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Biomedical subjects

T Yoshioka

Publications and source records attributed to T Yoshioka.

At least 235 records · Page 13Linked to original sources

Recombinant human granulocyte colony-stimulating factor attenuates inflammatory responses in septic patients with neutropenia.

OBJECTIVE: The objective of this study was to determine the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in septic patients with neutropenia. METHODS: Twenty consecutive septic patients were administered rhG-CSF subcutaneously (2 microg x kg(-1) x d(-1)) for 5 days (group G). They were compared with 14 septic patients treated earlier without rhG-CSF (group N). All patients in both groups met the criteria of total leukocyte count (TLC) less than 5,000/mm3 and C-reactive protein (CRP) more than 10 mg/dL. Changes in TLC, absolute neutrophil count (ANC), CRP, respiratory index (RI), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Goris's Multiple Organ Failure (MOF) index were evaluated. In addition, nucleated cell count (NCC), differentiation in bone marrow aspiration, neutrophil phagocytic and bactericidal activity, serum concentrations of interleukin-6 (IL-6) and IL-8 as inflammatory markers, and plasma concentration of leukocyte elastase (LE) as an indicator of the tissue injury were evaluated in group G. RESULTS: In group G, TLC, ANC, NCC, and neutrophil functions increased significantly, whereas CRP, IL-6, and IL-8 decreased reciprocally. There was no deterioration of LE and RI. Consequently, the APACHE II score and MOF index improved. In group N, however, CRP showed no change concomitant with the APACHE II score and MOF index. CONCLUSION: Administration of rhG-CSF attenuates inflammatory responses without inducing tissue injury in septic patients with neutropenia.

APACHE↗

Homotypic adhesion through carcinoembryonic antigen plays a role in hepatic metastasis development.

We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 microg/ml) LS-LM4 cells under a Ca2+-free condition as compared with the control (P<0.01). Anti-CEA antibody (100 microg/ml) inhibited cell aggregation under a Ca2+-free condition (P<0.05). Treatment with anti-E-cadherin antibody (60 microg/ml) plus anti-CEA antibody (100 microg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca2+. In vivo, there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group (P<0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control (P<0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA.

Animals↗

Non-synchronous double adenoma of the parathyroid gland.

A 46-year-old female underwent an excision of a parathyroid adenoma diagnosed as recurrent primary hyperparathyroidism 24 years after the initial excision of a parathyroid adenoma. We report a case of non-synchronous double adenomas of the parathyroid glands documented histopathologically.

Adenoma↗

Immunohistochemical and molecular studies on malignant transformation in mature cystic teratoma of the ovary.

OBJECTIVES: To determine a useful tumor marker for detecting squamous cell carcinoma arising in a dermoid cyst, and to find the molecular pathogenesis of this condition. METHODS: In 4 cases of squamous cell carcinoma arising in a dermoid cyst and 22 cases of dermoid cyst, we studied tissue expressions and serum levels of squamous cell carcinoma antigen (SCC), CA 19-9 and CA 125, and the mutation of the p53 tumor suppressor gene. RESULTS: Three of 4 malignant cases had either positive SCC expressions or elevated serum SCC levels. The mean serum SCC level in benign cases was below the cut-off level. CA 19-9 and CA 125 were not detected in squamous cell carcinoma. p53 overexpressions were observed in all malignancies. CONCLUSION: These results suggested that the serum SCC might be a useful marker for detecting squamous cell carcinoma arising in a dermoid cyst, and that the mutation of p53 might be one of the genetic events in the malignant transformation of a dermoid cyst.

Adult↗

Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schönlein purpura nephritis.

OBJECTIVE: To study the influence of deletion/insertion polymorphism in the 16th intron of the angiotensin converting enzyme (ACE) gene on clinical manifestations of Henoch-Schönlein purpura nephritis. STUDY DESIGN: Cross sectional study. ACE gene polymorphism was determined in patients (4-15 years old at onset) with Henoch-Schönlein purpura nephritis (n = 40) and compared with that in patients with IgA nephropathy (n = 79). MAIN OUTCOME MEASURES: ACE genotypes, systemic blood pressures, urine protein excretion rate, haematuria, creatinine clearance, serum ACE activities. RESULTS: The initial clinical manifestations of both Henoch-Schönlein purpura nephritis and IgA nephropathy were no different among homozygotes for insertion (II) and deletion (DD), and heterozygotes (ID) for the ACE gene. In patients with Henoch-Schönlein purpura nephritis, the incidence of moderate to heavy proteinuria at four and eight years after onset was more than five times higher in the DD genotype than in the II or ID genotypes. No such trend was seen in patients with IgA nephropathy. The number of patients with Henoch-Schönlein purpura nephritis in whom proteinuria resolved at four and eight years after onset was significantly lower in the DD genotype compared with the II genotype, whereas no differences were detected among the three different genotypes in patients with IgA nephropathy. Plasma ACE activities in patients with the DD genotype were significantly higher than in those with non-DD genotypes. CONCLUSIONS: The ACE DD genotype predicts persistent proteinuria in Henoch-Schönlein purpura nephritis. The proteinuria might be related to a defective angiotensin system which is genetically determined by the D/I polymorphism.

Adolescent↗

Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia.

Leukocytes have been shown to contribute to ischemia-reperfusion injury in skeletal muscle. Pentoxifylline (PTXF), a xanthine-derived phosphodiesterase inhibitor, has received recent attention because of its action on leukocytes. To clarify the effects of PTXF in reperfusion injury, we measured the resting transmembrane potential difference (Em) and evaluated postcapillary venule microcirculation using intravital microscopy in rat skeletal muscle during ischemia and reperfusion. The infrarenal aorta was clamped for 90 min and then reperfused for 60 min. Persistent depolarization of the resting Em was observed in an ischemia-reperfusion (IR) group and was significantly repolarized in a PTXF group during the reperfusion period. The tissue water content was significantly reduced in the PTXF group, although no difference was noted in the tissue lactate content. Flowing erythrocyte velocity and wall shear rate in the PTXF group were significantly higher than in the IR group during the reperfusion period but without significant differences in vessel diameter and hemoglobin oxygenation. Blood flow measured by laser-Doppler flowmeter was also significantly improved in the PTXF group. Furthermore, the adherent leukocyte count was significantly reduced in the PTXF group during this same period. These results indicate that PTXF attenuated reperfusion-associated membrane injury and tissue edema and that PTXF suppressed leukocyte adhesion and improved hindlimb blood flow during the reperfusion period.

Animals↗

Identification and characterization of STK12/Aik2: a human gene related to aurora of Drosophila and yeast IPL1.

Mutations in aurora of Drosophila and related Saccharomyces cerevisiae IPL1 protein kinases are known to cause abnormal chromosome segregation. We earlier isolated a cDNA encoding a novel human protein kinase Aik which shares high amino acid identity with the Aurora/Ipl1 protein kinase family. In the present study, a second human cDNA highly homologous to aurora/IPL1 (Aik2) was identified and the nucleotide sequence was determined (gene symbol STK12). The C-terminal kinase domain of the STK12 encoded protein shares high amino acid sequence identity with those of mouse STK-1 (90%), rat AIM-1 (90%), human Aik (69%), mouse IAK1/Ayk1 (69%), Xenopus pEg2 (68%), Drosophila Aurora (62%), and yeast Ipl1 (45%), whereas the N-terminal domain of the STK12 protein shares little homology with those of Aurora/Ipl1 family members except for AIM-1 and STK-1. Northern blotting analyses revealed that STK12 expression was high in thymus, while low level expression was detected in small intestine, testis, colon, spleen, and brain. The STK12 protein content in HeLa cells is low in S phase, but it accumulates during M phase. STK12 was mapped to human chromosome 17p13.1 by fluorescence in situ hybridization. The chromosome location of STK12 was further defined using a radiation hybrid panel (Stanford G3), that showed a linkage with marker WI-7901 (LOD Score 7.83) located between D17S938 and D17S786.

Animals↗

Investigation of the possible role of sialic acid in calcium oxalate urolithiasis.

OBJECTIVE: It is considered that sialic acid in urine comprises two different types of sialic acid, that is, the free sialic acid and the bound one which exists as a basic component of urinary macromolecules. The present studies were performed to clarify the role of sialic acid in urine and compare the excretion and concentrations of sialic acid in urine between calcium oxalate (CaOx) stone formers and healthy subjects. METHODS: First, we prepared the crystal surface binding substances from whole human urine. The crystal surface binding substances were digested with sialidase and both the inhibitory activity on CaOx crystal growth and concentrations of sialic acid before and after sialidase digestion were measured. The inhibitory activity of free sialic acid in ultrafiltered urine was also measured. The excretion and concentration of sialic acid in urine from patients with CaOx urolithiasis and healthy controls were determined and compared. RESULTS: The inhibitory activity of crystal surface binding substances on CaOx crystal growth did not show any significant difference before and after sialidase digestion. The free sialic acid had also no effect on CaOx crystal growth. There was no statistically significant difference between CaOx stone formers and healthy controls on the excretion and concentration of sialic acid in urine. The free:bound sialic acid ratio in urine was considered 1:0.97 and 1:1.33 for healthy controls and CaOx stone formers respectively (p = NS). CONCLUSIONS: It is suggested that neither the free sialic acid nor the bound one in urine has a significant inhibitory effect on CaOx crystal growth.

Calcium Oxalate↗

Laparoscopic adrenalectomy. Comparison of the transperitoneal and retroperitoneal approach.

OBJECTIVES: The efficacy of transperitoneal (TP) and retroperitoneal (RP) laparoscopic adrenalectomy was compared. METHODS: Twenty-nine patients (male: 13; female: 16) with benign adrenal tumor were evaluated in this study. Seventeen were treated with the TP, and 12 with the RP approach. RESULTS: Convalescence for the TP group took longer than that for the RP group and postoperative pain was stronger for the TP than the RP group, although the difference was not significant. In addition, the amount of blood loss was larger for the TP than the RP group. When the cases were divided according to site of disease, the operating time for the right side was 351 min for the TP group and 347 min for the RP group, while that for the left side was 528 min for the TP group and 267 min for the RP group. CONCLUSIONS: Therefore, we recently prefer the RP approach for left adrenalectomy, but consider either approach suitable for the right side. The reason for this preference is that shortening the operating time is most important, also in the case of laparoscopic adrenalectomy because of the resulting reduced blood loss and the patients' early convalescence.

Adolescent↗

Effect of tazarotene, an acetylenic retinoid, on human dermal fibroblast.

The inhibitory effect of tazarotene, an acetylenic retinoid, on human dermal fibroblast in vitro was compared to that of all-trans-retinoic acid. The proliferation of fibroblasts was inhibited by both retinoids at the concentration of 1 microM after 5 days of culture. Synthesis of DNA and collagen was inhibited by both retinoids concentration-dependently up to 10 microM, although tazarotene was weaker in the inhibition of collagen synthesis. These results suggest the possible usefulness of tazarotene in the treatment of fibrotic diseases.

Bromodeoxyuridine↗

The effect of acute cold exposure and norepinephrine on uncoupling protein gene expression in brown adipose tissue of monosodium glutamate-obese mice.

Abnormal regulation of mitochondrial uncoupling protein (UCP) gene expression was studied in brown adipose tissue (BAT) of monosodium glutamate (MSG)-induced obese mice. UCP mRNA levels in control mice increased markedly after acute cold exposure; however, MSG-obese mice showed an impaired response. In contrast, an injection of norepinephrine (NE) induced a comparable increase in UCP mRNA levels in control and MSG-obese mice. These results suggest that the impairment in the cold-induced increase in UCP mRNA is due to a deficient sympathetic input to BAT and/or to a diminished response of BAT to endogenous NE, which constitutes the mechanism of impaired thermoregulation in obese mice in a cold environment.

Adipose Tissue, Brown↗

Biochemical properties of human oral polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMN) isolated from the oral cavity of healthy human volunteers, spontaneously generated superoxide, nitric oxide (NO) and other reactive oxygen species (ROS) which exhibited strong luminol chemiluminescence (LCL). To understand the physiological roles of oral PMN (OPMN), biochemical properties of the cells were analyzed. Biochemical analysis revealed that OPMN were already primed under physiological conditions. Western blot analysis revealed that they strongly expressed the inducible type of NO synthase (NOS II) and exhibited the activity to catalyze tyrosine phosphorylation of various proteins including a 115 kDa protein (cbl product). OPMN also generated H2O2 and .OH by some superoxide dismutase (SOD)-sensitive mechanism and released myeloperoxidase (MPO). Kinetic analysis using specific inhibitors revealed that OCl- generated by OPMN was predominantly responsible for the enhanced LCL. During the incubation under standard culture conditions, OPMN underwent apoptosis which proceeded more rapidly than that of the circulating PMN (CPMN). Immunochemical analysis revealed that expression of apoptosis-related gene products, such as Bcl-2, Bcl-xL and Bax, was below detectable levels with both cell types. However, caspase-3 but not caspase-1 was markedly activated in OPMN. These results indicate that the primed OPMN spontaneously generate ROS and play an important role in the defense mechanism in the oral cavity and that the generated ROS activate caspase-3 thereby inducing apoptosis of the cells.

Apoptosis↗

A poison information service via an automated facsimile (fax) system: an adjunct to the operator-based service.

BACKGROUND: Poison centers are faced with the escalating costs of specialist staffing and increased investments in hardware and databases despite deficit funding. We developed an automated fax information system to access poison information from any fax machine without special training or equipment. METHODS: We provided a 3-month trial service of the fax system in conjunction with the regular operator-based service and analyzed the fax access log, followed by a questionnaire to the 2204 affiliate members regarding the use of the fax. RESULTS: A total 657 accesses to the fax system were made, of which 105 (16%) were unsuccessful; 342 (52%) were made to retrieve the user's manual, 85 (13%) to retrieve the index pages, and 230 (35%) to retrieve documentation on specific substances. The most frequently accessed items concerned disc battery ingestion (13.5%), salicylates (10.3%), mamushi viper (7.1%), acetaminophen (5.8%), and sodium hypochlorite (3.8%). The questionnaires were returned by 666 (30.2%) members; 93 (14%) had actually used the fax system with the average frequency of 1.8 times/user, 63% (59/93) of the respondents considered the service satisfactory, and 33% (31/93) said it was somewhat unsatisfactory. CONCLUSIONS: The automated fax information system was accepted and handled by users with only minor difficulty. A facsimile information service may have a valuable role in providing poisoning information and has potential benefits in cases of environmental disasters.

Consumer Behavior↗

[Augmented antitumor activity in combination chemotherapy of nedaplatin with etoposide].

Augmented antitumor activity in combination chemotherapy of Nedaplatin (NDP) or Cisplatin (CDDP) with Etoposide (ETP) against murine and human lung cancer cells was demonstrated. NDP and CDDP were administered once and ETP daily for five days via tail vein. In the mice bearing Lewis lung carcinoma, a combination of NDP and ETP resulted in synergistically enhanced inhibition of tumor growth, and prolonged survival in comparison with either NDP or ETP alone. NDP showed a more potent combination effect with ETP than CDDP did. These effects were also demonstrated in human lung cancer cell lines. Although body weight loss was enhanced by the combination of NDP or CDDP with ETP, it was tolerable, and no significant difference between NDP plus ETP and CDDP plus ETP was observed. Thrombocytopenia was not enhanced in the combined treatment of NDP with ETP. These results suggest the usefulness of the combination of NDP with ETP as a clinical therapy for lung cancer.

Animals↗

[Effect of chorei-to and gorei-san on calcium oxalate crystallization in human urine].

The inhibitory effect of two kinds of Kampou medicine, Chorei-to and Gorei-san, on calcium oxalate crystallization in human urine, was examined. Chorei-to or Gorei-san was administered to 15 healthy male volunteers for three consecutive days under normal dietary conditions and 24-hour urine samples were collected before and after the administration. Urinary parameters including calcium, phosphorus, uric acid, oxalate and citrate were measured on each sample obtained. The inhibitory effect on calcium oxalate crystallization was examined using part of the collected 24-hour urine. There was no significant difference in urinary parameters before and after Chorei-to administration. Gorei-san administration significantly increased magnesium excretion in urine. A significant inhibitory effect on calcium oxalate crystallization in human urine was recognized when Gorei-san was administered, whereas Chorei-to had no inhibitory effect on calcium oxalate crystallization in urine.

Adult↗

[Treatment of hepatocellular carcinoma by segmental SMANCS Lipiodol-TAE].

Segmental SMANCS Lipiodol TAE (Seg. SMANCS Lp-TAE) using SMANCS was used to treat HCC in 58 patients and was evaluated in comparison with Seg. Lp-TAE using Epirubicin performed in 50 patients with respect to the course of atrophy of the embolized area, recurrence rate and side effects. On serial CT (Lp-CT) performed after TAE, in cases with P type in which the tumor is present in the periphery of the embolized area and showing Type I homogeneous accumulation of Lp within the tumor, the incidence of atrophy in the embolized area including the tumor was high and the recurrence rate was low. Although no significant difference in the recurrence rate was noted between the groups in which SMANCS and EPI were used, there were more cases with marked atrophy and a lower recurrence rate in the former. No difference was found in post-procedural side effects such as fever between the two groups, while hypotension was rarely observed during the procedure in the group in which SMANCS was used and was easily managed with intravenous steroids. The present results suggest that Seg. SMANCS Lp-TAE is an effective local treatment for HCC limited to a subsegment or segment.

Aged↗

Biotransformation of nitroso aromatic compounds and 2-oxo acids to N-hydroxy-N-arylacylamides by thiamine-dependent enzymes in rat liver.

The formation of N-hydroxy-N-arylacylamides from nitroso aromatic compounds and 2-oxo acids was investigated using rat liver subcellular fractions. Activities were found in both mitochondria and cytosol, except for activities for phenylpyruvate and glyoxylate; the former did not produce N-hydroxy-N-phenylphenylacetamide and the latter nonenzymatically produced N-hydroxy-N-phenylformamide with nitrosobenzene (NOB). The cytosolic activity of N-hydroxy-N-phenylglycolamide formation was indicated to be due to transketolase, which utilized hydroxypyruvate as a glycolic aldehyde donor to NOB. With mitochondria, 2-oxo acids (including hydroxypyruvate) served as substrates for the biotransformation of NOB to the corresponding N-hydroxy-N-phenylacylamides. The substrate preference was 2-oxobutyrate > pyruvate > 2-oxoisovalerate > 2-oxoisocaproate > 2-oxovalerate > 2-oxo-3-methylvalerate, judging from Vmax/half-saturating concentration for mitochondria values. The half-saturating concentrations for NOB were nearly constant. The mitochondrial activity was due to pyruvate dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex (BCDHC). By using partially purified BCDHC, pyruvate and 2-oxobutyrate were found to be common substrates for both of the enzymes, and 2-oxoisovalerate was shown to be the most effective substrate for BCDHC. Analysis by the Taft equation indicated that the polar effects, rather than the steric effects, of the alkyl groups of 2-oxo acids are important for BCDHC-catalyzed formation of N-hydroxy-N-phenylacylamides. A positive Hammett constant obtained for the formation of N-hydroxy-N-arylisobutyramides indicates that an electron-withdrawing substituent makes the nitroso compounds susceptible to BCDHC-catalyzed biotransformation.

Animals↗

Superoxide dismutase-like activity of metal substituted lactoferrin derivatives.

Lactoferrin (LF) is an iron-binding glycoprotein present in various secretions including milk and the specific granules of neutrophils. The main biological properties of this protein are thought to concern the regulation of iron absorption, antimicrobial activity and modulation of neutrophil activity. Copper bound LF (Cu-LF) inhibited the stimulation-dependent reduction of cytochrome c (Cyt. c) in guinea pig peritoneal neutrophils (GPMN) but were without effect on NADPH oxidase activity of the respiratory burst. However, Cu-LF stimulated the stimulation-dependent production of hydrogen peroxide as seen with superoxide dismutase (SOD). Similar but weaker inhibition of Cyt. c reduction than that shown by Cu-LF was observed with manganese-LF (Mn-LF) but not with ferrous-LF (Fe-LF) or apo-LF (Apo-LF). The inhibitory activity was concentration-dependent and the ID50s of Cu-LF and of Mn-LF were 0.1 and 5 microM, respectively. Reactive oxygen species (ROS) detected by luminol chemiluminescence (LCL) of stimulated-GPMN were partially inhibited by Cu-LF. Changes in LCL of stimulated GPMN induced by Cu-LF were similar to those of superoxide dismutase (SOD). Thus, it is concluded that low concentrations of Cu-LF had SOD-like activity and high concentrations of Cu-LF inhibited the stimulation-dependent generation of ROS.

Animals↗