PubMed Health⌕ Search

Biomedical subjects

M Minato

Publications and source records attributed to M Minato.

At least 19 recordsLinked to original sources

Multiple activation of mitogen-activated protein kinases by purified independent CCN2 modules in vascular endothelial cells and chondrocytes in culture.

CCN2 consists of 4 distinct modules that are conserved among various CCN family protein members. From the N-terminus, insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C repeat (VWC), thrombospondin type 1 repeat (TSP1) and C-terminal cysteine-knot (CT) modules are all aligned tandem therein. The multiple functionality of CCN2 is thought to be enabled by the differential use of these modules when interacting with other molecules. In this study, we independently prepared all 4 purified module proteins of human CCN2, utilizing a secretory production system with Brevibacillus choshinensis and thus evaluated the cell biological effects of such single modules. In human umbilical vascular endothelial cells (HUVECs), VWC, TSP and CT modules, as well as a full-length CCN2, were capable of efficiently activating the ERK signal transduction cascade, whereas IGFBP was not. In contrast, the IGFBP module was found to prominently activate JNK in human chondrocytic HCS-2/8 cells, while the others showed similar effects at lower levels. In addition, ERK1/2 was modestly, but significantly activated by IGFBP and VWC in those cells. No single module, but a mixture of the 4 modules provoked a significant activation of p38 MAPK in HCS-2/8 cells, which was activated by the full-length CCN2. Therefore, the signals emitted by CCN2 can be highly differential, depending upon the cell types, which are thus enabled by the tetramodular structure. Furthermore, the cell biological effects of each module on these cells were also evaluated to clarify the relationship among the modules, the signaling pathways and biological outcomes. Our present results not only demonstrate that single CCN2 modules were potent activators of the intracellular signaling cascade to yield a biological response per se, while also providing new insight into the module-wise structural and functional relationship of a prototypic CCN family member, CCN2.

Blotting, Western↗

Why do we help a micropreemie to live?

UNLABELLED: Helping a "micropreemie" to live by aggressive interventions may sometimes seem unnatural. However, utilitarian assessment of benefits derived from lifesaving efforts for a micropreemie is considered inappropriate. The goal in treating premature infants has advanced from fetal salvage to achieving "intact survival", which represents a new therapeutic target. In this way, the record for lifesaving in extremely low-birthweight infants is continually being broken. Why do we help a micropreemie to live? Moral and ethical emotions are the underlying reasons for the aggressive care devoted to premature infants, including micropreemies. Such human feelings might even be considered the purpose of life. Human emotion is the impetus for aggressive efforts to improve the survival prospects of premature infants. The beautiful and delicate nature of a newborn is compelling. The high-order emotion of empathy for another's misfortune is also important. Most human emotions are related to an awareness of death, and micropreemies are near death. In Oriental thought, a human being is a growing product of nature. Forces of nature and changes in a living being follow nature's rules. First and foremost, an individual life is part of the long chain of existence beginning before the self and continuing beyond it. An immature human being, even a newborn, is simultaneously a complete entity and part of nature's long chain of being, which has a wholeness of its own that affirms a micropreemie's right to life. A fetus is a member of human society in the sense that there is an overall reverence for life as a quality that lives on. CONCLUSION: The limit that bioethics must not exceed is the sanctity of life. We believe that the birth of a micropreemie is an important and serious event. We profoundly wish that a micropreemie might live and thrive, because we on earth must live with the continual presence and imminence of death.

Affect↗

Endogenous nitric oxide and endothelin-1 in persistent pulmonary hypertension of the newborn.

UNLABELLED: We studied changes in endogenous nitric oxide (NO) synthesis and endothelin-1 (ET-1) production in infants with persistent pulmonary hypertension of the newborn (PPHN). We determined concentrations of serum NO metabolites, i.e., nitrites and nitrates (NOx), and of plasma ET-1 in five infants with PPHN (PPHN group) and in 25 healthy full-term neonates (control group). In both groups, serum NOx concentrations increased over time and plasma ET-1 concentrations decreased with age. The differences in serum NOx concentrations between groups were not significant at < 12 h and 24 h of age; however, they were significantly higher in the PPHN group than in the control group at 5 days of age. The differences in plasma ET-1 concentrations between groups were not significant at 5 days of age, but were significantly higher in the PPHN group than in the control group at < 12 h and 24 h of age. CONCLUSION: Limited endogenous nitric oxide synthesis and elevated endogenous endothelin-1 production during the first few days of life may contribute to pulmonary hypertension in infants with persistent pulmonary hypertension of the newborn.

Age Factors↗

A case of pulmonary hypoplasia associated with intrauterine brainstem necrosis.

UNLABELLED: An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy. CONCLUSION: These findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement.

Adolescent↗

Spontaneous labor increases nitric oxide synthesis during the early neonatal period.

BACKGROUND: This paper aimed to assess the influence of spontaneous labor upon endogenous nitric oxide (NO) and endothelin 1 (ET-1) during transition to extrauterine life. METHODS: The serum levels of NO metabolites (the sum of nitrites and nitrates (NOx)) and the plasma level of ET-1 were determined in 53 healthy full-term infants (spontaneous labor group; n=40, cesarean delivery group; n=13). In both groups, blood samples were obtained from a cord vein at birth and from a peripheral vein at 5 days of age. RESULTS: The differences in serum NOx concentrations between the spontaneous labor group and the elective cesarean group were not significant at birth. By the age of 5 days, serum NOx concentrations had risen significantly in the spontaneous labor group to become significantly higher in the elective cesarean group. CONCLUSION: It is speculated that spontaneous labor might enhance endogenous NO synthesis at 5 days of age.

Adaptation, Physiological↗

A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia.

Missense mutations in the calcium-sensing receptor (CaSR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were studied, and we found a novel CaSR missense mutation with polymerase chain reaction single-strand conformational polymorphism analysis. The mother, grandmother, and aunt of the baby all had FHH. A heterozygous missense mutation in exon 6 that substitutes a glutamic acid for the glycine at codon 557 (Gly557Glu), which corresponds to the extracellular domain of CaSR, was identified and shown to cosegregate with the disease. Identification of the mutation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH.

Adult↗

Physiologic significance of nitric oxide and endothelin-1 in circulatory adaptation.

BACKGROUND: The purpose of the present paper was to evaluate the physiologic significance of nitric oxide (NO) and endothelin (ET)-1 in circulatory adaptation in the neonate. METHODS: The serum levels of NO metabolites (NOx; the sum of nitrites and nitrates) and the plasma level of ET-1 were determined in 14 healthy full-term infants at 0-6 h, 24 h and 5 days after birth. We measured the heart rate, the mean systemic blood pressure and the mean pulmonary arterial pressure, estimated by pulsed Doppler echocardiography, at each time point. RESULTS: The serum concentration of NOx was lowest at birth and increased with age. The plasma concentration of ET-1 was highest at birth and decreased with age. The ratio of NOx to ET-1 was inversely related to the estimated mean pulmonary arterial pressure in the early neonatal period. The ratio of NOx to ET-1 was not correlated with the systemic blood pressure. CONCLUSION: Increased NO synthesis and decreased production of ET-1 during the early neonatal period may contribute to the decrease in pulmonary arterial pressure.

Adaptation, Physiological↗

Using polymerase chain reaction for rapid sex-determination of a case of sirenomelia.

A rare case of sirenomelia with its autopsy findings is reported. The 1188 g infant was delivered by cesarean section at the 36th week of gestation, and died at 4 h of life. Physical and pathologic findings included sirenomelia (a single lower extremity mass), lung hypoplasia, bilateral renal agenesis, blind-ending colon, severe deformity of the bony pelvis, an imperforate anus, absence of the bladder, and a single umbilical artery. Because of the difficulty in determining the sex of the infant, PCR directed against the SRY gene was performed. The PCR-based sex determination is a rapid technique in patients with ambiguous genitalia.

Autopsy↗

Endothelium-derived relaxing and contracting factors during the early neonatal period.

The interaction and relative potency of nitric oxide, an endothelium-derived relaxing factor, and endothelin-1, an endothelium-derived contracting factor, may be important in the transition from fetal to extrauterine life. The change in level of nitric oxide during the early neonatal period has not been measured. Accordingly, the serum levels of nitric oxide metabolites (the sum of nitrite and nitrate) and plasma endothelin-1 were determined in 20 healthy neonates at birth, at 12 and 24 h postnatally, and at the age of 5 d. The lowest serum concentration of nitric oxide metabolites was observed at birth (26.2 +/- 9.1 micromol l(-1), mean +/- SD) and increased with age, whereas the highest plasma concentration of endothelin-1 was observed at birth (14.0 +/- 6.7 pg ml(-1)) and decreased with age. These changes suggest that nitric oxide and endothelin-1 play roles in the circulatory adaptation of the neonate to extrauterine life.

Adaptation, Physiological↗

Bacterial changes in neonatal intensive care unit.

Organisms routinely cultured from throat swabs and infectious agents of sepsis and/or meningitis were reviewed. During the last 12 years, Klebsiella pneumoniae and Escherichia coli have been replaced by Staphylococcus aureus and Pseudomonas aeruginosa as the predominant isolates from throat swabs after admission. These change in the etiologic pattern of infectious agents of sepsis and/or meningitis, i.e., K. pneumoniae, E. coli, S. aureus, P. aeruginosa and staphylococcus epidermidis, were in agreement with the organisms isolated from the throat swabs after admission. The S. aureus isolated from throat swabs after admission showed a decrease in the bacterial activity of cloxacillin, cephazolin and cefotaxime since 1978.

Bacteria↗

Plasma concentration of granulocyte-colony-stimulating factor in neonates.

We determined the plasma concentration of granulocyte-colony-stimulating factor (GCSF) and the neutrophil count in 108 infants (gestational age 23-41 weeks; birthweight 478-4935g). The GCSF levels in the very low birthweight infants without infection were comparable to those in the full-term infants. Infants as premature as 23 weeks of gestation showed similar GCSF levels to mature neonates. GCSF levels decreased significantly by day 7 after birth. The levels were not significantly correlated with the neutrophil count. The mean plasma level of GCSF increased significantly when infection developed and was significantly higher in the infants with sepsis than in those with non-septic infections (p < 0.01). The results suggest that GCSF may be the major determinant of neutrophil kinetics both during fetal life and after birth.

Birth Weight↗

Nitric oxide and endothelin 1 during postnatal life.

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

Aging↗