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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 811 records · Page 45Linked to original sources

Proposed new criteria for early carcinoma of the esophagus.

The criteria of early carcinoma of the stomach, defined in 1981, has gained worldwide acceptance. A few proposals of a criteria for early carcinoma of the esophagus have been made; however, these criteria have not been internationally accepted, as the rate of recurrence is high in patients with early carcinoma of the esophagus, as determined by these criteria. In patients with submucosal carcinoma of the esophagus, metastasis to lymph nodes was present in 32.5 per cent at the time of the operation, and the five year survival rate was only 54.5 per cent. On the other hand, while the incidence of epithelial or mucosal carcinoma, or both, is only 2.2 per cent (46 of 2,130) in patients with carcinoma of the esophagus, the incidence has been remarkably increased and the five year cumulative survival rate for patients with epithelial carcinoma or mucosal carcinoma, or both, is now 88.4 per cent. Thus, we consider that the criteria for early carcinoma of the esophagus to be mucosal carcinoma as well as epithelial carcinoma regardless of the presence or absence of lymph node metastasis, and that a submucosal carcinoma should be excluded from the classification of early carcinoma of the esophagus.

Esophageal Neoplasms↗

Body configuration and joint moment analysis during standing long jump in 6-yr-old children and adult males.

The purpose of the present study was to compare the body configurations and the joint function during standing long jump in 6-yr-old children and adult males. Twelve healthy adult males and eight (one male and seven females) 6-yr-old kindergartners participated in this study. Subjects performed standing long jump on a force platform with full effort. Body segment and joint angles were analyzed by high speed videography (100 frames.s-1). Using kinetic and kinematic data, joint moments, power, and work done were calculated through a free body diagram. Average standing long jump performances were +1.5 SD above Japanese norm in both adults and children. A wide range of motion of the lower limb segments during flight phase was found in the adults. In the crouch prior to take off, joint muscle power peaks appeared in the same order, and joint contribution to the total work done showed almost the same values in both adults and children. It is suggested that gross motor pattern before take off is almost accomplished by the 6-yr-old. Judging by hip joint work, adult performance was much better than that of children, since the adults exerted relatively higher negative work from the onset of preparatory movement to the point of lowest center of gravity during crouch. It was concluded that skilled 6-yr-old children have not fully developed either hip negative work during preparatory movement or body configuration in the flight phase, although gross motor pattern before take off phase was accomplished to skilled adult level.

Adult↗

[An evaluation of surgical treatment for giant bullae].

We have experienced 67 operative cases of giant emphysematous bullae of the lung. For the bilateral lesions, two stage operation was performed in five cases and one stage operation under median-sternotomy in 12 cases. Twenty six cases were subjected to Naclerio-Langer's method, 25 cases to partial resection or plication and 15 cases to lobectomy. At the earlier period lobectomy was the treatment of choice, but, recently lobectomy was avoided for the conservation of pulmonary function. In terms of the improvement of pulmonary function, there was no difference between Naclerio-Langer's method and partial resection by Autosuture. In conclusion, for the treatment of giant bullae, partial resection by Autosuture is preferable because of improvement of pulmonary function and one stage median-sternotomy for bilateral lesions also are effective.

Adult↗

[Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders].

The effectiveness of sulbactam/cefoperazone (SBT/CPZ) on severe infections associated with hematological diseases was evaluated in a nation-wide multicenter clinical study. SBT/CPZ (4-6 g/day), a 1:1 combination of SBT and CPZ, was given intravenously to 437 patients with hematological disorders. The underlying diseases included acute nonlymphocytic leukemia, acute lymphocytic leukemia, malignant lymphoma, multiple myeloma, myelodysplastic syndrome and others. Thus, 94.3% of the patients had hematological malignancies. The complicating infections included sepsis in 41 cases; sepsis suspected in 205; pneumonia in 47; urinary tract infection in 15; fever of unknown origin in 59; and others in 70. Clinical efficacies of SBT/CPZ were as follows; markedly effective, 83 cases; effective, 170; fairly effective, 59; and ineffective, 110. The efficacy rate (markedly effective plus effective) was 60.0% as a whole. The efficacy rate of SBT/CPZ in sepsis and suspected cases, which accounted for 56.3% of the infections, was 59%. Mild side effects such as skin rash were observed in 15 patients (3.1%). As for abnormal laboratory test results, transient increases in GOT, GPT, A1-P, LDH, etc. were observed in 42 patients (8.6%). Therefore, SBT/CPZ is considered to be a useful drug in empiric therapy for severe infections associated with hematological diseases.

Adolescent↗

[A case of completely unroofed coronary sinus with persistent left superior vena cava].

A 34-year-old female presented with exertional dyspnea. Investigation by echocardiography and cardiac catheterization showed completely unroofed coronary sinus with persistent left superior vena cava (PLSVC) (coronary sinus atrial septal defect, absence of the coronary sinus, and PLSVC-left atrium connection) combined with tricuspid valve regurgitation. Angiocardiography made by injection into the PLSVC demonstrated that the PLSVC was connected to the hemiazygos vein before it drained into the left atrium and the left innominate vein was absent. Although jugular vein pressure rose up to 18 mmHg when the PLSVC was temporarily occluded, it remained unchanged. Therefore, simple ligation of the PLSVC was selected for therapy. Patch closure of the atrial septal defect, tricuspid valve repair, and ligation of the PLSVC was performed successfully.

Adult↗

[Comparison of positivity between density gradient centrifugal method and whole blood method in lymphocyte surface marker analysis with flow-cytometry].

The lymphocyte surface marker analysis with flow-cytometry is usually performed using a density gradient centrifugal method or a whole blood method. We have compared these two methods using several monoclonal antibodies and have found the significant difference in positivity all monoclonal antibodies except TCR-1 (anti alpha/beta receptor on T-lymphocyte). We found the significantly higher positivity of Leu12 and HLA-DR as well as lower of the other monoclonal antibodies by using whole blood method than by density gradient centrifugal method. We conclude that it is necessary to make a distinct description of the method used in the surface marker analysis.

Adult↗

Quantitative analysis of serum IL-6 and its correlation with increased levels of serum IL-2R in HIV-induced diseases.

We have devised a luminescence sandwich ELISA for the quantification of IL-6 in both sera and cell culture supernatants, which had a detection limit of 100 fg/ml of test sample. By using the luminescence sandwich-ELISA, low but measurable levels of IL-6 (9.5 pg/ml on average) were found in the sera from normal individuals. The serum levels of IL-6 were elevated in HIV-seropositive asymptomatic carriers (55.5 pg/ml on average), and the IL-6 levels were correlated with the degree of HIV-induced disease progression (AIDS-related complex 106.8 pg/ml on average and (AIDS 283 pg/ml). IL-6 immunoreactivity in the sera of AIDS patients eluted at a 25,000 m.w. major peak, which was biologically active and heat-stable, and a 500,000 m.w. minor peak in size-exclusion HPLC. Interestingly, a significant correlation was observed between the serum IL-6 levels and soluble IL-2R levels. In vitro, HIV infection of PHA-activated PBMC led to enhanced release of IL-6 into the culture supernatants. Moreover, soluble IL-2R release was markedly increased by adding exogenous IL-6, whereas it was decreased by adding the neutralizing anti-IL-6 mAb to the cultures. These results demonstrate that increased IL-6 levels are significantly associated with sIL-2R levels, and suggest a cause of the increased levels of this receptor in patients with HIV infection. Furthermore, both serum IL-6 and serum IL-2R levels in HIV infection reflect the stage of the HIV-induced disease.

Cells, Cultured↗

Identification of a soluble IL-2 receptor beta-chain from human lymphoid cell line cells.

A clone was isolated from the human lymphoid cell line YT that displayed IL-2R beta, and was found to express much higher levels of IL-2R beta than the original cells. Combining cell surface iodination, affinity labeling of the released soluble protein, and fluorescence sandwich-ELISA for both IL-2 and IL-2.(soluble)(s)IL-2R beta reactants revealed the presence of IL-2-binding protein in the culture supernatant as soluble forms of IL-2R beta. By using the fluorescence sandwich-ELISA elevated levels of sIL-2R beta were measured in culture supernatants of human T cell leukemia virus I positive T cell lines. In addition to this constitutive production of sIL-2R beta, normal PBMC could release low levels of IL-2R beta by stimulation with PHA. In contrast, this was not found in certain human T cell leukemia virus I negative T cell, B cell and macrophage lines. Immunoprecipitation of the soluble protein with IL-2R beta-specific mAb characterized it as an apparent 50- to 55-kDa molecule that is distinct from the 45-kDa soluble IL-2R alpha. Moreover, 10 to 15% of the total cell surface molecules were released into culture supernatants. These results suggest that the released IL-2R beta might serve as an immunoregulatory function in IL-2 dependent both normal and abnormal immune responses.

Humans↗

Increased plasma brain natriuretic peptide levels in DOCA-salt hypertensive rats: relation to blood pressure and cardiac concentration.

Four experimental groups of rats treated with (1) DOCA-salt, (2) DOCA or (3) salt, and (4) controls were used to study the participation of brain natriuretic peptide (BNP) in the development of hypertension. Plasma and cardiac tissue concentrations of BNP as well as atrial natriuretic peptide (ANP) were measured in each group by using radioimmunoassays specific to rat BNP or ANP. Plasma BNP levels in DOCA-salt hypertensive group were higher than those in control (p less than 0.01), salt (p less than 0.01) and DOCA (p less than 0.01) groups. A positive correlation was observed between plasma BNP levels and blood pressure (r = 0.70, p less than 0.001) and between plasma ANP levels and blood pressure (r = 0.62, p less than 0.001). Plasma BNP/ANP ratio increased parallel with elevation of blood pressure. Plasma BNP levels correlated negatively with atrial BNP concentration (r = -0.33, p less than 0.05), but positively with ventricular BNP (r = 0.76, p less than 0.001). Compared with controls, tissue BNP-45/gamma-BNP ratio in the DOCA-salt rats was lower in atrium, but higher in ventricle. Thus, in DOCA-salt hypertension atrial BNP decreased with exhaustion of stored BNP-45, while ventricular BNP increased as BNP-45 accumulated. These results suggest that BNP is a novel cardiac hormone, synthesized, processed and secreted in response to changes in blood pressure. BNP may play different roles in controlling blood pressure than those assumed by ANP.

Animals↗

A role of lyso-phosphatidylcholine in GM3-dependent inhibition of epidermal growth factor receptor autophosphorylation in A431 plasma membranes.

EGF-dependent receptor autophosphorylation (EDRA) in A431 plasma membrane was specifically stimulated by lysophospholipids having phosphorylcholine head group (e.g., lyso-phosphatidylcholine; lyso-PC) but not other lysophospholipids, in the absence of detergent. In contrast, GM3 specifically inhibited EDRA under the same experimental conditions in which lyso-PC stimulated EDRA. This GM3-dependent inhibition was more efficient in the absence (vs. presence) of a detergent (Triton X-100). These results indicate an essential role of lyso-PC in GM3-regulated EGF receptor functions.

Cell Line↗

Polyethylene glycol modification of the monoclonal antibody A7 enhances its tumor localization.

The F(ab')2 fragment of murine monoclonal antibody A7 was covalently bonded to polyethylene glycol (PEG, molecular weight: 5000) and the conjugate was compared to the parent F(ab')2 fragment by in vitro and in vivo studies. PEG-conjugated antibody fragment retained its antigen-binding activity in a competitive radioimmunoassay. The conjugate had a longer half-life and showed increased accumulation in tumors. Although the tumor: blood ratio for parent F(ab')2 fragment was higher than that for the conjugate, it showed higher value than whole MAb A7. The tissue: blood ratios were kept low with the conjugate, indicating that the conjugate was uptaken to normal organ with lesser extent, as compared with parent F(ab')2 fragment. Our findings indicate that this PEG-conjugated F(ab')2 fragment could be a promising carrier for use in targeting cancer chemotherapy.

Animals↗

Primary structure of the oligo-1,6-glucosidase of Bacillus cereus ATCC7064 deduced from the nucleotide sequence of the cloned gene.

The gene coding for Bacillus cereus ATCC7064 (mesophile) oligo-1,6-glucosidase was cloned within a 2.8-kb SalI-EcoRI fragment of DNA, using the plasmid pUC19 as a vector and Escherichia coli C600 as a host. E. coli C600 bearing the hybrid plasmid pBCE4 accumulated oligo-1,6-glucosidase in the cytoplasm. The cloned enzyme coincided absolutely with B. cereus oligo-1,6-glucosidase in its Mr (65,000), in its electrophoretic behavior on a polyacrylamide gel with or without sodium dodecyl sulfate, in its isoelectric point (4.5), in the temperature dependence of its stability and activity, and in its antigenic determinants. The nucleotide sequence of B. cereus oligo-1,6-glucosidase gene and its flanking regions was determined with both complementary strands of DNA (each 2838 nucleotides). The gene consisted of an open reading frame of 1674 bp commencing with a ATG start codon and followed by a TAA stop codon. The amino acid sequence deduced from the nucleotide sequence predicted a protein of 558 amino acid residues with a Mr of 66,010. The amino acid composition and Mr were comparable with those of B. cereus oligo-1,6-glucosidase. The predicted N-terminal sequence of 10 amino acid residues agreed completely with that of the cloned ligo-1,6-glucosidase. The deduced amino acid sequence of B. cereus oligo-1,6-glucosidase was 72% and 42% similar to those from Bacillus thermoglucosidasius KP1006 (DSM2542, obligate thermophile) oligo-1,6-glucosidase and from Saccharomyces carlsbergensis CB11 alpha-glucosidase, respectively. Predictions of protein secondary structures along with amino acid sequence alignments demonstrated that B. cereus oligo-1,6-glucosidase may take the similar (alpha/beta)8-barrel super-secondary structure, a barrel of eight parallel beta-strands surrounded by eight alpha-helices, in its N-terminal active site domain as S. carlsbergensis alpha-glucosidase and Aspergillus oryzae alpha-amylase.

Amino Acid Sequence↗

Distribution and molecular form of immunoreactive big endothelin-1 in porcine tissue.

In the present study a specific and sensitive radioimmunoassay for big endothelin-1 was developed. Half maximal inhibition of binding of radioiodinated big endothelin-1 was observed at 58 pg/tube and big endothelin-1 was detectable as low as 2 pg/tube. With this assay, the regional distribution of big endothelin-1 was determined in porcine tissue and compared to the distribution of an immunoreactive endothelin. Considerable amount of immunoreactive big endothelin-1 was observed in the aortic intima (0.84 +/- 0.094 pg/mg wet tissue; mean +/- S.D.) and the lung (0.47 +/- 0.055), but there was a low concentration in other tissue including the kidney inner medulla, which has been shown to be abundant in immunoreactive endothelin. Furthermore the molecular form of immunoreactive big endothelin-1 in aortic intima was found to be big ET-1[1-39], but the molecular form of major immunoreactive big endothelin-1 in the lung is big endothelin-1[22-39] with big endothelin-1[1-39] being minor.

Amino Acid Sequence↗

Isolation of NPY-25 (neuropeptide Y[12-36]), a potent inhibitor of calmodulin, from porcine brain.

In the present purification of low molecular weight fractions (Mr: 2000-4000) containing basic peptides, twenty nmol of novel calmodulin binding peptide, possessing a potent affinity for calmodulin, was isolated from 18 kg of porcine brain. By analysis with gas phase sequencer, the sequence was determined to be APAEDLARYYSALRHYINLITRQRY. Carboxy terminus of the peptide was determined to be Tyr-NH2. The peptide was a carboxy terminal pentacosanepeptide of neuropeptide Y and was termed NPY-25. NPY-25 competitively inhibited the activation of cAMP-phosphodiesterase through CaM binding in a Ca++ dependent fashion, but did not inhibit the basal activity of cAMP phosphodiesterase. NPY-25 elicited a more potent activity than did neuropeptide Y. IC50 values of NPY-25 and Neuropeptide Y were 0.06 microM and 0.54 microM respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗

An attempt to structurally convert mu-selective morphine toward delta-receptor binding: dimerization based on enkephalin conformation.

In order to elucidate the substrate specificities for mu- and delta-opioid receptors, dimerization of the mu-specific morphine molecule was attempted, based on the hypothesis of the possible relationship between the molecular conformation of endogenous enkephalin and its selectivity for each opioid receptor. The NOR2 ([normorphine]N-CH2-CH2-N[normorphine]) thus synthesized exhibited agonist activity showing a preference for binding with the delta-opioid receptor, compared with the parent morphine molecule. Antagonist activity was also observed for NOR3 ([normorphine]N-CH2-CH2-CH2-N[normorphine]).

Animals↗

The importance of Val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-activity relationship based on the crystal structure of the papain-E-64-c complex.

Based on the crystal structure of the papain-E-64-c complex, 3-dimensional binding modes of a series of epoxysuccinyl amino acid derivatives to the papain active site have been constructed and the structure-inhibitory activity relationship has been analyzed using the accessible surface area and nonbonded energy parameters. The result indicates the importance of the hydrophobic interaction between the amino acid side chain of the inhibitor and the papain Val-157 residue for revealing the potent inhibitory activity.

Amino Acid Sequence↗

A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells.

Our previous study suggested that N,N-dimethylsphingosine, but not unsubstituted sphingosine, could be a modulator of protein kinase C in epidermoid carcinoma A431 cells, since N,N-dimethyl-D-erythrosphingenine showed a stronger stereospecific effect on protein kinase C activity in comparison with N,N-dimethyl-L-erythrosphingenine, unsubstituted D- or L-erythrosphingenine, and gangliosides (Igarashi, Y., Hakomori, S., Toyokuni, T., Dean, B., Fujita, S., Sugimoto, M., Ogawa, T., El-Ghendy, K., and Racker, E. (1989) Biochemistry 28, 6796-6800). Other studies also indicated that commercial sphingosine preparation has an enhancing effect on epidermal growth factor (EGF) receptor kinase activity in A431 cells (Davis, R. J., Girones, N., and Faucher, M. F. (1988) J. Biol. Chem. 263, 5373-5379; Faucher, M. F., Girones, N., Hannun, Y. A., Bell, R. M., and Davis, R. J. (1988) J. Biol. Chem. 263, 5319-5327). In the present paper, we report (i) the effect of N,N-dimethylsphingosine as compared with lyso-glycosphingolipids and other sphingolipid breakdown products on EGF receptor autophosphorylation and (ii) demonstration of endogenous N,N-dimethylsphingosine synthesis and the virtual absence of unsubstituted sphingosine in A431 cells. The autophosphorylation of EGF receptor in the absence of detergent was strongly enhanced by N,N-dimethyl-D-erythrosphingenine; this effect was even obvious in the absence of EGF and synergistic in the presence of EGF. Similar enhancing activity was not produced by N,N-dimethyl-L-erythrosphingenine, D- and L-erythrosphingenine, N-monomethyl-D-erythrosphingenine, N-acetyl-D-erythrosphingenine, or the five lyso-glycosphingolipids tested. Labeling of sphingosine in A431 cells by culturing in medium containing [3H]Ser for various durations, followed by extraction and isolation of sphingolipids by standard procedures, resulted in clear bands corresponding to N,N-dimethylsphingosine and ceramide, whereas the band corresponding to sphingosine was virtually absent. The bands corresponding to N,N-dimethylsphingosine and ceramide intensified when cells were treated with metabolic inhibitor for UDP-Glc:Cer beta-Glc transferase (which causes accumulation of ceramide). These results indicate that N,N-dimethylsphingosine acts as a stereospecific enhancer for EGF receptor kinase and is able to produce EGF-like activity in vitro even in the absence of EGF and detergent. Under physiological conditions, N,N-dimethylsphingosine is the major catabolite resulting from ceramide breakdown.

Carcinoma, Squamous Cell↗