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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 649 records · Page 36Linked to original sources
PubMed1993

Genetic and chemical polymorphisms of saponins in soybean seed.

The variation in saponin composition in soybean seeds is explained by different combinations of five genes controlling the utilization of soyasapogenol glycosides as substrates. The function of these genes is variety-specific and organ-specific. Phenotypes of over 1000 soybeans were classified into eight saponin types, and the frequency of phenotypes was different between the cultivated [Glycine max (L.) Merr.] and the wild soybean (G. soja Sieb. & Zucc.). The AaBc saponin type predominated in G. soja (58.4% of test collections), but was only found in 0.3% of G. max. Four unidentified arabinoside saponins were detected in the seeds of the AaBc type soybeans. The mode of inheritance of saponin types is explained by a combination of co-dominant, dominant and recessive acting genes. The combined chemical and genetic data show that the directed manipulation of soybean saponin composition is a possibility for the future.

Arabinose↗
PubMed1993

Tumor necrosis factor-alpha induces circular forms of human immunodeficiency virus type-1 DNA in the persistently infected low-level expressing cell line, ACH-2.

The low human immunodeficiency virus type-1 (HIV-1) expressing T-cell line, ACH-2, was used to investigate accumulation of the circular, extrachromosomal form of HIV DNA (HD) after tumor necrosis factor-alpha (TNF-alpha) induction. We chose the 2 long terminal repeat (LTR) circular form to analyze unintegrated HD by polymerase chain reaction (PCR), using primer pairs which flank the 2 LTR HD. Approximately a 10-fold increase in 2 LTR HD was detected intracellularly in the TNF-alpha-induced ACH-2 cells using an end point-dilution assay. To examine the cellular compartment location of the 2 LTR HD accumulation, ACH-2 cells were fractionated into cytoplasmic and nuclear components and further subjected to PCR. A 4- to 5-fold increase in the 2 LTR HD signal was observed in the nuclear fraction. These results indicate that unintegrated HD increases in a chronically infected cell line after TNF-alpha induction. This phenomenon, which previously had been observed only with acute infections, may offer insight into basic pathogenic mechanisms.

Cell Line↗
PubMed1993

Major glycoproteins in carp CNS myelin: homology to P0 protein with HNK-1/L2 carbohydrate epitope.

We studied the myelin protein profiles of carp from a phylogenetic point of view. The carp central nerve myelin contained two reactive bands, 28 and 25 kDa, demonstrated with anti-bovine P0 antibody. Their molecular weights are slightly different from those of two positive bands found in carp peripheral myelin. The N-terminal amino acid sequences of these four positive bands were identical to one another and showed high homology with those of mammalian P0 protein, suggesting that carp central myelin contains the P0-like protein. Lectin binding analysis revealed that carbohydrate structure of the P0-like proteins in carp central myelin is similar to those in peripheral myelin of carp and other vertebrates. Further, the carp P0-like glycoproteins, like the P0 proteins of other vertebrates, reacted with antibodies that recognize the HNK-1/L2 carbohydrate epitope. We conclude that the major structural glycoprotein in central myelin of the carp is homologous to P0 protein in peripheral myelin of other higher classes of vertebrates.

Amino Acid Sequence↗
PubMed1993

Piroxicam has at least two epitopes for contact photoallergy.

We have demonstrated previously in guinea pigs that the induction of photocontact sensitivity to piroxicam (PXM) also induces a state of cross-reactive contact hypersensitivity to two compounds having structurally related elements, thimerosal (TMS) and thiosalicylate (TOS). The present study was conducted to determine whether oral administration of TOS would desensitize guinea pigs previously photosensitized with PXM. At the same time, the spectrum of reactivities against these compounds and against tenoxicam (TXM) which resembles only piroxicam was assessed by appropriate sensitizing and eliciting protocols. As expected, animals photosensitized to PXM developed reactivities against all four compounds, PXM and TXM (photosensitivity) and TMS and TOS (contact sensitivity). By contrast, photosensitization with TXM induced cross-reactivity only against PXM. Moreover, the induction of contact sensitivity against TMS or TOS induced photosensitive cross-reactivity to PXM, but not to TXM. Finally, the oral administration of TOS produced a transient desensitization only for TMS and TOS. These results suggest that photosensitization with PXM induces two distinct reactivities. The first reactivity cross-reacts with TMS and TOS and is suppressible with orally administered TOS. The second cross-reacts only with TXM and is not suppressible with oral TOS. We conclude that PXM acquires at least two distinct immunogenic epitopes when exposed to UVA irradiation.

Administration, Oral↗
PubMed1993

A cross-reaction between piroxicam-photosensitivity and thiosalicylate hypersensitivity in lymphocyte proliferation test.

We examined the cross-reaction between photosensitivity to piroxicam (PXM) and contact sensitivity to thiosalicylate (TOS) by a lymphocyte proliferation test (LPT) in guinea pigs. The lymph node cells (LNCs) plus peritoneal exudate cells (PECs) from guinea pigs contact-sensitized with TOS remarkably cross-proliferated to PXM under UVA (4 J/cm2) irradiation. On the other hand, the PXM-photosensitized LNCs+PECs also cross-proliferated to TOS. From these results, the reciprocal cross-reaction between TOS-hypersensitivity and PXM-photosensitivity was reconfirmed by the in vitro LPT, indirectly indicating that the PXM-photosensitivity is a cell (probably T cell)-mediated PXM photoallergy in its nature. The TOS-primed LNCs+PECs did not cross-proliferate to UVA (4 J, 180 J or 500 J/cm2)-pretreated PXM (UVA-PXM) although it is supposed to contain several photoproducts of PXM. Furthermore, the TOS-primed LNCs developed a remarkable proliferative cross-response to the PECs pulsed with PXM under UVA (4 J/cm2) irradiation (photo-PXM-modified PECs), but not to the PECs pulsed with PXM or UVA-PXM. Therefore, it is presumed that the cross-reactive molecule, which is easily formed from PXM under UVA irradiation, is unstable, and that the formation of complete antigen by the generation of this molecule and its photobinding needs the coexistence of PECs, PXM and UVA irradiation at the same time in the culture.

Animals↗
PubMed1993

Unintegrated two-long terminal repeat circular human T lymphotropic virus DNA accumulation during chronic HTLV infection.

Accumulation of unintegrated human T lymphotropic virus (HTLV) DNA was analyzed in long-term T cell lines infected with HTLV type I (HTLV-I) or type II (HTLV-II). By using a polymerase chain reaction-based assay, amplified products of expected size were obtained in all of the HTLV-I-infected (n = 7) and HTLV-II-infected (n = 8) cell lines. The signal intensities of the hybridizing band varied greatly among the cell lines and did not correlate with HTLV p24gag antigen production. Further analysis of HTLV-I-infected clones demonstrated considerable variability in the unintegrated DNA accumulation, suggesting that either the epigenetic status of the host cell or some environmental factor determines the occurrence of unintegrated DNA. The presence of lower levels of unintegrated DNA in most of the HTLV-infected, long-term cell lines presumably results in persistent noncytopathic infection.

Base Sequence↗
PubMed1993

Alterations in circulating and cardiac tissue concentrations of brain natriuretic peptide in spontaneously hypertensive rats.

OBJECTIVE: This study was designed to investigate the modification of plasma and cardiac tissue brain natriuretic peptide concentrations in spontaneously hypertensive rats and Wistar-Kyoto rats in relation to those of atrial natriuretic peptide during the development of hypertension. METHODS: Blood pressure, tissue weight, and plasma and cardiac tissue atrial natriuretic peptide and brain natriuretic peptide concentrations were measured in conscious 5, 10, and 18 week old, spontaneously hypertensive, and in corresponding normotensive rats. Pharmacokinetics of atrial natriuretic peptide and brain natriuretic peptide were also examined. RESULTS: Plasma concentrations of both atrial natriuretic peptide and brain natriuretic peptide in hypertensive rats increased significantly with development of hypertension. The pattern was not in parallel, so that the brain natriuretic peptide/atrial natriuretic peptide ratio was high in spontaneously hypertensive rats. Concentrations of brain natriuretic peptide in the cardiac ventricle were already higher in hypertensive rats than in controls as early as 5 weeks of age, whereas atrial natriuretic peptide concentrations in the ventricle, predominantly in the left ventricles, and the highest brain natriuretic peptide/atrial natriuretic peptide ratio was in the left ventricles from 18 week old spontaneously hypertensive rats. Pharmacokinetics showed that the plasma half lives of atrial natriuretic peptide and brain natriuretic peptide were not different between the two strains. CONCLUSIONS: Although raised blood pressure stimulates both atrial natriuretic peptide and brain natriuretic peptide, production of brain natriuretic peptide in the ventricles is already increased in the prehypertensive stage, and in older hypertensive rats, it is more responsive to progression of hypertension than atrial natriuretic peptide. It is suggested that regulation of production and secretion of the two natriuretic peptides is not temporally coordinated during development of hypertension in this model.

Animals↗
PubMed1993

The fetal thymus stores immature hemopoietic cells capable of differentiating into non-T lineage cells constituting the thymus stromal element.

Immature hemopoietic cell lines were established by transforming fetal thymocytes in vitro with a ts mutant of Abelson murine leukemia virus. They are positive for c-kit and IL-2R alpha but negative for lineage specific markers. Their TCR and Ig heavy chain genes are in germline configuration, and are expressed as germline gene transcripts. When these cell lines were stimulated in vitro with IL-1 their morphology changed into that of typical macrophages (M phi). Subsequent analysis of a particular clone, which displayed the morphological change at the highest efficiency among established cell lines, indicated that the clone possesses the capacity to differentiate into I-A-M phi capable of secreting several cytokines, and supporting the proliferation of fetal and adult thymocytes in vitro. If their surface markers are considered, their normal counterparts would be present in a minor subset of CD4-CD8- double-negative cells in the thymus in early development. The results raise the possibility that the thymic organ at an early stage of development stores immature hemopoietic cells capable of differentiating into a non-T lineage constituting the thymic stromal elements.

Abelson murine leukemia virus↗
PubMed1993

Molecular dynamics simulation of 1,2-dilauroyl-L-phosphatidylethanolamine binding to phospholipase A2: an attempt to explain the selective hydrolysis of substrate fatty acid ester at position 2.

To improve our understanding of why phospholipase A2 (PLA2) specifically catalyzes the hydrolysis of the fatty acid ester bond at position 2, not at position 1, of 1,2-diacyl-3-sn-phosphoglycerides, the binding of each fatty acid chain of 1,2-dilauroyl-L-phosphatidyl-ethanolamine (DLPE), a natural substrate, to bovine pancreas PLA2 was examined by molecular dynamics (MD) simulations. Two different binding modes were considered, i.e., the respective hydrocarbon chains of 1- and 2-lauroyl fatty acid esters were located at the PLA2 binding sites usually observed in the complex crystals (Form A2) and at the reverse sites (Form A1). Although the total energies of both forms fluctuated within nearly the same range during the 80 ps MD simulations, the binding mode of DLPE to the PLA2 catalytic site through the coordination to Ca2+ was much more advantageous in Form A2 than that in Form A1; significant deviation of the Ca2+ position from its starting structure was observed in the MD simulation of Form A1. The result suggests the importance of Ca2+ in the selective recognition and catalytic function of PLA2 toward the 2-positioned fatty acid ester of phosphoglyceride substrates.

Animals↗
PubMed1993

Cutaneous reactions induced by calcium channel blocker: high frequency of psoriasiform eruptions.

Fifteen cases with cutaneous reactions to calcium channel blockers (Ca-antagonist), dihydropiridine (including nicardipine, nifedipine, nisoldipine), verapamil, and diltiazem are reported. The patients from Yokohama City University Hospital and affiliated hospitals included 4 males and 11 females with cardiovascular diseases. Their average age was 64.7 (54 to 82) years. They had been taking Ca-antagonists for an average of 95 days (7 days to 10 years) before they developed dermatitis. The frequency of reactions to Ca-antagonists was high with diltiazem (5/16:31.25%) and dihydropyridine (7/16:43.75%), including nifedipine (4/7), nisoldipine (1/7), and nicardipine (2/7). Stevens-Johnson syndrome (MCOS) was associated only with verapamil. A notable type of eruption was the psoriasiform type, including exacerbation of psoriasis, which was resolved or easily controlled after discontinuation of the drug. Provocation tests verified the Ca-antagonist as the cause in 7 cases of psoriasiform eruption. The frequency of positive patch tests to Ca-antagonists was low except for diltiazem. Patch tests with diltiazem showed positive reactions in 54% (7 of 13 patients), based on our experience and papers published in Japan. Ca-antagonists are occasional causes of a wide spectrum of cutaneous reactions and should also be considered as causative factors in patients who develop psoriasiform eruptions or in patients whose psoriasis is exacerbated while using these drugs.

Aged↗
PubMed1993

Generalized eruptive histiocytoma: report of a pediatric case.

A one-year-old boy was seen with brownish, flat papules on his face, neck and upper arms. The lesions were symmetric, discrete, slightly raised, firm to the touch, and asymptomatic papular eruptions. Histological and immunohistochemical investigation revealed monomorphous infiltration of S-100 negative, lysozyme negative, and alpha 1-antitrypsin negative, but alpha 1-antichymotrypsin positive and vimentin positive histiocytic cells with small numbers of lymphocytic cells. The histiocytic cells did not show any foamy changes in the cytoplasm. No giant cells were found. The lesions increased in number during the first few years and then spontaneously regressed by the sixth year of age, leaving partial brownish pigmentation.

Child↗
PubMed1993

Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections.

Although chronic fatigue syndrome (CFS) is known to be the syndrome that begins with an acute flu-like illness that may be due to the exposure to an infectious agent, there has been no convincing evidence on the causative agents. Recently, human T-lymphotropic virus type II (HTLV-II)-like virus has been reported to be associated with the CFS by using HTLV Western blot analysis and polymerase chain reaction. However, some investigators could not detect HTLV-II by indirect immunofluorescence analysis. Lately, CFS patients have been reported in Japan. We detected all 30 tested patients with CFS were seronegative for HTLV-II, HTLV-I and HIV by specific peptide ELISA and Western blot. Further, PCR analysis was negative for HTLV-II and retrovirus was not detected by coculture method with patients' PBMC. Thus, known human retrovirus infections do not cause a CFS in Japan.

Blotting, Western↗
PubMed1993

Follow-up study of patients treated with monoclonal antibody-drug conjugate: report of 77 cases with colorectal cancer.

A total of 77 patients with advanced colorectal cancer, including postoperative patients with liver, lung and peritoneal metastases, were treated with single or multiple injections of monoclonal antibody A7-neocarzinostatin (A7-NCS). A follow-up study of the patients treated with A7-NCS was done and the clinical outcome was compared with that of patients given other chemotherapies. In the postoperative patients with liver metastasis, the A7-NCS treatment prolonged survival time when compared with systemic administration of anticancer drugs, while it showed a similar survival time to chemoembolization using multiple anticancer agents suspended in a lipid contrast medium. Among the patients who underwent surgical resection of primary cancer, with or without liver metastasis, there was no difference in overall 5-year survival rate between the group treated with A7-NCS and the group treated with the other chemotherapies. However, the survival time of the patients treated with A7-NCS was longer than that of the patients treated with the other chemotherapies. In addition, the patients given a higher dose of A7-NCS had a longer survival time than the patients given a lower dose of A7-NCS. Human anti-mouse antibody was detected in all the A7-NCS-treated patients examined. There were no serious side effects in any of the patients given A7-NCS. Thus, this study indicates that the A7-NCS treatment is safe and useful for colorectal cancer patients, though some problems remain, such as optimization of injection dose, route, interval, etc., and overcoming human anti-mouse antibody development.

Adult↗
PubMed1993

Enhanced tumor localization of radiolabeled Fab fragments of monoclonal antibody A7 in nude mice bearing human pancreatic carcinoma xenografts.

Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the immunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoscintigraphy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low normal tissue/blood ratio of radioactivity. In this study, 125I-labeled Fab fragments produced by papain digestion of MAb A7 were injected intravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The radioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was 1.00 +/- 0.24 and 9.68 +/- 2.54 at 2 and 24 h after injection, respectively. The tumor tissue/blood ratio of radioactivity was significantly higher than those of normal organs at 24 h after injection. Moreover, the tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the 125I-labeled Fab accumulation level was much less than that of 125I-labeled intact MAb A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, 125I-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MAb A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.

Animals↗
PubMed1993

Production, binding and cytotoxicity of human/mouse chimeric monoclonal antibody-neocarzinostatin conjugate.

A human/mouse chimeric Fab monoclonal antibody A7 (chFabA7) was covalently coupled to neocarzinostatin (NCS) by the SPDP method at various chFabA7:NCS substitution ratios. The antigen-binding activity of the conjugate, examined by ELISA using fixed antigen-positive colon cancer cells, was identical to that of the parent chFabA7 when one mole of NCS was conjugated, but was reduced with 2 or 3 moles of conjugated NCS. By means of a colony-forming assay, the cytocidal effect of the conjugate on antigen-positive cancer cells was found to be stronger than that of free NCS, whereas in antigen-negative cancer cells it was similar to that of free NCS. This effect was attenuated by adding an excess amount of monoclonal antibody A7. These findings indicate that the conjugate has an antigen-specific cytocidal action, and thus chFabA7-NCS is a promising tool for targeting cancer chemotherapy.

Animals↗
PubMed1993

S-nitrosocysteine, but not sodium nitroprusside, produces apamin-sensitive hyperpolarization in rat gastric fundus.

1. To investigate the pharmacological properties of the membrane hyperpolarization induced by electrical field stimulation (EFS), sodium nitroprusside (SNP) and S-nitrosocysteine (NO-Cys) in circular smooth muscle cells of the rat gastric fundus (forestomach), the effects of various potassium channel blockers on these hyperpolarizations were investigated. 2. EFS (50 microseconds, 20 Hz, 3 pulses, 10-50 V) produced inhibitory junction potentials (i.j.ps), in the presence of atropine (1 microM) and guanethidine (1 microM). NO-Cys and SNP produced hyperpolarization of the membrane in the rat gastric fundus. L-NG-nitroarginine (L-NNA) inhibited the i.j.ps, but not the hyperpolarization induced by NO-Cys and SNP. This inhibitory action of L-NNA on the i.j.ps was partly reversed by subsequent application of L-arginine (1 mM) but not by D-arginine. 3. Oxyhaemoglobin (Oxy-Hb; 5 microM) inhibited these hyperpolarizations, although a higher concentration of Oxy-Hb was required to inhibit the SNP-induced hyperpolarization. Hydroquinone (50 microM) inhibited only the hyperpolarization induced by NO-Cys. 4. Apamin (1 microM) partly inhibited i.j.ps and NO-Cys-induced hyperpolarization, but not the SNP-induced hyperpolarization. Tetraethylammonium (TEA; 1 mM), 4-aminopyridine (4-AP; 1 mM) or glibenclamide (1 microM) did not affect hyperpolarization induced by NO-Cys and SNP. 5. 8-Bromo cyclic guanosine 3':5'-monophosphate (1 mM) also produced hyperpolarization. Apamin (1 microM), TEA (1 mM) and glibenclamide (5 microM) all failed to inhibit this hyperpolarization. 6. These results indicate that NO-Cys and EFS hyperpolarize the membrane by activating apaminsensitive and TEA-resistant K+ channels and favour the hypothesis that a NO-liberating substance may act as a neurotransmitter in non-adrenergic, non-cholinergic (NANC) neurones in the rat forestomach.Our results also suggest that increase in cyclic GMP may cause apamin-resistant hyperpolarization but the apamin-sensitive hyperpolarization is mediated by another mechanism.

Animals↗