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Biomedical subjects

M Maekawa

Publications and source records attributed to M Maekawa.

At least 19 recordsLinked to original sources

Efficacy of gemtuzumab ozogamicin on ATRA- and arsenic-resistant acute promyelocytic leukemia (APL) cells.

Acute promyelocytic leukemia (APL) cells express a considerable level of CD33, which is a target of gemtuzumab ozogamicin (GO), and a significantly lower level of P-glycoprotein (P-gp). In this study, we examined whether GO was effective on all-trans retinoic acid (ATRA)- or arsenic trioxide (ATO)-resistant APL cells. Cells used were an APL cell line in which P-gp was undetectable (NB4), ATRA-resistant NB4 (NB4/RA), NB4 and NB4/RA that had been transfected with MDR-1 cDNA (NB4/MDR and NB4/RA/MDR, respectively), ATO-resistant NB4 (NB4/As) and blast cells from eight patients with clinically ATRA-resistant APL including two patients with ATRA- and ATO-resistant APL. The efficacy of GO was analyzed by (3)H-thymidine incorporation, the dye exclusion test and cell cycle distribution. GO suppressed the growth of NB4, NB4/RA and NB4/As cells in a dose-dependent manner. GO increased the percentage of hypodiploid cells significantly in NB4, NB4/RA and NB4/As cells, and by a limited degree in NB4/MDR and NB4/RA/MDR cells. Similar results were obtained using blast cells from the patients with APL. GO is effective against ATRA- or ATO-resistant APL cells that do not express P-gp, and the mechanism of resistance to GO is not related to the mechanism of resistance to ATRA or ATO in APL cells. Leukemia (2005) 19, 1306-1311. doi:10.1038/sj.leu.2403807; published online 26 May 2005.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Development of the amygdalohypothalamic projection in the mouse embryonic forebrain.

The amygdalohypothalamic projection, a major component of the stria terminalis, is involved in the conduction of emotional and olfactory information integrated in the amygdala to the hypothalamus to elicit emotional reactions. Despite the extensive studies on functional aspects of the amygdaloid complex, developmental mechanisms of the amygdala and related structures are still poorly understood. To investigate the development of the amygdalohypothalamic projection in the mouse embryonic brain, carbocyanine dye was applied to the amygdala to label the growing axons anterogradely and to the hypothalamus to label the amygdaloid neurons retrogradely. The initial outgrowth of the stria terminalis was found to be as early as E11.5. The pathway crossed in a saddle over the internal capsule, another prominent connection in the developing forebrain of the mammalian embryo. Bipolar immature neurons were distributed along the stria terminalis at the telencephalo-diencephalic boundary, and the internal capsule was also surrounded by these cells. These cells expressed immunoreactivities to calretinin and the lot-1 antigen which has been shown to be involved in guidance of the developing lateral olfactory tract. Ultrastructural analysis revealed an adherens-like junction between the stria terminalis and the apposed cells, implying contact-mediated guidance. These results suggest that, in the development of the stria terminalis, the axonal outgrowth is guided by a mechanism similar to that of the developing lateral olfactory tract, a major amygdalopetal connection.

Adherens Junctions↗

Influence of socio-economic background and antenatal care programmes on maternal mortality in Surabaya, Indonesia.

OBJECTIVE: To determine the risk factors, such as socio-economic background, quality of antenatal care and availability of family planning, responsible for high maternal mortality in Surabaya, Indonesia. METHODS: The study used a case-control design. Descriptive, bivariate and multivariate analyses were carried out, comparing 59 maternal deaths and 177 women survivors in the referral hospital, from 1996 to 1999. RESULTS: The risk factors for maternal mortality were: living outside of Surabaya [odds ratio (OR) = 11.7, 95% confidence interval (CI) = 5.0-29.2], unemployment (OR = 4.4, 95% CI = 1.7-13.8), unavailability of toilet facilities (OR = 2.9, 95% CI = 1.0-7.7), <4 antenatal visits (OR = 2.5, 95% CI = 1.1-5.5) and initial visit to antenatal care facilities after the fourth month of pregnancy (OR = 3.0, 95% CI = 1.3-7.0). There was no significant association between maternal mortality and the availability of family planning. CONCLUSION: Low socio-economic background and the availability of antenatal care have a significant influence on maternal mortality in Surabaya, Indonesia.

Adult↗

Reduced effect of gemtuzumab ozogamicin (CMA-676) on P-glycoprotein and/or CD34-positive leukemia cells and its restoration by multidrug resistance modifiers.

Gemtuzumab ozogamicin (CMA-676), a calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, has recently been introduced clinically as a promising drug for the treatment of patients with acute myeloid leukemia (AML), more than 90% of which express CD33 antigen. However, our recent study suggested that CMA-676 was excreted by a multi- drug-resistance (MDR) mechanism in P-glycoprotein (P-gp)-expressing leukemia cell lines. We analyzed the in vitro effects of CMA-676 on leukemia cells from 27 AML patients in relation to the amount of P-gp, MDR-associated protein 1 (MRP1), CD33 and CD34, using a multi-laser-equipped flow cytometer. The cytocidal effect of CMA-676, estimated by the amount of hypodiploid portion on cell cycle, was inversely related to the amount of P-gp estimated by MRK16 monoclonal antibody (P = 0.004), and to the P-gp function assessed by intracellular rhodamine-123 accumulation in the presence of PSC833 or MS209 as a MDR modifier (P = 0.0004 and P = 0.002, respectively). In addition, these MDR modifiers reversed CMA-676 resistance in P-gp-expressing CD33(+) leukemia cells (P = 0.001 with PSC833 and P = 0.0007 with MS209). In CD33(+) AML cells from 13 patients, CMA-676 was less effective on CD33(+)CD34(+) than CD33(+)CD34(-) cells (P = 0.002). PSC833 partially restored the effect of CMA-676 in CD33(+)CD34(+) cells. These results suggest that the combined use of CMA-676 and a MDR modifier will be more effective on CD33(+) AML with P-gp-related MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Development of the blood-testis barrier in the mouse is delayed by neonatally administered diethylstilbestrol but not by beta-estradiol 3-benzoate.

A group of newborn mice were treated with 1 micro g dose-1 individual-1 of diethylstilbestrol (DES) on alternate days, from days 1 to 11 postnatally. Another group of mice were treated similarly with 125 ng dose-1 individual-1 of beta-estradiol 3-benzoate (E2B). The testes were sequentially examined up to 84 days of age using light and electron microscopy. Spermatogenic cells in the DES-treated mice differentiated normally from birth until 17 days of age, when they differentiated into pachytene spermatocytes and remained at this meiotic prophase for the next 10 days approximately. The cells then began to differentiate further, ultimately forming spermatozoa by 49 days of age. Confocal and electron microscopy showed that the blood-testis barrier did not form until 28 days of age in the DES-treated mice, and a delay in the functional maturation of this structure, as the blood-testis barrier, was confirmed by intercellular tracer experiments. The arrest of spermatogenesis at the meiotic prophase may have been attributable to the DES-induced defective formation of the blood-testis barrier. No delay of the blood-testis barrier formation was detected in the E2B-treated mice. Thus, DES and E2B, both of which are known as potent oestrogenic compounds, had different effects on the Sertoli cells.

Animals↗

Comparison of a new system (Compactdry SCD) with conventional methods for quantitative urine cultures.

AIMS: Compactdry SCD, a new quantitative, ready-to-use and self-diffusible dry medium sheet urine culture system, was compared with conventional methods to evaluate the results of quantitative urine cultures. METHODS & RESULTS: Compactdry SCD was tested on 25 urine specimens, and results compared with those of traditional culture methods. The results from Compactdry SCD analysis correlated well with those from the standard plate count (SPC) method. In fact, the correlation was stronger than that dipslide systems and SPC. Even low-count bacteriuria (< 103 cfu ml(-1) and mixed bacteriuria were detected by Compactdry SCD. CONCLUSIONS: The Compactdry SCD system provides results comparable to those obtained by SPC: simple interpretation, ease of use, long-term storage and good sensitivity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report suggesting that the Compactdry SCD system has many advantages over traditional quantitative urine culture methods and that it is both appropriate and practical for clinical use.

Bacteria↗

Effect of concentrate level and feeding management on chewing activities, saliva production, and ruminal pH of lactating dairy cows.

Eight ruminally cannulated lactating Holstein cows were used in a double 4 x 4 Latin square to determine the effects of 1) proportion of barley silage [40, 50, and 60% of dry matter (DM)] in the diet, and 2) feeding a total mixed ration (TMR) compared with separate ingredients (SI) on chewing activities, saliva production, and ruminal pH. Although cows fed SI were offered a diet containing 50% silage, they actually consumed a diet containing 43% silage (DM basis). Dry matter intake and milk yield were similar for all diets (18.2 kg of DM/d and 27.2 kg/d, respectively). Cows fed the 40% silage TMR spent more time eating than cows fed SI (243 vs. 198 min/d), but rumination time was similar (546 min/d). Eating time was similar among the TMR diets, but rumination time increased from 498 to 516 and 584 min/d as silage in the TMR increased from 40 to 50, and then to 60%, respectively. The secretion of saliva per gram of feed was 4.43, 3.18, and 1.19 ml/g of DM with consumption of silage, TMR, and concentrate, respectively. Resting salivation rate was similar for all diets (101 ml/min). Regardless of the diet, cows secreted 239 +/- 17 L/d of saliva, and ruminal pH was below 5.8 for 10 h/d. Results indicated increased chewing time did not increase total daily saliva secretion because increased eating and ruminating saliva was associated with decreased resting saliva. Feeding SI increased the risk of acidosis, because cows ate a higher proportion of concentrate than intended.

Animal Feed↗

Chewing activity, saliva production, and ruminal pH of primiparous and multiparous lactating dairy cows.

Four multiparous (MP) and four primiparous (PP) ruminally cannulated lactating Holstein cows were used in a double 4 x 4 Latin square design to study the chewing behavior, saliva production, and ruminal pH of cows in the first or subsequent lactation. Cows were fed one of four diets; three total mixed rations containing 40, 50, or 60% silage (DM basis), and a separate ingredient diet containing 50% concentrate. Dry matter intake was higher for MP cows than for PP cows (19.2 vs. 17.1 kg/d) but not as a percentage of body weight (2.97 +/- 0.06%). Multiparous cows spent more time eating than PP cows (260 vs. 213 min/d, respectively), even after adjustment for dry matter intake (13.8 vs. 12.4 min/kg DM). Multiparous cows also spent more time ruminating per day than PP cows (560 vs. 508 min/d, respectively). Eating salivation rate was not affected by parity, but resting salivation rate was higher for MP cows than for PP. Although MP cows spent more time chewing than PP cows, total daily saliva production was only numerically higher for MP cows because the increase in saliva produced during chewing was accompanied by a decrease in saliva produced during resting. Furthermore, pH profiles tended to be lower for MP cows than for PP cows. Multiparous cows may have a greater risk of incurring acidosis than PP cows because increased salivary secretion associated with increased chewing may not sufficiently compensate the increment of fermentation acids produced in the rumen due to high feed intake.

Animals↗

A p53 polymorphism associated with increased risk of hepatitis C virus infection.

Incidence of polymorphisms on exon 4 (CGC vs. CCC, p53Arg vs. p53Pro, A2 allele vs. A1 allele at codon 72, respectively) of the p53 gene was compared in 75 cases with hepatitis C virus (HCV) infection and 232 noninfected control subjects in a defined geographical area in Japan. Polymorphism was analyzed by the polymerase chain reaction-single strand conformation polymorphism method using DNA from peripheral blood leukocytes. When all cases and controls were compared, there was no significant correlation between hepatitis C virus (HCV) infection and the p53 polymorphism in question. However, when male cases infected with HCV type 1b, the most common viral genotype, were compared with controls matched by sex and age, significantly higher homozygotes for p53Pro were found in cases compared with controls (P=0.039). Significantly higher allelic frequency of this polymorphism was also observed with cases (P=0.010). We found no significant statistical difference between the p53 polymorphism and other genotypes of HCV (2a, 2b and others). On the basis of our study we believe there exists a significant correlation between male homozygotes for p53Pro with HCV type 1b infection.

Codon↗

N-Methyl-D-aspartate-induced c-Fos expression is enhanced in the forebrain structures related to emotion in Fyn-deficient mice.

Fyn tyrosine kinase is thought to be involved in the control of neuronal intracellular signal transduction elicited by neurotransmitter stimulation. Emotional disorders, such as fearfulness in Fyn-deficient mice, prompted us to investigate the neural mechanisms that lead to defective emotional expression by using functional neuroanatomical methods. In order to examine the reactivity of a specific neural network to excitatory neurotransmitter administration, we mapped the distribution of c-Fos-immunoreactive neurons after administering N-methyl-D-aspartate (NMDA) to control and mutant mice at the subthreshold dose for seizure induction. The induction of neuronal c-Fos-immunoreactivity by NMDA was enhanced in the Fyn-deficient mice, and there was a much greater increase in immunopositive neurons in certain well-defined areas, such as the amygdaloid medial nuclear subdivisions, hypothalamic paraventricular nucleus, and midbrain periaqueductal gray, of the mutant. NMDA-induced c-Fos expression was attenuated by pretreatment with D-(-)-2-amino-5-phosphonovaleric acid, a competitive NMDA antagonist, both in the control and the mutant mice. These findings suggest that the excitability of the projection system from the amygdala to the hypothalamus and midbrain, the main pathways of emotional expression, is enhanced in Fyn-deficient mice.

Amygdala↗

Spiral, herringbone, and triple-decker silver(I) complexes of benzopyrene derivatives assembled through eta(2)-coordination.

Three novel silver(I) complexes with benzopyrene derivatives were synthesized and characterized in this paper. Treatment of AgClO(4)*H(2)O with 7-methylbenzo[a]pyrene (L(1)) afforded [Ag(2)(L(1))(toluene)(0.5)(ClO(4))(2)](n)() (1) which exhibits a 2-D sheet structure with double-stranded helical motifs. Reaction of AgCF(3)SO(3) with dibenzo[b,def ]chrysene (L(2)) gave rise to an unprecedented cocrystallization structure, ([Ag(2)(L(2))(CF(3)SO(3))(2)][Ag(2)(toluene)(2)(CF(3)SO(3))(2)])(n)() (2), formed by a 2-D neutral lamellar polymer and a 1-D neutral rodlike one. The ligand benzo[e]pyrene (L(3)) coordinated to silver(I) ions generating a closed triple-decker tetranuclear complex [Ag(4)(L(3))(4)(p-xylene)(ClO(4))(4)] (3) which can be regarded as a stacking polymer owing to existing intermolecular pi-pi stack interactions. The structural diversity of the silver(I) coordination polymers with polycyclic aromatic hydrocarbons is not only related to the stacking patterns of free polycyclic aromatic hydrocarbons in the crystalline state, but also the geometric shapes of the molecules for these free ligands. In addition, the coordination of solvents to metal ions plays a crucial role in the formation of the unprecedented coordination polymeric architectures. The ESR spectroscopic results, conductivity, and synthesis properties are also discussed.

Journal Article↗