Biomedical subjects

M Nagashima

Publications and source records attributed to M Nagashima.

At least 91 records · Page 5Linked to original sources

PubMed1998

Effects of a monoclonal antibody to P-selectin on recovery of neonatal lamb hearts after cold cardioplegic ischemia.

BACKGROUND: The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia. METHODS AND RESULTS: Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic arrest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 micrograms/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70 +/- 4% in control versus 77 +/- 2% in group P-sel, P < 0.01), maximum positive first derivative of pressure (dP/dt) (64 +/- 7% in control versus 73 +/- 5% in group P-sel, P < 0.05), and maximum negative dP/dt (61 +/- 6% in control versus 70 +/- 6% in group P-sel, P < 0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135 +/- 40% in control versus 205 +/- 43% in group P-sel, P < 0.05). Myocardial myeloperoxidase activity was significantly lower (P < 0.05) in group P-sel (4.7 +/- 3.2) versus control (16.0 +/- 10.1). (Units are change in absorbance/min/g tissue.) CONCLUSIONS: The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion.

Animals↗

PubMed1998

Glutamate transporter GLT-1 is transiently localized on growing axons of the mouse spinal cord before establishing astrocytic expression.

The glutamate transporter GLT-1 is expressed in astrocytes of the mature brain and spinal cord. In the present study, we examined its expression in the developing mouse spinal cord. By in situ hybridization, 35S-labeled antisense oligonucleotide probes for GLT-1 mRNA consistently labeled the mantle zone/gray matter from embryonic day 11 through the adult stage. However, immunohistochemistry with a specific antibody visualized distinct regional and cellular localizations during the time between the fetal and postnatal stages. At fetal stages, GLT-1 immunoreactivity predominated in the marginal zone/white matter, observed as tiny puncta in cross-sections and as thin fibers in longitudinal sections. The GLT-1-immunopositive structures were also labeled for neuron-specific enolase, a glycolytic enzyme specific to postmitotic neurons and endocrine cells. By electron microscopy, GLT-1 immunoreactivity was detected in axons forming frequent enlargements and was focally localized on a small portion of the axolemma, particularly that facing adjacent axons. At early postnatal stages, GLT-1 disappeared from axons in white matter tracts and, instead, appeared in astrocytic processes surrounding various neuronal elements in the gray matter. Therefore, before switching to astrocytic expression, GLT-1 is transiently expressed in neurons and localized in differentiating axons. Together with our previous finding on the localization of glutamate transporter GLAST in radial glial fibers, GLT-1 and GLAST are thus localized during development on distinct directional cellular elements along which young neurons elongate their axons or move their cell bodies, respectively.

ATP-Binding Cassette Transporters↗

PubMed1998

hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors.

hSmad (mothers against decapentaplegic)-related proteins are important messengers within the Transforming Growth Factor-beta1 (TGF-beta1) superfamily signal transduction pathways. To further characterize a member of this family, we obtained a full length cDNA of the human hSmad5 (hSmad5) gene by rapid amplification of cDNA ends (RACE) and then determined the genomic structure of the gene. There are eight exons and two alternative transcripts; the shorter transcript lacks exon 2. We identified the hSmad5 promoter region from a human genomic YAC clone by obtaining the nucleotide sequence extending 1235 base pairs upstream of the 5' end of the cDNA. We found a CpG island consistent with a promoter region, and we demonstrated promoter activity in a 1232 bp fragment located upstream of the transcription initiation site. To investigate the frequency of somatic hSmad5 mutations in human cancers, we designed intron-based primers to examine coding regions by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Neither homozygous deletions or point mutations were found in 40 primary gastric tumors and 51 cell lines derived from diverse types of human cancer including 20 cell lines resistant to the growth inhibitory effects of TGF-beta1. These results suggest that the hSmad5 gene is not commonly mutated and that other genetic alterations mediate the loss of TGF-beta1 responsiveness in human cancers.

Alternative Splicing↗

PubMed1998

Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway.

The transforming growth factor beta (TGF-beta) superfamily is a family of multifunctional cytokines that transduce signals via serine/threonine kinase receptors. Recent studies revealed that Mothers against dpp (Mad) in Drosophila and its homologs play important roles in the intracellular signal transduction of the serine/threonine kinase receptors. In mammals, one of the Mad homologs, MADH2 (also termed Smad2), was reported to be a mediator of TGF-beta and activin signaling and was found mutated in some of the colon and lung cancer cases. We describe here the genomic organization of the human MADH2 gene. The gene is composed of 12 exons; 2 exons 1, i.e., exon 1a and 1b, are used separately or in conjunction to form exon 1a-exon 1b-exon 2 alternatively spliced mRNA. The 2 exons 1 are closely located, and the MADH2 mRNAs are transcribed from two promoters in one CpG island. The promoter activity in the 5' upstream sequence was confirmed by the luciferase assay. The 3' end of the mRNA is heterogenous, and we found several polyadenylation signals. Northern blot analysis revealed high expression of the MADH2 mRNA, e.g., in skeletal muscle, heart, and placenta. RT-PCR assay using primers in exons 2 and 4 and direct nucleotide sequencing proved that exon 3 is spliced out in about 10% of MADH2 in human placenta. These data will be valuable for studying the MADH2 function in both normal cells and cancer cells.

Activins↗

PubMed1998

A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome.

Mutations in a human cardiac Na+ channel gene (SCN5A) are responsible for chromosome 3-linked congenital long QT syndrome (LQT3). Here we characterized a de novo missense mutation (R1623Q, S4 segment of domain 4) identified in an infant Japanese girl with a severe form of LQT3. When expressed in oocytes, mutant Na+ channels exhibited only minor abnormalities in channel activation, but in contrast to three previously characterized LQT3 mutations, had significantly delayed macroscopic inactivation. Single channel analysis revealed that R1623Q channels have significantly prolonged open times with bursting behavior, suggesting a novel mechanism of pathophysiology in Na+ channel-linked long QT syndrome.

Animals↗

PubMed1998

Long-term results of Yoshino total knee arthroplasties in rheumatoid arthritis.

A review was made of 267 Yoshino total knee arthroplasties performed on 184 patients with rheumatoid arthritis between June 1978 and December 1983. The average duration of follow-up was 14.3 years. Of these patients 46.7% died during the follow-up period. The main causes of death were cardiac disease, respiratory disease and renal disease. According to the Japanese Orthopaedic Association (JOA) knee rating system, JOA scores decreased significantly with time after surgery, but remained significantly higher than the preoperative scores. The flexion angle after surgery had decreased compared with the preoperative flexion angle and decreased further 3 years after surgery and later. The cumulative survival rate was 88.6%. This rate was mainly affected by postoperative infection and aseptic loosening of the tibial components.

Adult↗

PubMed1998

Three-dimensional imaging and osteometry of adult human skulls using helical computed tomography.

To make a digital image database of human craniology, we optimized the three-dimensional (3-D) images of 29 dried human skull specimens by helical computed tomography (CT). For the verification of the quantitative exactitude of these image data, we manually measured nine items of direct distances between standard anthropologic points on each skull and the corresponding distances projected on the CT monitor by specifying the respective points. The results obtained by the two methods of manual and CT measurements were compared and statistically analyzed. The CT measurements were so exact that the lower limit of correlation coefficients (95% of the confidence interval) between the two results was more than 0.8 in six items; i.e., maximal cranial length and breadth, minimal frontal breadth, bizygomatic breadth, distance between ectomolares and nasion-basion length. In contrast, the CT results were less well correlated with the manual measurements of three items; i.e., distance between bilateral mastoidales, total facial height, and nasal breadth. We concluded that the qualitative representation of 3-D CT images was adequate, although some quantitative data may be incorrect. The inaccuracy is suspected to be due to the difficulty in specifying the standard points on the CT images, and due to the differences in measurement procedures between the direct and projected distances.

Adult↗

PubMed1998

[Surgical management of patent ductus arteriosus in low body weight infants].

Between January 1980 and December 1994, seventeen premature infants weighing less than 2500 g underwent surgical management for the isolated patent ductus arteriosus (PDA). Indometacine therapy for closure of PDA was not effective for all these patients. In terms of the body weight at birth, they were divided into two groups; Group I (G-I) consisted of ten patients with birth weight less than 1000 g and Group II (G-II) of seven patients weighing more than 1000 g. The age at operation was 22.1 +/- 15.4 days in the G-I and 14.3 +/- 11.4 days in the G-II. The ductus was ligated in all patients but one of the G-II, in whom it was divided. There were five (50%) hospital deaths in the G-I and none in the G-II. The causes of death in the G-I were related to necrotizing enterocolitis (NEC) in two and infant respiratory distress syndrome (IRDS), acute renal failure, and broncho-esophagial fistula in each. The age at operation tended to be older in nonsurvivors rather than in survivors in the G-I (28.0 +/- 16.8 days vs. 16.2 +/- 14.0 days, respectively, but the difference did not reach significance). Before surgery, all patients in the G-I required mechanical ventilator support and nine of them were associated with IRDS. In contrast, only two patients in the G-II needed mechanical ventilation preoperatively. The postoperative period of intubation was also significantly longer in the G-I than in the G-II (51.6 +/- 35.2 days vs. 2.2 +/- 1.5 days, respectively, p < 0.05). In conclusions, the surgery for PDA can be safely performed even in small premature babies weighing less than 1000 g. When medical therapy for PDA is not effective in the premature patients, the surgical management should be considered as early as possible before their conditions become worse due to such critical complications as NEC, IRDS, and renal failure.

Cardiac Surgical Procedures↗

PubMed1998

Granulocyte and monocyte apheresis suppresses symptoms of rheumatoid arthritis: a pilot study.

To investigate if granulocyte and monocyte apheresis mitigates the symptoms of rheumatoid arthritis (RA), and influences production of panmyelocytes (CD15+ CD16- cells) at the bone marrow level, 27 RA patients who had elevated granulocyte counts were recruited. The granulocyte and monocyte apheresis column (G-1 column) is an extracorporeal type device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. Patients received apheresis of 1 hr duration twice per week, 8 times over a period of 4 weeks. To prepare CD15+CD16- cells, iliac bone marrow aspirate was obtained at baseline and at 2 weeks after completion of the apheresis course. Ex-vivo proliferation of bone marrow low density cells and production of IgM-RF were also investigated. Following granulocyte and monocyte apheresis, there was a suppressed tendency in the number of CD15+CD16- cells in patients with high bone marrow CD15+CD16- cell counts at baseline. Clinical assessments 2 weeks after the completion of apheresis therapy showed improvements in swollen joint count (P < 0.001), tender joint count (P < 0.001) and duration of morning stiffness (P < 0.005). The results suggest that granulocytes and monocytes/macrophages have a pathological role in RA and apheresis treatment to reduce or suppress these cells should benefit patients with RA.

Adult↗

PubMed1998

Transsphenoidal-transtuberculum sellae approach for supradiaphragmatic tumours: technical note.

The Classic transsphenoidal approach may not afford sufficient exposure for a supradiaphragmatic tumour adjacent to the pituitary stalk. Various transcranial approaches have been utilized to access such a lesion with adequate results. This report describes a less invasive technique, termed "transsphenoidal-transtuberculum sellae approach". This modified transsphenoidal approach requires a bone ablation of the tuberculum sellae, the limbus sphenoidalis, and a portion of the planum sphenoidale, in addition to an opening of the anterior floor of the sella turcica. The dura mater on the tuberculum sellae and the pituitary fossa is sectioned with a bilateral obliteration of the anterior intercavernous sinus. The anterior pituitary gland is not necessarily resected. The optic chiasm, optic nerves, pituitary stalk, and tuber cinereum can be directly observed, making it possible to safely dissect a lesion from these structures. Utilizing this approach, we have removed 14 supradiaphragmatic tumours without complications and dealt with other lesions such as optic nerve injuries or cerebrospinal fluid rhinorrhea, leaving pituitary function intact. The transsphenoidal-transtuberculum sellae approach for accessing small supradiaphragmatic tumours is a useful procedure requiring only a minor modification of the classic transsphenoidal technique.

Adenoma↗

PubMed1998

Postischemic hyperthermia exacerbates neurologic injury after deep hypothermic circulatory arrest.

BACKGROUND: Aggressive surface warming is a common practice in the pediatric intensive care unit. However, recent rodent data emphasize the protective effect of mild (2 degrees - 3 degrees C) hypothermia after cerebral ischemia. This study evaluates different temperature regulation strategies after deep hypothermic circulatory arrest with a survival piglet model. METHODS: Fifteen piglets were randomly assigned to 3 groups. All groups underwent 100 minutes of deep hypothermic circulatory arrest at 15 degrees C. Brain temperature was maintained at 34 degrees C for 24 hours after cardiopulmonary bypass in group I, 37 degrees C in group II, and 40 degrees C in group III. Neurobehavioral recovery was evaluated daily for 3 days after extubation by neurologic deficit score (0, normal; 500, brain death) and overall performance category (1, normal; 5, brain death). Histologic examination was assessed for hypoxic-ischemic injury (0, normal; 5, necrosis) in a blinded fashion. RESULTS: All results are expressed as mean +/- standard deviation. Recovery of neurologic deficit score (12.0 +/- 17.8, 47.0 +/- 49.95, 191.0 +/- 179.83; P = .05 for group I vs III), overall performance category (1.0 +/- 0.0, 1.4 +/- 0.6, 2.8 +/- 1.3; P < .05 for group I vs III), and histologic scores (0.0 +/- 0.0, 1.0 +/- 1.2, 2.8 +/- 1.8; P < .05 for group I vs III cortex) were significantly worse in hyperthermic group III. These findings were associated with a significantly lower cytochrome aa3 recovery determined by near-infrared spectroscopy in group III animals (P = .0041 for group I vs III). No animal recovered to baseline electroencephalographic value by 48 hours after deep hypothermic circulatory arrest. Recovery was significantly delayed in the hyperthermic group III animals, with a lower amplitude 14 hours after the operation, which gradually increased with time (P < .05 for group III vs groups I and II). CONCLUSIONS: Mild postischemic hyperthermia significantly exacerbates functional and structural neurologic injury after deep hypothermic circulatory arrest and should therefore be avoided.

Animals↗

PubMed1998

Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers.

In mammals, one of the Mad homologues, Smad2, was reported to be a mediator of TGF-beta signaling, and was found mutated in some cases of colon and lung cancers. To extend the analysis of this gene, we previously investigated the genomic organization of the human Smad2 gene and defined the structure of 12 exons and flanking introns. In this study, we designed 11 sets of intron-based primers to examine the entire coding region of the Smad2 gene. By the PCR-SSCP method using these primers, we screened genomic DNA sequences of colorectal cancers for mutations of the Smad2 gene. Though there was no mutation within all exons of the Smad2 gene, two of 60 sporadic colorectal cancers displayed deletions in the polypyrimidine tract preceding exon 4. Deletions of this region were also detected in colon cancer cell lines, and were clustered within cells exhibiting microsatellite instability. Deletions in the polypyrimidine tract had various effects on pre-mRNA splicing, but had no effect on the splicing of the Smad2 gene in these cases. However, our data support the idea that the polypyrimidine tract in the splicing acceptor site is a target of mutations in mismatch repair-deficient tumors.

Base Sequence↗

PubMed1998

Response of parathyroid hormone to anaerobic exercise in adolescent female athletes.

It has been shown that moderate exercise suppresses parathyroid hormone (PTH) secretion, while strenuous exercise is apt to induce continuous secretion, which has a negative effect on bone mineral densities (BMD). The present study investigated a typical response of PTH to brief exercise. The study group comprised six adolescent female basketball players whose BMD were within normal limits. Maximal anaerobic power by three-step cycling was loaded on each subject. The first blood sample was drawn 30 min prior to testing test, the second was immediately following, the third was 15 min after, and the fourth was 30 min after. The proportional change in plasma volume was -11.5% immediately following (P < 0.05), +2.1% 15 min after, and +5.5% at 30 min after exercise (P < 0.05). The expected value was calculated on the assumption of no effect, except changes in plasma volume, by exercise. The measured values of PTH and calcium (Ca) immediately after exercise were lower than each of the expected values (P < 0.05 for both). At 15 min after, there was no significant difference between expected and measured values of PTH, Ca and magnesium (Mg), respectively. At 30 min after, the measured value of Ca and Mg was higher than each expected value (P < 0.05 for both). It was concluded that PTH secretion is suppressed transiently immediately after maximal anaerobic exercise and is then stimulated during the recovery time in normal BMD subjects.

Adolescent↗

PubMed1998

Ventilatory control during exercise in normal children.

We investigated the relation between age and respiratory control during exercise in 80 children aged 6.4-17.6 y (42 male, age, 11.6 +/- 3.3 y; body weight, 41.3 +/- 14.7 kg; and 38 female, age, 12.6 +/- 2.7 y; body weight, 42.5 +/- 9.3 kg). Exercise tests were performed on a treadmill after a standard symptom-limited Bruce protocol. Data were analyzed separately for boys and girls. At rest and at peak exercise, the ratio of minute ventilation to carbon dioxide production (VE/VCO2), the ratio of effective alveolar ventilation to carbon dioxide production (VA/VCO2), the ratio of pulmonary dead space to tidal volume (Vd/Vt), and arterial PCO2 (PaCO2) were not correlated with age. At the exercise intensity of ventilatory anaerobic threshold, the PaCO2 increased, and the VA/VCO2 decreased, significantly with age, whereas the Vd/Vt was not related to age. Linear regression analysis demonstrated that the slope of the relationship between VE and VCO2 (deltaVE/deltaVCO2) and the slope of the relationship between VA and VCO2 (deltaVA/deltaVCO2) decreased with age. There were no gender differences in the regression slopes and the intercepts of the relationships. Results show that younger children breathe more during exercise to eliminate a given amount of CO2 to keep PaCO2 set point slightly but significantly lower than older children. This age dependence must be considered in investigating ventilatory control during exercise in children.

Adolescent↗

PubMed1998

The relationship between R amplitude in lead V5 (RV5) and left ventricular mass in the groups of adolescent subjects classified by body composition.

How the amplitude of the R wave in lead V5 (RV5) of the ECG represents the left ventricular (LV) mass was investigated in 894 students aged 15 (boys: 545, girls: 349). The influence of body composition [ie, percentage of body fat (%fat)] was taken into consideration. A significant correlation was found between RV5 amplitude and LV mass for both genders. However, the relationship was stronger for boys than for girls. The students were then divided into 3 groups; that is, those at either the top or bottom 10th percentile (low or high-fat range) and the rest of the students (middle-fat range), depending on the % fat calculated by the bioelectrical impedance method. The significant correlation between RV5 and LV mass was found only for the 2 groups of boys whose percentage fat was in the low or middle-fat range. The correlation coefficients were 0.40 and 0.34, respectively. Moreover, in the boys' low-fat range, the RV5 of students whose LV mass was large (> or =90th percentile), was significantly higher (p<0.01) than in the other ranges. Setting a particular cutoff point of RV5 in the low-fat range of boys improved sensitivity as well as specificity (20-30% better among all boys) for detecting large LV mass. These observations suggest that classification of subjects by body composition could be improve the reliability of ECG assessment for left ventricular hypertrophy, although the gender and number of subjects in whom improvement is expected are limited.

Adolescent↗

PubMed1998

Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunoglobulinemia E which were attenuated by suplatast tosilate (IPD-1151T).

A 29-year-old man developed atopic bronchial asthma in association with eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE as well as the serum level of eosinophil cationic protein (ECP). The drug, however, did not affect the positivity for specific IgE antibodies against common allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were measured to be undetectable in serum before or during therapy. However, the expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood eosinophils were detected before and during therapy, which were unchanged by therapy with IPD-1151T. The present results suggest that different mechanisms other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may underlie Kimura's disease and atopic bronchial asthma regarding the findings of eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.

Adult↗

PubMed1998

BE-31405, a new antifungal antibiotic produced by Penicillium minioluteum. I. Description of producing organism, fermentation, isolation, physico-chemical and biological properties.

A new antifungal antibiotic, BE-31405, was isolated from the culture broth of a fungal strain, Penicillium minioluteum F31405. BE-31405 was isolated by adsorption on high porous polymer resin (Diaion HP-20), followed by solvent extraction, precipitation and crystallization. BE-31405 showed potent growth inhibitory activity against pathogenic fungal strains such as Candida albicans, Candida glabrata and Cryptococcus neoformans, but did not show cytotoxic activity against mammalian cells such as P388 mouse leukemia. The mechanism studies indicated that BE-31405 inhibited the protein synthesis of C. albicans but not of mammalian cells.

Animals↗

PubMed1998

[Morphological studies on lower margins of nasal aperture in the skull of Hokkaido Japanese].

It is well-known that the lower margins of nasal aperture in the human skull may be classified into the following four types, i.e., Forma anthropina, Forma infantilis, Fossae praenasales and Clivus nasoalveolaris, and that the rates of appearance of these four types differ with races. In the present study we made morphological studies on the lower margins of nasal aperture of 465 Hokkaido Japanese skulls, 463 skulls with symmetrical nasal aperture and 2 skulls with asymmetrical one, and compared the findings with those of all races in the world, especially of the Japanese, Ainu, Moyoro Man, Hamanaka Site Man and Eskimo. Forma anthropina was found in 330 skulls (71.27 +/- 2.10%) among the 463, marking the highest rate. Forma infantilis, found in 74 skulls (15.98 +/- 1.70%) among the 463, marked the second highest rate. Fossae praenasales, found in 42 skulls (9.07 +/- 1.33%) among the 463, marked the third highest rate. These 42 cases of Fossae praenasales were further classified into three types, i.e., sub-Forma infantilis, 17 (40.48%), typical Fossae prenasales, 23 (54.76%) and sub-Clivus nasoalveolaris, 2 (4.76%). Clivus nasoalveolaris, found in 17 skulls (3.67 +/- 0.87%) among the 463, marked the lowest rate. As a whole, the rates of the four types in the Hokkaido Japanese were close to those in the other groups of the Japanese in Kinai and Hokkaido (Ito).

Adult↗