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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 325 records · Page 18Linked to original sources
PubMed1998

[Angiographic diagnosis and management of bleeding from the digestive organs].

Gastrointestinal bleeding is recently seen less often by the angiographer. This is mainly due to advances in endoscopy, and nuclear medicine. When patients with gastrointestinal bleeding are referred, endoscopic diagnosis and therapy should be performed at first. However, when it is impossible to diagnose or to control the bleeding, angiography must be considered as soon as possible. Intra-abdominal bleeding should be diagnosed by angiography at first. In both cases, embolization is generally safe and effective depending on the advance of occlusive agents.

Angiography↗
PubMed1998

[Combined chemotherapy with low-dose cisplatin, tegafur and uracil in a case with neck recurrence of laryngeal cancer].

The patient was a 60-year-old man with progressive neck recurrence of laryngeal squamous cell carcinoma. As a previous treatment, he had undergone irradiation (primary: 60 Gy; neck: 45 Gy) after two cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 daily; day 1:5-fluorouracil 1,000 mg/m2 daily; day 1-5) and planned neck dissection. For a neck recurrence, he had received five cycles of low-dose cisplatin (5 mg/body daily: day 1-5) with tegafur and uracil (600 mg/body daily: day 1-7) every week. As an outpatient, he then received ten cycles of low-dose cisplatin (10 mg/body daily: day 3, 6) with tegafur and uracil (600 mg/body daily: day 1-7) every week. The size of the tumor did not decrease with the above chemotherapy, but no remarkable growth of the cancer was seen, and no toxic effect of the chemotherapy was observed. He continued his job for 30 weeks just as before he had fallen sick. Chemotherapy of low-dose cisplatin with tegafur and uracil was suggested to be useful for the patient with recurrent laryngeal squamous cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Purification and characterization of PAMP-12 (PAMP[9-20]) in porcine adrenal medulla as a major endogenous biologically active peptide.

Proadrenomedullin N-terminal 20 peptide (PAMP-20) is a potent hypotensive peptide processed from the adrenomedullin (AM) precursor. We developed a specific radioimmunoassay which recognizes the C-terminal region of PAMP-20. Using this radioimmunoassay, the distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations of ir-PAMP were observed in the adrenal medulla and in the atrium, and these values were comparable to the corresponding concentrations of ir-AM. The concentration of ir-PAMP was almost the same as that of ir-AM in the kidney, while ir-PAMP was significantly lower than ir-AM in the ventricle, lung, and aorta. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks of ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP-20; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9-20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion, and the effect was comparable to that of PAMP-20. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control.

Adrenal Medulla↗
PubMed1997

Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats.

The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.

Adrenomedullin↗
PubMed1997

Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid.

Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). However, patients who relapse from ATRA-induced complete remission (CR) have difficulty in obtaining a second CR with a second course of ATRA therapy alone. We tested the efficacy of a new synthetic retinoid, Am80, in APL that had relapsed from CR induced by ATRA in a prospective multicenter study. Am80 is approximately 10 times more potent than ATRA as an in vitro differentiation inducer, is more stable to light, heat, and oxidation than ATRA, has a low affinity for cellular retinoic acid binding protein, and does not bind to retinoic acid receptor-gamma. Patients received Am80, 6 mg/m2, orally alone daily until CR. Of 24 evaluable patients, 14 (58%) achieved CR. The interval from the last ATRA therapy was not different between CR and failure cases. The clinical response was well correlated with the in vitro response to Am80 in patients examined. Adverse events included 1 retinoic acid syndrome, 1 hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15 hypercholesterolemia, but generally milder than those of ATRA, which all patients had received previously. Am80 is effective in APL relapsed from ATRA-induced CR and deserves further trials, especially in combination with chemotherapy.

Adult↗
PubMed1997

X-ray crystal structure determination and molecular dynamics simulation of prophospholipase A2 inhibited by amide-type substrate analogues.

X-ray crystal structures of bovine pancreas prophospholipase A2 (proPLA2) inhibited by two amide-type inhibitors, [(R)-2-dodecanoyl-amino-1-hexanolphosphocholine (DAHPc) and (R)-2-dodecanoylamino-1-hexanolphosphoglycol (DAHPg)], were determined to R = 0.208 and 0.215 using reflections with up to 2.1 A resolution, respectively. Both complex crystals lacked defined electron densities for the prosequence of the N-terminal and for a loop region consisting of residues 65-70, retaining the disordered feature observed in free proPLA2 despite stabilization due to complex formation. The polar and nonpolar moieties of the amide-type inhibitors were located in the calcium-binding pocket and in the N-terminal alpha-helical hydrophobic region of the enzyme, respectively. As for the amide group of the inhibitor, which is lacking in the true substrate, a strong hydrogen bond was formed between the NH of the inhibitor and the unprotonated N(delta1) atom of His-48, resulting in the tight binding of the inhibitor to proPLA2, as well as to PLA2. The 20-30 times more potent inhibitory activity of DAHPg than DAHPc toward PLA2 could be explained by hydrogen bond formation between the glycol OH of DAHPg and the carbonyl O of Asp-49. The seven residues of the N-terminal prosequence of proPLA2, though disordered, block the access of a water molecule to Ala-1 of PLA2 or change the hydrogen-bonding property of Ala-1 alpha-amino group, resulting in breakage of the water-mediated hydrogen-bond network which is commonly formed in PLA2. The results of molecular dynamics (MD) calculation in an aqueous solution at 300 K indicate that this, rather than the close contact between the prosequence and the residues 65-70 loop region, is the main reason why the latter region becomes flexible in proPLA2, compared with in PLA2.

Animals↗
PubMed1997

Single molecule imaging of fluorophores and enzymatic reactions achieved by objective-type total internal reflection fluorescence microscopy.

Imaging of single fluorescent molecules has been achieved in a relatively simple manner using objective-type total internal reflection fluorescence microscopy (TIRFM). Switching from epi-fluorescence microscopy to objective-type TIRFM was achieved by translation of a single mirror in the system. Clear images of single molecules of an orange fluorescent dye, Cy3, were obtained with a fluorescence-to-background ratio of 12, using a conventional high aperture objective (PlanApo, 100 x, NA 1.4) with ordinary coverslips and immersion oil. This method allowed visualization of single molecules under scanning probe microscopes. Taking advantage of the technique of single molecule imaging, individual ATP turnovers have been visualized with a fluorescent ATP analogue, Cy3-ATP, using a simple experimental strategy. Clear on/off signals were obtained that correspond to the association and dissociation of single Cy3-ATP/ADP molecules with a single myosin head molecule. This method will allow a variety of single-molecular assays of biomolecular functions to be performed using fluorescently labeled substrates, ligands, messengers, and biologically active molecules. Thus, the present technique provides a simple yet powerful and universal tool for researchers to probe the events of single molecules.

Adenosine Triphosphatases↗
PubMed1997

Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension in patients <20 years of age.

To elucidate the pathophysiologic significance of adrenomedullin in pulmonary hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI) concentrations in blood samples obtained from various sites during cardiac catheterization by using radioimmunoassay in patients with pulmonary hypertension in comparison with patients without pulmonary hypertension. In patients with pulmonary hypertension, plasma AM-LI concentrations were significantly elevated and there was a significant uptake of AM-LI in pulmonary circulation, indicating the involvement of adrenomedullin in the cardiovascular regulation of pulmonary circulation in pulmonary hypertension.

Adolescent↗
PubMed1997

The glycoproteins that occur in the colloids of senescent porcine pituitary glands are clusterin and glycosylated albumin fragments.

Periodic acid-Schiff-positive colloids occur in the pituitary glands of many vertebrates. These colloids are surrounded by folliculo-stellate (FS) cells and increase dramatically in number and size with age. The characterization of these colloidal substances is necessary for the establishment of FS cell function. In a previous study we showed that these colloids in the senescent pituitary contain a number of glycoproteins; however, the characterization of these glycoproteins has not yet been carried out. To characterize the pituitary colloid, we purified the colloids by centrifugation and Percoll gradient. The isolated colloids were unable to be solubilized in a regular buffer since they were very dense. However, solubilization was accomplished in sodium dodecyl sulfate (SDS) lysis buffer following treatment with exoglycosidase. Analysis using SDS-polyacrylamide gel electrophoresis showed that the porcine pituitary colloids contain four proteins, CP26, CP40, CP48 and CP60, whose estimated molecular weights were 26 kD, 36-43 kD, 48 kD, and 60 kD, respectively. Staining with concanavalin A (ConA) showed that both CP26 and CP40 were glycoproteins. Moreover, N-terminal amino acid sequencing and Western blot analysis revealed CP26, CP48 and CP60 to be porcine albumin while CP40, the major protein in the colloids, proved to be clusterin. Therefore we report here that the glycoproteins that occur in senescent porcine pituitary colloids are of two types, namely, albumin fragments and clusterin.

Aging↗
PubMed1997

Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells.

Recent clinical studies in China showed that As2O3 is an effective and relatively safe drug in the treatment of acute promyelocytic leukemia (APL). We found previously that As2O3 can trigger apoptosis of APL cell line NB4 cells, which is associated with downregulation of bcl-2 gene expression and modulation of PML-RAR alpha chimeric protein. To further understand the mechanisms of this alternative therapy for APL, we investigated in this report the effects of a wide range of concentrations of As2O2 on cultured primary APL cells, all-trans retinoic acid (ATRA)-susceptible (NB4 cells) and ATRA-resistant (MR2 subclone) APL cell lines. The results indicated that As2O3 had dose-dependent dual effects on APL cells: inducing preferentially apoptosis at relatively high concentrations (0.5 to 2 micromol/L) and inducing partial differentiation at low concentrations (0.1 to 0.5 micromol/L). The rapid modulation and degradation of PML-RAR alpha proteins, which was induced by As2O3 at 0.1 to 2 micromol/L, could contribute to these two effects. Bone marrow and peripheral blood examination showed that myelocyte-like cells, probably as a result of partial in vivo differentiation, and degenerative cells increased after 2 to 3 weeks of continuous in vivo As2O3 treatment when leukemic promyelocytes decreased. In conclusion, combination of induction of apoptosis and partial differention could be the main cellular mechanisms of As2O3 in the treatment of APL, and PML-RAR alpha could play an important role in determining the specific effects of As2O3 on APL cells.

Antineoplastic Agents↗
PubMed1997

Subpiconewton intermolecular force microscopy.

We refined scanning probe force microscopy to improve the sensitivity of force detection and control of probe position. Force sensitivity was increased by incorporating a cantilever with very low stiffness, 0.1 pN/ nm, which is over 1000-fold more flexible than is typically used in conventional atomic force microscopy. Thermal bending motions of the cantilever were reduced to less than 1 nm by exerting feed-back positioning with laser radiation pressure. The system was tested by measuring electrostatic repulsive forces or hydrophobic attractive forces in aqueous solutions. Subpiconewton intermolecular forces were resolved at controlled gaps in the nanometer range between the probe and a material surface. These levels of force and position sensitivity meet the requirements needed for future investigations of intermolecular forces between biological macromolecules such as proteins, lipids and DNA.

Eyeglasses↗
PubMed1997

Myosin subfragment-1 is fully equipped with factors essential for motor function.

The sliding velocity of actin filaments propelled by chicken skeletal myosin subfragment-1 (S1) was measured when the tail end of S1 was specifically bound to the glass surface. To achieve the specific binding, a regulatory light chain was replaced by a recombinant fusion protein of biotin-dependent transcarboxylase (BDTC) and chicken gizzard smooth muscle regulatory light chain (cgmRLC). The BDTC-cgmRLC of S1 was then attached to the glass surface using a biotin-avidin system. The velocity of actin filaments caused by S1 bound to the surface in this manner was 6.8 +/- 0.6 microm/sec at 29 degrees C, which was 3.5-fold greater than that (1.9 +/- 0.3 microm/sec) when bound directly to the surface as in previous studies, but similar to that caused by native chicken skeletal myosin (6.5 +/- 0.6 microm/sec). The actin-activated Mg-ATPase activity was similar to that of S1 before the RLC of S1 was exchanged for BDTC-cgmRLC. The results indicate that S1 can produce a normal fast movement of actin filaments as well as hydrolyse ATP and generate force.

Animals↗
PubMed1997

Analysis of lymph node metastasis in early gastric cancer: rationale of limited surgery.

BACKGROUND: Since the majority of patients with early gastric cancer show long-term survival after surgery, a special attention must be directed to preserving gastric function in these patients. Little is known about the protocol of surgical treatment appropriate for early gastric cancer patients. This study was designed to determine the appropriate surgical procedure for early gastric cancer. METHODS: The clinicopathologic features of 52 patients with node-positive early gastric cancer were reviewed retrospectively from hospital records between 1969 and 1994 and were compared with those of 582 patients with node-negative early gastric cancer. Nodal status of positive nodes in the 52 cases was investigated. RESULTS: Depth of invasion, lymph vessel invasion, and tumor size were associated with lymph mode metastasis. Node-positive patients with early gastric cancer had a poorer survival rate than node-negative patients (P < 0.05). Patients with five or more positive nodes and positive nodes distant from the common hepatic artery showed an extremely poor prognosis. CONCLUSIONS: The surgical procedures most appropriate for the treatment of early gastric cancer are as follows: (1) local gastric resection without lymphadenectomy for mucosal cancers of < 2 cm in diameter and for elevated submucosal cancers of < 1 cm in diameter, (2) gastrectomy with dissection of the perigastric nodes, the nodes along the left gastric artery and the common hepatic artery, for the treatment of other early gastric cancers.

Aged↗