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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 343 records · Page 19Linked to original sources
PubMed1997

Localization of plasminogen activators and their inhibitor in squamous cell carcinomas of the head and neck.

BACKGROUND: Plasminogen activators (PAs) and their inhibitors are thought to play an important role in tumor invasion and metastasis. However, there have been few reports in which histologic localization of PAs has been demonstrated in head and neck tumors. METHODS: We examined the patterns of expression of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and vitronectin in head and neck squamous cell carcinomas using immunohistochemical techniques. We also studied the correlation between the immunohistologic expression of these fibrinolytic proteins and the clinical staging of the tumor. RESULTS: Of 28 tumor specimens, 15 (54%) showed immunoreactivity for u-PA; 8 (36%), for t-PA; and 23 ( 82%), for PAI-1. There was a significant correlation between PAI-1 expression and the extent of the primary tumor. CONCLUSIONS: The present study demonstrates the existence and possible pathophysiologic significance of u-PA and PAI-1 in squamous cell carcinomas of the head and neck.

Carcinoma, Squamous Cell↗
PubMed1997

CD45-associated protein is a lymphocyte-specific membrane protein expressed in two distinct forms.

CD45-AP is a recently identified CD45-associated protein. The two proteins interact specifically through their respective transmembrane segments. Northern hybridization analysis of CD45+ T lymphocytes and their CD45- variants demonstrated that the production of CD45-AP and CD45 mRNA is regulated independently. On the other hand, Western blotting analysis indicated that the CD45-AP protein has a shorter half-life in the absence of CD45 in three out of four variants. Similar analysis of various types of leukocytes demonstrated that CD45-AP is expressed in T, B, and pre-B cells, but not in plasma cells or cells of the monocyte/macrophage lineage. Two forms of CD45-AP mRNA exist in all types of CD45-AP-expressing lymphocytes analyzed. One form corresponds to the previously reported CD45-AP cDNA and the other form encodes an additional 12 amino acids at the N terminus. The two CD45-AP proteins are identical in their capacity for specific binding to CD45, but employ different mechanisms for endoplasmic reticulum membrane translocation.

Amino Acid Sequence↗
PubMed1997

Improved surgical results after combining preoperative hyperthermia with chemotherapy and radiotherapy for patients with carcinoma of the rectum.

PURPOSE: The aim of this study is to evaluate long-term results of preoperative hyperthermia combined with chemotherapy and irradiation (HCR therapy) in patients with carcinoma of the rectum. METHODS: Postoperative prognoses were compared among 36 patients with carcinoma of the rectum, who were given preoperative HCR therapy followed by surgery, and 52 patients undergoing surgery alone without any preoperative therapy. RESULTS: There were significant differences in the prognosis between patients given preoperative HCR therapy plus surgery and those having surgery alone, and five-year survival rates were 91.3 and 64 percent, respectively. Particularly, for patients with tumors invading beyond the muscularis propria and/or with positive lymph node metastasis, a significantly longer survival was obtained with HCR plus surgery than in surgery alone (86.5 vs. 50.9 percent and 92.9 vs. 51.7 percent, respectively). However, no significant differences were observed in the postoperative prognosis for cases with no lymph node metastasis and/or with tumors limited to the muscularis propria between these two groups. CONCLUSIONS: These data clearly demonstrated the effectiveness of preoperative HCR therapy for improving long-term results of patients with carcinoma of the rectum, especially those demonstrating an advanced stage of disease.

Aged↗
PubMed1997

The operative indications for proximal gastrectomy in patients with gastric cancer in the upper third of the stomach.

While proximal gastrectomy is often performed for early gastric cancer in Japan, it remains unclear whether or not proximal gastrectomy should be performed for advanced gastric cancer. This study was designed to determine the operative indications for proximal gastrectomy in patients with gastric cancer in the upper third of the stomach. A total of 1691 patients with gastric cancer were reviewed retrospectively from hospital records during the period from 1969 to 1994, and the clinicopathologic characteristics of 82 patients who underwent proximal gastrectomy were compared with those of 150 patients who underwent total gastrectomy. Lymph node metastasis along the lower part of the stomach was observed in gastric cancers which had invaded beyond the muscularis propria of the stomach, but not in those confined to the muscularis propria. Three patients with gastric cancer that had invaded beyond the muscularis propria and metastasized to nodes along the lower part of the stomach were cured by total gastrectomy. However, there was no difference in the postoperative survival rates of the patients treated with proximal gastrectomy and those treated with total gastrectomy, irrespective of tumor stage and depth of invasion. Thus, proximal gastrectomy should be performed for gastric cancer when the depth of invasion is confined to the muscularis propria of the stomach.

Aged↗
PubMed1997

Endoscopic local injection of a new drug delivery formulation, anticancer drug bound to carbon particles, for digestive cancers: pilot study.

A new dosage formulation consisting of an anticancer drug bound to activated carbon particles was developed for the treatment of digestive cancer in patients in whom operation is contraindicated. The new formulation is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site compared to distribution of the drug in aqueous solution. In 12 patients with histologically proven carcinoma (7 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), an anticancer drug bound to carbon particles (total dose, 40-100 mg peplomycin or 250-500 mg methotrexate per person) was injected endoscopically into the primary lesions. Eleven of the 12 patients are currently alive, 12-64 months after therapy, or they died without evidence of cancer 12-98 months after the treatment. One patient has remained cancer-free for 32 months after a second course of the new formulation therapy given to treat a recurrence detected 26 months after the first treatment. Endoscopic injection of this new dosage formulation seems to control these digestive cancers in patients in whom operation is contraindicated.

Adenocarcinoma↗
PubMed1997

Performance evaluation of a large axial field-of-view PET scanner: SET-2400W.

The SET-2400W is a newly designed whole-body PET scanner with a large axial field of view (20 cm). Its physical performance was investigated and evaluated. The scanner consists of four rings of 112 BGO detector units (22.8 mm in-plane x 50 mm axial x 30 mm depth). Each detector unit has a 6 (in-plane) x 8 (axial) matrix of BGO crystals coupled to two dual photomultiplier tubes. They are arranged in 32 rings giving 63 two-dimensional image planes. Sensitivity for a 20-cm cylindrical phantom was 6.1 kcps/kBq/ml (224 kcps/microCi/ml) in the 2D clinical mode, and to 48.6 kcps/kBq/ml (1.8 Mcps/microCi/ml) in the 3D mode after scatter correction. In-plane spatial resolution was 3.9 mm FWHM at the center of the field-of-view, and 4.4 mm FWHM tangentially, and 5.4 mm FWHM radially at 100 mm from the center. Average axial resolution was 4.5 mm FWHM at the center and 5.8 mm FWHM at a radial position 100 mm from the center. Average scatter fraction was 8% for the 2D mode and 40% for the 3D mode. The maximum count rate was 230 kcps in the 2D mode and 350 kcps in the 3D mode. Clinical images demonstrate the utility of an enlarged axial field-of-view scanner in brain study and whole-body PET imaging.

Bone Neoplasms↗
PubMed1997

New retinoids and arsenic compounds for the treatment of refractory acute promyelocytic leukemia: clinical and basic studies for the next generation.

All-trans retinoic acid (ATRA) is a potent differentiation drug for acute promyelocytic leukemia (APL) and is now incorporated into first-line therapy. However, ATRA resistance has become a major clinical problem. This limitation has prompted the development of alternative agents with desirable pharmacologic properties. We describe (1) our recent clinical trial using the new synthetic retinoid Am80 to overcome acquired resistance to ATRA and (2) basic in vitro effects of arsenic trioxide, a possible alternative to ATRA, on APL cells. A total of 19 APL patients who had relapsed after ATRA-induced complete remissions (CRs) received 6 mg/m2 Am80 p.o. daily until CR; 11 (58%) patients achieved a CR between days 20 and 58 (median day 37). The in vitro sensitivity to Am80, based on PML immunostaining, correlated well with the clinical effect in all patients tested. All three patients whose blasts were sensitive to Am80 in vitro despite a poor response to ATRA achieved CRs. Thus, Am80 might be an effective compound for the treatment of refractory APL and is a promising alternative retinoid. Since arsenic compounds have reportedly induced CRs in APL patients in China, we studied the in vitro effect of arsenic and other metal ions on myeloid leukemia cell lines. The effects of arsenic were limited mainly to APL cells, and the arsenic concentration was critical for the APL cell line NB4: 1 microM As3+ induced time-dependent apoptosis, whereas 0.1 microM As3+ allowed partial NB4 cell differentiation. Arsenic trioxide was equally effective when used on ATRA-resistant NB4 cells. Among the clinical leukemia samples tested, the in vitro cytotoxic effects of As3+ were observed selectively in APL cells, regardless of their ATRA sensitivity. These data suggest that APL cells are sensitive to As3+ and that As3+ acts on APL cells via a different pathway to ATRA.

Antineoplastic Agents↗
PubMed1997

Oxytocin enhances action potentials in pregnant human myometrium--a study with microelectrodes.

OBJECTIVE: Our purpose was to quantitatively assess the effects of oxytocin on membrane properties in the pregnant human myometrium. STUDY DESIGN: Specimens were obtained from the lower uterine segment during cesarean section at term. Electrical activity was recorded from individual cells by a conventional microelectrode method and the membrane functions were analyzed. RESULTS: Two types of spontaneous action potentials were seen: a long plateau potential and a spike-like action potential. With no change in the resting membrane potential, low concentrations of oxytocin either evoked an action potential with a plateau phase, increased the amplitude and duration of the plateau potential, or increased the frequency of generation of action potentials. Oxytocin also lowered the threshold for evoking an action potential. Higher concentrations depolarized the membrane with an associated reduction in membrane resistance. CONCLUSION: Oxytocin augments the excitability of pregnant human myometrial cells by multiple actions on the membrane, affecting both frequency and amplitude of action potentials.

Action Potentials↗
PubMed1997

Production of adrenomedullin in human vascular endothelial cells.

To examine the production of adrenomedullin (AM) in human vascular endothelial cells, AM concentrations in cultured endothelial cells derived from the human umbilical vein and the conditioned media of the cells were measured in the present study. The cultured endothelial cells secreted immunoreactive AM (ir-AM) into the medium at a rate of 14.7 +/- 3.0 fmol/10(6) cells/24 h with an intracellular ir-AM of 5.2 +/- 0.8 fmol/l0(6) cells. Analysis by reverse phase high performance-liquid chromatography (HPLC) showed that ir-AM in both the cells and the conditioned medium eluted at the position identical to that of human AM(1-52). Treatment with dexamethasone significantly augmented the secretion of ir-AM from the cells without any effect on the intracellular ir-AM concentration. Northern blot analysis showed not only the presence of the 1.6 kb human AM precursor mRNA in the endothelial cells, but also its increased expression in the dexamethasone-treated cells. Thus, AM was synthesized and secreted by the human endothelial cells of the umbilical vein, and glucocorticoid augmented the AM production. These findings suggest not only the role of AM as a local modulator of the vascular tone but also the possibility that endothelial cells contribute to circulating AM in the human blood.

Adrenomedullin↗
PubMed1997

Ultrastructural analysis of the vestibular nerve in Ménière's disease.

Numerical analysis of the vestibular nerve in Méniè's disease was performed. Vestibular nerve specimens were obtained from three patients with classical clinical findings of Ménière's disease during retrosigmoid vestibular neurectomy. For each patient, an ultrathin section, including an entire cross-section of the nerve specimen, was examined. Fiber counts of nerve specimens with definite pathologic findings were compared with caloric testing results. A significant correlation was found between reduced vestibular response and the incidence of abnormal nerve fibers and also the density of the abnormal nerve fibers. However, the number of nerve fibers with pathologic findings was small. Results of the present study demonstrate no general degeneration of nerve fibers caused by the disease process of Ménière's disease.

Adult↗
PubMed1997

Expression of a novel aristaless related homeobox gene 'Arx' in the vertebrate telencephalon, diencephalon and floor plate.

We have isolated a novel homeobox gene that is expressed in the vertebrate central nervous system and which shows striking similarity to the Drosophila al gene in the homeodomain (85% identity) and in a 17 amino acid-sequence near the carboxyl-terminus. This gene was designated Arx (aristaless related homeobox gene) in consideration of its structural similarity to the al gene. Arx was highly conserved between mouse and zebrafish. Neuromeric expression in the forebrain and longitudinal expression in the floor plate were observed in mouse and zebrafish. The expression of Arx in the ganglionic eminence and ventral thalamus overlapped regionally with that of Dlx1, but the cell layer where Arx is expressed differed from that of the Dlx1. This gene was also found to be expressed in the dorsal telencephalon (presumptive cerebral cortex) of mouse embryos. The structure and expression pattern of Arx with respect to any possible relationship to al and Dlx1, as well as the function of Arx in the floor plate are discussed.

Amino Acid Sequence↗
PubMed1997

Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic ventral lateral geniculate nuclear formation.

The Brx1 homeobox gene has been isolated and shown to be expressed in the zona limitans intrathalamica (ZLI) of the mouse embryo. Brx1 is a member of the Brx gene family and comprises the genes for Brx1a and Brx1b, which differ in the sequence in the region located on the 5'-terminal side of the homeobox. The complete amino acid sequences of the open reading frame of Brx1a and Brx1b were determined and each was found to be similar to that of Rgs, the mouse homologue of the Rieger syndrome associated human RIEG gene (RGS), to the extent that the sequence of Rgs has been clarified. Brx1 was strongly expressed in the mammillary area as well as in the ZLI of the mouse embryonic brain. Homologues of Brx1a and Brx1b were isolated in chick in which the expression of Brx1 in the ventral diencephalon was well conserved. The expression of Brx1 along with that of Sonic hedgehog (Shh), Nkx2.2, Dlx1 and Arx was examined at the time of the formation of ZLI in mouse embryos. The expression of Shh was initially noted in the ventricular zone of the presumptive ZLI and was then replaced by that of Brx1 at the time of radial migration of the neuroepithelial cells. Nkx2.2 was widely expressed in the ventricular zone of presumptive ZLI and also as a narrow band in the mantle zone. The expression of Dlx1 and Arx in the presumptive ventral thalamus extended as far as ZLI and overlapped with that of Brx1. The Dlx1- and Arx-expressing cells in ZLI, which extended towards the lateral (pial) surface of the diencephalic wall, differed from those expressing Nkx2.2 and Brx1. The embryonic ventral lateral geniculate nucleus present in the visual pathway was eventually formed from these cells. Each homeobox gene was also expressed regionally in the nucleus, suggesting that the nucleus is comprised of subdivisions.

Amino Acid Sequence↗
PubMed1997

Toxic effects of arsenic (As3+) and other metal ions on acute promyelocytic leukemia cells.

Since arsenic compounds reportedly induced complete remission in patients with acute promyelocytic leukemia (APL) in China, we studied the in vitro effect of metal ions including As3+, As5+, Cd2+, Ga3+, Ge4+, Hg2+, Se4+, and Zn2+ on myeloid cell lines. One-tenth microM As3+ caused growth suppression and morphological changes resembling differentiation in NB4 cells, but did not induce the maturation-markers, CD11b, CD14 and NBT-reductase. More than 1 microM As3+ caused the time- and dose-dependent apoptosis of NB4 cells. Other metal ions at the same concentrations induced neither morphological changes nor apoptosis in myeloid cell lines including NB4, whereas Cd2+, Ga3+, and Hg2+ induced moderate and non-specific growth suppression. All-trans retinoic acid (ATRA)-resistant NB4 cells were similarly sensitive to As3+. Among the clinical leukemia samples, As3+ was selectively toxic to APL cells regardless of ATRA-sensitivity. These findings suggest that APL cells are sensitive to As3+, and that As3+ acts on APL cells via a different pathway than ATRA.

Apoptosis↗
PubMed1997

Pharmacokinetics and boron uptake of BSH (Na2B12H11SH) in patients with intracranial tumors.

We evaluated retrospectively the pharmacokinetics and boron uptake of BSH (mercaptoundecahydrododecarborate) for Boron Neutron Capture Therapy (BNCT) in 123 patients undergoing craniotomy for intracranial tumors. The pharmacokinetics revealed that BSH could move easily from blood to the peripheral organs; it was retained there and elimination was very slow. BSH after intra-arterial infusion (i.a.) was found to move into the peripheral organs more easily than after intra-venous (i.v.) infusion. In patients with malignant glioma, the average values of boron concentration in tumor and the tumor to blood ratio (T/B ratio) after i.a. infusion were 26.8 +/- 19.5 micrograms/g (range, 6.1-104.7 micrograms/g) and 1.77 +/- 1.30 (range, 0.47-6.65) respectively. On the other hand, after i.v. infusion the values were 20.9 +/- 12.2 micrograms/g (range, 7.0-39.7 micrograms/g) and 1.30 +/- 0.65 (range, 0.61-2.94) respectively. The differences are not statistically significant. Boron uptake in malignant glioma was about three times higher than low grade glioma. We found a good correlation between boron uptake and time interval from BSH infusion, and 15-20 hours after BSH infusion the boron concentration in tumor was above 20 micrograms/g 10B in 69% of the malignant glioma patients; T/B ratio was above one in 75%, and above two in 44% of them. We recommend intra-venous infusion of BSH clinically since it is safer, and results in sufficient boron concentration in tumor, and the planned irradiation might be optimal around 15-20 hours after the BSH infusion for treating malignant glioma.

Adolescent↗
PubMed1997

Early gastric cancer mimicking advanced gastric cancer.

The clinicopathological features of 37 early gastric cancers mimicking advanced gastric cancer were reviewed retrospectively, and were compared with 596 other early gastric cancers and 126 mp gastric cancers, defined as gastric cancer invading the muscularis propria of the stomach. A greater tumour size (P < 0.005), submucosal invasion (P < 0.005), lymph node and lymph vessel invasion (P < 0.005) and vascular invasion (P < 0.025) were found more frequently in early gastric cancers mimicking advanced gastric cancers than in other early gastric cancers. There were no significant differences in the clinicopathological findings between early gastric cancers mimicking advanced gastric cancers and mp gastric cancers. Patients with early gastric cancers mimicking advanced gastric cancers showed a lower survival rate than patients with other early gastric cancers, but a higher survival than those with mp gastric cancers. The macroscopic appearance of an advanced gastric cancer was an indicator of massive submucosal invasion and lymph node metastasis in early gastric cancer. As early gastric cancers mimicking advanced gastric cancers showed similar clinicopathological findings to mp gastric cancers, these cancers should be treated as mp gastric cancers.

Female↗
PubMed1997

Inhibitory effects of genistein on ATP-sensitive K+ channels in rabbit portal vein smooth muscle.

1. Effects on the pinacidil-induced outward current of inhibitors of tyrosine kinases and phosphatases were investigated by use of a patch-clamp method in smooth muscle cells of the rabbit portal vein. 2. A specific tyrosine kinase inhibitor, genistein, inhibited the pinacidil-induced current in a concentration-dependent manner with an IC50 of 5.5 microM. Superfusion of Ca2+-free solution did not affect this inhibitory effect of genistein. At higher concentrations, genistein inhibited the voltage-dependent Ba2+ and K+ currents with IC50 values of > 100 microM and 75 microM respectively. Tyrphostin B46 (30 microM), a tyrosine kinase inhibitor, also inhibited the pinacidil-induced current by 70% of the control. 3. Sodium orthovanadate (100 microM), an inhibitor of tyrosine phosphatase, slightly but significantly enhanced both the pinacidil-induced and delayed rectifier K+ currents. Daidzein (100 microM), an inactive analogue of genistein, did not inhibit these currents. 4. Neither herbimycin A (1 microM), lavendustin A (30 microM), tyrphostin 23 (10 microM), which are also tyrosine kinase inhibitors, nor wortmannin (10 microM), a phosphatidylinositol 3-kinase inhibitor, had an effect on either the pinacidil-induced or delayed rectifier K+ currents. Epidermal growth factor (EGF; 1 microg ml(-1)) did not induce an outward current or enhance the pinacidil-induced current. 5. Pinacidil alone, in the cell-attached configuration, or pinacidil with GDP, in the inside-out configuration, activated a 42 pS channel in the smooth muscle cells of the rabbit portal vein. Genistein (30 microM) reduced the channel's open probability without inducing a change in unitary conductance at any holding potential (-30 to +20 mV). 6. In the inside-out configuration, genistein at 30 microM did not change the mean channel open time, but reduced the burst duration. At 100 microM genistein abolished channel opening. The inhibitory potencies with which 30 and 100 microM genistein acted on the unitary current of the ATP-sensitive K+ channel were similar to those seen in the whole-cell voltage-clamp configuration. 7. Although direct inhibitory actions of genistein on the ATP-sensitive K+ channels are not ruled out, our results suggest that a protein tyrosine kinase may play a role in the regulation of ATP-sensitive K+ channel activity in the rabbit portal vein.

Animals↗