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Biomedical subjects

H Kubota

Publications and source records attributed to H Kubota.

At least 163 records · Page 9Linked to original sources

Relation between radiographic mottle for double and single emulsions.

The radiographic density fluctuations produced by using dual screen-film systems are designated as the radiographic mottle. The density fluctuation of the radiographic mottle for the double emulsions at a density of the double emulsions consists of those for the front and back emulsions on a radiograph. However, the relation between the Wiener spectra of the radiographic mottle for the double and single emulsions had not been studied. Hence we compared the Wiener spectra of the radiographic mottle for the double emulsions with the sum of those for the front and back emulsions on the same radiographs and with the sum of those for the emulsions at the same densities. At all densities of more than 0.62 for lower spatial frequencies (< or = 1 mm-1), the Wiener spectral values of the radiographic mottle for the double emulsions were greater than the sum of those for the front and back emulsions for both comparisons on the same radiographs and at the same densities. In order to investigate the reason of the above phenomena, we separated the Wiener spectral values of the radiographic mottle for various densities into those of the three factors, i.e., quantum mottle, structure mottle, and film granularity, and performed the same comparisons as the radiographic mottle. Also, to explain the results for the three factors, we obtained the Wiener spectral values of the spatial fluctuations of the light exposure or the fluorescence intensity and the gradients of the characteristic curves of the film for the double and single emulsions of the x-ray film. As a result of the investigation, we found that the phenomena on the radiographic mottle were caused by that (1) on the same radiographs the squares of the gradients of the characteristic curves for the double emulsions were about 5.3 times as great as those for the single emulsion at densities of more than 0.62 of the double emulsions, and (2) at the same density of more than 0.62 those were more than about 2.2 times as great as those for the single emulsion.

Biophysical Phenomena↗

Optimum tube voltage for chest radiographs obtained by psychophysical analysis.

Many kinds of x-ray films having various characteristic curves have been developed for chest radiographs. In general, a phototiming device for determination of a mAs value which gives a proper exposure has been used for a chest radiography. For each film, however, the x-ray tube voltage has been determined by the subjective evaluation of radiologists or radiological technologists. In this paper, we propose a new method for determining the optimum tube voltage for chest radiographs using psychophysical analysis. The optimum density and the optimum density range of a screen/film system are obtained from the gradient curve of film and the minimum perceptible contrast delta Dmin [Acta Radiol. Diagnos. 4, 463-476 (1966)]. The optimum tube voltage, by which the lowest density of a mediastinum and the highest density of a lung field just cover the optimum density range, is obtained using the x-ray photon spectrum and sensitivity spectrum of the screen. This objective method does not depend on personal subjective evaluation, therefore it is available for the determination of optimum tube voltage for chest radiographs to be observed by many doctors of various departments.

Humans↗

Spiro-substituted piperidines as neurokinin receptor antagonists. III. Synthesis of (+/-)-N-[2-(3,4-dichlorophenyl)-4-(spiro-substituted piperidin-1'-yl)butyl]-N-methylbenzamides and evaluation of NK1-NK2 dual antagonistic activities.

To discover a novel NK1-NK2 dual antagonist, we have synthesized a series of spiro-substituted piperidines utilizing YM-35375 as a lead compound, and evaluated affinities for NK1 and NK2 receptors. In the N-methylbenzamide moiety, introduction of methoxy groups increased affinity for the NK1 receptor without a significant loss of affinity for the NK2 receptor. We also found that a conformation in which the phenyl groups of the N-methylbenzamide and 3,4-dichlorophenyl moieties are close to each other through a cis-amide bond, may be favorable for showing high affinity for the NK1 receptor and that a hydrogen bond-accepting group in the spiro-substituted piperidine moiety may be crucial for exhibiting high affinity for the NK2 receptor. Among the compounds prepared, YM-44778 (31) showed high and well-balanced affinity for NK1 and NK2 receptors (IC50 values of 18 and 16 nM, respectively). This compound also exhibited potent antagonistic activities against both NK1 and NK2 receptors (IC50 values of 82 and 62 nM, respectively) in isolated tissues.

Animals↗

Spiro-substituted piperidines as neurokinin receptor antagonists. II. Syntheses and NK2 receptor-antagonistic activities of N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides.

In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10(-9) M. Among these compounds, (+/-)-1'-[4-(N-benzoyl-N-methylamino)-3- (3,4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2-oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84 nM, respectively). It showed more potent inhibitory activity (ID50 20 micrograms/kg (i.v.)) against [beta-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41 micrograms/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41 microgram/kg.

Amides↗

Spiro-substituted piperidines as neurokinin receptor antagonists. I. Design and synthesis of (+/-)-N-[2-(3,4-dichlorophenyl)-4-(spiro [isobenzofuran-1(3H),4'piperidin]-1'-yl)butyl]-N-methylbenzamide, YM-35375, as a new lead compound for novel neurokinin receptor antagonists.

Analysis of the structural requirements of compound 1 (SR48968), a potent NK2 receptor antagonist, revealed that the 4-phenyl group of the piperidine is essential for binding with the NK2 receptor and occupies an equatorial position. Energy calculation of a variety of substituted 4-phenyl piperidines revealed that spiro[isobenzofuran-1(3H),4'-piperidine] possesses a conformationally restricted equatorial phenyl group. Our compound 12 (YM-35375) possessing this spiro-substituted piperidine bound to the NK2 receptor with an IC50 value of 84 nM and to the NK1 receptor with an IC50 value of 710 nM. It showed more potent inhibitory activity (ID50 41 micrograms/kg (i.v.)) against [beta-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than (+/-)-SR48968 (ID50 68 micrograms/kg (i.v.)). YM-35375 may be a new lead compound for novel NK2 receptor antagonists or NK1-NK2 dual antagonists.

Animals↗

Interlocking wedge osteotomy for cubitus varus deformity.

The authors reviewed 20 patients with cubitus varus deformity who were treated with the interlocking wedge osteotomy. All deformities including medial, posterior tilt and internal rotation of the distal fragment can be simultaneously corrected with this osteotomy. There were 14 males and 6 females whose average age was 5.0 years at injury and 14.1 years at surgery. The average follow-up period was 37 months. Thirteen patients had excellent results, 6 good, and 1 poor. The mean carrying angle was improved from 21.5 degrees of varus to 8.8 degrees of valgus, compared to 9.4 degrees of valgus on the uninjured side. The mean flexion of the elbow increased from 123.9 degrees to 134.3 degrees, and the mean hyperextension decreased from 12.0 degrees to 7.5 degrees. Three-dimensional correction and stable fixation can be achieved with this osteotomy.

Child↗

[Mass screening for prostate cancer--how to eliminate clinically insignificant cancer].

The ultimate aim of the mass screening program for prostate cancer is to decrease prostate cancer mortality, which can be demonstrated only in a well-designed and well-controlled trial comparing screened and unscreened populations. However, no trials have been performed to demonstrate the effect of this program. Some reports claimed that such a program includes the high possibility of detecting clinically insignificant cancer, for example, latent cancer. In this paper, early cancer detection and treatment in mass screening program are discussed.

Humans↗

[Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade: report a case].

The ruptured thoracic aortic aneurysm has had severely high mortality. A 71-year-old male who suddenly fainted away was admitted to our hospital. He was in shock on arrival. Computed tomography and echo cardiogram demonstrated ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade. Aortic arch replacement was performed using the selective cerebral perfusion under deep hypothermia. The recovery of his consciousness was delayed, and he had right hemiplegia postoperatively, but his state was improved gradually. Finally he complained only slight degree of aphasia, paralysis. An immediate and aggressive emergency operation is a only method to salvage the patient who has ruptured aneurysm of the thoracic aorta.

Aged↗

Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product.

Mouse Spa-1 gene with a region homologous to the human rap1GAP gene is transcriptionally induced in the lymphocytes by mitogenic stimulation. Herein we have cloned a cDNA for its human counterpart. SPA-1 cDNA encodes a 130-kDa protein (p130(SPA-1)) consisting of proline-rich regions and rap1GAP-related domain followed by a coiled-coil stretch. Baculovirally expressed p130(SPA-1) exhibited GTPase-activating protein (GAP) activity for Rap1 and Rap2, but not for Ras, Rho, Cdc42, Rac, and Ran, with comparable specific activity to the rap1GAP gene product (p85/95(rap1GAP)). In the cells, p130(SPA-1) was mostly localized at the perinuclear membranous region co-localizing with Rap1 and Rap2. Expression of SPA-1 and rap1GAP genes tended to be segregate in various tissues, lymphoid tissues expressing abundant SPA-1 transcript without rap1GAP, while those such as brain, kidney, and pancreas exhibiting rap1GAP mRNA with little SPA-1. Promyelocytic HL-60 cells, which expressed p130(SPA-1) with little p85/95(rap1GAP) in uninduced state, showed progressive decline in p130(SPA-1) and conversely drastic increase in p85/95(rap1GAP) as they ceased from proliferation and differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate. These results suggested that products of SPA-1 and rap1GAP genes, albeit comparable GAP activity for Rap1 and Rap2, functioned in the distinct contexts depending on cell types and/or states.

Amino Acid Sequence↗

Involvement of NK1+ CD4- CD8- alphabeta T cells and endogenous IL-4 in non-MHC-restricted rejection of embryonal carcinoma in genetically resistant mice.

Non-MHC-restricted rejection mechanisms against the murine MHC-negative F9 embryonal carcinoma cells were analyzed. Strains of C57BL/6 (B6) background were resistant to the tumors irrespective of H-2 haplotypes, while others, including BALB/c background, were susceptible. This resistance was suggested to be mediated primarily by the host thymus-dependent alphabeta T cells, since both athymic B6 nude and normal B6 mice depleted with alphabeta T cells showed susceptible phenotype. The difference of the nature of alphabeta T cells infiltrating in H-2-identical B6- and BALB.B-derived tumors was then comparatively analyzed. It was revealed that unique T cells with NK1+ CD4- CD8- (double negative (DN)) alphabeta TCR+ phenotype were accumulated significantly in B6, but few in BALB.B mice. The population freshly isolated from the F9 tumor tissues preferentially expressed potent IL-4 mRNA, and was suggested to be mostly responsible for the endogenous IL-4 production. Indeed, the injection of either anti-NK1.1 or anti-IL-4-neutralizing Ab into the normal B6 rendered them significantly susceptible to the tumor cells. These results strongly suggested that NK1+ DN alphabeta T cells were responsible primarily for the rejection mechanisms against F9 tumors. Histologically, F9 tumors in B6 mice were characterized by abundant macrophage infiltration and massive tumor necrosis, neither of which was observed in those in BALB.B nor B6 mice preinjected with anti-IL-4 Ab, indicating that both histologic features in the resistant strain were dependent on the endogenous IL-4. Present results provide one of the first instances in which a recently emerging minor T cell subpopulation, thymus-dependent NK1+ DN alphabeta T cells, plays an essential role in anti-tumor responses in vivo.

Animals↗

Characterization of cis-acting sequences and trans-acting signals regulating early growth response 1 and c-fos promoters through the granulocyte-macrophage colony-stimulating factor receptor in BA/F3 cells.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) activates a set of genes such as c-fos, jun, myc, and early growth response gene 1 (egr-1). Studies on BA/F3 cells that express hGM-CSF receptor (hGMR) showed that two different signaling pathways controlled by distinct regions within the beta subunit are involved in activation of c-fos/c-jun genes and in c-myc, respectively. However, the region(s) of the beta subunit responsible for activation of the egr-1 gene and other regulatory genes has not been identified. We describe here how egr-1 promoter is activated by hGMR through two regions of the beta subunit, with these regions being required for activation of the c-fos promoter. Coexpression of dominant negative (dn) Ras (N17ras) or dn JAK2 almost completely suppressed the activation of egr-1 and c-fos promoters. Deletion analysis of egr-1 promoter showed two cis-acting regions responsible for activation by hGM-CSF or mouse interleukin-3 (mIL-3), one between nucleotide positions (nt) -56 and -116, and the other between nt -235 and -480, which contains tandem repeats of the serum response element (SRE) sites. Similar experiments with the c-fos promoter showed that cis-acting regions containing the SRE/AP-1 sites is sufficient for activation by hGM-CSF. Based on these observations, we propose that signaling pathways activating egr-1 and c-fos promoters are controlled by SRE elements, either through the same or overlapping pathways that involve JAK2 and Ras.

Animals↗

Tissue-specific subunit of the mouse cytosolic chaperonin-containing TCP-1.

We have cloned a novel Tcp-1-related mouse testis cDNA encoding a polypeptide of 531 amino acids which shares 81.2% identity with the zeta subunit of the mouse cytosolic chaperonin-containing TCP-1 (CCT). Immunoblot analysis of mouse testis CCT subunits separated by 2-dimensional gel electrophoresis indicates that this novel gene, Cctz-2, encodes a CCT subunit of Mr 57 000 and pI 7.1. Cctz-2 mRNA is detected only in testis whereas the other Cctz gene, Cctz-1, is expressed in all tissues investigated. The CCTzeta-2 subunit may have specific functions in the folding of testicular proteins and for interactions with testicular molecular chaperones.

Amino Acid Sequence↗

Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human.

Sipa1, previously called Spa1, is transcriptionally induced in the murine lymphoid cells following mitogenic stimulation and encodes a protein with a domain related to Rap1 GTPase activating protein (Rap1GAP) at the N-terminus and to PEST sequences followed by a leucine zipper motif at the C-terminus. Herein mouse genomic Sipa1, which consisted of 16 exons, was cloned. Gene linkage analysis using (BXD) recombinant inbred strains indicated that Sipa1 was mapped to the most centromeric region of chromosome 19 syntenic with the long arm of human chromosome 11. Human SIPA1 cDNA exhibited a striking homology to that of mouse throughout the entire region, with the overall identity being 90% at the amino acid level. Human genomic clones, which hybridized with both mouse and human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated. Fluorescence in situ hybridization (FISH) analysis using the human genomic clones indicated that SIPA1 was indeed mapped to chromosome 11q13, most likely to the 11q13.3 subregion. It was further indicated by double-color FISH that SIPA1 was located in the centromeric neighborhood of CCND1/ PRAD1, a presumed BCL1 oncogene.

Animals↗

In vivo gene transfer and overexpression of focal adhesion kinase (pp125 FAK) mediated by recombinant adenovirus-induced tendon adhesion formation and epitenon cell change.

Adhesion formation is a frequent complication of tendon injury repair: however, little is known about its mechanisms. The intracellular focal adhesion kinase (FAK)-related signaling pathway may be one of the mechanisms involved in the induction of tendon adhesions. The replication deficient adenovirus containing the FAK gene (pp125 FAK) was constructed and named Adv-Fak. By in vitro transductions with the recombinant virus, overexpression of the FAK protein was documented in transduced cultured primary tendon cells. By in vivo direct injection of Adv-FAK into the space between the tendon and tendon sheath of White Leghorn chickens, FAK gene transfer with overexpression of the FAK protein was detected by immunohistological staining. The morphology of these stained cells changed from the normal flat shape to cuboid. The group with overexpressed adenovirus-mediated FAK had significant adhesion formation, as seen by increased work of flexion (118.197 +/- 29.616), compared with the group with overexpressed adenovirus-mediated beta-galactosidase (67.507 +/- 36.066) (p < 0.0393) and the group with adenovirus-mediated FAK antisense gene transfer (60.357 +/- 48.562) (p < 0.0211). Histological examination of the samples from tendons with Adv-FAK showed fibers between the tendon and tendon sheath; there were no fibers in the cavities of samples of injured tendons infected with Adv-beta gal. Moreover, at the application site of the former tendons, a thick fiber layer without epitenon cells was built up on the outer surface, whereas a thin fiber layer with clear epitenon cells was observed in the tendons to which Adv-beta gal was applied. Our results show that overexpression of FAK can induce tendon adhesion formation in vivo. This indicates that FAK and the FAK-related signaling pathway may be involved in the process of tendon adhesion formation. Understanding the details of this process may help to prevent tendon adhesion and improve healing.

Adenoviridae↗

Hemoptysis from an emphysematous bulla developing after open-heart surgery: report of a case.

We present herein the case of a 62-year-old woman with an emphysematous bulla who developed intractable hemoptysis 16 days after undergoing mitral and aortic valve replacement with tricuspid annuloplasty. A bronchoscopic examination with balloon occlusion of the bronchial lumen revealed that the blood source was the right middle lobe bronchus. A computed tomographic (CT) scan of the chest subsequently demonstrated a blood-filled emphysematous bulla in the right middle lobe. A right middle lobectomy was performed and the bulla was observed to be swollen with clotted blood. The respiratory tract bleeding stopped immediately after the lobectomy. Pathohistological examinations suggested that disruption of the pulmonary vessels in the wall of the bulla had caused the respiratory tract bleeding.

Aortic Valve Insufficiency↗

Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

Adult↗

Biomechanical and histologic characteristics of canine flexor tendon repair using early postoperative mobilization.

The purpose of this experimental study was to evaluate the mechanical and histologic healing of flexor tendon repairs using an early active motion protocol. Three different flexor tendon repair techniques in zone II were used. Forty-seven lacerated canine flexor profundus tendons from 25 dogs were repaired and evaluated at 5, 10, and 21 days after surgery. Eight of 9 Kessler repairs ruptured at days 5 and 10. None of the 19 Savage repairs or the 19 dorsal tendon splint repairs ruptured; 3 of 19 dorsal tendon splint repairs failed owing to adhesions. Smooth tendon gliding was obtained in all specimens in which repair was successful. The gap strength values for both the Savage and dorsal tendon splint repairs improved significantly for day-21 specimens compared to day-5 or day-10 specimens. The ultimate tensile strength showed no reduction during the 3-week period of tendon healing for both repairs. Histologically, there was evidence of progressive healing without surrounding adhesions. The improved suture techniques have the potential to withstand the stress produced by active digital motion protocols.

Animals↗

Effect of immobilization, immediate mobilization, and delayed mobilization on the resistance to digital flexion using a tendon injury model.

This study employed a tendon injury model in chickens to determine the effect of immobilization, immediate mobilization, and delayed mobilization on the energy required to fully flex the digit following surgical trauma to the tendon, as determined by measurement of the work of flexion (WOF). The immobilized group showed no increased WOF at 3 days compared to the zero time control values, followed by significant increased WOF at 1 week (36%), 2 weeks (41%), and 3 weeks (63%). The immediate mobilization tendons showed an initial 36% rise in the work of flexion at 3 days, which increased to 40% at 1 week, and then decreased to baseline control values by 3 weeks. Delaying the period of mobilization until 5 days was not shown to significantly lower the peak WOF value at 1 week, but delaying the period of mobilization until 3 days lowered the peak WOF value at 1 week dramatically to 13%; both the 3- and 5-day delayed-mobilization groups returned to baseline WOF values by 3 weeks. From these data, it can be assumed that there is an early increase in the work necessary for flexion of the injured operated digit and tendon that is present in the immediately mobilized tendons at 3 days and persists to 1 week and that does not appear until 1 week in the immobilized tendons; this rise in WOF can be blunted by delaying the institution of mobilization.

Animals↗