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Biomedical subjects

T Iwamoto

Publications and source records attributed to T Iwamoto.

At least 181 records · Page 10Linked to original sources
PubMed1997

Effects of antioxidants on the oxidative susceptibility of low-density lipoprotein.

An important event in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low-density lipoprotein (LDL) initiated by a free radical-driven lipid peroxidation process. Vitamin E acts as a lipophilic chain-breaking antioxidant, while water-soluble chain-breaking antioxidants such as vitamin C or uric acid suppress the oxidation of LDL initiated by aqueous radicals. In this study, we established a new method of measuring the lag time of inhibited lipid peroxidation using the lipophilic azo radical initiator V-70:2-2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) and investigated in vitro the susceptibility of LDL to oxidation using this method when lipid- and water-soluble antioxidants were added. When the lipid-soluble antioxidant, vitamin E, was added to LDL, the lag time was extended whereas a higher dose of vitamin E led to a shortened lag time of V-70-induced lipid peroxidation in LDL. These results suggest that vitamin E radicals (tocopheroxyl radicals) act as prooxidants during the autoxidation of LDL. It was also shown that the shortened lag time induced by higher doses of vitamin E was restored when lipid- and water-soluble antioxidants were added simultaneously, which suggests that vitamin E radicals derived from vitamin E are subsequently reduced by vitamin C to regenerate vitamin E. Thus, the interaction between lipid- and water-soluble antioxidants provides an important function in maintaining LDL resistance to oxidation.

Adult↗
PubMed1997

The effects of 20 days bed rest on serum lipids and lipoprotein concentrations in healthy young subjects.

The effects of 20 days bed rest (BR) on serum lipids and lipoprotein concentrations were investigated in 23 healthy young subjects (13 males and 10 females, aged 19 to 25 yr.). After 20 days BR, VO2max was reduced in both genders, but body composition did not change. The ratio of glucose area to insulin area during an oral glucose tolerance test decreased gradually throughout BR, which suggested a decrease in insulin sensitivity. Estimated changes in plasma volume from the beginning of BR were largest at day 3 of BR (-9.1% in females and -3.4% in males) and seemed to return the initial level at the end of BR in both genders. The increase in serum triglycerides and the decrease in high density lipoprotein (HDL) cholesterol, and apolipoprotein AI were observed in both genders during BR. In a smaller study of 4 males and 5 females, 20 days BR was associated with a decrease in HDL, cholesterol, a decrease in apolipoprotein AI and apolipoprotein AII, decrease in a plasma postheparin lipoprotein lipase activity and an increase in very low density lipoprotein triglyceride. Overall, the data suggested that the decrease in lipoprotein lipase activity and insulin sensitivity may contribute to the impairment in HDL metabolism.

Adult↗
PubMed1997

Image cytometry for quantitative analysis of DNA in the testes of infertile men with varicocele: comparison with flow cytometry.

PURPOSE: The first aim of this study is to evaluate the usefulness of image cytometry comparing flow cytometry to analyze the spermatogenesis using testicular biopsy specimens obtained from infertile male. The second is to investigate the spermatogenesis of infertile men with varicocele by image cytometry. MATERIALS AND METHODS: A total of 76 biopsy specimens of testicular tissue were obtained from 38 infertile men with varicocele and 6 specimens of normal testicular tissue controls were obtained from 6 volunteers at vasectomy. They were evaluated by image cytometry and pathohistological examination. Out of 76 specimens, 21 biopsy tissues were also analyzed by flow cytometry, and the results by both image cytometry and flow cytometry were compared. Two specimens from Sertoli cell only testes were also examined by image and flow cytometry. RESULTS: In comparative study, image cytometry revealed a decrease in the proportion of haploid and diploid cells (18.8 +/- 6.6% and 32.4 +/- 7.4%), and an increase in that of tetraploid cells (21.8 +/- 5.6%) vs. the flow cytometry findings (haploid, 25.9 +/- 9.2%; diploid, 36.8 +/- 6.5% and tetraploid, 15.1 +/- 5.9%). Image cytometric analysis of the testes of varicocele patients showed 15.9 +/- 5.6% haploid, 31.7 +/- 7.9% diploid and 16.2 +/- 8.9% tetraploid cells in the left testis of infertile men, while their right testis showed 16.6 +/- 5.4% haploid, 30.0 +/- 7.6% diploid and 17.2 +/- 6.4% tetraploid cells. The testes of normal men showed 37.6 +/- 8.3% haploid, 19.4 +/- 4.8% diploid and 17.4 +/- 5.8% tetraploid cells. The left and the right testes of the patients with varicocele showed a lower proportion of haploid cells and a higher proportion of diploid cells vs. the testes from normal men. The proportions of the haploid and diploid cells are correlated with sperm concentration. CONCLUSION: Image cytometry could exclude interstitial cells, Sertoli cells, and sperm on the static image, so produced an accurate assessment of spermatogenesis. The alteration in the germ cell population in the testes of infertile men with varicocele suggested that the impairment mostly affected the cells in the meiotic stage.

Adult↗
PubMed1997

[An autopsy case of multiple myeloma with pineal body and spinal cord dura mater infiltration].

An autopsy case of multiple myeloma (IgD lambda type) with pineal body and spinal cord dura mater infiltration is reported. The 63-year-old man was diagnosed as multiple myeloma (IgD lambda type). He was treated with melphalan and prednisolone. Extra bone marrow masses developed 1 year after the onset. He died with renal failure. At autopsy there were many extra bone marrow masses including pineal body and dura mater of the thoracic cord. Microscopic examination revealed that those mass lesions consisted of neoplastic plasma cells. Myeloma cells also infiltrated perivascular space near the pineal body, subdural space of the cerebrum and brain stem. The cells were labeled VS 38 c immunohistochemically. We discussed routes of the metastasis to the central nervous system of the multiple myeloma. This case suggests that the way of myeloma cells infiltration to the pineal body is hematogenous metastasis, because pineal body have no blood brain barrier.

Dura Mater↗
PubMed1997

[A case of 47XYY syndrome presenting with male infertility].

A 32-year-old man was referred to our hospital for primary infertility of a 4.5-year duration. Neither character nor intelligence disorders were observed. Bilateral testes measured 16 ml each. Sperm density was 0-0.1 x 10(6)/ml on 3 separate occasions. Endocrine examinations were all within normal limits. Maturation arrest was found on testicular biopsy. Karyotyping showed 47, XYY inversion. Polymerase chain reaction revealed no deletion of the azoospermic factor (AZF) gene on the Y chromosome. This is the 6th case reported in the Japanese literature of the 47XYY syndrome presenting with male infertility.

Adult↗
PubMed1997

Factors affecting longevity.

In view of the fact that hypercholesterolemia occurs in 31.4%, hypertension in 16.7% and the smoking rate is 58.8% in males (Table 8), risk factors are not low. Despite this, we Japanese preserve a leading position regarding longevity. I hope that I have provided some evidence supporting the proposal that apparently not only a low fat intake but other factors including genetic make up and a relatively high antioxidant intake contribute to our longevity.

Antioxidants↗
PubMed1996

A novel isothiourea derivative selectively inhibits the reverse mode of Na+/Ca2+ exchange in cells expressing NCX1.

No.7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate), a selective inhibitor of the Na+/Ca2+ exchanger (NCX1), has been newly synthesized. It dose-dependently inhibited Na+i-dependent 45Ca2+ uptake and Na+i-dependent [Ca2+]i increase in cardiomyocytes, smooth muscle cells, and NCX1-transfected fibroblasts (IC50 = 1.2-2.4 microM). Inhibition was observed without prior incubation with the agent and was completely reversed by washing cells with buffer for 1 min. Interestingly, No.7943 was much less potent in inhibiting Na+o-dependent 45Ca2+ efflux and Na+o-induced [Ca2+]i decline (IC50 = >30 microM), indicating that it selectively blocks the reverse mode of Na+/Ca2+ exchange in intact cells. In cardiac sarcolemmal preparations consisting mostly of inside-out vesicles, the agent inhibited Na+i-dependent 45Ca2+ uptake and Na+o-dependent 45Ca2+ efflux with similar, but slightly lower, potencies (IC50 = 5.4-13 microM). Inhibition was noncompetitive with respect to Ca2+ and Na+ in both cells and sarcolemmal vesicles. These results suggest that No.7943 primarily acts on external exchanger site(s) other than the transport sites in intact cells, although it is able to inhibit the exchanger from both sides of the plasma membrane. No.7943 at up to 10 microM does not affect many other ion transporters nor several cardiac action potential parameters. This agent at these concentrations also did not influence either diastolic [Ca2+]i or spontaneous beating in cardiomyocytes. Furthermore, No.7943 markedly inhibited Ca2+ overloading into cardiomyocytes under the Ca2+ paradox conditions. Thus, No.7943 is not only useful as a tool with which to study the transport mechanism and physiological role of the Na+/Ca2+ exchanger but also has therapeutic potential as a selective blocker of excessive Ca2+ influx mediated via the Na+/Ca2+ exchanger under pathological conditions.

Animals↗
PubMed1996

Effect of terminal ileal transposition on gallbladder bile composition following proctocolectomy.

Enterohepatic circulation of bile acid is impaired and the percentage of secondary bile acids in bile decreases after proctocolectomy and ileo-anal anastomosis. Moreover, the site-specific function and morphology of the terminal ileum are likely to be damaged by acute and chronic inflammation because the ileum is being used as a reservoir in this procedure. A jejunal segment was interposed between the terminal ileum and the anus to spare the terminal ileum from being used as a reservoir following proctocolectomy in dogs. We performed this study to investigate the effects of this procedure on gallbladder bile lipid composition. Adult mongrel dogs underwent either terminal ileal transposition procedure (n = 7) or conventional ileoanal anastomosis (n = 7) following two-stage proctocolectomy. The animals were laparotomized and gall-bladder bile was collected 12 weeks later. In the terminal ileal transposition group, the total bile acid concentration significantly decreased (P < 0.01), while the secondary bile acid percentage did not. In the conventional group, the percentage of secondary bile acid significantly decreased (P < 0.05), while the total bile acid concentration remained unchanged. Proximal transposition of the terminal ileum may have an advantage in preserving the percentage of secondary bile acid in gallbladder bile. This procedure effects bile lipid metabolism differently than conventional ileo-anal anastomosis.

Animals↗
PubMed1996

Phosphorylation-dependent regulation of cardiac Na+/Ca2+ exchanger via protein kinase C.

The cardiac Na+/Ca2+ exchanger (NCX1) plays a major role in the extrusion of Ca2+ from cardiomyocytes. We studied the role of protein phosphorylation in the regulation of cardiac NCX1 using CCL39 stably overexpressing the canine cardiac NCX1 and rat neonatal cardiomyocytes. In both cell types, the NCX1 protein immunoprecipitated with a chicken anti-NCX1 antibody exhibited a significant basal phosphorylation that was further enhanced by treatment with endothelin-1, acidic fibroblast growth factor, phorbol 12-myristate 13-acetate, or okadaic acid. In contrast, calphostin C, K252a, or EGTA inhibited the phosphorylation. The phosphorylation occurred on two major tryptic phosphopeptides (P1 and P2) exclusively on serine residues. Evidence is presented suggesting that P2 was derived from an N-terminal half (amino acids 240-475) of the central cytoplasmic domain of NCX1 and was phosphorylated directly by protein kinase C (PKC). The agents that increased NCX1 phosphorylation significantly enhanced both the forward and reverse modes of Na+/Ca2+ exchange. This exchange activation exhibited a very good correlation with the NCX1 phosphorylation. In NCX1-transfected cells, PKC down-regulation following prolonged exposure to phorbol 12-myristate 13-acetate abolished the acidic fibroblast growth factor-induced activation of exchange activity. On the other hand, cell ATP depletion reduced the exchange activity and abolished the effects of the above agents on exchange activity. These results indicate that the cardiac NCX1 is up-regulated by PKC-catalyzed phosphorylation. The cardiac NCX1 thus could play an important role in the previously reported negative inotropic actions of phorbol esters and other PKC-activating agents.

Adenosine Triphosphate↗
PubMed1996

The multiple endocrine neoplasia type 2B point mutation alters long-term regulation and enhances the transforming capacity of the epidermal growth factor receptor.

The RET proto-oncogene encodes a member of the receptor tyrosine kinase family. Multiple endocrine neoplasia type 2B (MEN 2B) is caused by the mutation of a conserved methionine to a threonine in the catalytic domain of the RET kinase. When the MEN 2B point mutation was introduced into the epidermal growth factor (EGF) receptor (M857T EGFR), the intrinsic tyrosine kinase activity of the mutant receptor was similar to that of wild-type EGF receptor and remained ligand-dependent. However, the mutant receptor showed an enhanced transforming capacity compared to the wild-type receptor as judged by its ability to mediate the growth of NIH 3T3 cells in soft agar. Using the oriented peptide library approach to examine substrate specificity, the M857T mutation was found to be associated with a decrease in the selectivity of the receptor for Phe and an increase in the selectivity for acidic residues at the P + 1 position as compared to wild-type EGF receptor. Short-term responses to EGF were similar in cells expressing wild-type and M857T EGF receptors. However, significant differences in receptor down-regulation were observed between the two receptors. These data demonstrate that the MEN 2B point mutation alters the substrate specificity of receptor tyrosine kinases and suggest that the enhanced oncogenesis associated with the MEN 2B mutation may be due in part to alterations in receptor regulation.

3T3 Cells↗
PubMed1996

Effect of terminal ileal transposition on intestinal absorption following proctocolectomy.

A terminal ileal transposition procedure, in which a distal jejunal segment is interposed between the terminal ileum and the anus following proctocolectomy, is described. Adult mongrel dogs had either terminal ileal transposition (n = 5) or ileoanal anastomosis (n = 6) following two-stage proctocolectomy. Untreated dogs were used as controls (n = 7). Twelve weeks after the second-stage operation, a perfusion study was performed. After terminal ileal transposition the transposed terminal ileum showed a high absorptive capability for sodium, chloride and bile acids (P < 0.05, P < 0.05 and P < 0.001 respectively). After ileoanal anastomosis the absorptive capability of the terminal ileum was not enhanced significantly. In the mid-jejunum, the absorption of bile acids, chloride and glucose was enhanced (all P < 0.05) only after terminal ileal transposition. Terminal ileal transposition improves the absorptive capability of the terminal ileum and the mid-jejunum compared with conventional ileoanal anastomosis in this model.

Anastomosis, Surgical↗
PubMed1996

Gallstone formation and gallbladder bile composition after colectomy in dogs.

A high prevalence of gallstones has been described in patients following colectomy. The aim of this study was to examine whether lithogenicity is attributed to colectomy. In the present study, changes in gallbladder bile composition and the mechanism of gallstone formation after colectomy were examined in dogs. Ten mongrel dogs underwent restorative proctocolectomy. Seven dogs which received sham operations served as controls. Over a 12-week postoperative period, samples of gallbladder bile, formed gallstones and serum were collected and analyzed. In 7 of the 10 (70%) colectomized dogs, gallstones were found in the gallbladder, while the control dogs had no stones. Macroscopically the gallstones were similar to black pigment stones observed in humans. Chemical analysis and Fourier transform-infrared spectroscopy examination revealed that the stones were composed mainly of sodium bilirubinate and proteins, with minor amounts of calcium salts and cholesterol. Significant increases in biliary pH and concentrations of ionized calcium and unconjugated bilirubin were observed in the gallbladder bile of the colectomy group compared with that of the control group. The total bile acid and total bilirubin concentrations were significantly decreased in the colectomy group. Cholesterol crystal nucleation did not occur. The inhibitory effect of gallbladder bile on calcium carbonate precipitation in an in vitro assay system was preserved even after colectomy. In conclusion, proctocolectomy increases the concentration of unconjugated bilirubin in gallbladder bile and induces pigment gallstones which are composed mainly of sodium bilirubinate and proteins since calcium ions and cholesterol are stabilized in dogs.

Animals↗
PubMed1996

AT1 receptor antagonist, TCV 116, does not prevent cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats.

1. We investigated the effects of direct blockade of angiotensin II (AngII) by a potent, non-peptide angiotensin II toff 1 (AT1) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats. 2. Six week old male Dahl salt-sensitive rats (n = 44) were fed a 4% salt diet and were simultaneously given various doses of TCV 116 orally for 7 weeks. Each control group received vehicle alone. 3. Dietary high salt intake elevated blood pressure continuously and caused left ventricular hypertrophy in rats treated with vehicle. TCV 116 had a minor effect on the rise in blood pressure. Left ventricular mass (left ventricular weight/body-weight) decreased slightly but not significantly, in rats treated with 3 mg/kg per day of TCV 116 (n = 8). Higher doses of TCV 116 (6 and 10 mg/kg per day; n = 8 each) did not show a decrease in left ventricular mass compared with the vehicle control. 4. These results suggest that AngII blockade has only minor effects on hypertension and on cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats and that the renin-angiotensin system may not contribute to the development of cardiac hypertrophy in Dahl salt-sensitive rats on a moderately high-salt diet.

Angiotensin Receptor Antagonists↗
PubMed1996

The Y chromosome region essential for spermatogenesis.

We analyzed DNA from 153 Japanese men with azoospermia or severe oligozoospermia whose Y chromosomes were cytogenetically normal. A total of 23 loci on the Y chromosome were examined: 15 loci within interval 6 including YRRM1 and DAZ, and 8 loci outside interval 6. Microdeletions were observed in 20 individuals. All deletions involved at least one locus within interval 6. The YRRM1 gene deletion was found in 4 patients, of whom 2 also lacked the SMCY gene. The remaining 16 individuals shared the absence of 10 loci between DYS7C and DYS239 including the DAZ gene. Among them, 13 were azoospermic while 3 showed a little sperm production, indicating that the common deletion resulted in phenotypic diversity. Since there is no region commonly deleted in all patients, azoospermia caused by deletion of the Y chromosome long arm may be genetically heterogeneous.

Adult↗
PubMed1996

Effect of endothelin 1 on fibrinolysis and plasminogen activator inhibitor 1 synthesis in rat mesangial cells.

Endothelins (ETs) have been known to have a variety of biological functions such as mitogenic stimulation, natriuresis and the stimulation of the proteolytic activity in addition to vasoconstrictive action, which may participate in the process of glomerular diseases pathophysiologically. In this study, the effects of ET-1 on fibrinolysis, plasminogen activator inhibitor 1 (PAI-1) synthesis and PAI-1 mRNA expression were examined in cultured rat mesangial cells (MCs). The addition of ET-1 (10(-11) to 10(-7) M) into MC cultures reduced fibrinolytic activities assayed by fibrin autography in a dose-dependent manner. For the assay of PAI-1 synthesis, MC culture media metabolically labeled with 35S-methionine were analyzed by SDS-PAGE with fluorography and immuno-precipitation using rabbit antirat PAI-1 antibody. Exposure to ET-1 for 24 h produced a clear dose-dependent effect on the PAI-1 release from the MCs. PAI-1 mRNA expression was also enhanced in parallel with the concentration of ET-1 in the conditioned media. These findings indicate that ET-1 participates in fibrinolysis and the PAI-1 synthesis by MCs, which may thus regulate the degradation of the extracellular matrix in the glomerular microenvironment.

Animals↗
PubMed1996

[Correlation between periventricular lucency and extracranial arterial lesions].

This study was done to clarify relationships between the degree of periventricular lucency (PVL), and lesions in the carotid arteries and the legs as detected with B-mode ultrasonography and the ankle pressure index, respectively. According to the distribution of PVL on computed tomography, 45 patients were divided into 2 groups: 22 patients with diffuse PVL (from the periventricular white matter to the subcortical area, DPVL group) and 23 patients with PVL localized in the frontal deep white matter (LPVL group). Plaque, defined as a thickened intima-media complex of 2.1 mm or more, was divided into two types; mural plaque and nodular plaque. Hypertension was more common in the DPVL group than in control groups, which consisted of 70 age-matched patients with cerebral thrombosis without PVL (CTH group) and 50 controls with neither PVL nor cerebrovascular lesions (NCT group). All patients in the DPVL group met the diagnostic criteria for Binswanger's disease proposed by Bennett DA. The incidence of low API indices (< 0.9) in the DPVL group (45%) was significantly higher than that in the NCT group, and it was slightly higher than that in the LPVL group. Carotid lesions, mainly nodular plaques, were seen in 82% of patients in the DPVL group and in 74% of those in the LPVL group; these percentages were significantly higher than those in the CTH (49%) and NCT (40%) groups. In particular, bilateral carotid lesions were more common in the DPVL group than in the other three groups. The degree of PVL correlated with lesions in the carotid arteries and the legs. These correlations suggest that the arterial lesions not only resulted from a risk factor (hypertension) for PVL, but also promoted PVL by causing extra- and intra-cranial arterial lesions. Furthermore, they imply that LPVL is a precusor to DPVL.

Aged↗
PubMed1996

[An elderly patient with Ph1-positive chronic myelomonocytic leukemia].

An 80-year-old man with leukocytosis was admitted to our hospital on February 20, 1995. There were no blasts in the peripheral blood, but leukocytosis, associated with marked monocytosis, anemia, and thrombocytopenia was observed. The bone marrow was hyperplastic and there was a slight decrease in megakaryocytes. The myelogram showed 5.6% blasts + promyelocytes, and there was no basophilia. Mild dysplasia of third-line cells was observed. Chromosome analysis yielded 47, XY, +8, t (9;22) (q34;q11), and the Philadelphia (Ph1) chromosome and trisomy 8 were detected. Fluorescence in-situ hybridization revealed a large ber. Because the French-American-British (FAB) cooperative group diagnostic criteria for chronic myelomonocytic leukemia (CMMoL) were fulfilled and the Ph1 chromosome was detected, a diagnosis of Ph1-positive CMMoL was made. Hydroxyurea was given for cytoreduction and the patient has been followed with no evidence of acute transformation for about one year. CMMoL is classified as a myelodysplastic syndrome. However, it is rare to find the Ph1 chromosome in patients with these syndromes, and there have been very few reports of its detection in CMMoL. CMMoL may not be a single disease entity, and it may be useful to investigate more cases like the present one, to reassess this disease.

Aged↗