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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 199 records · Page 11Linked to original sources
PubMed1999

Iodine-131 human-mouse chimeric Fab monoclonal antibody A7 guided surgery for colorectal cancer patients: a pilot study.

This study was conducted to determine the clinical usefulness of radioimmunoguided surgery (RIGS) using human-mouse chimeric Fab monoclonal antibody A7 (ch-Fab-A7) for colorectal cancer patients. Ten colorectal cancer patients were given iodine-131-labeled ch-Fab-A7 intravenously (i.v.) 2 to 7 days prior to RIGS. The RIGS was carried out using a portable gamma detecting probe (GDP). Tumor localization was identified by GDP intraoperatively in 4 of the ten patients, while liver metastasis and lymph node metastasis were identified in 2 patients and 1 patient, respectively. The GDP revealed tumor/surrounding tissue radio(gamma)count ratios of 1.5 or greater in 8 of the ten resected tumors. Although RIGS using ch-Fab-A7 is a promising tool for intraoperatively identifying the tumor localization of colorectal cancer, 125I, rather than 131I, should be used as a tracer for RIGS to enhance the accuracy of ch-Fab-A7.

Adenocarcinoma↗
PubMed1999

Esophageal carcinoma showing a long stricture due to prominent lymphatic permeation: report of a case.

Some esophageal diseases such as carcinoma, esophagitis, and collagen diseases have often been reported to show a diffusely thickened esophageal wall in the roentogenogram findings. In the current report, a preoperative upper gastrointestinal series and an endoscopic examination showed a diffusely infiltrative type carcinoma, but other examinations did not suggest any diseases such as esophagitis or collagen diseases which might cause a thickening of the esophageal wall or a constriction of the esophagus. A postoperative histological examination revealed the primary carcinoma to remain only within the mucosal layer, while a large degree of lymphatic vessel permeation reached the adventitia over a wide area. An extraordinary degree of lymphatic permeation spread through the esophageal wall, and stromal fibrosis developed as a result of such lymphatic permeation. These histological phenomena might thus have led to the macroscopic appearance of infiltrative type esophageal carcinoma.

Carcinoma, Squamous Cell↗
PubMed1999

Protection by a cyclic AMP-specific phosphodiesterase inhibitor, rolipram, and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis.

OBJECTIVE AND DESIGN: To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis. MATERIAL: Male BALB/c mice were used. Macrophages/Kupffer cells isolated from P. acnes-primed murine liver were used for the in vitro study. TREATMENT: Type IV phosphodiesterase (PDE)-specific inhibitor, rolipram, was administered (10, 30 mg/kg, p. o.). Dibutyryl cyclic AMP (dbcAMP) was injected (10, 100 mg/kg, i.p.) into the mice. METHOD: Plasma TNFalpha estimated by the use of an L-929 cell cytotoxic assay and plasma transaminase activities were measured for the in vivo study. The LPS-induced production of TNFalpha in vitro from the cultured macrophage/Kupffer cells was determined by ELISA. RESULTS: Rolipram suppressed the elevation of plasma transaminases induced by injection of LPS, and dbcAMP had a tendency to suppress them. Both agents attenuated the LPS-induced release of TNFalpha in vivo, and suppressed the TNFalpha production from the cultured macrophage/Kupffer cells. CONCLUSIONS: These results suggest that rolipram and dbcAMP have potential to inhibit TNFalpha production from activated macrophage/Kupffer cells, and it may be partially involved in the protecting effect in the P. acnes/LPS hepatitis model.

Animals↗
PubMed1999

Novel distribution of adrenomedullin-immunoreactive cells in human tissues.

Adrenomedullin (AM) is a novel hypotensive and vasodilator peptide. We previously examined the localization of AM in human, rat, and porcine tissues using a polyclonal antibody against synthetic human AM[40-52]. We demonstrated that AM is widely distributed in the endocrine and neuroendocrine systems, but not in the heart, kidney, or blood vessels, although high levels of AM mRNA were detected in the latter tissues. In this study, we further investigated the distribution of AM by using two newly developed monoclonal antibodies against synthetic human AM peptides, [12-25] and [46-52]. AM immunoreactivity was observed in cardiac myocytes, vascular smooth muscle cells, endothelial cells, and renal distal and collecting tubules. In addition, AM-immunoreactive (IR) cells were found in mucosal and glandular epithelia of the digestive, respiratory, and reproductive systems, as well as the endocrine and neuroendocrine systems. These findings indicate that AM-IR cells are more widely distributed in human tissues and suggest that AM might play multiple biological roles in humans.

Adrenomedullin↗
PubMed1999

Charge pairing of headgroups in phosphatidylcholine membranes: A molecular dynamics simulation study.

Molecular dynamics simulation of the hydrated dimyristoylphosphatidylcholine (DMPC) bilayer membrane in the liquid-crystalline phase was carried out for 5 ns to study the interaction among DMPC headgroups in the membrane/water interface region. The phosphatidylcholine headgroup contains a positively charged choline group and negatively charged phosphate and carbonyl groups, although it is a neutral molecule as a whole. Our previous study (Pasenkiewicz-Gierula, M., Y. Takaoka, H. Miyagawa, K. Kitamura, and A. Kusumi. 1997. J. Phys. Chem. 101:3677-3691) showed the formation of water cross-bridges between negatively charged groups in which a water molecule is simultaneously hydrogen bonded to two DMPC molecules. Water bridges link 76% of DMPC molecules in the membrane. In the present study we show that relatively stable charge associations (charge pairs) are formed between the positively and negatively charged groups of two DMPC molecules. Charge pairs link 93% of DMPC molecules in the membrane. Water bridges and charge pairs together form an extended network of interactions among DMPC headgroups linking 98% of all membrane phospholipids. The average lifetimes of DMPC-DMPC associations via charge pairs, water bridges and both, are at least 730, 1400, and over 1500 ps, respectively. However, these associations are dynamic states and they break and re-form several times during their lifetime.

Binding Sites↗
PubMed1999

An autocrine or a paracrine role of adrenomedullin in modulating cardiac fibroblast growth.

OBJECTIVE: The aim of the present study was to determine the role of adrenomedullin (AM) in cardiac fibroblasts. METHODS: The production and secretion of AM were examined in cultured neonatal rat cardiac fibroblasts, and the effects of AM on proliferation and protein synthesis of these cells were assessed by [3H]thymidine and [3H]phenylalanine incorporation, respectively. RESULTS: Cultured cardiac fibroblasts secreted AM into the medium time-dependently at a rate of 20.3 +/- 3.0 fmol/5 x 10(4) cells/48 h, mean +/- S.D. Northern blot analysis showed expression of preproAM mRNA of 1.6 kb in these cells. In addition, 10(-6) mol/l of angiotensin II (Ang II) and endothelin-1 (ET-1) significantly increased the AM secretion by 55 and 48%, respectively. Synthetic AM significantly reduced 10(-6) mol/l Ang II- or 10(-7) mol/l ET-1-stimulated [3H]thymidine and [3H]phenylalanine incorporation in a dose-dependent manner, and these effects were attenuated by a calcitonin gene-related peptide (CGRP) type 1 receptor antagonist, CGRP(8-37). Synthetic AM also had a dose-dependent stimulatory effect on cAMP accumulation in these cells, which was significantly attenuated by CGRP(8-37). A cAMP analogue, 8-bromo-cAMP, mimicked the AM effects, inhibiting the Ang II-stimulated [3H]thymidine and [3H]phenylalanine incorporation. Blockage of the effect of endogenous AM by anti-AM monoclonal antibody not only significantly reduced the basal level of intracellular cAMP, but also enhanced the [3H]thymidine and [3H]phenylalanine incorporation into the cells. CONCLUSIONS: Cultured neonatal rat cardiac fibroblasts produce and secrete AM, and the secreted AM may inhibit proliferation and protein synthesis of these cells. AM may exert these inhibitory effects partly by elevating intracellular cAMP. It is suggested that AM has an important role in modulating the growth of cardiac fibroblasts in an autocrine or a paracrine manner.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

A simple immunoradiometric assay for measuring the entire molecules of adrenomedullin in human plasma.

We developed a one-step two-site immunoradiometric assay (IRMA) using two kinds of monoclonal antibodies, which enables us to directly measure the entire molecules of adrenomedullin (AM) (the sum of mature-type AM (abbreviated, m-AM) amidated at the C-terminus and Gly-extended non-amidated AM) in human plasma using a small amount of sample (100 microl) without prior extraction. The detection limit of this assay was 0.5 pmol/l for a 100-microl sample. Intra- and inter-assay precisions were 3.4-7.3% and 5.8-7.6%, respectively. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-118%. The mean total AM in plasma of healthy subjects was 9.00+/-2.13 pmol/l, whereas m-AM was 1.05+/-0.24 pmol/l. This method, together with our previously reported simplified method to specifically measure m-AM (Ohta et al., Clin Chem 1999;45:244-251), allows facile estimation of the plasma concentration of AM-Gly by subtracting m-AM from the total AM measured by the procedure described in this paper. We were able to show that the concentration of total AM in patients with sepsis was markedly higher than that in the healthy controls and that the ratios of m-AM/total AM were significantly different between the controls and patients.

Adrenomedullin↗
PubMed1999

Secretion and clearance of the mature form of adrenomedullin in humans.

In the biosynthesis of adrenomedullin (AM), glycine-extended AM, an intermediate form (iAM) processed from proAM is converted to AM[1-52]-NH2, the bioactive mature form of AM (mAM), by enzymatic amidation. We earlier showed that both molecular forms of AM circulate in human plasma. In the present study, to investigate the secretion and clearance sites of mAM and iAM in humans, we examined the plasma mAM and iAM concentrations in the femoral artery and vein (FA and FV), the aortic root and coronary sinus (AO and CS), and the pulmonary artery and capillary (PA and PC) of patients with ischemic heart disease. Plasma mAM in FV was significantly (p<0.001) higher than in FA. There also was a significant (p<0.001) step-up in the plasma mAM of the CS as compared to the AO. In contrast, plasma mAM was significantly (p<0.001) reduced in the PC as compared to the PA. However, such differences were not observed in plasma iAM levels. These findings suggest that in humans the vasculature of the lower extremities and the heart produce and secrete mAM and that the lung is a clearance site of circulating mAM.

Adrenomedullin↗
PubMed1999

Adrenomedullin-like immunoreactivity in the rat hypothalamo-neurohypophysial tract.

Adrenomedullin-like immunoreactivity in the hypothalamo-neurohypophysial tract in colchicine-treated and hypophysectomized rats was examined by immunohistochemistry. Adrenomedullin-like immunoreactive (AM-LI) neurons were localized in the hypothalamic areas, including the paraventricular nuclei and the supraoptic nuclei. Abundant AM-LI fibers and varicosities were found in the hypothalamoneurohypophysial tract and the internal zone of the median eminence in the colchicine-treated and hypophysectomized rats, whereas in control rats few AM-LI fibers were observed. These results suggest that the axons of the AM-LI neurons in the hypothalamus may terminate in the neurohypophysis.

Adrenomedullin↗
PubMed1999

Plasma and urine levels of adrenomedullin and proadrenomedullin N-terminal 20 peptide in chronic glomerulonephritis.

Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. We examined the plasma and urinary levels of these peptides in patients with chronic glomerulonephritis (CGN). The mean plasma AM concentration of the patients with CGN did not differ from that of control subjects (4.17 +/- 0.17 v 3.87 +/- 0.21 fmol/mL, respectively), whereas urinary AM excretion was significantly less in the patients with CGN (5.96 +/- 0.95 v control, 8.93 +/- 1.02 fmol/mg of creatinine; P < 0.05). Plasma concentrations and urinary excretion of PAMP were significantly less for the patients with CGN compared with control subjects (0.91 +/- 0.08 v 1.23 +/- 0.20 fmol/mL; P < 0.05 and 25.0 +/- 3.0 v 35.0 +/- 3.6 fmol/mg of creatinine, respectively; P < 0. 05). The plasma AM concentration was negatively correlated with plasma renin activity (r = -0.58; P < 0.01) and aldosterone concentration (r = -0.40; P < 0.05). Urinary excretions of AM and PAMP showed significant correlations with urine excretion of sodium (r = 0.39; P < 0.05 and r = 0.49; P < 0.01, respectively). These findings suggest that AM and PAMP may have roles in the regulation of sodium in patients with CGN.

Adrenomedullin↗
PubMed1999

A case of laryngeal neurinoma with neurofibromatosis 2.

We present a case of a laryngeal neurinoma in a patient with neurofibromatosis 2. A 39-year-old man presented to our hospital with multiple complaints including progressive bilateral hearing loss, dizziness, dyspnea, dysphagia, and a 9-year history of right lower leg weakness. Magnetic resonance imaging demonstrated multiple lesions including bilateral cerebellopontine angle tumors, a foremen magnum tumor, multiple tumors of the spinal cord, a laryngeal tumor, and several retrocervical tumors. Fiberoptic laryngoscopy revealed a large submucosal supraglottic tumor. The laryngeal tumor was visualized through microlaryngoscopy and excised with a KTP laser directed through a quartz fiber.

Adult↗
PubMed1999

A morphological and morphometric study of the peripheral process of the human vestibular nerve following posterior cranial fossa neurectomy.

Three vestibular nerve specimens removed at transmeatal neurectomy were studied in order to understand better retrograde degeneration and regeneration after vestibular neurectomy in the posterior cranial fossa. In two cases this procedure followed retrolabyrinthine retrosigmoid posterior fossa vestibular neurectomy. The subjects, three patients with Menière's disease, were compared with one another and two autopsy controls with no known otological problem. The specimens were obtained at the distal end of the internal auditory canal and transversely sectioned. Many collapsed Schwann cell basement membranes were observed. The ratio of small-diameter nerve fibres increased significantly after neurectomy. Onion bulb formation around myelinated nerve fibres with small diameters and Schwann cell proliferation around the soma of vestibular ganglion cells reflected remyelination. We conclude that peripheral processes of vestibular nerve fibres can undergo retrograde degeneration and subsequent regeneration after transection of the central process.

Aged↗
PubMed1999

Vasorelaxation and inhibition of the voltage-operated Ca2+ channels by FK506 in the porcine coronary artery.

Using fura-2 fluorometry, the effects of FK506, an immunosuppressant, on changes in cytosolic Ca2+ concentrations ([Ca2+]i) and tension were investigated in porcine coronary arterial strips. The effects of FK506 on the activity of voltage-operated Ca2+ channels were examined by applying a whole cell patch clamp to the isolated smooth muscle cells of porcine coronary artery. FK506 inhibited the sustained increases in both [Ca2+]i and tension induced by 118 mM K+ depolarization and 100 nM U46619 in a concentration-dependent manner (1-30 microM). The extent of inhibition of the K+-induced contraction was greater than that of the U46619-induced contraction. The increases in [Ca2+]i and tension induced by histamine and endothelin- in the presence of extracellular Ca2+ were also inhibited by 10 microM FK506. FK506 (10 microM) had no effect on Ca2+ release induced by caffeine or by histamine in the Ca2+-free solution. FK506 (10 microM) had no effect on the [Ca2+]i-tension relationships of the contractions induced by cumulative increases of extracellular Ca2+ during K+ depolarization or stimulation with U46619. In the patch clamp experiments, FK506 (30 microM) partially inhibited the inward current induced by depolarization pulse from -80 mV to 0 mV. In conclusion, FK506 induces arterial relaxation by decreasing [Ca2+]i mainly due to the inhibition of the L-type Ca2+ channels, with no effect on the Ca2+ sensitivity of the contractile apparatus.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy.

We investigated the effect of the histone deacetylase inhibitors (HDIs), trichostatin A and trapoxin A on leukemia cells and cell lines from the viewpoint of differentiation induction. TSA induced differentiation in erythroid cell lines by itself, whereas it synergistically enhanced the differentiation that was directed by all-trans retinoic acid (ATRA) or vitamin D3 in U937, HL60 and NB4 cells. The combined treatment of HDI with ATRA induced differentiation in ATRA-resistant HL60 and NB4 cells. The transcriptional expression during the treatment with HDI was examined in HL60, U937 and MEG-O1. Cell cycle-regulator genes (p21waf1 and p16INK4A) were upregulated or constantly expressed, erythroid-specific genes (GATA-1, beta-globin) were silent or downregulated, and housekeeping genes (beta-actin and GAPDH) were constantly expressed. Twelve of 35 (34%) clinical samples from AML patients ranging from M0 to M7 also displayed both phenotypical and morphological changes by the treatment with TSA alone. HDIs are thus the potent inducer or enhancer of differentiation in acute myeloid leukemia and regulate transcription in an ordered manner.

3T3 Cells↗
PubMed1999

No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer.

BACKGROUND: It remains unknown whether extended surgery improves the survival rate of patients with gastric cancer. This study was a review of combined pancreaticosplenectomy with total gastrectomy for gastric cancer. METHODS: The clinicopathological details of 190 patients who underwent combined pancreaticosplenectomy with total gastrectomy between 1969 and 1996 were compared retrospectively with those of 206 patients who underwent total gastrectomy with splenectomy alone. RESULTS: There was no statistical difference in the survival rate when pancreaticosplenectomy was added to total gastrectomy. The mortality rate was similar, but the morbidity rate was higher in patients who had pancreaticosplenectomy. Six patients who had direct pancreatic invasion and two thought to have involved lymph nodes along the splenic artery survived for more than 5 years after operation. In the latter group, the metastatic lymph nodes along the splenic artery could have been resected without pancreatectomy. CONCLUSION: Since a combined pancreaticosplenectomy adds no survival advantage to total gastrectomy for gastric cancer, this procedure should no longer be regarded as routine.

Female↗
PubMed1999

Sodium butyrate blocks interferon-gamma (IFN-gamma)-induced biosynthesis of MHC class III gene products (complement C4 and factor B) in human fetal intestinal epithelial cells.

Human intestinal epithelial cells have been established as local sites for complement biosynthesis. In this study, we investigated the effects of IFN-gamma and sodium butyrate on biosynthesis of MHC class III gene products (complement C4 and factor B) in the human fetal intestinal epithelial cell line INT-407. IFN-gamma induced a dose- and time-dependent increase in C4 and factor B secretion. However, sodium butyrate dose-dependently inhibited IFN-gamma-induced C4 and factor B secretion. These effects were also observed at the mRNA level. Immunoblotting indicated that IFN-gamma induced a rapid activation of Stat1alpha, and fluorescence immunohistochemistry detected a translocation of Stat1alpha into the nucleus within 1 h. However, the translocation of Stat1alpha was not affected by the addition of sodium butyrate. Nuclear run-on assay indicated that IFN-gamma induced a weak increase in the transcription rate of factor B gene, and sodium butyrate did not affect this response. IFN-gamma and sodium butyrate induced a counter-regulatory effect on C4 and factor B secretion: IFN-gamma acted as a potent inducer, but sodium butyrate potently abrogated these responses. These are mainly regulated through the post-transcriptional mechanism.

Blotting, Northern↗
PubMed1999

Cell density of adrenomedullin-immunoreactive cells in the gastric endocrine cells decreases in antral atrophic gastritis.

AIMS: Adrenomedullin (AM) is a novel hypotensive and vasorelaxing peptide recently isolated from human phaeochromocytoma tissue, and is widely distributed in various organs. In this study we examined the localization of AM-immunoreactive (IR) cells in the gastric mucosa and AM-IR cell density in antral atrophic gastritis. METHODS AND RESULTS: Gastric mucosal tissues were taken from the gastric body and antral mucosa of 52 patients (27 men, 25 women; mean age 56.0 (range 20-86) years). Immunohistochemical analysis revealed that AM-IR cells were present in the pyloric glands, but not in the fundic glands, and that AM-IR cells were stained positively for chromogranin A and gastrin. The percentage of AM-IR cells vs chromogranin A- and gastrin-IR cells was 42 and 56%, respectively. The number of AM-IR cells decreased with the progression of severity of atrophic changes in the pyloric gland, and also of mononuclear cell infiltration. There was no correlation between the number of AM-IR cells and the degree of neutrophilic infiltration. Similar findings were also obtained for gastrin-IR cells. CONCLUSION: AM-IR cells are present in the endocrine cells including gastrin-IR cells in the pyloric glands. These results suggest that AM may contribute to gastrin secretion in the pyloric glands.

Adrenomedullin↗