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Biomedical subjects

M Iwai

Publications and source records attributed to M Iwai.

At least 109 records · Page 6Linked to original sources

Innervated radial thenar flap for sensory reconstruction of fingers.

A radial thenar flap, which is supplied by the superficial palmar branch of the radial artery and innervated by the superficial branch of the radial nerve, was used in four patients for sensory reconstruction of the fingers. Two patients had degloving injuries of the hand and two had amputation injuries of the thumb. Three of the cases underwent free-flap transfers, and one case underwent a reverse-flow island flap. The size of these flaps was about 3 x 5 cm except in one case, where a 15 x 5 cm flap combined with a radial forearm flap was used. Sensory reinnervation was excellent and donor site morbidity was minimal in all four cases. An innervated radial thenar flap from the ipsilateral hand offers an alternative choice to reconstruct large palmar defects of the fingers.

Adolescent↗

Exaggeration of acute liver damage by hepatic sympathetic nerves and circulating catecholamines in perfused liver of rats treated with D-galactosamine.

Effects of electrical stimulation of the hepatic nerves on acute liver damage were examined using isolated rat liver perfused in situ, 24 hours after intraperitoneal injection with D-galactosamine (800 mg/kg). The leakage of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) from the liver was used as markers of acute liver damage. In perfused livers after treatment with galactosamine, nerve stimulation (20 V, 20 Hz, 2 ms) increased the leakage of LDH and AST about 3-fold over the basal level accompanied by the decrease in flow rate, whereas with control livers the leakage of LDH and AST into the effluent was almost undetectable throughout the perfusion. The rapid increase in the leakage of LDH and AST was observed during nerve stimulation even under conditions where perfusion flow was maintained constant. Such effects of hepatic nerve stimulation on galactosamine-treated livers were mimicked well by infusion of noradrenaline or phenylephrine, and inhibited by the alpha1-antagonist bunazosin. Artificial reduction of perfusion flow alone did not induce the rapid leakage of LDH and AST into the effluent. On the other hand, low concentration (10 nmol/L) of noradrenaline only minimally decreased the flow rate but apparently augmented liver cell damage. The acute liver damage augmented by noradrenaline was dependent on extracellular Ca2+. These results indicate that in the liver, already having been injured slightly, the activation of hepatic sympathetic nerves and circulating catecholamines exaggerates acute liver damage through an action on liver cells, which depends on the influx of extracellular Ca2+.

Adrenergic alpha-Agonists↗

Antitumor activity of 2-amino-4,4 alpha-dihydro-4 alpha, 7-dimethyl-3H-phenoxazine-3-one, a novel phenoxazine derivative produced by the reaction of 2-amino-5-methylphenol with bovine hemolysate.

2-Amino-4,4 alpha-dihydro-4 alpha,7-dimethyl-3H-phenoxazine-3-one (Phx) was synthesized by the reaction of 2-amino-5-methyl-phenol with bovine hemolysates. Since Phx is a phenoxazine derivative like actinomycin D, which exerts a strong anti-tumor effect by intercalating DNA, we examined the effects of Phx on cell proliferation and cell cycle progression in human epidermoid carcinoma cells (KB cells). Phx inhibited the proliferation of Kb cells in a dose-dependent manner. When KB cells were incubated for 9 h with medium containing 50 microM Phx, a transient accumulation of cells in S and G2/M phase was observed and at 24 h many of cells had lower DNA content. Although Phx had antitumor activity, the drug did not intercalate DNA, showing a different mode of action from actinomycin D.

Animals↗

Fibrotic focus in invasive ductal carcinoma: an indicator of high tumor aggressiveness.

Histological examination of invasive ductal carcinoma of the breast often demonstrates the presence of an extensive central fibrotic focus (FF). The clinicopathological significance of the FF, or scar, in primary invasive ductal carcinoma is still ambiguous. One hundred and fifty-three cases of invasive ductal carcinoma (IDC) were classified into two groups, those with and those without FF. The differences in frequency of immunohistochemically detected overexpression of c-erbB-2 protein and nuclear accumulation of p53 protein, and the labeling index of proliferating cell nuclear antigen (PCNA), as well as histopathological parameters were compared between these two groups. IDCs smaller than 50 mm with FF showed a higher frequency of high-grade tumors, a higher frequency of lymph node metastasis, and a significantly higher frequency of c-erbB-2 protein overexpression than those without FF. In tumors of 20 mm or less, the incidence of nuclear accumulation of p53 protein was significantly higher in tumors with than those without FF. Tumors with FF showed a significantly higher PCNA labeling index than those without FF, regardless of tumor size. The present results indicate that the presence of FF is an important clinicopathological parameter associated with a higher degree of malignancy in IDCs, especially those smaller than 50 mm. Therefore, dividing IDCs into those with and those without FF appears to be meaningful clinicopathologically.

Adult↗

Synthesis of secretory protein in regenerating liver of rat after partial hepatectomy.

Albumin immunoreactivity in the liver was examined on days 2, 5 and 10 after two-thirds partial hepatectomy by light and ultrastructural immunoperoxidase methods and the ultrastructural area of the rough endoplasmic reticulum (ER) in hepatocytes was measured. Albumin immunoreactivity was seen in the rough ER and Golgi apparatus of all hepatocytes in the hepatectomized liver and ultrastructural analysis showed a significantly greater area of rough ER on day 5 than on days 2 or 10. Albumin mRNA was studied by the in situ hybridization technique using radioisotopes and their numbers were determined visually. Albumin mRNA was present as grains in all hepatocytes and the grains varied in number during regeneration of the liver, being more abundant on day 5 than on days 2 or 10. The activity of [3H]-leucine incorporated into albumin synthesis, an indicator of translational activity, was higher on days 5 and 10 than on day 2 and was highest on day 5. In conclusion, albumin synthesis varied during liver regeneration after partial hepatectomy, being reduced at the peak of cell proliferation on day 2 and being most active on day 5.

Albumins↗

Elevated amylase is related to the development of respiratory failure in organophosphate poisoning.

1. A retrospective study of organophosphate (OP) poisoning in the intensive care unit was performed to analyze the incidence of respiratory failure. 2. The patients were treated initially with gastrointestinal decontamination including gastric lavage and the administration of activated charcoal with cathartic. Further management included intravenous pralidoxim and atropine and ventilatory support. 3. Of the 32 OP poisoning patients, 16 patients developed respiratory failure and received ventilatory support. 4. An increase in plasma amylase above the normal range on the day of admission was related to the development of respiratory failure. 5. In OP poisoning, the elevation of amylase level was predictive of the subsequent respiratory failure.

Adult↗

Requirement for transglutaminase in progesterone-induced decidualization of human endometrial stromal cells.

Differentiation of endometrial stromal cells (decidualization) is essential for embryo implantation and maintenance of pregnancy. By sequential complementary DNA subtractive hybridization, one of the messenger RNAs (mRNA) induced by progesterone in human endometrial stromal cells decidualized in vitro was identified as that of a tissue transglutaminase type II (TGase). TGase mRNA was induced within 6 h after the addition of progesterone to the culture, and the effect was dose dependent. Both the TGase inhibitor monodansylcadaverine and oligodeoxynucleotide complementary to the TGase mRNA inhibited the decidualization, as assessed by PRL production and morphological transformation. Expression of TGase mRNA in human decidua and endometria exposed to high levels of progesterone in vivo was demonstrated by Northern blotting and in situ hybridization. These data suggest that TGase is necessary for the decidualization of human endometrial stromal cells and that clarification of the mechanism of action of TGase will facilitate further insight into the diagnosis and treatment of infertility.

Base Sequence↗

[Use of AmpliSensor to quantitate gene expression in small amounts of samples: comparison with the quantitative RT-PCR method using CCD imaging system].

Quantitative PCR methods are potentially useful for determining levels of specific gene expression and gene dosage. Previously we developed a non-radioisotopic quantitative RT-PCR method by utilizing the PCR amplification kinetics and CCD image analyzer. Recently, based on the principle of fluorescence energy transfer, the AmpliSensor system that can quantitate the PCR products concurrent to amplification in a single reaction vessel has been described. Herein, we compared the results obtained by both methods. cDNAs were synthesized from 10 human endometrial biopsy specimens. Aliquots of cDNA were used for quantitation by gel/image analyzer or AmpliSensor assay system. For estimation of the initial amount of the template(I), regression equations of the form:y = I x Ex, where y is the amount of PCR products and x is the number of cycles, were fitted to the data in the linear portion of the semi-logarithmic graphs. The relative levels of beta-actin cDNA estimated by AmpliSensor assay system was in good agreement (r = 0.91) with those of the gel/image analyzer assay system, which is cumbersome, time-consuming and needs post-amplification procedures. The AmpliSensor assay is suitable for a quantitative PCR assay based on PCR kinetics, and is applicable for diagnostic testings.

Actins↗

The mechanism of action of hepatic sympathetic nerves on ketone-body output from perfused rat liver. The effect of the interaction of noradrenaline with ATP on the release of beta-hydroxybutyrate.

The regulatory mechanism of ketone-body output by the hepatic sympathetic nerves was studied in rat liver perfused in situ. Enrichment of the perfusion medium with 1 mM octanoate increased the basal ketone-body output from the liver up to 1.5 mumol.min-1.g liver-1. Under these conditions, electrical stimulation of the hepatic nerves (20 V, 20 Hz, 2 ms) decreased the output of both acetoacetate and beta-hydroxybutyrate, and was accompanied by an accumulation of beta-hydroxybutyrate in the liver. The effects of nerve stimulation were inhibited by the alpha 1-antagonist bunazosin (10 microM). However, noradrenaline, a typical sympathetic neurotransmitter, at a concentration of 1 microM decreased the output of acetoacetate but did not affect beta-hydroxybutyrate output. Prostaglandin F2 alpha at a concentration of 10 microM produced an effect similar to treatment with noradrenaline, without a decrease in beta-hydroxybutyrate output. ATP at 50 microM, however, decreased the output of both acetoacetate and beta-hydroxybutyrate and increased the tissue concentration of beta-hydroxybutyrate, mimicking the effect of nerve stimulation. Moreover, in the presence of 0.2 microM ATP, a concentration that produced neither metabolic nor hemodynamic changes, noradrenaline (1 microM) was shown to decrease the beta-hydroxybutyrate output. These results indicate the possible involvement of ATP in the action of hepatic sympathetic nerves on beta-hydroxybutyrate output from the liver, presumably through its interaction with noradrenaline.

3-Hydroxybutyric Acid↗

Antimicrotubule effects of the novel antitumor benzoylphenylurea derivative HO-221.

The antitumor action of HO-221, a novel benzoylphenylurea derivative, was studied. The in vitro cytotoxic strength of HO-221 was investigated, as measured by IC50 values, compared with those of other drugs with different action mechanisms, using Chinese hamster lung (CHL) cells, mouse leukemia L1210 cells and human promyelocytic leukemia HL-60 cells. Morphological alterations following treatment were observed under a phase contrast microscope, and the mitotic index was determined at regular intervals to check for accumulation of metaphase cells. HO-221 was found to have a very strong toxic effect on all cell types, equal to that of the spindle poisons used as controls. HO-221 also produced the same specific morphological changes as the spindle poisons, with a significant accumulation of metaphase cells. A chromosome analysis of treated cells showed that HO-221 frequently induced polyploid and aneuploid cells, but without accompanying chromosome-breaking activity. An in vivo mouse bone marrow micronucleus assay was also carried out. The assay allowed the in vivo identification of a chromosome breaker or a spindle poison through the measurement of the relative sizes of micronuclei produced and erythrocytes. HO-221 was found frequently to induce relatively large micronuclei, an action regarded as specific to spindle poisons. It was thus demonstrated that HO-221 acts as a spindle poison both in vitro and in vivo. In order to investigate the mechanism of this action, a study of tubulin assembly using purified calf brain tubulin was carried out, which demonstrated clearly that HO-221 inhibits microtubule assembly. A detailed investigation of the action mechanism of HO-221 as a spindle poison is now called for.

Animals↗

Expression of messenger ribonucleic acid for gonadal steroid receptors in the human pelvic peritoneum.

OBJECTIVE: To investigate the expression of messenger RNA (mRNA) for gonadal steroid hormone receptors in the human pelvic peritoneum. DESIGN: Analysis of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) mRNA expressions in the pelvic peritoneum was carried out using the quantitative reverse transcription-polymerase chain reaction (PCR) method. SETTING: Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, Japan. PATIENTS: Pelvic peritoneal tissues from patients with (n = 10) and without (n = 10) endometriosis who had undergone gynecological surgery were studied. RESULTS: Estrogen receptor, PR, and AR mRNAs were detected in all pelvic peritoneal samples analyzed. In the pelvic peritoneum of patients without endometriosis, ER mRNA levels were significantly lower in the luteal phase than in the follicular phase. This cyclic profile of ER mRNA expression was not observed in the pelvic peritoneum of patients with endometriosis. During the follicular phase, ER mRNA levels in the pelvic peritoneum of patients with endometriosis were significantly lower than those of patients with endometriosis. Neither PR nor AR mRNA levels in the pelvic peritoneum of either patient group showed significant cyclic variations throughout the menstrual cycle. A comparison of PR and AR mRNA levels in the pelvic peritoneum of the endometriosis and the nonendometriosis groups revealed no significant differences. CONCLUSIONS: These data indicate a decrease in ER gene expression in the pelvic peritoneum of patients with endometriosis during the follicular phase. This suggests that the possible responsiveness of peritoneal cells to estrogen may be related to the occurrence and/or development of endometriosis.

Adult↗

Expression of leukaemia inhibitory factor (LIF) receptor in human placenta: a possible role for LIF in the growth and differentiation of trophoblasts.

Leukaemia inhibitory factor (LIF) is a cytokine that displays multiple activities in various tissues and is essential for blastocyst implantation in mice. In the human uterus, LIF is expressed in endometrial tissue and the decidua. To elucidate the role it plays, the mRNA levels for two LIF receptor (R) subunits, LIF-R and gp130, were examined in human endometrium, placenta and decidua by Northern blot hybridization. The expression of LIF-R gene was detected in the chorionic villus during the first trimester, in term placenta, and at lower levels in the decidua. The expression of LIF-R gene was not detectable in non-pregnant endometrium. The expression of the gp130 gene was detected in all tissues examined. During pregnancy, there was no significant change in the mRNA concentration of LIF-R in the placenta, while that of gp130 increased after the second trimester. The human choriocarcinoma cell line, BeWo, was found to express LIF-R and gp130. LIF inhibited forskolin-induced human chorionic gonadotrophin (HCG)-beta production by BeWo in a dose-dependent manner, and it ameliorated forskolin-induced growth suppression. These findings suggest that LIF plays a regulatory role in trophoblast growth and differentiation during pregnancy in human placenta.

Base Sequence↗

Efficacy of an epidural test dose in adult patients anesthetized with isoflurane: lidocaine containing 15 micrograms epinephrine reliably increases arterial blood pressure, but not heart rate.

When continuous epidural anesthesia is combined with general anesthesia, the only objective sign of intravascular migration of the epidural catheter are the increments of heart rate (HR) or arterial blood pressure after a local anesthetic test dose containing epinephrine. However, the efficacy of a simulated intravenous (IV) test dose in adult patients under general anesthesia has not been determined. Thirty adult patients were randomly assigned to one of two groups, each of which was anesthetized with 1% end-tidal isoflurane and nitrous oxide after endotracheal intubation. The epinephrine group (n = 15) was given 3 mL of 1.5% lidocaine with epinephrine (1:200,000) IV to simulate an IV administered epidural test dose. The saline group (n = 15) was identical to epinephrine group, but received 3 mL of normal saline IV. HR and arterial blood pressure were measured at 20-s intervals for 4 min after IV injection. In the epinephrine group, significant increases in HR compared with the baseline value were observed from 40 to 80 s after the IV test dose with a mean maximum HR increase of 24 +/- 2 bpm (mean +/- SEM) occurring at 48 +/- 3 s. However, 5 of 15 patients in the epinephrine group developed HR increments smaller than 20 bpm (sensitivity 67%). Since HRs were essentially unchanged in the saline group, specificity, positive predictive value (+PV), and negative predictive value (-PV) were 100%, 100%, and 75%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sinus node recovery function is relatively well preserved under halothane anaesthesia in children.

The purpose of this study was to evaluate the effect of halothane on sinus node recovery time (SNRT). Nine children with congenital heart disease scheduled for cardiac catherization were studied. After the routine procedure, the sinus node was paced at rates of 120, 150 and 180 beats per minute. SNRTs were measured with control conditions and under 1 MAC halothane anaesthesia. The absolute SNRT was standardized and expressed as '%SNRT' and 'Corrected SNRT (CSNRT)'. CSNRT was slightly prolonged by halothane (P = 0.042), while the %SNRT was not significantly prolonged. We conclude that the recovery function of the sinus node is relatively well preserved under 1 MAC halothane in children.

Anesthesia, Inhalation↗

Induction of tissue inhibitor of metalloproteinase 3 gene expression during in vitro decidualization of human endometrial stromal cells.

Endometrial stromal differentiation (decidualization) is essential for implantation of the developing blastocyst. To investigate the process of progesterone (P)-induced decidualization of human endometrial stromal cells (ESC), a complementary DNA library enriched with P-induced genes was constructed from cultured human ESC by subtractive hybridization and the polymerase chain reaction. One of the isolated clones was the complementary DNA for the tissue inhibitor of metalloproteinase-3 (TIMP-3), a recently identified member of the human TIMP family. When human ESC were cultured in the presence of P for 6 days, the induction of TIMP-3 messenger RNA (mRNA) expression was observed by Northern blotting. In contrast, the marked induction of PRL mRNA expression and morphological changes were observed after 9 days of culture. P-induced TIMP-3 mRNA expression was dose dependent, and this induction was inhibited by the antiprogestin RU486. Estrogen did not induce TIMP-3 mRNA expression under similar conditions. In situ hybridization analysis of endometria from nonpregnant women revealed that the TIMP-3 mRNA expression was restricted to predecidualized stromal cells. At the feto-maternal interface, TIMP-3 expression was observed in fetal extravillous trophoblasts that had invaded the maternal decidual tissues as well as in the maternal decidual cells. These findings suggest that TIMP-3 is a sensitive indicator of ESC decidualization, and that the induction of TIMP-3 expression in decidual cells and trophoblasts may be important in the regulation of trophoblast invasion.

Adult↗

Regulation of sex steroid receptor gene expression by progesterone and testosterone in cultured human endometrial stromal cells.

Progesterone (P) is known to regulate sex steroid receptors in uterine cells. However, its precise regulation at the messenger ribonucleic acid (mRNA) level is unclear. In this study we examined the effects of P and testosterone (T) on the regulation of sex steroid receptors in cultured human endometrial stromal cells (ESC), using the quantitative reverse transcriptase polymerase chain reaction method. We isolated ESC from human endometrial tissues and cultured them with or without P (10(-6) mol/L) or T (10(-8) mol/L) for 9 days. Incubation with P decreased progesterone receptor (PR), estrogen receptor, and androgen receptor mRNA levels in cultured human ESC to 0.56 +/- 0.04-, 0.53 +/- 0.08-, and 0.84 +/- 0.04-fold (mean +/- SE), respectively. T also decreased PR, estrogen receptor, and androgen receptor mRNA levels in cultured human ESC to 0.48 +/- 0.06-, 0.52 +/- 0.05-, and 0.82 +/- 0.04-fold (mean +/- SE), respectively. These decreases by P and T occurred in a dose-dependent manner. We also examined the sex steroid receptor levels in human ESC cultured for 0, 3, 6, and 9 days. The PR mRNA level in ESC without P was increased in a time-dependent manner. This increase was also inhibited by P, and the mRNA level in the presence of P was almost constant throughout the culture period. Our results demonstrated that P or T is a regulator of sex steroid receptors in ESC and that this regulation may influence the responsiveness to P of decidual change in ESC.

Base Sequence↗