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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 631 records · Page 35Linked to original sources
PubMed1993

CD4dull+ hematopoietic progenitor cells in murine bone marrow.

CD4+ cells comprise approximately 3% to 6% of murine bone marrow (BM) cells. The majority are CD4dull+, but there are two distinct sub populations: CD4 brightly positive Gr-1- cells (CD4hiGr-1-) and CD4+ Gr-1+ cells (CD4loGr-1lo). CD4hiGr-1- cells are considered to be mature T cells by cell surface antigen expression and morphology. CD4loGr-1lo cells, which comprise approximately 0.6% of the BM cells, express small amount of B220 and Thy1 antigens. Interestingly, colony-forming units (CFU)-spleen and CFU-C are not enriched in this population. However, when injected into lethally irradiated mice, CD4loGr-1lo cells were shown to differentiate into T-cell, B-cell, and myelo-monocyte lineages when assayed 26 weeks after transplantation. Furthermore, donor-derived CD4loGr-1lo cells were present in the recipients' BM at least 16 weeks after transplantation. These observations suggest that murine CD4loGr-1lo cells in BM have self-renewal capability and retain the ability to differentiate into at least three lineages in long-term hematopoiesis.

Animals↗
PubMed1993

Murine bone morphogenetic protein-4 gene: existence of multiple promoters and exons for the 5'-untranslated region.

A murine genomic clone of about 16 kilobases encompassing putatively entire bone morphogenetic protein (BMP)-4 gene has been isolated. Comparison with the cDNA clones revealed the existence of at least five exons on the 3' side of the clone. There are two alternative transcriptional start sites, one is for the first exon the other for the second, the resulting exon organization in mRNA is I-III-IV-V and II-III-IV-V, respectively. The coding region is dispersed between exons IV and V. Both promoter regions carry no canonical TATA box but carry GC rich sequences.

Amino Acid Sequence↗
PubMed1993

Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.

A novel hypotensive peptide was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. Since this peptide is abundant in normal adrenal medulla as well as in pheochromocytoma tissue arising from adrenal medulla, it was designated "adrenomedullin". The peptide, consisting of 52 amino acids, has one intramolecular disulfide bond and shows slight homology with calcitonin gene related peptide. It was found to elicit a potent and long lasting hypotensive effect. The peptide circulates in blood in a considerable concentration, but it was not found in brain. These data suggest that adrenomedullin is a new hormone participating in blood pressure control. Occurrence of adrenomedullin indicates the possible existence of a novel system for circulation control.

Adrenal Gland Neoplasms↗
PubMed1993

Dimeric form of calcitonin gene-related peptide in the porcine thyroid gland.

In this study we investigated peptides that increase rat platelet cAMP in porcine thyroid gland. Gel filtration of extracts from porcine thyroid gland showed high and low molecular weight activity. Low molecular weight activity contained peptides, including calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI). We isolated a high molecular weight peptide (M. W. 11,000) showing potent activity able to increase rat platelet cAMP in porcine thyroid gland. The peptide's N-terminal sequence was determined to be Ser-X-Asn-Thr-Ala-Thr- by gas phase sequencer analysis, a sequence identical to that of porcine CGRP. The peptide had CGRP immunoreactivity as well as platelet cAMP elevating activity. By gel filtration HPLC, synthetic human CGRP (M. W. 3790) was eluted in a position corresponding to M. W. 5,500. These results suggest that judging from its high molecular weight the above peptide is a dimeric form of CGRP.

Amino Acid Sequence↗
PubMed1993

Constitutive expression and production of tumor necrosis factor-beta in T-cell lines infected with HTLV-I and HTLV-II.

A highly sensitive enzyme-linked immunoassay was developed to detect soluble levels of TNF-beta. Analysis of TNF-beta in culture supernatants from long-term T-cell lines infected with human T-cell lymphotropic virus (HTLV) types I and II demonstrated elevated levels of TNF-beta when compared with uninfected T-cell lines. Presence of interleukin-2 in the culture medium showed a synergistic effect upon TNF-beta production. Further, constitutive expression of TNF-beta mRNA was observed in most cell lines infected with HTLV-I or HTLV-II. These results demonstrate that infections with HTLV-I/II can alter production of TNF-beta, presumably via the transactivation of TNF-beta promoter by the tax protein of HTLV-I and HTLV-II.

Cell Line↗
PubMed1993

Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain.

We have identified a novel transcription unit of 105 kilobases (called the Golli-mbp gene) that encompasses the mouse myelin basic protein (MBP) gene. Three unique exons within this gene are alternatively spliced into MBP exons and introns to produce a family of MBP gene-related mRNAs that are under individual developmental regulation. These mRNAs are temporally expressed within cells of the oligodendrocyte lineage at progressive stages of differentiation. Thus, the MBP gene is a part of a more complex gene structure, the products of which may play a role in oligodendrocyte differentiation prior to myelination. One Golli-mbp mRNA that encodes a protein antigenically related to MBP is also expressed in the spleen and other non-neural tissues.

Alternative Splicing↗
PubMed1993

Conformation of deltorphin-II in membrane environment studied by two-dimensional NMR spectroscopy and molecular dynamics calculations.

Two-dimensional homonuclear Hartmann-Hahn spectroscopy and NOESY (nuclear Overhauser effect and exchange spectroscopy) 1H-NMR techniques have been used to obtain complete proton resonance assignments and to perform a conformational investigation of deltorphin-II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2), a naturally occurring delta-selective opioid peptide, in the membrane-mimetic micelles of perdeuterated dodecylphosphocholine. This was done in order to examine conformational characteristics that would be closely related to the selectivity towards the delta-opioid receptor. With the use of the proton-proton distances derived from NOESY measurements, 50 possible three-dimensional structures were generated by means of distance-geometry calculations, and 25 of them were subjected to the molecular-dynamics simulations of 10 ps, which were energetically constrained for the NOE interproton distances. Most of the possible conformers simulated showed a common feature such that the conformation of deltorphin-II is characterized by the S-shaped back-bone structure in which the turn conformation of the Val-Val-Gly-NH2 sequence is located under the helically folded conformation of the N-terminal Tyr-D-Ala-Phe-Glu sequence. The possible relationship between this conformational characteristic and the delta-opioid-receptor selectivity has been discussed.

Amino Acid Sequence↗
PubMed1993

Surgical treatment of esophageal carcinoma in patients eighty years of age and older.

Before 1979, no patient 80 years of age or older had been operated on at our institution for esophageal cancer, while in the middle period (1980-1984), three patients were operated on, and postoperative pulmonary complications and operative death occurred in 66.7 and 33.3%, respectively. However, in the recent period (1985-1990), there was no postoperative morbidity or mortality in the five cases over age 80. On the other hand, there were 12 patients over age 80 who did not undergo operation, of whom all died of cancer. In the eight operated patients over age 80, two cases are still alive 17 and 34 months after operation. According to the above findings, when the patient's general condition is evaluated to be sufficient to tolerate the operation and the cancer is judged to be resectable, esophageal resection is thought to be indicative in all patients over eighty.

Aged↗
PubMed1993

Significant clinical response of activated carbon adsorbed-peplomycin against esophageal cancer: a pilot study.

Activated carbon particle adsorbed-peplomycin (PEP-CH) was administered to three patients who had advanced esophageal cancer and its clinical usefulness was evaluated. The PEP-CH was injected endoscopically into the tumor or the adjacent normal esophageal tissue. Case 1 and case 3 were treated by topical injection of PEP-CH with or without surgery and case 2 was subjected to the PEP-CH treatment with radiation. The barium swallow and endoscopic examination exhibited a marked tumor reduction in all the patients at the end of the PEP-CH treatment. Although a marked clinical response was seen, case 1 died of postoperative complication. Two patients were capable of oral food intake after the treatment, which had been impossible before the treatment. There were no serious adverse side effects caused by the PEP-CH treatment in all the patients. PEP-CH should prove valuable as a new form of chemotherapy for the treatment of esophageal cancer patients.

Aged↗
PubMed1993

Increased tumor localization by monoclonal antibody A7 after F(ab')2 fragmentation in athymic nude mice bearing human pancreatic carcinomas.

Much recent research has been directed toward the use of monoclonal antibodies (MoAbs) for the immunodetection of solid tumors. In pancreatic cancer, conventional immunoscintigraphy using intact MoAbs remains disappointing. In this study, 125I-labeled F(ab')2 fragments produced by pepsin digestion of MoAb A7 were injected intravenously into nude mice bearing human pancreatic cancer, HPC-YS, xenografts that have previously been shown to react specifically with MoAb A7. The tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments of MoAb A7 increased with time and was much higher than those for normal tissues. Moreover, the tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments was greater than that of intact MoAb A7, although the F(ab')2 accumulation was less than that of intact MoAb A7 in the tumor. These results suggest that F(ab')2 fragments of MoAb A7 may be suitable carriers of radionuclides for immunodetection of human pancreatic cancer.

Animals↗
PubMed1993

Intratumoral administration of neocarzinostatin conjugated to monoclonal antibody A7 in a model of pancreatic cancer.

We investigated the following in athymic nude mice with xenografts of a human pancreatic carcinoma: 1) clearance of the murine monoclonal antibody A7 from the carcinoma; and 2) the antitumor effect of neocarzinostatin conjugated to MAb A7 (A7-NCS) on the carcinoma following intratumoral injection. Compared with 125I-labeled normal mouse IgG, a significantly larger amount of 125I-labeled A7 remained in the tumor after intratumoral injection. Neocarzinostatin conjugated to MAb A7 showed a greater antitumor activity against human pancreatic cancer than neocarzinostatin alone after intratumoral administration. The conjugate completely suppressed tumor growth macroscopically during the experiment. Tumor tissue in mice became necrotic 32 days after injection with A7-NCS. These observations suggest that the intratumoral injection of A7-NCS offers promise in treating pancreatic carcinoma.

Animals↗
PubMed1993

A target K+ channel for the LP-805-induced hyperpolarization in smooth muscle cells of the rabbit portal vein.

The resting membrane potential of smooth muscle cells of the rabbit portal vein was -51.2 mV. LP-805 (8-tert-butyl-6,7-dihydropyrrolo[3,2-e] 5-methylpyrazolo [1,5-a] pyrimidine-3-carbonitrile) hyperpolarized the membrane to -62.3 mV (10 microM) and inhibited the burst spike discharges as measured using the microelectrode method. In dispersed smooth muscle cells, LP-805 (10 microM) generated an outward-current with a maximum amplitude of 68 pA at a holding potential of -40 mV in experiments using the voltage-clamp procedure. The reversal potential of the outward current evoked by LP-805 was -82 mV and this value was close to the equilibrium potential for K+ (-80 mV) in the present ionic conditions, suggesting that LP-805 activated the K+ channel. Generation of both the hyperpolarization and the outward current by LP-805 was inhibited by glibenclamide (> or = 1 microM). Using the cell-attached and cell-free patch-clamp (in the presence of GDP) procedures, the maxi-K+ channel current (150 pS) could be recorded in the absence of LP-805; application of LP-805 additionally opened a small conductance K+ channel current (15 pS) without change in the activity of the maxi-K+ channel. The maxi-K+ channel was sensitive to charybdotoxin (0.1 microM) and to intracellular Ca2+ ([Ca2+]i) concentration. The 15 pS channel was insensitive to [Ca2+]i and charybdotoxin, but sensitive to intracellular ATP concentration. Glibenclamide (> 1 microM) inhibited the 15 pS K+ channel activated by LP-805.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Protein kinase C activates the non-selective cation channel in the rabbit portal vein.

Effects of protein kinase C (PKC) on a non-selective cation channel current (Ins) were investigated using smooth-muscle cells of the rabbit portal vein. Neither bath application of the PKC activator, phorbol 12,13-dibutyrate (PDBu; 1 microM), nor the internal application of guanosine 5'-[gamma-thio]-triphosphate (GTP[gamma S]; 3 microM) elicited any current at the holding potential of -60 mV. However, when GTP[gamma S] (3 microM) was present in the pipette, PDBu elicited a sustained inward current, in a concentration-dependent manner, at the holding potential of -60 mV. On the other hand, an inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate (300 nM and 1 microM) had no effect on the membrane current even when GTP[gamma S] (3 microM) was in the pipette. The current amplitude induced by PDBu in the presence of GTP[gamma S] in the pipette was markedly reduced following pretreatment with 10 microM staurosporine, a PKC inhibitor. Neither a reduction in the Cl- concentration in the pipette nor addition of niflumic acid to the bath inhibited the inward current, and the reversal potential estimated from the current/voltage relationship was about -5 mV (physiological salt solution containing 5 mM Ba2+/high CSCl), which revealed that the main component of the current is Ins. An internal application of pertussis toxin markedly reduced the amplitude of Ins induced by PDBu. These results indicate that PKC activates a sustained component of Ins in cooperation with an activated pertussis-toxin-sensitive G protein in the rabbit portal vein.

Alkaloids↗
PubMed1993

K channel openers activate different K channels in vascular smooth muscle cells.

The properties of K channels activated by K channel openers (nicorandil, cromakalim, pinacidil, etc.) were investigated using conventional microelectrode and patch-clamp methods. In single smooth muscle cells of the rat and rabbit portal veins, K channel openers produced an outward current sensitive to glibenclamide, 4-AP, and TEA (1 mM), but insensitive to apamin and charybdotoxin. Glibenclamide-sensitive K channels in both tissues had a small unitary conductance (10 pS and 15 pS) and were inhibited by intracellular ATP. The activity of the 15 pS channel in the rabbit portal vein was not changed by an increase in the intracellular free Ca concentration, but the activity of the 10 pS channel in the rat portal vein was markedly modified by Ca concentration. These results coincided with previous observations using a conventional microelectrode and whole-cell voltage-clamp experiments. In the inside-out membrane patch, the 10 pS channel in the rat portal vein was activated by the application of K channel openers, while the 15 pS channel in the rabbit portal vein was rapidly inactivated, even in the presence of K channel openers. GDP, but neither GTP gamma S nor GDP beta S, reopened the 15 pS channel in the presence of K channel openers. These results suggested that the 15 pS channel had two channel states, that is, both operative and inoperative states, while the 10 pS channel did not have an inoperative state. The K channel openers open the ATP-sensitive K channel only at the operative state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Isolation, characterization, and transmission of human T-lymphotropic virus types I and II in culture.

Highly sensitive coculture methods were developed both for isolation of human T-lymphotropic virus types I and II (HTLV-1 and HTLV-II) from infected individuals and for productive infection of lymphoid cells. Mitogen-activated peripheral blood mononuclear cells (PBMC) from 13 HTLV-I- and 20 HTLV-II-positive specimens were cocultured with an equal number of mitogen-activated PBMC from HTLV-seronegative individuals, and culture supernatants were tested for the presence of soluble p24gag antigens at weekly intervals for 4 weeks. Eleven of 13 (85%) HTLV-I and 14 of 20 (70%) HTLV-II cultures were positive for p24 antigens. None of the 17 HTLV-seroindeterminate or six HTLV-seronegative specimens were positive for the presence of p24 antigen. The isolation rates for HTLV-I and HTLV-II by an alternative whole-blood lysis procedure were comparable to those obtained by standard PBMC cultures. Furthermore, cocultivation of PHA-stimulated PBMC from healthy donors with lethally irradiated HTLV-I- and HTLV-II-infected cell lines (SP and Mo-T, respectively) resulted in productive viral infection, as reflected by the appearance of p24gag antigens concomitant with specific genomic amplification of HTLV proviral DNA after 3 weeks of cocultivation. Thus, the cocultivation technique provides a highly sensitive and specific procedure both for HTLV isolation and for infection of target cells.

Base Sequence↗
PubMed1993

The role of monoclonal antibody A7 as a drug modifier in cancer therapy.

An anticancer antibiotic, neocarzinostatin (NCS), was covalently conjugated to the murine monoclonal antibody A7 (mAb A7), which recognizes the glycoprotein on the cell surface of human colon cancer. The biological and pharmacological properties of the conjugate (A7-NCS) were examined and compared with those of unconjugated NCS. A7-NCS exhibited a strong binding and cytotoxicity to the cell and an antigen-specific tumor accumulation. Significant tumoricidal effects in vivo were observed in the antigen-positive tumor-bearing mice treated with A7-NCS, whereas NCS mixed with mAb A7 and NCS alone were relatively ineffective. In the antigen-negative tumor, the tumoricidal effect of A7-NCS was lower than in the antigen-positive tumor. The NCS concentration in blood and tumor were significantly elevated by conjugation to mAb A7. The NCS localization in tumor was higher in the antigen-positive tumor than in the antigen-negative tumor. Death due to acute toxicity was observed at a dose of 20 units (U) NCS in mice treated with unconjugated NCS, whereas toxicity was seen with a much higher dose of NCS (100 U) if the drug was conjugated to the mAb. These findings show that mAb A7 confers more favorable pharmacological properties on an anticancer drug, making it potentially more useful for cancer chemotherapy.

Animals↗
PubMed1993

Endoscopic local injection of a new drug-delivery format of peplomycin for superficial esophageal cancer: a pilot study.

BACKGROUND: A new drug-delivery format comprising activated carbon particles adsorbing peplomycin (PEP-CH) was developed for the treatment of superficial esophageal cancer. METHODS: The drug distribution was measured in rats that received subcutaneous injections of PEP-CH or peplomycin aqueous solution. In 6 patients with superficial esophageal cancer, peplomycin as PEP-CH, 5-10 mg once a week for 4-10 weeks (total, 40-100 mg/patient) was injected endoscopically into primary lesions. RESULTS: Rats given PEP-CH had significantly higher peplomycin levels in the regional lymph nodes and the injection site than rats given aqueous solution. Five patients have survived to the present or died without cancer after 27-72 months. The remaining patient has survived without cancer for 8 months after a second course of PEP-CH against recurrence. CONCLUSIONS: PEP-CH therapy seems to have a good therapeutic effect on superficial esophageal cancer, although the present clinical study may have been biased by patient selection.

Aged↗