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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 811 records · Page 45Linked to original sources

Inhibition of tumor growth and neovascularization by an anti-gastric ulcer agent, irsogladine.

Irsogladine used clinically as an anti-gastric ulcer agent, at 10(-6)-10(-4)M, inhibited cell proliferation and tubular morphogenesis of vascular endothelial cells, but the proliferation of human epidermoid cancer or glioma cells was not inhibited by this drug, even at 10(-4)M. In vivo studies demonstrated that p.o. administration of irsogladine significantly inhibited tumor growth of human glioma cells in mice, and histological analysis showed a dramatic decrease of the neovascularization in the tumors. In mice transplanted with chambers containing human glioma cells or hepatic cancer cells, irsogladine also inhibited angiogenesis. These in vivo and in vitro assays demonstrate that irsogladine may be a unique and potent inhibitor of tumor angiogenesis.

Animals↗

[Legionella infection in occupational and environmental health].

Air condition systems are indispensable for amenity in the work environment. It is known that Legionella species are widely distributed in the water of cooling towers, and that the bacteria are responsible for community-acquired pneumonia (Legionnaires' disease) and for influenza-like symptoms (Pontiac fever). Furthermore, Legionella species are associated with building-related illness. In Japan, however, prevention and countermeasures are inadequate against legionellosis compared to those of Europe and the USA. This is because occupational and environmental medicine in Japan has not been based on a microbiological point of view, and that workplace inspections have not covered cooling towers. Therefore, Legionella species in the water of coolig towers have not been routinely monitored in the work environment. This review describes the microbiological characteristics of Legionella species, their habits in the environment, the source and route of infection, the pathogenesis, the symptoms and treatment of legionellosis, outbreaks of this disease throughout the world, and how to deal with this organism in the work environment to prevent legionellosis.

Environmental Health↗

Risk factors for lymph node metastasis from intramucosal gastric carcinoma.

BACKGROUND: Although regional lymph node metastasis from intramucosal early gastric carcinoma (EGC) is rare, it is very important to clarify the characteristics of patients having lymph nodal metastases in order to determine appropriate therapy. METHODS: The authors investigated 1196 patients with solitary intramucosal EGC who underwent resection at the National Cancer Center Hospital in Tokyo, with special reference to lymph node metastases. Eight clinicopathologic factors (age, sex, tumor: size, location, macroscopic type, histologic type, histologic ulceration of the tumor, and lymphatic vessel invasion) were investigated by univariate and multivariate analyses for their possible relationship to lymph node metastasis. RESULTS: Lymph node metastases were found in 43 patients (3.5%). Univariate analysis revealed that younger age (< 57 years), macroscopic depressed type, larger tumor size (> or= 30 mm), undifferentiated histologic type, histologic ulceration of the carcinoma, and lymphatic vessel invasion had a significant association with regional lymph node metastasis. Multivariate analysis revealed that lymphatic vessel invasion, histologic ulceration of the tumor, and larger size (> or = 30 mm) were independent risk factors for regional lymph node metastasis. The incidence of lymph node metastasis from intramucosal EGC negative for these 3 risk factors was only 0.36% (1 in 277 patients). CONCLUSIONS: Lymphadenectomy is unnecessary for patients with small intramucosal EGC with neither histologic ulceration of the tumor nor lymphatic vessel invasion because the incidence of regional lymph node metastasis is extremely low in those patients. The therapeutic options for such patients would be local resection or endoscopic resection.

Age Factors↗

A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 7 (matrilysin) using monoclonal antibodies.

A one-step sandwich enzyme immunoassay (EIA) system for human matrix metalloproteinase 7 (MMP-7, matrilysin, EC 3.4.24.23) was established with a pair of monoclonal antibodies prepared against the zymogen of MMP-7 (proMMP-7) purified from CaR-1 human rectal carcinoma cells and against an oligopeptide corresponding to the C-terminal domain of human proMMP-7. ProMMP-7 in samples was allowed to simultaneously react with both solid-phase and peroxidase-labeled antibodies. Sensitivity of the EIA system in the presence of EDTA was 0.05 microgram/l (1.5 pg/assay) and linearity was obtained between 0.156-10 micrograms/l (4.68-300 pg/assay). ProMMP-7 levels in human sera from healthy subjects were shown to be in the range of 10.7 +/- 18.8 micrograms/l. Gel filtration analyses indicated that proMMP-7 makes polymers after treatment with EDTA and suggested that proMMP-7 exists as polymers in normal human sera.

Amino Acid Sequence↗

Distribution and organization of peripheral capillaries in dental pulp and their relationship to odontoblasts.

BACKGROUND: Developmental and chronological changes in the peripheral capillaries of the dental pulp and their relationship to odontoblasts during dentin formation has not been sufficiently detailed. This study aims to elucidate the morphological changes of the peripheral capillaries in relation to the life cycle of odontoblasts. METHODS: Peripheral capillaries of the dental pulp were examined in the labial region of rat incisors and in the crown region of rat molars by using light, transmission, and scanning electron microscopy. RESULTS: Before the start of dentin formation, continuous capillaries formed a coarse vascular network under the odontoblast layer. With the start of dentin deposition, capillaries began to invade into the odontoblast layer and finally located close to the predentin, where they formed a dense vascular network consisting of fenestrated capillaries. In the incisors, dentin was formed actively even near the incisal tip, and fenestrated capillaries continued to locate in the odontoblast layer. In the molars, however, the activity of dentin deposition gradually decreased with the advance of dentin formation, and the fenestrated capillaries altered to continuous capillaries and withdrew from the predentin border to the odontoblastic-pulpal border shortly before the cessation of active dentin deposition. CONCLUSIONS: It is concluded that the changes in the peripheral capillaries are closely related to the secretory activity of the odontoblasts. To facilitate a rapid and sufficient supply of raw materials from the bloodstream to the calcifying front, peripheral capillaries first approach the odontoblasts, invade into the odontoblast layer close to the predentin with increases in density, and finally alter the endothelium from the continuous to the fenestrated type in compliance with the nutritional requirements of the odontoblasts, which lay down the dentin. When the activity of odontoblasts decreases, capillaries first alter the endothelium from the fenestrated to the continuous type, then retreat from the odontoblast layer, and finally locate below the odontoblast layer.

Animals↗

Structural characterization and location of disulphide linkages of a potent vasodilatory peptide, recombinant maxadilan, by a multiple mass spectrometric approach.

A multiple mass spectrometric strategy using fast-atom bombardment (FAB) and matrix-assisted laser desorption/ionization (MALDI) has been used to confirm the sequence and to locate the disulfide linkages of recombinant maxadilan (r-maxadilan) (average molecular mass 7422.5 Da), a potent vasodilatory peptide from Lutzomyia longipalpis. MALDI measurements of intact r-maxadilan, its reduced form and its pyridylethylated form (p-maxadilan) indicated the presence of four Cys residues without major post-translational modifications. FAB and FAB-tandem mass spectrometry measurements of chymotryptic digests of p-maxadilan were sufficient to map the primary structure of p-maxadilan, though the complementary use of MALDI was necessary for complete mapping using Asp-N digestion due to a strong suppression observed in FAB. Assignment of the Cys-5-Cys-9 linkage was achieved by comparison of FAB mass spectra before and after reduction of tryptic digests of r-maxadilan. Since the molecular weight of the peptide fragment containing the Cys-18-Cys 55 linkage is more than 4000, MALDI measurement was indispensable for assignment of this linkage. The results fully support the value of the multiple mass spectrometric strategy in the structural characterization of peptides and proteins.

Amino Acid Sequence↗

Differences in immune functions between human T-lymphotropic virus type I carriers and patients with adult T-cell leukemia/lymphoma.

A variety of immunologic tests were compared between human T-lymphotropic virus type I (HTLV-I) carriers and patients with adult T-cell leukemia/lymphoma (ATL). The mitogenic responses of the lymphocytes to concanavalin A and phytohemagglutinin were depressed in the ATL patients but not in the carriers, while the response to pokeweed mitogen in the carriers and ATL patients was depressed compared to the HTLV-I-seronegative controls. A positive tuberculin reaction in the carriers was as frequent as in the controls, but less frequent in the ATL patients. A marked inhibition of the intracellular multiplication of Legionella pneumophila was observed within the monocytes isolated from the carriers, but not in the ATL patients or the normal controls. These results indicate that the ATL patients have severe immunodeficiency, while the HTLV-I carriers have some activation of anti-microbial activity in monocytes although they are somewhat immunosuppressed.

Adult↗

Portal vein branch occlusion induces cell proliferation of cholestatic rat liver.

Portal vein branch occlusion induces atrophy of occluded hepatic lobes, concomitantly associated with the complementary hypertrophy of unoccluded lobes. In this context, selective embolization of the portal vein branch supplying the area to be resected has been performed prior to extended hepatectomy to reduce the risk of postoperative liver failure. However, carcinoma of the hepatic hilus is often associated with obstructive jaundice. At present it is still obscure whether cholestatic hepatocytes can also respond well to the proliferation stimuli caused by the portal vein branch embolization. To clarify this point, we made a rat model of portal vein branch ligation in combination with cholestasis. As an indicator of proliferation, we determined the activity of DNA polymerase alpha and the mitotic index. The results demonstrate that, even in the cholestatic liver, the expression of DNA polymerase alpha in unoccluded lobes was induced by contralateral portal vein branch ligation. The maximal degree of DNA polymerase alpha induction in the cholestatic liver was similar to that in the noncholestatic liver, i.e., fivefold above that in the resting liver. The level of DNA polymerase alpha activity correlated well with the mitotic index in the same tissue. Furthermore, the cell proliferation after the portal vein branch occlusion is not suppressed by the preceding external biliary drainage, which had been shown to suppress the liver regeneration after partial hepatectomy. From these results, it is concluded that portal vein branch ligation induces liver cell proliferation in unoccluded lobes, irrespective of the presence of cholestasis.

Alanine Transaminase↗

Effect of fentanyl citrate analgesia on glucose production following trauma in rats.

The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.

Analgesia↗

Effect of fentanyl citrate anesthesia on protein turnover in patients with esophagectomy.

The objectives of this study were to determine whether high doses of fentanyl anesthesia reduced the surgical stress level and to elucidate the effect of fentanyl anesthesia on protein turnover after esophagectomy. Seventeen male patients with esophageal cancer were divided into two groups, conventional anesthesia (CA) and fentanyl anesthesia (FA). The FA patients received 134.0 +/- 15.3 microg/kg fentanyl citrate and the CA patients 15.7 +/- 7.4 microg/kg fentanyl during the surgery. Protein turnover was measured by the method of bolus infusion of [15N]glycine (1 g). High dose of fentanyl anesthesia reduced cortisol levels during the surgery (CA 38.0 +/- 13.8 pg/ml vs FA 13.5 +/- 2.4, P < 0.05) and interleukin-6 levels in the plasma after the surgery (P < 0.02). The postoperative nitrogen retention was greater with fentanyl anesthesia than with conventional anesthesia. Both protein synthesis and breakdown rates were increased with fentanyl anesthesia, while they were unaltered in CA patients. Postoperative fibrinogen synthesis rate was greater with FA than with CA (CA 51.1 +/- 9.2%/day vs FA 100.9 +/- 14.0, P < 0.01). The protein turnover and fibrinogen synthesis data suggested a shorter duration of shock phase in FA patients than in CA patients. We concluded that a high dose of fentanyl anesthesia reduced surgical stress levels and shortened the postoperative shock phase, resulting in a nitrogen-sparing effect.

Acute-Phase Proteins↗

Ligation of portal vein branch induces DNA polymerases alpha, delta, and epsilon in nonligated lobes.

Ligation of a portal vein branch supplying 70% of the rat liver causes compensatory hypertrophy of the nonligated hepatic lobes with concomitant atrophy of the ligated lobes. To elucidate the mechanism of this response, the induction of the replication enzymes DNA polymerases alpha, delta, epsilon, as well as proliferating cell nuclear antigen (PCNA), were investigated in nonligated lobes after portal branch ligation. The induction patterns were compared with the well studied liver regeneration after 70% partial hepatectomy. DNA polymerases alpha, delta, and epsilon in the liver were extracted with 5 mM KCl (low-salt extract), then with 600 mM KCl (high-salt extract). DNA polymerases alpha, delta, and epsilon in low-salt extract were partially separated on a hydroxyapatite column and quantified. All enzyme activities in the nonligated lobes started to increase within 24 hr and reached maximum levels by 48 hr after portal branch ligation. These patterns were quite similar to those obtained with the remnant liver after partial hepatectomy. In low-salt extract, DNA polymerase delta and epsilon were prominent, while, in high-salt extract, largely DNA polymerases alpha and some activity of epsilon were recovered. PCNA was also induced after both portal branch ligation and partial hepatectomy, reaching maximum levels at 48 hr. From the similar changes in DNA polymerases and PCNA, our data indicate that portal branch ligation induces hepatocyte proliferation in the nonligated lobes in a way similar to partial hepatectomy.

Animals↗

A new type of growth exhibited by Trimmatostroma abietis.

Trimmatostroma abietis initially grew as hyphae when grown in various media containing yeast extract or bactopeptone. It grew as segmented elements (lumbricoid elements) characterized by bidirectional growth, when grown in Czapek-Dox broth or yeast nitrogen base supplemented with 1% glucose. A lumbricoid element usually was 10-70 microns in length, with transverse septation only and contained 3 to 15 cells. Growth and propagation, as revealed by time-lapse photomicrography occurred as follows. Elements usually grew by apical elongation without widening; after simple apical elongation adjacent parts of two central cells eventually started to grow, resulting in the separation of the element into two.

Microscopy, Electron↗

Development of fat within a meningioma.

We report a tentorial meningioma containing fat. Multiple areas of fatty density or intensity in the tumour were seen on CT and MRI, which corresponded histologically to lipomatous components. CT 10 years previously had demonstrated a smaller tumour without evidence of fatty components. We found only five cases in the literature in which fatty density was demonstrated within a meningioma on CT and a lipomatous component histologically proved. Xanthomatous change, with lipid in tumour cells, causes decrease in density on CT, but not to the levels of fat. As both lipomatous components and xanthomatous change show similar intensity on MRI, CT can be helpful in differentiating these two conditions. To our knowledge, our case is the only one in which the advent of fatty tissue was confirmed during follow-up.

Adipose Tissue↗

Electrophysiologic mechanisms of adverse effects of class I antiarrhythmic drugs (cibenzoline, pilsicainide, disopyramide, procainamide) in induction of atrioventricular re-entrant tachycardia.

We evaluated the electrophysiological mechanisms of adverse effects of class I antiarrhythmic drugs (cibenzoline in seven patients, pilsicainide in two, and disopyramide in two, and procainamide in three) in the induction of orthodromic atrioventricular re-entrant tachycardia (AVRT). In 14 patients (10 males, 4 females; mean age 37 +/- 18 years) who had inducible AVRT despite the administration of class I drugs, electrophysiological effects of class I antiarrhythmic drugs were evaluated using programmed electrical stimulation techniques. In 4 out of 6 patients with a manifest accessory pathway, class I drugs induced unidirectional conduction block of the accessory pathway (antegrade conduction block associated with preserved retrograde conduction) and enhanced the induction of AVRT with atrial extrastimulation. In eight patients with a concealed accessory pathway, the outward or inward expansion of the tachycardia induction zone was observed in patients who had greater prolongation of the conduction time than the refractory period of the retrograde accessory pathway after class I drugs. During ventricular extrastimulation, the induction of bundle branch re-entry after class I drugs initiated the AVRT in patients with either manifest or concealed accessory pathways. We conclude that the adverse effects of class I drugs are mainly due to induction of unidirectional retrograde conduction of the manifest accessory pathway and the greater prolongation of the retrograde conduction time of the concealed accessory pathway than the refractory period, regardless of the sub-classification of class I drugs.

Adolescent↗

Stem-cell factor regulates the expression of cyclin A and retinoblastoma gene product in the growth and differentiation pathway of human megakaryocytic cells.

The biological effects of c-kit ligand (stem-cell factor: SCF) on an immortalized human megakaryocytic cell line (CMK) was evaluated using methods including the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, surface marker analysis, DNA cell-cycle analysis and immunoblotting. SCF stimulated the growth of CMK cells. Incubation with SCF resulted in increased expression of IIb/IIIa platelet-related glycoprotein (gpIIb, IIIa), indicating enhanced differentiation of CMK cells. Treatment of CMK cells with SCF resulted in a decrease in the subpopulation in the G1 phase, with a reciprocal increase in those in the S phase and the G2 + M phase. Moreover, SCF significantly increased cellular expression of cyclin A, a regulatory subunit of cyclin-dependent protein kinase (CDK), and the ratio of phosphorylated/dephosphorylated retinoblastoma gene product (RB protein). These results suggest that SCF stimulates the growth and differentiation of megakaryocytic cells possibly through mechanisms related to the activation of cell-cycle-dependent serine/threonine kinase and inactivation of the nuclear tumor-suppressor gene product.

Cell Differentiation↗

Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end products of catecholamine biosynthetic pathway.

The N-terminal 52-, 70-, and 157-amino acids-deleted mutants and wild-type tyrosine hydroxylases were expressed in Escherichia coli and utilized to investigate the roles of the N-terminus in the catecholamine inhibition on enzyme activity. Their lysate's supernatants were used as enzyme samples. Three catecholamines, namely dopamine, norepinephrine, and epinephrine, affected both wild-type and mutant enzymes after preincubation in the mode of mixed inhibition, and the most marked alteration among the kinetic parameters produced by the deletion was the increase in the inhibition constants. The deletions also abolished the catecholamine-induced shift of the pH profile of the enzyme activity toward a more acidic pH optimum. All three mutants responded to catecholamines almost in the same way. These results suggest that the three catecholamine end products exert their inhibition on tyrosine hydroxylase to the same extent and that the N-terminal 52 amino acid residues contain the key sequence in mediating the inhibitory action.

Catalysis↗

Ectopic accumulation of 99mTc-HMDP in primary lung cancer in comparison with CT findings.

The purpose of this study was to evaluate the frequency and the extent of extraosseous 99mTc-HMDP accumulation in 412 patients with primary lung cancer. CT scanning was also performed and we compared the extraosseous uptake by lung cancer with the internal structure of the tumor on CT scans. The extent of ectopic 99mTc-HMDP accumulation was classified as low, moderate or high. CT scans were used to evaluate the size and internal structure of the tumor, including calcification and necrosis. Ectopic 99mTc-HMDP accumulation in primary lung cancer was found in 32 patients (7.7%), and included 2 cases (0.5%) of high uptake, 8 cases (1.9%) of moderate uptake, and 22 cases (5%) of low uptake. No difference in uptake was observed among the histological types, but a relationship between tumor size and 99mTc-HMDP extraosseous accumulation was observed. CT scans of the 32 tumors exhibiting ectopic 99mTc-HMDP accumulation revealed 5 cases of calcification in the tumor and 18 cases of tumor necrosis. The factors promoting ectopic 99mTc-HMDP accumulation were considered to be tumor size and calcification or necrotic change. In patients with neither calcification nor necrosis, other factors such as increased calcium metabolism and altered vascular permeability may be involved.

Adenocarcinoma↗

Angiogenesis as a new target for cancer treatment.

Neovascularization is often required for rapid growth of solid tumors and also limits vascular metastasis of tumor cells. Neovascularization-targeting agents are a recent innovation that may be a novel means of anticancer therapy. These antiangiogenic drugs have been developed by targeting cell proliferation of vascular endothelial cells, basement-membrane-degrading enzymes, angiogenic factors/receptors, extracellular matrix, angiogenesis signaling, and cell-cell/cell-matrix interactions. In this report, we describe how tumor angiogenesis occurs and how antiangiogenic agents are developed.

Animals↗