Biomedical subjects

N Iwasaki

Publications and source records attributed to N Iwasaki.

At least 37 records · Page 2Linked to original sources

PubMed2001

Immunocytochemical study of G(i)2alpha and G(o)alpha on the epithelium surface of the rat vomeronasal organ.

To investigate in detail the distribution of G protein subtypes G(i)2alpha and G(o)alpha along the surface of the vomeronasal epithelium, we used double labeling immunocytochemical methods and electron microscopy. We examined the immunoreactivity of these surface structures with antibodies against G(i)2alpha and G(o)alpha. G(i)2alpha- and G(o)alpha-positive cells were observed at the epithelial surface and were evenly distributed. Electron microscopy revealed that strong immunoreactivities to both antibodies were observed on the microvilli and knob-like surface structures of receptor cells. No immunoreactivity was found on the microvilli or surface membranes of supporting cells. This expression pattern is similar to that reported for putative pheromone receptors. These data confirm that there are two distinct classes of vomeronasal receptor cells expressed at the surface of the epithelium. These two classes of receptors correspond to the same G(i)2alpha- and G(o)alpha-positive cells distributed in cell body layers of the epithelium and in the axon terminals in the accessory olfactory bulb.

Animals↗

PubMed2001

Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 1. Conversion of 5-substituent on oxazolidinone.

A structure-activity relationship (SAR) study on 5-substituted oxazolidinones as an antibacterial agent is described. The oxazolidinones, of which 5-acetylaminomethyl moiety was converted into other functions, were prepared and evaluated for antibacterial activity. Elongation of the methylene chain (8) and conversion of the acetamido moiety into guanidino moiety (12) decreased the antibacterial activity. The replacement of carbonyl oxygen (=O) by thiocarbonyl sulfur (=S) enhanced in vitro antibacterial activity. Especially, compound 16, which had the 5-thiourea group, showed 4-8 stronger in vitro activity than linezolid. Our SAR study revealed that the antibacterial activity was greatly affected by the conversion of 5-substituent.

Anti-Bacterial Agents↗

PubMed2001

Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 2. Relationship between lipophilicity and antibacterial activity in 5-thiocarbonyl oxazolidinones.

5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents considering the hydrophobic parameters of the molecule. The structure-activity relationship (SAR) study revealed that the antibacterial activity on 5-thiocarbonyl oxazolidinones was significantly affected by the lipophilicity, especially the calculated log P value and the balance between 5-hydrophilic (or hydrophobic) substituent and hydrophobic (or hydrophilic) substituents on the benzene ring. Some of 5-thiocarbonyl oxazolidinones were found to have good in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Anti-Bacterial Agents↗

PubMed2001

Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 3. Synthesis and evaluation of 5-thiocarbamate oxazolidinones.

A series of 5-thiocarbamate oxazolidinones was prepared and tested for in vitro and in vivo antibacterial activities. The results of in vitro antibacterial activity indicated that the 5-thiocarbamate group was a suitable substituent for the activity by the 5-moderate hydrophilicity. The compounds within a favorable logP value range were found to have potent in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Compounds 3a and 4h were superior to linezolid in both in vitro and in vivo potency and were considered to be hopeful compounds. We also discuss the pharmacokinetic properties of several compounds in mice.

Anti-Bacterial Agents↗

PubMed2001

An improved synthesis of butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224).

A new and facile route for the synthesis of the novel gastrointestinal prokinetic butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (1b), which exhibited potent gastro- and colon-prokinetic activities by oral administration without significant side effects, was established. The key intermediate, butyl 4-amino-1-piperidineacetate (16), was prepared from commercially available 4-amino-1-benzylpiperidine (2) in a high yield with four steps. Compound 1b was prepared by condensation of commercially available 4-amino-5-choloro-2-methoxybenzoic acid (7) with 16 in 84% yield. This improved synthetic route was appropriate for large-scale synthesis of 1b.

Gastrointestinal Agents↗

PubMed2001

Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a common cause of maturity-onset diabetes of the young in Japanese subjects.

Mutations in transcription factors that play a role in the development of the endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have been associated with diabetes. Cell type-specific members of the basic helix-loop-helix (bHLH) family of transcription factors play essential roles in the development and maintenance of many differentiated cell types, including pancreatic beta-cells. Neurogenin 3 is a bHLH transcription factor that is expressed in the developing central nervous system and the embryonic pancreas. Mice lacking this transcription factor fail to develop any islet endocrine cells and die postnatally from diabetes. Because neurogenin 3 is required for the development of beta-cells and other pancreatic islet cell types, we considered it a candidate diabetes gene. We screened the coding region of the human neurogenin 3 gene (NEUROG3) for mutations in a group of unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three sequence variants: a deletion of 2-bp in the 5'-untranslated region (NEUROG3-g.-44-45delCA), a G-to-A substitution in codon 167 (g.499G/ A), resulting in a Gly-to-Arg replacement (G/R167), and a T-to-C substitution in codon 199 (g.596T/C), resulting in a Phe/Ser polymorphism F/S199. These polymorphisms were not associated with MODY, thereby suggesting that mutations in NEUROG3 are not a common cause of MODY in Japanese patients.

Amino Acid Substitution↗

PubMed2001

The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes.

The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial. The prevalence of this polymorphism and its effects on clinical characteristics have now been evaluated with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and normal control subjects (n = 1,212) recruited by 10 institutions located in seven different cities in Japan. The allele frequency for the Ala12 variant was significantly lower in the type 2 diabetic group than in the control group (2.39 vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12 variant, the diabetic subjects with this variant exhibited a significantly higher serum concentration of total cholesterol (P = 0.001), manifested a reduced capacity for insulin secretion as evaluated by homeostasis model assessment (P = 0.007), and tended to possess a higher level of HbA1c. These data suggest that the Ala12 variant is associated with a reduced risk for the development of diabetes in the general population, but that it may be also a risk factor for insulin deficiency and disease severity in individuals with type 2 diabetes.

Adult↗

PubMed2001

Effect of NaClO treatment on bonding to root canal dentin using a new evaluation method.

The purposes of this study were to investigate the reliability and efficiency of a new evaluation method for resin bonding to root canal dentin, which measures both marginal adaptation and shear bond strength simultaneously, and to determine the effects of root canal irrigants on resin bonding. A wet bonding system (Single Bond) and a self-etching primer system (Clearfil Mega Bond) were employed; NaClO was used as a root canal irrigant. No gaps or changes in bond strength were observed despite the NaClO treatment when the wet bonding system was employed, while the gap formation ratio increased, and bond strength decreased with longer NaClO treatment time when the self-etching primer system was employed. These findings suggested that this new experimental method was effective for evaluating resin systems to the root canal wall dentin which is affected by irrigation with NaClO.

Animals↗

PubMed2001

[A new machinability test machine and the machinability of composite resins for core built-up].

A new machinability test machine especially for dental materials was contrived. The purpose of this study was to evaluate the effects of grinding conditions on machinability of core built-up resins using this machine, and to confirm the relationship between machinability and other properties of composite resins. The experimental machinability test machine consisted of a dental air-turbine handpiece, a control weight unit, a driving unit of the stage fixing the test specimen, and so on. The machinability was evaluated as the change in volume after grinding using a diamond point. Five kinds of core built-up resins and human teeth were used in this study. The machinabilities of these composite resins increased with an increasing load during grinding, and decreased with repeated grinding. There was no obvious correlation between the machinability and Vickers' hardness; however, a negative correlation was observed between machinability and scratch width.

Acrylic Resins↗

PubMed2001

[Regional variation in bone mineral density and motor function in children with cerebral palsy].

Bone mineral density (BMD) and motor activity of the upper extremities, were studied in 18 children with spastic cerebral palsy (CP group) and 12 age-matched normal boys (control group). The motor activity was monitored by a piezoelectric transducer. Whole body BMD as well as BMD of the head, upper limbs, ribs, spine, pelvis, and lower limbs was evaluated by dual energy x-ray absorptiometry. In the CP group, BMDs were lower compared to control group in the whole body and in all the body regions (except for the head) especially in the pelvis and lower limbs. BMDs of these regions were higher in walking patients than in bed-ridden, rolling, and crawling patients. Motor activities in the upper extremities were lower in the CP than in the control group. BMD increased with developing motor activity in the upper extremities. These results implicate diminished BMDs of the lower limbs and pelvis, which are associated with standing and walking, to the high incidence of femur fractures in CP.

Absorptiometry, Photon↗

PubMed2001

[Diabetes mellitus].

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. Genetic factors contribute to the development of diabetes. Some forms such as the condition called maturity-onset diabetes of the young(MODY) result from mutations in a single gene. Other forms such as type 1 or type 2 diabetes are multifactorial in origin with different combinations of genes together with non-genetic factors contributing to the development of hyperglycemia. MODY has been a good model for studying the genetics and pathophysiology of diabetes. This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1 alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5, NeuroD1/MODY6 and Islet(Isl)-1/MODY7. Mutations in HNF-1 alpha/MODY3 are the most common cause of MODY in Japanese identified to date accounting for about 15% of cases of MODY. Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of MODY. Clinical studies indicate that patients with MODY are generally not obese and that all forms of MODY are characterized by pancreatic beta-cell dysfunction. Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal cysts. Female carriers may also exhibit abnormalities in the upper vagina and uterus. Genetic approach for type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to date. The responsible gene for NIDDM1 was recently identified to be Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American type 2 diabetes.

Diabetes Mellitus↗

PubMed2000

Significant evidence for linkage of febrile seizures to chromosome 5q14-q15.

Febrile seizures (FSs) represent the most common form of childhood seizure. In the Japanese population, the incidence rate is as high as 7%. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p), have been mapped. Furthermore, a mutation in the voltage-gated sodium (Na(+))-channel beta1 subunit gene ( SCN1B ) at chromosome 19q13.1 was identified in a family with a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)). These loci are linked to some large families. In this study, we conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families. Significant linkage was found at D5S644 by multipoint non-parametric analysis using GENEHUNTER ( P = 5.4 x 10(-6)). Estimated lambda(s)at D5S644 was 2.5 according to maximum likelihood analysis. Significant linkage disequilibria with FS were observed at the markers D5S644, D5S652 and D5S2079 in 47 families by transmission disequilibrium tests. These findings indicate that there is a gene on chromosome 5q14-q15 that confers susceptibility to FSs and we call this gene FEB4.

Child, Preschool↗

PubMed2000

Action tremor during object manipulation in Parkinson's disease.

In previous studies of fingertip forces during precision grip in subjects with Parkinson's disease (PD), we observed regular oscillations in isometric force. The present study characterizes the nature of these oscillations. Fingertip forces were recorded from the index finger and thumb during precision grip-lifts with a 300 g and 900 g object in 10 subjects with PD and 20 healthy control subjects. Fourier analysis confirmed that all subjects with PD exhibited force oscillations with a clearly definable frequency (approximately 7-11 Hz). Five of these subjects also exhibited a second lower frequency peak (approximately 5 Hz). Approximately half of the 20 control subjects displayed a single frequency peak (approximately 8-12 Hz), which was generally lower in amplitude than in the subjects with PD (representing enhanced physiological tremor), whereas the remaining control subjects had low-amplitude, broad-based spectra (representing physiological tremor). The amplitude of the force oscillations was higher for lifts with the heavier object in both the control subjects and subjects with PD. L-Dopa resulted in a decreased tremor amplitude but did not influence the frequency. The force oscillations of the two opposing digits normal to the grip surfaces were in phase, whereas the oscillations tangential to the grip surfaces were often out of phase. The results suggest that the multipeaked force rate trajectories reported previously are caused by action tremor. The similarity of force oscillations in subjects with PD and healthy control subjects suggests common tremor-generating mechanisms and supports the notion that the parkinsonian action tremor (AT) is an exaggerated form of physiological tremor. These findings provide insight into the impaired hand function observed in individuals with PD.

Adult↗

PubMed2000

No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4gamma gene (HNF4G) in Japanese patients with MODY.

AIMS/HYPOTHESIS: Mutations in the transcription factor hepatocyte nuclear factor (HNF)-4alpha are the cause of one form of maturity-onset diabetes of the young, MODY1. The HNF-4gamma is structurally related to HNF-4alpha and is expressed together with HNF-4alpha in pancreatic islets. We therefore tested the hypothesis that genetic variation in the HNF-4gamma gene (HNF4G) is associated with MODY in Japanese subjects. METHODS: We screened the protein coding region of HNF4G (exons 3-11) for mutations in 57 unrelated Japanese subjects with MODY by amplifying each exon and adjacent intron region using the polymerase chain reaction (PCR) and specific primers and then directly sequencing the PCR products. The frequency of each variant was compared between patients with MODY and a group of non-diabetic subjects. RESULTS: We found ten sequence variants, two of these were located in exons: exon 6, a silent substitution in codon 144, c.432A/G and exon 7, a G-to-A substitution in codon 190 (c.570G/A) resulting in a conservative Met-to-Ile substitution (M/I190) in the putative ligand-binding region of HNF-4gamma protein. The remaining eight variants were located in introns. There was no significant difference in the frequency of these polymorphisms between subjects with MODY and non-diabetic control subjects. CONCLUSION/INTERPRETATION: Genetic variation in the coding region of HNF4G is unlikely to be a major cause of MODY in Japanese people.

Amino Acid Sequence↗

PubMed2000

Coracoacromial arch decompression in rotator cuff surgery.

In rotator cuff surgery it is important to obtain adequate decompression of the coracoacromial arch. However, it is difficult to localize the impingement site preoperatively. Based on histological and morphological studies and the clinical findings in 45 patients and 15 cadavers, we have tried to determine the impingement site. In addition, as a part of these investigations, we assessed the clinical outcome for 100 patients. Soft tissue decompression was indicated in 12 shoulders, anterior acromioplasty in 67 and anterior acromioplasty with coracoplasty in 21. According to Neer's criteria there were 92 satisfactory and 8 unsatisfactory results. The mean postoperative UCLA score was 33.4 points and the results were rated excellent in 78, good in 18 and fair in 4.

Acromion↗

PubMed2000

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Adult↗

PubMed2000

Force distribution through the wrist joint in patients with different stages of Kienböck's disease: using computed tomography osteoabsorptiometry.

The pattern of subchondral bone density has been considered to reflect the stress distribution that occurs under physiologic loading conditions. To determine the force distribution through the wrist joint with Kienböck's disease in living subjects, we applied a computed tomography osteoabsorptiometry and investigated the subchondral bone density pattern across the radio-carpal joint of 6 normal subjects and 10 patients suffering from Kienböck's disease (Lichtman's stage IIIA, 5 patients; stage IIIB, 5 patients). A single density maximum was found in each scaphoid and lunate fossa in all normal subjects. Among the subjects with Kienböck's disease, the current analysis demonstrated that the density maximum area significantly increased in the scaphoid fossa and decreased in the lunate fossa from stage IIIA to IIIB group. These findings indicate that the load is shifted away from the lunate to the scaphoid with the progression of Kienböck's disease in living subjects.

Absorptiometry, Photon↗

PubMed2000

Modification of the Sauvé-Kapandji procedure with extensor carpi ulnaris tenodesis.

The Sauvé-Kapandji procedure is a useful treatment option for osteoarthritis of the distal radioulnar joint. Recent reports of a painful unstable proximal ulnar stump prompted us to develop a method of stabilizing the proximal stump of the ulna during the Sauvé-Kapandji procedure by using a half-slip of the extensor carpi ulnaris. Thirteen osteoarthritic wrists (8 primary and 5 traumatic) in 8 men and 5 women with an average age of 50 years were treated by this method. The length of the follow-up periods averaged 36 months. Pain improved in all patients after surgery but pain was elicited over 1 ulnar stump by direct pressure. Both pronation/supination and flexion/extension had statistically significant improvement with the exception of flexion. Grip strength improved in all wrists after surgery. Postoperative x-rays improved alignment in both coronal and lateral planes. Stabilization of the proximal ulnar stump associated with Sauvé-Kapandji procedure is a useful procedure to prevent an unstable ulnar stump in the treatment of osteoarthritis of the distal radioulnar joint.

Adult↗