begin at 21 days, and almost all hair cells were missing at 90 days. Further, morphological changes in the utricular maculae appeared at one year, and a severe loss of hair cells was observed at 18 months. In contrast, the cristae ampullaris remained well preserved until the age of 18 months. The phenotype of the abnormal gene in these mutant mice correlates to the morphological abnormalities seen in the vestibule.

Animals↗

Vascular permeability of the stria vascularis in experimental endolymphatic hydrops.

Vascular permeability of the stria vascularis was morphologically examined in hydrops animals, using the tracer method of horseradish peroxidase (HRP). The reaction product of HRP was observed in the capillary of the stria vascularis, not outside of it. The finding suggests that the vascular permeability of the stria vascularis is unchanged in Kimura's hydrops model.

Animals↗

Morphological changes of cochlea in a strain of new-mutant mice.

The hearing ability and histological characteristics of the cochlea of a strain of new-mutant mice were analyzed. This new mutant arose as a spontaneous mutation in the C3H/He stock. The genetic mode is autosomal recessive and the animals show abnormal behavior such as circling, head-tossing and hyperactivity. The audiological findings exhibited no recordable auditory brain stem response (ABR) in any homozygotes at ages ranging from 11 days to 117 days. For morphological examination, we used 36 homozygote with ages ranging from 10 days to 18 months. The primary morphological abnormalities were observed in the organ of Corti. The stereocilia of the outer hair cells showed disarray throughout the whole cochlea, although outer hair cell cytoplasm became fully developed, including the nerve terminals. Age-dependent degeneration of the outer hair cells subsequently occurred from the basal to the apical part of the cochlea. The earliest change demonstrated in the outer hair cells was cuticular degeneration. Although the abnormalities of the inner hair cells occurred late, a complete loss of inner and outer hair cells was demonstrated. The stria vascularis was well preserved at a later age as were spiral ganglion cells. These histological findings confirm that this mouse is classified as a neuroepithelial-type mutant. As this animal was expected to have a single gene abnormality, molecular genetic studies on this animal can provide important information on the nature of histological changes of the hair cell from a mode of gene action.

Acoustic Stimulation↗

Transport of HRP through Reissner's membrane in experimental endolymphatic hydrops.

Unilateral endolymphatic hydrops was produced in guinea pigs by cauterization of the endolymphatic sac. Measurements of compound action potential (CAP), cochlear microphonics (CM) and negative summating potential (-SP) confirmed endolymphatic hydrops three months after surgery. In both control and hydropic ears, reaction product of HRP was observed only on the perilymphatic surface of the epithelial cells of Reissner's membrane after 10 min perfusion, while it was observed on both the endolymphatic and perilymphatic surfaces after 30 min perfusion. Epithelial tight junctions were not stained and labelled pinocytotic vesicles were observed in the epithelial cells. These findings suggest that the transport of HRP through Reissner's membrane is unchanged in endolymphatic hydrops and that the epithelial junctions are tight regardless of the distension of Reissner's membrane.

Animals↗

Molecular cloning and sequence analysis of cDNA for the catalytic subunit 1 alpha of rat kidney type 1 protein phosphatase, and detection of the gene expression at high levels in hepatoma cells and regenerating livers as compared to rat livers.

A cDNA clone containing the full coding sequence of a type 1 protein phosphatase catalytic subunit 1 alpha has been isolated from a rat kidney lambda gt 10 library. The protein sequence deduced from the cDNA contains 330 amino acid residues with a molecular mass of 38 kDa. The cDNA clone from rat kidney was 89% identical at the nucleotide level in the coding region to type 1 protein phosphatase 1 alpha from rabbit skeletal muscle. However, the two protein sequences were completely identical. The type 1 alpha protein phosphatase from rat kidney shows 49% homology of amino acid sequence to the rat type 2A alpha protein phosphatase. Thus, the protein sequence of type 1 alpha protein phosphatase was completely conserved between rat and rabbit. The mRNA levels of type 1 protein phosphatase were determined in rat liver, AH13, a strain of rat hepatoma, and regenerating rat liver by Northern blot analysis using the cDNA fragment as a probe, under which conditions a single mRNA of 1.5 kb was detected. The mRNA levels of AH13 were remarkably increased when compared to those of normal ivers, whereas the mRNA levels of regenerating livers were slightly but significantly increased. These results demonstrate a marked increase in gene expression of type 1 protein phosphatase in hepatoma cells, suggesting an important role of the type 1 protein phosphatase in hepatocarcinogenesis.

Amino Acid Sequence↗

Spontaneous isolated intra-abdominal mesenteric fibromatosis. Case report.

Magnetic resonance imaging in a 54-year-old Japanese man showed a huge low-intensity abdominal mass on T1 WI and a high-intensity tumoral structure with low-intensity bundles on T2 WI. The histologic diagnosis was intra-abdominal mesenteric fibromatosis. As the levels of tissue estrogen and progesterone receptors were not elevated (both less than 5 FMOL/mg), tamoxifen treatment was not indicated.

Fibroma↗

Comparative studies on myelin proteins in mammalian peripheral nerve.

Myelin proteins in mammalian peripheral nerve were studied comparatively. 1. While each content of P1 and P2 in the myelin varied among species, additional content of P1 and P2 are relatively constant. 2. The antigenic determinants of P2 for induction of experimental allergic neuritis were reported. 3. Amino acid sequence analysis of P0 revealed that P0 is conserved across species and belongs to the immunoglobulin superfamily. 4. The characteristic carbohydrate chain of P0 containing sulfate and sialic acid showed a positive reaction to the molecule-related immunity and adhesion. 5. Molecular architecture of the myelin is discussed.

Amino Acid Sequence↗

Ionic currents involved in vasodilating actions of E4080, a newly synthesized bradycardia-inducing agent, in dispersed smooth muscle cells of the rabbit portal vein.

The effects of E4080 [(E)-N-[3-[N'-(2-(3,5-dimethoxyphenyl)ethyl)-N'-methyl)amino)propyl]-4- (4-(1H-imidazol-1-yl)phenyl)-3-butenamide dihydrochloride dihydrate] on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (ICa), a transient outward current (ITO), a sustained outward current (ISO) and an oscillatory outward current (IOO), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (Ih). When ICa was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 microM E4080 increased and higher concentrations (10 microM) inhibited ICa, whereas, at the holding potential of -60 mV, E4080 (greater than 1 microM) consistently inhibited ICa, in a concentration-dependent manner. E4080 inhibited ITO, ISO (greater than or equal to 1 microM) and Ih (greater than or equal to 0.1 microM) concentration dependently. Inasmuch as 1 microM E4080 did not inhibit ICa at the holding potential of -80 mV, the inhibition of ITO induced by 1 microM E4080 was not related to the inhibition of ICa. When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 microM) produced a maintained outward current (14.0 +/- 15.3 pA), which was inhibited by glibenclamide. I infinity was inhibited by E4080 (greater than or equal to 0.1 microM) and application of 1 microM glibenclamide partly restored I infinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Cyclosporin-A induced gingival overgrowth--strain differences in the rats].

Cyclosporin-A (CsA) which is an effective immunosuppressive agent to control the rejection of organ transplants causes gingival overgrowth as one of accompanying side effects. However, the mechanism of this particular gingival overgrowth still remains unclear. This seems to be largely due to the difficulty of reproducing gingival overgrowth in experimental animals, especially in rodents. The purpose of the present study was to establish a rat model for CsA-induced gingival overgrowth. Specific pathogen-free Fischer and Sprague-Dawley rats (20 days old) were used and fed a caries inducing diet containing CsA. The degree of gingival overgrowth was measured, and histological examination of the gingival sections was performed. The results obtained were as follows; 1. Marked gingival overgrowth was noted around mandibular molars of all rats fed died 2000 containing 56% sucrose supplemented with CsA (a diet of 120-200 mg/kg). This overgrowth was more conspicuous in buccal than in lingual gingiva. However, there were no differences between the two strains of rat in the macroscopic findings as well as in the severity of CsA-induced gingival overgrowth. 2. Rats receiving CsA treatment for 40 days (at 63 days of age) showed the maximum level of gingival overgrowth in both strains of rats. When the gingival sulcus depths at 48 days of age were compared, the S.D. rats seemed to be a higher responder to CsA than the Fischer rats. 3. CsA treated rats showed significantly higher plaque scores than untreated rats. However, CsA-induced gingival overgrowth was little affected by this enhancement of plaque accumulation in the rats infected with S. sobrinus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal tubular lesions induced by human Bence Jones protein in the rat: N-acetyl-beta-D-glucosaminidase as a sensitive marker.

The renal tubular lesion induced by human Bence Jones proteins (BJPs) in the rat was investigated to elucidate the initial role of BJPs in the genesis of renal tubular damage in myeloma kidney. Human BJP extracted from the urine collected from a patient with lambda light chain myeloma was given intraperitoneally to Sprague-Dawley rats with a daily dose of 300 mg/day for 5 days (BJP group, n = 16). Daily urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), which may represent the intensity of tubular damage, was measured. On days 10 and 20 after start of the injection, the kidneys were removed and examined by light and electron microscopy. The renal content of NAG was also measured to estimate the lysosomal activity. Both urinary and renal tissue NAG were significantly higher in the BJP group than in control rats injected with bovine serum albumin (n = 16). The most characteristic changes were found in the proximal tubules of the BJP group; the number and size of lysosomes were increased, and some showed enlargement with autophagic vacuolation. However, these were not found in the control group. There were no obvious changes in the distal tubules in either group, and the glomeruli appeared to be intact. These results suggest that BJP directly damages the proximal tubules via the process of catabolism, resulting in injury to these cells, and that the urinary NAG is a sensitive marker to detect early tubular damage by BJP.

Acetylglucosaminidase↗

Characterization of monoclonal anti-rabbit apolipoprotein E antibodies and chemical composition of lipoproteins separated by anti-apolipoprotein E immuno-affinity chromatography.

Six mouse monoclonal antibodies against rabbit apolipoprotein E (apo E) have been developed. Of these monoclonal antibodies, clone 5 revealed a high affinity for purified apo E, very low density lipoprotein (VLDL) and beta-VLDL. This monoclonal antibody was used to prepare an immunoaffinity column. Coupled to Sepharose 4B, this antibody allowed complete removal of lipoproteins containing apo E from plasma of New Zealand white (NZW) rabbits; 62, 46, 14, and 3% of VLDL-, IDL-, LDL-, and HDL-protein, respectively, were bound to the anti-apo E affinity column. The bound VLDL was significantly rich in free cholesterol (FC) and cholesteryl esters (CE) relative to the unbound VLDL, whereas bound IDL, LDL and HDL were significantly rich in FC only. All of the bound fractions were characterized by significantly increased ratios of FC/phospholipids (PL). These results indicate that the two lipoprotein populations with and without apo E have different lipid compositions. The relatively high content of cholesterol in lipoproteins containing apo E suggests a contribution of apo E to plasma cholesterol transport.

Animals↗

[Trans-sternal bilateral thoracotomy for bilateral lung lesions].

The trans-sternal bilateral thoracotomy had been used widely in the early days of cardiac surgery, but since the 1960's the median sternotomy has played a great part in open heart surgery. Recently, the simultaneous bilateral thoracotomy has been used for bilateral lung lesions such as bilateral giant bullae, bilateral pneumothoraces and bilateral metastatic lung tumors. Since 1965 we have performed 6 operations using trans-sternal bilateral thoracotomy for several bilateral lung lesions. The diseases which led to the use of the trans-sternal bilateral thoracotomy technique were 2 cases of bilateral simultaneous pneumothoraces and 4 cases of bilateral lung metastatic tumors. The ages of the patients ranged from 17 to 45 years old. The operative blood loss was between 100 and 810 gm. No case showed postoperative respiratory distress or severe thoracic pain. It would like to be pointed out that the trans-sternal bilateral thoracotomy is the most ideal approach for the multiple bilateral lung metastatic lesions which often invade the chest wall or diaphragm.

Adolescent↗

Disappearance of minimal residual lymphoblastic leukemia cells 6 months after allogeneic bone marrow transplantation without GVHD.

The recent development of the polymerase chain reaction (PCR) has enabled us to determine the hypervariable sequence of immunoglobulin heavy chain known as complementarity determining region (CDR)-III. We amplified the leukemia-specific CDR-III from common acute lymphoblastic leukemia (cALL) cells using the PCR and determined its sequence. To detect minimal residual leukemia (MRL) cells, a second round PCR was performed with clone-specific primers corresponding to 5' and 3' ends of CDR-III to detect MRL cells. A million-fold diluted leukemia cells were clearly detected. Using stepwise diluted materials, the number of residual cells was semiquantitatively estimated. In one patient with cALL, induction chemotherapy resulted in a hematologically complete remission with only a 2-log reduction of the leukemia cells. MRL cells at a level of 10(-6) were also detected within 1 month after bone marrow transplantation (BMT), but leukemia cells were not detectable 6 months after BMT.

Adult↗

Arachidonic acid metabolism in articular chondrocytes.

In this study rabbit articular chondrocytes were cultured and the cells were labeled with 3H-arachidonic acid and 14C-stearic acid. 3H incorporation reached a plateau at four hours and 14C-incorporation reached a plateau at 24 hours. The 3H was associated mainly with phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) at the 2-position while 14C was found at the 1-position. When the double-labeled cells were incubated with bradykinin or ionophore A23187, a significant release of 3H into the medium was observed, while the 14C release was small. Approximately 90% of the 3H released was arachidonic acid. Small amounts of the released 3H were no longer associated with stearic acid; it was converted mainly into prostaglandin E2 (PGE2). When stimulated by either bradykinin or ionophore, a significant 3H loss was observed in cellular PC while there were no significant 3H changes in other phospholipids, triacylglycerols (TGs), or diacylglycerols (DGs). Although 14C of cellular lysophosphatidylcholine (lyso-PC) was not increased significantly, the 3H seemed to be released from the 2-position of PC by the action of phospholipase A2. There was no significant change in the breakdown of PC between palmitoyl-arachidonyl (16:0/20:4) and stearoyl-arachidonyl (18:0/20:4) species. Both A23187 and bradykinin may activate phospholipase A2, releasing arachidonic acid equally from the 2-position of PCs having either palmitic acid or stearic acid at the 1-position. Some of this material is converted to PGE2, but this conversion is low compared to other cell types.

Animals↗

[EEG data filing system with personal computer and magneto-optical disc].

We established a new computerized EEG filing system, in which an EEG machine was connected to an EEG filing unit which consisted of a personal computer with a 32 bit CPU, 18 channel analog -to-digital and digital-to-analog converters, and a magneto-optical disc driver. This system has the following merits. The system was space-saving, the space required to store the EEG data, being only 1/500 of that required for storing EEG record. Though the system had two independent EEG filing units, our original file configuration enabled us to have access to all of the recorded EEG data anytime for more than 10 years. The system enabled us to display EEG data continuously on the high resolution CRT, just as if turning the page of an EEG record paper, and through the quick scanning, enabled us to view the entire EEG pattern. Furthermore, the system enabled us to conduct reliable digital analysis for EEG data by entering the EEG data without artifacts into a data processor after confirmation on the display. In the system, we used data files with the MS-DOS operating system. This enabled us to analyze the data obtained by a personal computer operating on other systems, by transferring the data to a floppy disc operating on our system. Our EEG filing system allows quick access to data as well as mass data storage.

Electroencephalography↗