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Biomedical subjects

N Iwai

Publications and source records attributed to N Iwai.

At least 145 records · Page 8Linked to original sources
PubMed1995

[Antigenicity study of T-3761].

Antigenicity studies of T-3761, a new quinolone derivative, were conducted and the following results were obtained. 1. By active systemic anaphylaxis test in guinea pigs, neither immunogenicity nor allergenicity of T-3761 was noted. 2. By homologous 4-hour passive cutaneous anaphylaxis (PCA) test using the serum obtained from these guinea pigs, neither immunogenicity nor allergenicity of T-3761 was noted. 3. The potential of IgE antibody production in mice was examined by heterologous 24-hour PCA test in rats. But neither the potential of IgE antibody production nor allergenicity of T-3761 was noted. 4. By passive hemagglutination assay, we analysed the antibody titer in rats and dogs serum obtained from three-month toxicity repeated dose studies (oral and intravenously administration). But the hemagglutination response was negative and specific antibodies were not detected.

Anaphylaxis↗
PubMed1995

[Laboratory and clinical studies on SY5555 in pediatrics].

Laboratory and clinical studies were performed on SY5555, the first penem oral antibiotic developed in Japan, in the pediatric field. The following results were obtained. 1. Antibacterial activities of the drug against 42 strains of Streptococcus pneumoniae clinically isolated in 1993 were compared to those of 13 other drugs mainly composed of beta-lactam preparations. Minimum inhibitory concentration (MIC) values of SY5555 were below 0.39 micrograms/ml for all strains examined, thus the drug showed an excellent activities against benzylpenicillin (PCG)-resistant strains as well. When the antibacterial effects of individual drugs were compared using MIC50 and MIC90 as indices, SY5555 was the most effective against PCG-sensitive strains and similar to cefazolin (CEZ), cefotaxime (CTX), cefuzonam (CZON), amoxicillin (AMPC) and imipenem (IPM). It also showed excellent antibacterial effects against moderately PCG-resistant strains, and the activities were similar to IPM. Activities of SY5555 on highly PCG-resistant strains were similar to those of CTX, CZON and IPM. 2. SY5555 at a dose of 5 mg/kg or 10 mg/kg was administered to 16 pediatric patients in the fasting state or after meal to examine its plasma concentration and urinary excretion rate. The fecal excretion was measured in 5 affected children treated with this drug. When the drug at a dose of 5 mg/kg was administered to 11 older children, 5 with ages 5-12 years and 6 with ages 10-13 years in the fasting state and after meal, respectively. Peak plasma levels were reached at 1 hour after administration in the two groups, and they were 0.93 +/- 0.25 and 2.44 +/- 1.25 micrograms/ml, respectively. The plasma levels then decreased gradually with half-lives of 1.95 +/- 1.09 and 0.72 +/- 0.21 hours, respectively. Urinary recovery rates in the first 6 hours after administration were 1.98 +/- 0.82 and 4.13 +/- 1.40%, respectively. In 3 cases (6-9 years) treated with the drug at a dose of 10 mg/kg after meal, a peak of 1.58 +/- 0.81 micrograms/ml appeared 1 hour after administration with a half-life of 1.08 +/- 0.30 hours and with the urinary recovery rate in the first 6 hours after administration of 3.46 +/- 1.03%. When the drug at a dose of 10 mg/kg was administered to 2 infants (2-3 months post partum) after meal, a peak plasma level of 3.74 micrograms/ml appeared 1 hour after administration with a half-life of 1.19 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Increased numbers of argyrophilic nucleolar organizer regions between primary and metastatic sites predict tumor progression in stage IV and IV-S neuroblastoma.

BACKGROUND: A silver colloid technique to determine nucleolar organizer region (AgNOR) number was used to study the proliferative activity of Stage IV-S neuroblastoma in which a spontaneous tumor regression is often observed. METHODS: Primary regional lymph nodes and hepatic lesions from five children with Stage IV-S and five with Stage IV neuroblastoma were examined. RESULTS: Average AgNOR counts per tumor cell nucleus from all five children with Stage IV neuroblastoma were lowest in the primary lesions, intermediate in the metastatic regional lymph nodes, and highest in the distant metastases. However, in four Stage IV-S patients whose metastases later disappeared and showed no sign of recurrence, the average AgNOR number was similar in primary tumors and metastatic lesions. In the other patient with progressive metastases initially diagnosed as Stage IV-S, the data showed the same pattern as in Stage IV neuroblastoma. CONCLUSIONS: The unique AgNOR staining pattern may reflect the proliferative activity of Stage IV-S neuroblastoma. This method may provide further information to differentiate a subtype of metastatic neuroblastoma showing spontaneous tumor regression and/or favorable prognosis.

Adrenal Gland Neoplasms↗
PubMed1994

OK-432 therapy in 64 patients with lymphangioma.

Intralesional injection of OK-432 was employed to treat 64 lymphangiomas between 1986 and 1992. This was used as primary therapy for 46 lesions (group A), as treatment following incomplete surgical removal in 14 (group B), and as therapy after failure of bleomycin in 4 (group C). In group A (n = 46), total shrinkage of the lesion, without serious complications, was noted in 23; there was marked shrinkage in 8, slight shrinkage in 12, and no response in 3. Of the cystic lesions (n = 24), significant shrinkage occurred in 22; of the cavernous lesions (n = 22), only 9 improved after treatment. In groups B (n = 14) and C (n = 4) there was significant clinical improvement occurred in 5 and 2, respectively. No recurrence was noted during follow-up (6 to 87 months). The only side effects were fever lasting 2 to 4 days and a local inflammatory reaction of 3 to 7 days' duration. The local inflammation did not cause any damage to the overlying skin and did not lead to scar formation. These data suggest that intralesional injection of OK-432 is effective treatment for lymphangiomas and should be considered as the primary method of treatment.

Humans↗
PubMed1994

Cloning, expression and regulation of angiotensin II receptors.

Angiotensin II isoform 1 (AT1) receptor cDNAs were cloned by expression cloning from bovine adrenal and rat vascular smooth muscles. Human AT1 receptor was also cloned. Seven transmembrane structures emerged. A single type of receptor seems to interact with more than one type of G-protein. AT1 consists of subtypes AT1A and AT1B, and the regulation of the receptors occurs at many stages. The isoform AT2 was also expression cloned from rat pheochromocytoma cells. Although its ligand binding is not affected by GTP analogs, it is a seven transmembrane domain receptor. It mediates the inhibition of phosphotyrosine phosphatase by angiotensin II and AT2 specific CGP42112A; the inhibition was abolished by pertussis toxin. Thus, AT2 belongs to a new class of angiotensin receptors with unique signalling and regulatory mechanisms.

Amino Acid Sequence↗
PubMed1994

Molecular genetics of the SA gene.

1. We have recently identified a candidate gene for rat genetic hypertension, termed SA, by identifying an mRNA species that shows markedly higher expression in the kidneys of spontaneously hypertensive rats (SHR) than in those of Wistar-Kyoto rats (WKY). 2. Subsequent genetic co-segregation analyses by ourselves and others indicated that the SA gene locus did indeed influence blood pressure. Moreover, in a preliminary association study, we found an association of a polymorphism of the human SA gene with essential hypertension. 3. Further studies to identify functions of the SA gene products are required before reaching a definite conclusion.

Animals↗
PubMed1994

DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy.

BACKGROUND: The cardiac renin-angiotensin system has been suggested to be involved in the development of left ventricular hypertrophy. In humans, a strong correlation has been found between plasma angiotensin I-converting enzyme (ACE) activity and the insertion/deletion (I/D) polymorphism of the ACE gene, which has been reported to be associated with myocardial infarction, ischemic and idiopathic dilated cardiomyopathy, sudden death in hypertrophic cardiomyopathy, and restenosis after percutaneous transluminal coronary angioplasty. In the present study, we examined the possibility that the genotype of the ACE gene might influence the development of left ventricular hypertrophy. METHODS AND RESULTS: The study population consisted of 268 subjects randomly selected from our outpatient clinic. In 142 subjects, left ventricular mass (LVM) was determined by echocardiogram. The genotype of the ACE gene was determined by the polymerase chain reaction. ANCOVA revealed that the genotype of the ACE gene had no effect on blood pressure. The percentage of the explained variance of LVM with variables including diastolic blood pressure (DBP, P = .0001), body mass index (BMI, P = .0001), sex (P = .0009), and the genotype of the ACE gene (P = .0017) was 34.61%. Significant differences in the effects of the genotype of the ACE gene on LVM were observed between the II and DD (P = .0004) and between the ID and DD (P = .0077) genotypes. The percentage of the explained variance of the LVM/ht ratio with variables including sex (P = .134), age (P = .3655), the genotype of the ACE gene (P = .0014), BMI (P = .0001), and DBP (P = .0001) was 31.25%. Significant differences in the effects of the genotype of the ACE gene on LVM/ht were observed between the II and DD genotypes (P = .0003) and between the ID and DD genotypes (P = .0091). CONCLUSIONS: In addition to BMI and DBP, the genotype of the ACE gene was a significant predictor of LVM and LVM/ht in our study population.

Adult↗
PubMed1994

Human SA gene locus as a candidate locus for essential hypertension.

We have recently identified a candidate gene for rat genetic hypertension by identifying an mRNA species that shows markedly higher expression in the kidneys of spontaneously hypertensive rats than in those of Wistar-Kyoto rats. By using a restriction fragment length polymorphism, we carried out cosegregation analyses between the genotype of the SA gene and blood pressure in three F2 cohorts and observed significant effects of the SA gene on blood pressure in all of those cohorts. In the present study, we have isolated a human counterpart of the rat SA gene to investigate the possible association between the human SA gene and human essential hypertension. The deduced amino acid sequence from the isolated human SA cDNA consisted of 578 amino acid residues and had slight homology to a bacterial enzyme, acetyl-coenzyme A synthase. The human gene was mapped to the human chromosome 16 with the use of a rodent/human somatic hybrid cell panel. A restriction fragment length polymorphism was found with the restriction enzyme Pst I, and the allele frequencies were compared between hypertensive and control groups. The hypertensive group consisted of 89 individuals, and the Pst I rare allele (A2 allele) frequency in this group was 0.270. The control group consisted of 81 healthy normotensive individuals whose precise clinical data were available; the A2 allele frequency in this group was 0.09. Significant differences in the frequency of the A2 allele were observed between the hypertensive and control groups (P = .0001). The present findings provide favorable evidence that the SA gene is a candidate gene for human essential hypertension and also provide a starting point for future studies.

Adult↗
PubMed1994

Viability of one-cell bovine embryos cultured in vitro: comparison of cell-free culture with co-culture.

In this study, the quality (number of cells) and pregnancy rates of bovine blastocysts produced by in vitro maturation/in vitro fertilization (IVM/IVF) following cultivation in either cell-free culture or co-culture were compared. Bovine one-cell IVM/IVF embryos obtained 6 h after insemination were stripped of cumulus cells and assigned to either cell-free culture or co-culture with granulosa cell monolayers for 9 days (Expt 1) or 10 days (Expts 2 and 3). In Expt 3, day-7 (day 0 = day of insemination) blastocysts, day-8 expanded blastocysts and day-9 hatched blastocysts were air-dried, fixed and stained to determine the number of cells. Expanded blastocysts obtained in Expt 1 were cryopreserved using propylene glycol as a cryoprotectant and were used later for embryo transfer. There were no significant differences between cell-free culture and co-culture in the percentage of one-cell embryos that developed to 2- to 16-cells (66.7% versus 72.4% for Expt 1, 71.0% versus 78.2% for Expt 2). However, significantly more (P < 0.05) of the one-cell embryos co-cultured with granulosa cell monolayers developed to morula, blastocyst and expanded blastocyst stages compared with those in cell-free culture (35.0 versus 27.1%, 25.1 versus 14.2%, 15.6 versus 5.4% for Expt 1; 37.6 versus 24.0%, 25.7 versus 11.0%, 16.8 versus 3.0% for Expt 2). Only embryos co-cultured with granulosa cell monolayers hatched (Expt 2). Embryos co-cultured with granulosa cell monolayers also had higher (P < 0.01) numbers of cells (92 +/- 42 versus 56 +/- 21 for blastocysts, 149 +/- 53 versus 81 +/- 29 for expanded blastocysts).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Pharmacokinetic and clinical evaluation of cefozopran in the pediatric field].

We conducted a pharmacokinetic and clinical studies on cefozopran (CZOP), a new cephem antibiotic for injection. 1. Changes in serum levels of the agent after intravenous bolus injection at a dose of 20 mg/kg to 4 pediatric patients (age: 5-10 years) were observed. The levels at 30 minutes after injection were 32.9-73.4 micrograms/ml average: 55.4 +/- 18.1 micrograms/ml), then the levels gradually decreased with half-lives of 1.67-2.24 hours (average: 1.85 +/- 0.27 hours) to 0.8-1.8 micrograms/ml (average: 1.2 +/- 0.4 micrograms/ml) at 8 hours after injections. Urinary levels reached at the maximum as, 1,773-3,450 micrograms/ml (average: 2,693 +/- 698 micrograms/ml) within 0-2 hours or 2-4 hours after injection, and recovery rates from urine in the first 8 hours after injection were 55.4-91.1% (average: 71.6 +/- 16.8%). 2. Transition to cerebrospinal fluid was examined in cases with purulent meningitis and aseptic meningoencephalitis. In the meningitis case, the level in cerebrospinal fluid 1 hour after administration was 8.8 micrograms/ml in the second day after the start of 4 times a day intravenous bolus injections with 42.5 mg/kg at each dose; The ratio of the drug level in cerebrospinal fluid to that in serum was 24.0%. In the meningoencephalitis, the levels in cerebrospinal fluid 1 hour after administrations were 1.1 micrograms/ml and 1.5 micrograms/ml in the second and the sixth days respectively, after the start of 4 times a day intravenous bolus injections with 50 mg/kg at each dose; the ratio of the levels in cerebrospinal fluid to those in sera were 0.93% and 2.41% respectively, at the second and the sixth day. 3. CZOP was clinically evaluated in 29 cases (ages: 2 months to 15 years) of pediatric infectious diseases. The agent was administered 3-4 times daily with 17-50 mg/kg at each dose, continued for 5-13 days. Total doses were 1.95-24.05 g. Clinical efficacy was evaluated in a total of 28 cases (1 case of purulent meningitis, 2 cases of acute purulent tonsillitis, 20 cases of acute pneumonia, 3 cases of urinary tract infections, 1 case of purulent lymphadenitis in cervical part and 1 case of cellulitis in face); The efficacies were "excellent" in 22 cases and "good" in 6 cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1994

[Pharmacokinetic, bacteriological and clinical evaluation of biapenem (L-627) in the pediatric field].

Pharmacokinetic, bacteriological and clinical studies on biapenem (L-627), a newly developed carbapenem antibiotic, were performed in the field of pediatrics. 1. Antibacterial activities of biapenem against 54 strains of Streptococcus pneumoniae isolated in 1993 were compared with those of 13 other antibiotics, consisting primarily of beta-lactam compounds. Minimal inhibitory concentrations (MICs) of biapenem were < or = 0.78 micrograms/ml against all strains, and excellent values were obtained even against benzylpenicillin (PCG)-resistant strains. Based on MIC80 values, biapenem, imipenem, and cefuzonam showed highest antibacterial activities, followed by cefotaxime. 2. Blood concentrations and urinary excretion were studied after intravenous drip infusion of 6.0 mg/kg and 6.1 mg/kg of biapenem, given over 30 min., to two children (ages: 4 years and 11 years). Blood drug concentrations were 14.7 and 37.6 micrograms/ml, respectively (mean: 26.2 micrograms/ml), at 30 min. after starting infusion (at completion of infusion). Blood concentrations then declined gradually with half-lives of 0.66 and 1.16 hrs., respectively (mean: 0.91 hrs.). After 5.5 hrs., blood concentrations were no longer measurable in the former and 0.46 micrograms/ml in the latter. Urinary recovery rates of drug in the first 6 hrs. after starting administration were 65.8% and 60.9%, respectively (mean 63.4%). 3. Penetration of the drug to the cerebrospinal fluid (CSF) was studied in 2 patients with purulent meningitis. Biapenem, 31.6 mg/kg, was administered four times daily by 30-min. intravenous drip infusion. CSF concentration 1 hr. after administration was 8.54 micrograms/ml on the day of the start of treatment (day 0), and 3.00, 2.04, 16.1, 4.16, 3.24, and 1.60 micrograms/ml on days 1-7 of treatment, respectively. In a patient similarly administered with the drug at 33.7 mg/kg four times daily, the CSF concentration at 1.5 hrs. after administration was 2.62 micrograms/ml on the next day of the start of treatment. On days 2-7 of treatment, CSF concentrations at 0.5-1 hr. after administration were 4.60, 12.9, 20.6, and 1.32 micrograms/ml, respectively. 4. Clinical efficacy was evaluated in 27 patients with pediatric infections. The dose administered per dosage was 5.2-33.7 mg/kg. Three or four dosages were given daily. The duration of therapy ranged from 3 1/3 to 11 days. Total administered doses were between 0.675 and 20.475 g. Clinical efficacy was evaluated in a total of 24 patients (purulent meningitis 1, acute otitis media 1, acute bronchitis 2, acute pneumonia 19, acute urinary tract infection 1). Responses to treatment were excellent in 14 patients and good in 10 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

[Estimated prevalence of presenile dementia in Tottori prefecture].

A questionnaire study of dementia in the age group of 40-64 years old was performed among all hospitals and clinics in Tottori prefecture. Response rate was 52.9% (hospitals 53.2%, clinics 52.4%). A total of 100 patients (from April 1992 to March 1993) were reported. The estimated prevalence rate of all dementia in the age group of 40-64 years old was 81.4 per 100,000 population. Cerebrovascular dementia accounted for half and Alzheimer's disease, intoxication and trauma accounted for 14.0%, 11.5%, and 10.8% of dementia in the age group of 40-64 years old, respectively. There were several other types of dementia but numbers were very few. The estimated prevalence rates of cerebrovascular dementia in the age groups of 40-49, 50-59, and 60-64 years old were 0, 47.9 (male 66.0, female 31.5) and 113.2 (male 184.5, female 51.5), respectively. Those of Alzheimer's disease in the age groups of 40-49, 50-59, and 60-64 years old were 0, 5.6 (male 4.2, female 6.9) and 47.5 (male 50.3, female 45.0), respectively.

Adult↗
PubMed1994

[Pharmacokinetic, bacteriological and clinical evaluation of cefditoren pivoxil in pediatrics].

Pharmacokinetic, bacteriological, and clinical studies were performed in pediatrics on cefditoren pivoxil (CDTR-PI, ME1207) in granules. 1. Serum concentrations and urinary excretions of CDTR after administration of CDTR-PI to children (ages between 1 and 10) were investigated. Five cases were administrated with CDTR-PI at a dose level of 3 mg/kg 30 minutes after meal. Serum concentrations in these cases reached their peaks at 2 hours after administration with an average level of 1.23 +/- 0.34 micrograms/ml and diminished to 0.04 +/- 0.04 micrograms/ml at 8 hours after administration with a half-life of 1.60 +/- 0.38 hours. Urinary recovery rates of CDTR in the first 8 hours after administration of CDTR-PI averaged 14.9 +/- 0.9%. Five cases were administered with CDTR-PI at a dose level of 6 mg/kg 30 minutes after meal. Serum concentrations with the drug after meal reached their peaks at 1 hour after administration with an average level of 2.62 +/- 0.42 micrograms/ml and diminished to 0.21 +/- 0.11 micrograms/ml at 8 hours after administration with a half-life of 1.58 +/- 0.31 hours. Urinary recovery rates of CDTR in the first 8 hours after administration of CDTR-PI averaged 17.0 +/- 0.7%. These data also showed that serum and urinary concentrations of the drug depended on dose levels. 2. CDTR-PI was administered to 31 pediatric patients (their ages ranged between 1 year and 10 years) with various infections, and clinical and bacteriological effects and adverse reactions were investigated. Clinical effects were evaluable in 24 cases including 2 cases of scarlet fever, 1 case of acute pharyngitis, 12 cases of acute purulent tonsillitis, 4 cases of acute bronchitis, 5 cases of acute pneumonia. Clinical responses were excellent in 16 cases, effective in 8 cases, with an efficacy rate of 100%. Antimicrobial effects against a total of 16 strains identified or assumed to be pathogenic bacteria were evaluated. The 16 strains of bacteria included 4 strains of Staphylococcus aureus, 6 strains of Streptococcus pyogenes, 2 strains of beta-Streptococcus, 4 strains of Haemophilus influenzae. All the bacteria listed here were judged to have been eradicated except 2 strains of H. influenzae (1 was decreased and 1 was unchanged) thus, the eradication rate was 87.5%. Two strains of bacteria replaced infection causing bacteria. Streptococcus pneumoniae replaced S. pyogenes and S. aureus replaced H. influenzae. No adverse side reactions were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1993

Scientific basis for cancer prevention. Intermediate cancer markers.

Promising cancer clinical trials results involving the disruption of early stages of cancer with intervention agents such as tamoxifen or retinoids have led to significant new research interest in developing preventative strategy for the control of epithelial cancers. Key to the efficient progress in this field is a clear understanding of the complex biology of the early stages of cancerization that proceed on the epithelial surface. Systematic analysis of the biology of strategic targets such as growth factors is one approach to this problem. Gastrin-releasing peptide is an autocrine growth factor for certain types of lung cancer cells. Mechanisms involved in the production and activation of this peptide are discussed as an example of how rational approaches to neutralization of cancer promotion biology can be achieved. The tools to monitor the success of this type of intervention also emerge from the understanding of the biology of growth factors, and intermediate end point markers that determine the presence or effects of a growth factor are attractive candidates for evaluation. Additional biologic tools reflecting the early stages of the cancer process need to be validated for use in serially evaluating the status of the relevant epithelium so that the ongoing success of a cancer intervention procedure can be established. Through this type of translational research, important applications of molecular biology may greatly improve the success of preventative strategies for cancer control.

Anticarcinogenic Agents↗
PubMed1993

Cellular localization of angiotensin type 1 receptor and angiotensinogen mRNAs in the subfornical organ of the rat brain.

The cellular localization of angiotensin type 1 receptor (AT 1) and angiotensinogen mRNA expression in the subfornical organ (SFO) of the rat brain has been studied by means of non-radioactive in situ hybridization combined with immunocytochemistry for glial fibrillary acidic protein (GFAP) and Neutral red staining. The AT 1 receptor mRNA expression is shown to be within putative nerve cells without any association with the glial fibrillary acidic protein (GFAP)-immunoreactive (IR) cells. In contrast the angiotensinogen cRNA expression is associated predominantly with GFAP-IR cells. The results demonstrate that a neuronal AT 1 receptor mediates the actions of circulating angiotensin II on the SFO and that the angiotensinogen mRNA is predominantly expressed in the SFO astroglial cells.

Angiotensin I↗
PubMed1993

Biofeedback therapy for fecal incontinence after surgery for anorectal malformations: preliminary results.

Eight patients with fecal incontinence after surgery for anorectal malformations received one to four sessions of biofeedback therapy. The physiologic status of the anorectum before and after biofeedback therapy was investigated by anorectal manometry and electromyography of the external sphincter. The effectiveness of biofeedback treatment and the indications for its use in patients with fecal incontinence were investigated. Three of the four patients responded well to biofeedback therapy following three or four training sessions. However, in the other five patients who had only one or two sessions, a good response to the therapy was not obtained. Anorectal manometry and electromyography recordings of the external sphincter showed that biofeedback therapy improved voluntary sphincter function. The three good responders had an adequate and resting pressure both before and after biofeedback therapy and had good electrical activity of the external sphincter after therapy. In the presence of adequate resting and pressure, biofeedback therapy should be attempted for the treatment of fecal incontinence after correction of anorectal malformations before resorting to further surgical intervention. However, biofeedback therapy may not be suitable if the sphincters are markedly hypoplastic, or do not surround the anal canal after an inappropriate pull-through operation.

Anal Canal↗