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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 757 records · Page 42Linked to original sources
PubMed1991

Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy.

The possibility that urinary pepsinogen I is a tumor marker of stomach cancer after total gastrectomy was examined. To decide the cutoff level of urinary pepsinogen I after total gastrectomy, urine samples from 15 patients who had undergone total gastrectomy for stomach cancer in the early or advanced stages and had been free from recurrence for more than 5 years were examined by pepsinogen I-specific radioimmunoassay. The mean concentration of urinary pepsinogen I was 17.5 +/- 7.4 ng/ml and the cutoff level of urinary pepsinogen after total gastrectomy was set at 32 ng/ml (mean + 2 SD). Twenty-two of 74 cases who had undergone total gastrectomy for stomach cancer were regarded as positive. And 20 of these 22 positive cases had definite clinical signs of recurrence of stomach cancer. There were only two false-positive cases. These results suggest that urinary pepsinogen I will be an useful tumor marker in detecting the recurrence of stomach cancer after total gastrectomy.

Adenocarcinoma↗
PubMed1991

Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy.

The murine monoclonal antibody A7 (Mab A7) against human colon cancer was chemically modified with methoxypolyethylene glycol (PEG) (Mr 5000). A high substitution of PEG molecules on Mab A7 produced a progressive reduction in antibody-binding activity. The pharmacokinetic and immunological properties of PEG-modified monoclonal antibody A7 (Mab A7) and the PEG-modified F(ab')2 fragment, which retained their antibody-binding activity, were assessed and compared with the parent Mab A7 and the parent F(ab')2 fragment. Blood clearance of PEG-modified antibodies appeared to be diminished by PEG modification and was fitted by a two-compartment model. Low PEG-substituted Mab A7 showed less organ uptake in the liver and spleen and similar uptake in the lung and kidney, compared with the parent Mab A7. PEG-F(ab')2 showed less uptake in the liver and kidney. Both preparations exhibited less tissue:blood ratios in all resected organs as compared with parent antibodies. Tumor localization was enhanced by PEG modification for the F(ab')2 fragment, but not by PEG modification for the whole Mab A7. Multiple i.v. administration of PEG-modified antibody to rabbit did not appear to elicit a measurable immune response to the antibody portion of the conjugate. In conclusion, PEG-modified antibodies are promising reagents as drug carriers to the target tumor.

Animals↗
PubMed1991

Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution.

E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.

Binding Sites↗
PubMed1991

Increased secretion of brain natriuretic peptide and atrial natriuretic peptide, but not sufficient to induce natriuresis in rats with nephrotic syndrome.

The levels of immunoreactive brain natriuretic peptide (ir-BNP) and immunoreactive atrial natriuretic peptide (ir-ANP) were evaluated by radioimmunoassay in both the atrium, ventricle and plasma of adriamycin-induced nephrotic rats and control rats. There was no difference in right and left atrial concentrations of ir-BNP, however, a higher right atrial concentration of ir-ANP was observed in nephrotic rats than in controls (p less than 0.01). The ventricular ir-BNP and ir-ANP were increased in nephrotic rats compared to controls (BNP: p less than 0.001, ANP: p less than 0.001). Cardiac BNPs were composed of pro-BNP (gamma-BNP) and its C-terminal 45-amino-acid peptide (BNP-45). The ratio of BNP-45/gamma-BNP in nephrotic rats was higher than that of controls in both atria and in the ventricle. Plasma ir-BNP and ir-ANP were significantly higher in nephrotic rats than in controls (BNP: p less than 0.001, ANP: p less than 0.001), and each level was negatively correlated with urinary sodium excretion in nephrotic rats (BNP: r = -0.84, p less than 0.001, ANP: r = -0.88, p less than 0.001). These results suggest that production and secretion of both BNP and ANP are concomitantly stimulated by a decreased renal ability to eliminate sodium and water, but this secretion is insufficient to induce effective natriuresis in nephrotic rats.

Animals↗
PubMed1991

The Schizosaccharomyces pombe mam2 gene encodes a putative pheromone receptor which has a significant homology with the Saccharomyces cerevisiae Ste2 protein.

The fission yeast Schizosaccharomyces pombe has two mating-types, h+ (P) and h- (M). The mam2 mutant exhibits an h(-)-specific sterile phenotype. Nucleotide sequencing of the mam2 gene isolated from an S. pombe genomic library revealed an open reading frame composed of 348 amino acids. The deduced mam2 product is a hydrophobic protein of 39 kDa that has significant sequence similarity (26.3% for identical amino acids) with the transmembrane domains of the Saccharomyces cerevisiae STE2 product, the alpha-pheromone receptor. Hydropathicity analysis suggests that the Mam2 protein contains seven possible membrane-spanning domains and a carboxy-terminal hydrophilic region. The mam2 gene was disrupted and found to be non-essential for growth. An h- haploid strain harbouring this disrupted null allele failed to respond to the pheromone of h+ cells, P-factor. These observations imply that the mam2 gene encodes a receptor for P-factor. Transcription of mam2 was induced only when strains containing functional mat1-M allele were cultured under conditions of nitrogen starvation. The mam2 gene was also transcribed in h+/h- diploid strains. The fact that the map1/mam2 homozygous diploid cells are incapable of sporulation implies that the pheromone signalling system is necessary for sporulation in diploid cells.

Amino Acid Sequence↗
PubMed1991

Lugol stain for intraoperative determination of the proximal surgical margin of the esophagus.

An adequate proximal surgical margin is difficult to determine particularly in cases of esophageal carcinoma with surrounding intraepithelial invasion. We report here readily facilitated intraoperative approaches for detection of the exact margin of carcinomatous invasion of the esophagus. The resected specimen of the esophagus is incised longitudinally and placed in a 1% Lugol bath for 2-3 minutes. The normal squamous epithelium includes glycogen that interacts with the iodine of Lugol's solution and the normal epithelium of the esophagus becomes a uniform greenish-brown. A squamous cell carcinoma does not include glycogen, hence is not stained with this solution and a clear identification is feasible. Thus, a carcinomatous infiltration not recognizable in routine examinations becomes macroscopically visible when Lugol's solution is used.

Adult↗
PubMed1991

Modulation of the immune response to tumors by a novel synthetic compound, (4R)-3-benzoyl-N-[(1R)-1-phenylethyl]-4-thiazolidinecarboxamide (RS-0481).

RS-0481, (4R)-3-benzoyl-N-[(1R)-phenylethyl]-4-thiazolidinecarboxamide, is a compound that can re-establish the function of certain lymphoid cell populations impaired by the presence of a growing tumor in an animal. The compound markedly augmented the tumor-specific cytotoxic T lymphocytes, TDTH (delayed-type hypersensitivity T cells), and the nonspecific lymphokine-activated-killer-cell-like cell responses. It also enhanced the tumor-inhibitory effect of macrophages in tumor-bearing mice, but not in normal mice, indicating that it enhances the antitumor immune responses. Lymphocytes from RS-0481-treated tumor-bearing mice released significantly higher amounts of macrophage-activating factor(s) (MAF) and interleukin-2(IL-2)-like factors in culture compared with lymphocytes from untreated animals. Also, sera from treated tumor bearers showed elevated colony-stimulating factor (CSF) activity. Although the compound did not influence the factor-producing activity in mice without tumor, it enhanced the responsiveness of their bone marrow cells, T cells, and macrophages to CSF, IL-2, and MAF. It seems therefore possible that the compound enhances the responsiveness of immunocompetent cells to cytokines, resulting in a marked augmentation of antitumor T cell responses in tumor-bearing mice. Consistently it inhibited the development of lymph node metastasis of transplanted X5563 plasmacytoma, and we showed that T cells play a decisive role in this inhibition. The compound also counteracted the development of suppressor T cell activity in the spleen of tumor-bearing mice.

Adjuvants, Immunologic↗
PubMed1991

Effects of an immunosuppressant, FK506, on interleukin 1 alpha production by human macrophages and a macrophage-like cell line, U937.

A recently discovered immunosuppressive agent, FK506, has been shown to be effective primarily as an inhibitor of T cell responses in vitro, but little is known about its effects on accessory cell function. This study was undertaken to determine the effect of FK506 on interleukin 1 (IL-1) production by macrophages, by using a sensitive and specific enzyme-linked immunosorbent assay. FK506 partially suppressed IL-1 alpha release, from macrophage-like U937 cells stimulated with phorbol myristate acetate and from human monocytes and alveolar macrophages activated with lipopolysaccharide, in a dose-dependent manner. Moreover, it was indicated that FK506 suppressed not only IL-1 release but also IL-1 synthesis itself, by measurement of cell-associated IL-1 alpha of U937 cells. The optimal concentrations of FK506 for suppressing IL-1 alpha did not affect cell viability or proliferation, and were 10- to 100-fold lower than those of cyclosporin A. It is concluded that FK506 affects macrophage physiology, suppressing IL-1 alpha production significantly. Thus, FK506 has the potency to act on non-T cells and the effect on macrophages may play an additional role in preventing graft rejection.

Anti-Bacterial Agents↗
PubMed1991

Analysis of bites on three-dimensional vectorcardiography after coronary artery ligation in dogs.

The serial changes in the QRS loops of vectorcardiograms were investigated following ligation of a branch of the left anterior descending artery (LAD) by the three-dimensional rotation method in 18 dogs. Concave inflections of the QRS loop, defined as "bites," were best delineated when the loop was viewed from a left cranial or right caudal direction. Bites appeared 48 +/- 8 minutes after LAD ligation in all of the dogs, and their development was closely related to the temporal changes in the % sigma R and QRS point score on a standard 12-lead electrocardiogram. Q waves were not observed on the electrocardiograms in 9 dogs. In the remaining 9, they appeared 117 +/- 18 minutes after LAD ligation. The bite duration, area, and amplitude were compared with the anatomical extent of the infarcts. A significant positive correlation was found between bite duration and infarct size. The detection of bites on the three-dimensionally rotated vectorcardiogram appears to have a high sensitivity for anterior myocardial infarction and could potentially become a useful diagnostic tool.

Animals↗
PubMed1991

Cardiac content of brain natriuretic peptide in DOCA salt-hypertensive rats.

The cardiac content of immunoreactive rat brain natriuretic peptide (ir-rBNP) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats was measured by radioimmunoassay (RIA). The atrial content of ir-rBNP was significantly lower in the DOCA-salt group than in the control group (p less than 0.01). However, the ventricular content of ir-rBNP was markedly increased in the DOCA-salt group as compared to the other groups. Ir-rBNP level in the atria was negatively correlated with other groups. Ir-rBNP level in the atria was negatively correlated with blood pressure (r = -0.49, p less than 0.01), while that in the ventricle was positively correlated with blood pressure (r = 0.79, p less than 0.001). A significant correlation was observed between tissue levels of ir-rBNP and ir-rat atrial natriuretic peptide (rANP) both in atrium and ventricle (atrium, r = 0.63, p less than 0.001; ventricle, r = 0.95, p less than 0.001). These results raise the possibility that rBNP as well as rANP functions as a cardiac hormone, the production of which probably changes in response to increased of body fluid and blood pressure.

Animals↗
PubMed1991

Properties of sympathetic neuromuscular transmission and smooth muscle cell membranes in vascular beds.

In vascular smooth muscle tissues, the cycle of contraction-relaxation is mainly regulated by the cytosolic Ca, and many other factors, such as substances released from endothelial cells and perivascular nerve terminals (mainly sympathetic nerves). In this article, we introduce regional differences in specific features of ionic channels in vascular smooth muscle membranes (mainly on features of Ca, Na and K channels) in relation to mobilization of the cytosolic Ca. In many vascular tissues, neurotransmitters released from sympathetic nerve terminals activate post-junctional receptors, and subsequently modify ion channels (receptor-activated cation channel and voltage-dependent Ca channel), whereas in some tissues, ionic channels are not modified by receptor activations (pharmaco-mechanical coupling). However, activation of receptors, with or without modulation of ionic channels, regulates the cytosolic Ca through synthesis of second messengers. In addition, receptors distributed on prejunctional nerve terminals positively or negatively regulate the release of transmitters. Roles of neurotransmitters (mainly ATP and noradrenaline) are also discussed in relation to the generation of excitatory junction potentials.

Action Potentials↗
PubMed1991

IA antigen-positive epithelioid cells in experimentally induced granulomatous inflammation.

IA antigens on the cell membrane of inflammatory macrophages and epithelioid cells were investigated with immunoelectron microscopic method during development of granulomas induced by subcutaneous inoculation of 10(7) Mycobacterium lepraemurium into mice with and without hypersensitivity. In C57BL/6N (H-2b) immunogenetic high responder mice 6 weeks after infection majority (87%) of infiltrated cells were IA-positive. Two types of the staining reaction, strong and weak reactivity, were recognized among the positive cells. Strongly IA-positive cells showed lower phagocytosis (0.9/cell section) of mycobacteria than the weakly reacted cells (4.9/cell section). The strongly positive cells underwent morphological differentiation into large epithelioid cells during development of the hypersensitivity-type murine lepromas after 10 or more weeks of infection. Types of granulomas and IA-positive cells in C57BL/6N (nu/+) mice were identical to those found in C57BL/6N. In C57BL/6N (nu/nu) athymic nude mice initial infiltrating cells contained 38% of weakly IA-positive macrophages and a small number (7%) of strongly IA-positive macrophages. But the reactivity was lost later and only 4% of IA-positive cells remained in the granulomas without hypersensitivity. CBA/J (H-2k) low responder mice did not show IA-positive cells in either initial or late stage during the development of nonhypersensitivity-type murine lepromas. We suggest that the presence of IA-positive cells, particularly IA-positive epithelioid cells, in the lesions modulates the course of granulomatous tissue reaction in murine lepromas.

Animals↗
PubMed1991

Adaptability of restrained molecular dynamics for tertiary structure prediction: application to Crotalus atrox venom phospholipase A2.

In order to assess the adaptability and/or applicability of the restrained molecular dynamics (RMD) simulation for building a possible tertiary structure of a protein from the X-ray crystal structure of a family reference protein, the tertiary structure prediction of Crotalus atrox venom phospholipase A2 (PLA2) was attempted based on the X-ray crystal structure of bovine pancreatic PLA2. For the formation of secondary and tertiary structures from the fully extended starting structure, the RMD simulation with interatomic distance restraints and torsion angle restraints, which were derived from homologous amino acid sequence regions in the reference protein, was carried out until the molecular system was fully equilibrated. The predicted tertiary structure of C. atrox venom PLA2 was compared with its X-ray crystal structure, and furthermore the utility of this method was discussed by reference to the similar tertiary structure prediction of beta-trypsin from the X-ray crystal structure of an elastase.

Amino Acid Sequence↗
PubMed1991

Leiomyosarcoma of the skin with generalized metastases: electron microscopic and immunohistochemical study.

A 62-year-old woman with numerous (more than 50) tumors between 25 and 75 mm in diameter disseminated over most of her body surface is reported. Biopsied tissue specimens demonstrated that the tumors consisted mainly of spindle-shaped cells with nuclear pleomorphisms and relatively high mitotic rates. They were irregularly arranged; they sometimes mimicked storiform- and palisading-patterns. Immunohistochemistry revealed that the tumor cells were positive for muscle-specific actin, desmin, and myosin, but negative for S-100 protein. Electron microscopy confirmed myofilaments and dense patches in the cytoplasm. The metastatic potential of such leiomyosarcoma of the skin is indicated.

Cytoskeletal Proteins↗