Search PubMed⌕ Search

Biomedical subjects

M Nagano

Publications and source records attributed to M Nagano.

At least 127 records · Page 7Linked to original sources

[Reproductive histories of coastal and inland women with and without exposure to methylmercury in Kumamoto].

To examine the difference in abnormal conception by region and generation and its possible causes in the town of Tsunagi, which experienced intensive methylmercury-pollution during the 1950s and 1960s, reproductive histories of 109 women in 3 coastal villages and 64 controls in 5 inland villages were obtained by visit- and interview-study in 1991. There were about 290 married women in respective regions. The subjects were divided into 4 age groups to form 10-year-birth cohorts from 1915 to 1954. The rate of sterility and those who had never become pregnant after marriage, did not differ between coastal (7.3%) and inland women (6.3%). The younger the birth cohort, the smaller the total number of conceptions. The rate of abnormal conception, i.e., abnormal conception (abortion+stillbirth) per normal conceptions (total number of conceptions--number of artificial abortions), in the coastal women tended to increase after the 1960s with its peak (19%) in 1965-70. The rate in the inland women was already as high as 15% in 1945-50, and was constantly above 10% afterwards. However, it did not differ between the two groups during 1950-1970, when severe methylmercury-pollution occurred in the area. Breakdown of the abnormal conceptions in the inland women showed 4 stillbirths and 19 abortions, among the latter of which 16 were related to climbing up and down the hills to fetch water, hard agricultural work and agitation. The abnormal conceptions in the coastal women showed 3 stillbirths and 19 abortions. Sixteen of the latter were not related to any specific physical causes.

Aged↗

Prolactin receptor gene expression in the fetal rat.

The expression of mRNA encoding the long and short forms of the prolactin receptor (PRLR) in the fetal rat was examined using the method of reverse transcription-PCR. A 742 bp PCR product encoding the extracellular and transmembrane domains of the PRLR was detected in maternal and fetal liver and in fetal adrenal, kidney, small intestine, pancreas, brain, pituitary, thymus, lung and skin but not in fetal heart. Highest levels of the 742 bp PRLR transcript were detected in fetal adrenal (45.2% of levels in maternal liver), kidney (27.2%), small intestine (21.7%), pancreas (18.3%) and liver (10.8%), and tissue levels of the 742 bp product correlated positively (r = 0.92, P < 0.01) with the specific binding of the fetal lactogenic hormone rat placental lactogen II (rPL-II). These findings suggest that the PRLR may serve as a physiological binding protein for rPL-II in the rat fetus. There were striking differences in the relative expression of mRNA encoding the long and short forms of the PRLR. The long form of the receptor was expressed in maternal liver and placenta and in all fetal tissues studied except fetal heart. The short form of the receptor was also detected in maternal liver and placenta and fetal adrenal, kidney, small intestine, liver and thymus; in contrast, there was limited expression of the short-form of the receptor in fetal pancreas, pituitary and brain and no short form transcripts were detected in fetal lung, skin or heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Modifications of neurofilament proteins by possible metabolites of allyl chloride in vitro.

Chronic exposure to allyl chloride (ALL) is known to produce a central-peripheral distal axonopathy. In relation to the mechanism(s), the present study was conducted to examine the abilities of ALL and its putative metabolites, i.e., epichlorohydrin, glycerol alpha-monochlorohydrin, allyl alcohol and acrolein to cross-link proteins in vitro. Neurofilament-riched cytoskeletal proteins (1mg/ml) and ovalbumin (10mg/ml) were incubated with 160 mM tested chemicals except for acrolein at 0.5 mM and 1 mM. Time-dependent studies by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed that not only ALL, but also acrolein and epichlorohydrin exerted chemical modifications on axonal cytoskeletal proteins; while only acrolein-treated ovalbumin could manifest evidence of polymerization of the protein. Immunoblotting of PAGE-separated proteins confirmed that the high molecular weight proteins on the top of SDS-PAGEs were NF antigen-contained covalent cross-linked materials.

1-Propanol↗

Alterations in G-proteins in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters.

In order to explain the attenuated sympathetic support during the development of heart failure, the status of beta-adrenergic mechanisms in the failing myocardium was assessed by employing cardiomyopathic hamsters (155-170 days old) at moderate degree of congestive heart failure. The norepinephrine turnover rate was increased but the norepinephrine content was decreased in cardiomyopathic hearts. The number and the affinity of beta receptors in the sarcolemmal preparations were not changed in these hearts at moderate stage of congestive heart failure. While the basal adenylyl cyclase activity was not altered in sarcolemma, the stimulation of enzyme activity by NaF, forskolin, Gpp(NH)p or epinephrine was depressed in hearts from these cardiomyopathic hamsters. Since G-proteins are involved in modifying the adenylyl cyclase activity, the functional and bioactivities as well as contents of both Gs and Gi proteins were determined in the cardiomyopathic heart sarcolemma. The functional stimulation of adenylyl cyclase by cholera toxin, which activates Gs proteins, was markedly depressed whereas that by Pertussis toxin, which inhibits Gi proteins, was markedly augmented in cardiomyopathic hearts. The cholera toxin and pertussis toxin catalyzed ADP-ribosylation was increased by 37 and 126%, respectively; this indicated increased bioactivities of both Gs and Gi proteins in experimental preparations. The immunoblot analysis suggested 74 and 124% increase in Gs and Gi contents in failing hearts, respectively. These results suggest that depressed adenylyl cyclase activation in cardiomyopathic hamsters may not only be due to increased content and bioactivity of Gi proteins but the functional uncoupling of Gs proteins from the adenylyl cyclase enzyme may also be involved at this stage of heart failure.

Adenosine Diphosphate Ribose↗

The prolactin gene is expressed in the hypothalamic-neurohypophyseal system and the protein is processed into a 14-kDa fragment with activity like 16-kDa prolactin.

The 23-kDa form of prolactin (PRL) has been proposed to function as both a mature hormone and a prohormone precursor for different uniquely bioactive forms of the molecule. We have shown that the 16-kDa N-terminal fragment of PRL (16K PRL) inhibits angiogenesis via a specific receptor. In addition, 16K PRL stimulates natriuresis and diuresis in the rat, and kidney membranes contain high-affinity specific binding sites for this PRL fragment. 16K PRL can be derived from an enzymatically cleaved form of PRL (cleaved PRL). With the use of a specific 16K PRL antiserum, we have localized a 14-kDa immunoreactive protein in the paraventricular and supraoptic nuclei of the hypothalamus and in the neurohypophysis. Reverse transcription-polymerase chain reaction of RNA from isolated paraventricular nuclei showed the expression of the full-length PRL mRNA. The neurohypophysis was found to contain the enzymes that produce cleaved PRL, small amounts of PRL, and cleaved PRL. Medium conditioned by neurohypophyseal cultures, enriched with the 14-kDa immunoreactive protein, has antiangiogenic effects that are blocked by the 16K PRL antiserum. These results are consistent with the expression of PRL in the hypothalamic-neurohypophyseal system, and the preferential processing of the protein into a 14-kDa fragment with biological and immunological properties of 16K PRL.

Animals↗

Tissue distribution and regulation of rat prolactin receptor gene expression. Quantitative analysis by polymerase chain reaction.

The rat prolactin receptor (PRLR) exists as two forms, short and long. We have developed a quantitative polymerase chain reaction (Q-PCR) in order to measure the absolute number of mRNA molecules encoding both forms of PRLR in 16 tissues of adult female rats at two stages of the estrous cycle (proestrus and diestrus I) and in the mammary gland of 20-day pregnant and 7-day lactating rats. Using this technique, it was possible to detect as few as 500 molecules of a target mRNA per micrograms of total RNA. All tissues examined expressed the two forms of receptor transcripts, ranging from 1.8 x 10(3) molecules/micrograms of total RNA in the skeletal muscle to 2.9 x 10(7) molecules/micrograms of total RNA in the ovary. Fourteen tissues expressed the long form mRNA predominantly, the thymus and the kidney expressed both forms equally, and the liver expressed the short form predominantly. In the liver, the level of mRNA expression of the short form was approximately 2-fold higher in proestrus than in diestrus. In the ovary, uterus, and cerebral cortex, the expression of the long form transcript was higher in proestrus than in diestrus: 4-fold in the ovary, 2.8-fold in the uterus, and 1.4-fold in the cerebral cortex. In contrast, the hypothalamus and the pituitary expressed 1.6-fold more long form transcript in diestrus than in proestrus. These results indicate that PRLR mRNA is ubiquitously but variably expressed in a tissue-specific manner and is clearly regulated by the hormonal environment associated with the stage of the estrous cycle, pregnancy, and lactation.

Animals↗

Neuronal aromatase expression in preoptic, strial, and amygdaloid regions during late prenatal and early postnatal development in the rat.

Brain aromatase has been considered to be an important clue in elucidating the actions of androgen on brain sexual differentiation. Using highly specific anti-P450arom antiserum, the regional and subcellular distributions were immunohistochemically evaluated in the preoptic, strial, and amygdaloid regions of developing rat brains. Aromatase-immunoreactive (AROM-I) neurons were classified into three groups. The first, in which immunostaining occurs only during certain pre- or neonatal days (E16-P2), included the anterior medial preoptic nucleus, the periventricular preoptic nucleus, neurons associated with the strial part of the preoptic area, and the rostral portion of the medial preoptic nucleus. The second is a striking AROM-I cell group in the "medial preopticoamygdaloid neuronal arc," which extends from the medial preoptic nucleus to the principal nucleus of the bed nucleus of the stria terminalis and the posterodorsal part of the medial amygdaloid nucleus. The AROM-I neurons appeared by E16, reaching a peak in staining intensity between E18 and P2 and diminishing after the perinatal stage. After P14, a third group of AROM-I neurons emerged in the lateral septal nucleus, the oval nucleus of the bed nucleus of the stria terminalis, and the central amygdaloid nucleus. The second group was thought to be the major aromatization center in developing rat brains, while the center might partly shift to the third group of neurons after the late infantile stage. The distribution and developmental patterns were basically similar in males and females, suggesting that the neonatally prominent aromatase is not induced by male-specific androgen surges occurring around birth. On immunoelectron microscopy, subneuronal aromatase was predominantly localized on the nuclear membrane and endoplasmic reticulum, which appeared to be appropriate for the efficient conversion of androgen into estrogen just prior to binding to the nuclear receptors.

Amygdala↗

Synthesis and anticholinergic activity of the four stereoisomers of 4-(dimethylamino)-2-phenyl-2-(2-pyridyl)pentanamide.

The four stereoisomers of 4-(dimethylamino)-2-phenyl-(2-pyridyl)pentanamide were synthesized, and the absolute configurations were determined by X-ray crystallography. Pharmacological testing for anticholinergic activity revealed great differences in potency among 10 (2R,4R,IC50 = 0.40 microM), 11 (2S,4S,31 microM), 12 (2R,4S,170 microM), and 13 (2S,4R,0.13 microM). A new drug application for the racemate 8 (FK176, vamicamide) has been filed in Japan for the treatment of overactive detrusor syndrome.

Animals↗

Coexistence of the stigmoid body and estrogen receptor in some neuronal groups involved in rat reproductive functions.

Recent immunohistochemical studies have suggested that the forebrain distribution of stigmoid bodies, marked by an antibody against placental aromatase-associated antigen X-P2 (PAX), overlaps with that of the common binding sites of androgen and estrogen. In the present light- and electron-microscopy study the coexistence of stigmoid bodies and estrogen receptors (EsR) is immunohistochemically examined and quantitatively analyzed in the medial preoptic region, part of the bed nucleus of the stria terminalis and part of the medial amygdaloid nucleus of young female rats. Light microscopy with double immunostaining for PAX and EsR in all three regions indicates that 75-84% of the total of PAX-immunoreactive stigmoid structures are present in neurons which also contain EsR-immunoreactive nuclei, and that 75-78% of EsR-immunoreactive neurons contain PAX-immunoreactive inclusions. Electron microscopic analysis confirms that 70-80% of stigmoid body-containing neurons have EsR-immunoreactive nuclei. These results indicate that the majority of the stigmoid bodies and EsRs intimately coexist, strongly suggesting a functional interrelationship in brain regions which are involved in rat reproductive functions. Stigmoid bodies may play a role in subneuronal EsR mechanisms associated with aromatization in these sex steroid targets in rat brain.

Amygdala↗