Biomedical subjects

T Shimokawa

Publications and source records attributed to T Shimokawa.

At least 19 recordsLinked to original sources

PubMed2002

Nervous branch passing through an accessory canal in the sphenozygomatic suture: the temporal branch of the zygomatic nerve.

A nervous branch which passes through a small canal in the sphenozygomatic suture is sometimes observed during dissection. To examine the origin, course and distribution of this nervous branch, 42 head halves of 21 Japanese cadavers (11 males, 10 females) and 142 head halves of 71 human dry skulls were used. The branch was observed in seven sides (16.7%); it originated from the communication between the lacrimal nerve and the zygomaticotemporal branch of the zygomatic nerve or from the trunk of the zygomatic nerve. In two head halves (4.8%), the branch pierced the anterior part of the temporalis muscle during its course to the skin of the anterior part of the temple. The small canal in the suture was observed in 31 head halves (21.8%) of the dry skulls. Although this nervous branch is inconstantly observed, it should be called the temporal branch of the zygomatic nerve according to the constant positional relationship to the sphenoid and zygomatic bones. According to its origin, course and distribution, this nervous branch may be considered to be influential in zygomatic and retro-orbital pain due to entrapment and tension from the temporalis muscle and/or the narrow bony canal. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00276-002-0027-4.

Cadaver↗

PubMed2001

Aberrant muscle between the temporalis and the lateral pterygoid muscles: M. pterygoideus proprius (Henle).

During examination of the positional relationships between the lateral pterygoid and the temporalis muscles and the innervating nerves, an aberrant muscle was observed in three of 66 head halves. The aberrant muscle originated from the medial surface of the anteromedial muscle bundle of the temporalis (Shimokawa et al. 1998, Surg. Radiol. Anat. 20:329-334) and inserted into the inferolateral surface of the lower head of the lateral pterygoid. Due to its location, origin and insertion this aberrant muscle slip is considered to correspond to the pterygoideus proprius described by Henle (1858, Handbuch der Anatomie des Menschen). Based on the innervation findings, the present aberrant muscle might be considered as a remnant muscle bundle between the anteromedial muscle bundle of the temporalis and the lateral pterygoid during differentiation of the lateral masticatory muscle anlage.

Adult↗

PubMed2001

Polymorphism in promoter region of Fcalpha receptor gene in patients with IgA nephropathy.

We have recently identified two novel polymorphisms (-114T/C and +56T/C relative to the major transcription start site) in the functional promoter region of the Fcalpha receptor (FcalphaR) gene. Since altered FcalphaR expression may be associated with IgA nephropathy, we examined these promoter polymorphisms in this disease. Patients with IgA nephropathy (n = 90), patients with other primary glomerulonephritis (n = 50), and healthy adults (n = 83) were studied. Genotyping was performed by the polymerase chain reaction (PCR) followed by direct sequence analysis and was subsequently confirmed by PCR with mismatched primers followed by restriction fragment length polymorphism analysis. The study demonstrated that the frequency of the +56C allele in patients with IgA nephropathy (0.511) was significantly (P < 0.01) higher than that in patients with other primary glomerulonephritis (0.350) and healthy adults (0.337). In addition, a significant increase in the frequency of the +56CC genotype was observed in patients with IgA nephropathy (27.8% vs 10.0% in other GN and vs 9.6% in healthy adults). In contrast, no significant difference in the frequencies of the +56CC genotype and +56C allele was observed between other primary glomerulonephritis patients and healthy adults. The frequency of the -114CC genotype in patients with IgA nephropathy was significantly increased compared with those in both control groups (15.6% vs 4.0% in other GN and vs 2.4% in healthy adults). Polymorphisms of the FcalphaR promoter region therefore appear to be associated with susceptibility to IgA nephropathy, suggesting the importance of the FcalphaR gene and its expression in this disease.

Adolescent↗

PubMed2001

Application of pressure-controlled colon delivery capsule to oral administration of glycyrrhizin in dogs.

A colon delivery system has been used to improve the bioavailability of glycyrrhizin, a glycoside of glycyrrhetic acid. The bioavailability of glycyrrhizin is low when administered in conventional oral galenic dosage forms because glycyrrhizin is enzymatically hydrolysed both in the stomach and in the intestine. It was reasoned that if large amounts of glycyrrhizin were directly delivered to the colon, enzymatic activity should be reduced due to saturation so that intact glycyrrhizin could be absorbed into the systemic circulation. Based on this assumption, pressure-controlled colon delivery capsules (PCDCs) were used as a colon delivery system. Eight types of glycyrrhizin solution were prepared and were introduced into PCDCs. After oral administration of the test PCDCs to beagle dogs, blood samples were obtained over 24 h and plasma glycyrrhizin concentrations were measured by an HPLC method. With PCDCs containing aqueous glycyrrhizin and propylene glycol solutions, plasma glycyrrhizin levels were extremely low and the bioavailabilities of glycyrrhizin were 0.6% and 0.4%, respectively. When Labrasol was added to both types of glycyrrhizin solution, the bioavailability was improved to 4.6% for aqueous solution and 3.8% for propylene glycol solution. When a surfactant, Polysorbate 80, was added in combination with Labrasol, synergistic effects were not obtained. Furthermore, dose-dependent effects of Polysorbate 80 were not obtained. Labrasol, which is a component of self-emulsifying drug delivery systems (SEDDS), has been shown to strongly improve the bioavailability of glycyrrhizin from the colon.

Administration, Oral↗

PubMed2001

Expression of protein S in the murine heart and cultured mouse cardiomyocytes is down-regulated by cytokines.

Protein S (PS), a co-factor of activated protein C, is a vitamin K-dependent anticoagulant protein and is known to be produced extrahepatically. In the present study, the concentration of PS mRNA was determined tissue by tissue in the mouse, and it was high in lung, adrenal and heart as well as in liver. We further investigated the effects of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1) on the PS mRNA expression in murine tissues in vivo. Although LPS and TNF-alpha significantly decreased the expression level of PS mRNA in all tissues examined (e. g., lung, liver, heart, and kidney) and the PS antigen level in plasma, the suppressive effect of IL-1 on PS gene expression was limited to heart. More specifically, considerable amounts of PS mRNA and antigen were expressed in a cultured mouse cardiomyocyte cell line, and again, treatment with IL-1 decreased the PS expression in these cells. These observations raise a possibility that the expression of cardiac PS may contribute to the regional anticoagulant potential in heart, and suggest that the decreased PS expression by cytokines may result in an increase in the systemic and/or regional prothrombotic potential under inflammatory conditions.

Adrenal Glands↗

PubMed2000

Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells.

We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investigate the mechanism of this stimulation, we determined the redistribution of insulin-regulatable glucose transporter isotype 4 (Glut4). When fully differentiated C2C12 cells stably expressing myc-tagged Glut4 protein were treated with YM-126414, redistribution was dramatically increased in a dose-dependent manner (EC(50)=21 nM). These results indicate that YM-126414 is a novel glucose uptake stimulator for muscle cells by causing up-regulation of Glut4 redistribution in differentiated muscle cells. Our findings for the in vitro effects of YM-126414 suggest a direction for the development of new drugs for the treatment of type 2 diabetes.

Animals↗

PubMed2000

Down-regulation of murine tissue factor pathway inhibitor mRNA by endotoxin and tumor necrosis factor-alpha in vitro and in vivo.

Tissue factor pathway inhibitor (TFPI) is the protease inhibitor that regulates the extrinsic coagulation pathway initiated by the factor VIIa/TF complex. In this study, we first investigated tissue distribution of TFPI mRNA in the mouse and found that TFPI mRNA expression level was by far the highest in the lung, followed by the heart, adrenal, and adipose tissue. Since little has been known concerning the regulation of TFPI gene expression in vivo, we further analyzed the changes in the TFPI mRNA level in murine tissues after intraperitoneal injection of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1). LPS and TNF-alpha dramatically decreased TFPI mRNA expression in four tissues examined (e.g., lung, heart, kidney, and adipose tissue), whereas the suppressive effect of IL-1 on TFPI mRNA was limited. The down-regulation of TFPI mRNA expression by LPS and TNF-alpha was also observed in cultured mouse endothelial cells and in cardiomyocyte cell lines. The decreased TFPI mRNA expression by LPS and TNF-alpha in tissues and in the specific cell types may contribute to an increase in the local procoagulant potential, resulting in the thrombotic tendency under septic and/or inflammatory conditions.

Animals↗

PubMed2000

cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats.

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells. In the present study, we first cloned a rat PGC-1 gene from a brown adipose tissue cDNA library which encodes a predicted 796-amino-acid protein and exhibits respectively 98% and 95% identity with the mouse and human homologues. Next, we examined the effect of swimming exercise training on the level of expression of the PGC-1 gene in rat epitrochlearis (Epi) muscle. PGC-1 mRNA level in Epi muscle in rats that swam 2 h a day for 3 and 7 days increased dramatically by 154% and 163%, respectively, compared to the non-exercised control group. PGC-1 mRNA up-regulation was not observed in an immersion group treated at 35 degrees C during the training program but without swimming exercise. These results demonstrate that expression of the PGC-1 gene in Epi muscle is induced not only by cold exposure but also by prolonged low-intensity physical exercise.

Animals↗

PubMed2000

DNA induces apoptosis in electroporated human promonocytic cell line U937.

Experimental gene transfer has permitted a wide variety of studies on gene regulation and function. However, possible effects of the introduced DNA on cellular metabolism are not well understood. Here we demonstrated that introduction of DNA into a promonocytic cell line, U937, by electroporation caused extensive cell death. The toxicity of DNA was concentration-dependent. Various DNAs including plasmid and genomic DNAs all caused cell death, indicating that the toxicity is nucleotide sequence-independent. DNA-induced cell death was associated with internucleosomal DNA fragmentation, a decrease in cell size, and a considerable proportion of cells outside cell cycle. From these results, we concluded that cells died by apoptosis. Our findings have experimental implication for an important issue concerning the interpretation of experiments using gene transfer. In addition, we propose that our observed phenomenon may be relevant to an important immune defense mechanism in monocytes/macrophages that facilitates a response to certain viral infections.

Apoptosis↗

PubMed2000

Characteristics of intestinal absorption and disposition of glycyrrhizin in mice.

As basic studies to apply an intestinal pressure-controlled colon delivery capsule (PCDC) for glycyrrhizin (GZ), the characteristics of intestinal absorption and disposition of GZ were investigated in mice. In the in vivo study, after intravenous (iv) administration of GZ, 10 mg/kg dose, plasma GZ disappeared from the systemic circulation with t(1/2(alpha)) of 0.0063 h, thereafter, it slowly declined with t(1/2(beta)) of 15.23 h. The area under the plasma drug concentration versus time curve (AUC) values of iv (10 mg/kg), intracolonic (50 mg/kg) and intraduodenum (50 mg/kg) administrations were 115.1, 16.7 and 2.7 microgh/mL, respectively. The AUC values of plasma glycyrrhetic acid (GA), a degradation product after intracolonic and intraduodenum administrations were 2.8 and 8.4 microgh/mL, respectively. In the in situ closed loop study, the concentrations of GZ in plasma and liver after intracolonic administration were significantly increased (p<0.05) in comparison with those after intrajejunum or intraileum administration, while the concentration of GA in plasma and liver after intracolonic administration had trends to increase. These observations clearly suggest that the intracolonic administration is a useful way to improve the oral bioavailability of GZ and to enhance its pharmacological efficacy. These pharmacokinetic results of GZ suggest that GZ is a subject drug to be applied for the PCDC system we previously developed. The PCDCs formulation of GZ will enable us to carry GZ to the colon and enhance the oral bioavailability of GZ.

Animals↗

PubMed2000

Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcalphaR, CD89).

The Fc receptor for IgA (FcalphaR, CD89), a transmembrane glycoprotein, is expressed exclusively on human phagocytic cells including monocytes, macrophages, eosinophils, and neutrophils, and is capable of triggering various effector functions. In the present study, we identified and characterized, for the first time, the FcalphaR promoter. A 929-bp fragment of FcalphaR 5'-flanking sequence directed expression of a reporter gene specifically in monocytic cell line U937. Deletion analyses localized element(s) directing tissue-specific reporter gene expression to the 259 bp proximal to the translation initiation site. Within the region, the sequence between 59 and 197 bp downstream of the major transcription start site was shown to be essential for promoter activity. This sequence contains multiple potential binding sites for transcription factors which have been reported to function in myeloid-specific gene expression, including three CCAAT enhancer-binding protein (C/EBP)-binding sites, an NF-kappaB-binding site, an Spl site, an Ets family protein consensus-binding site, and a Myb-binding site. In addition, we identified two polymorphisms (C-->T transition) at the positions 114 bp upstream and 56 bp downstream of the major transcription start site, and demonstrated that the FcalphaR promoter region carrying both the -114T and +56T alleles had significantly lower promoter activity than that harboring the C alleles at both sites. Characterization of this promoter will facilitate further analyses of activation stimuli and transcription factors involved in FcalphaR-mediated immune system, and provide new insights into the mechanism(s) underlying altered FcalphaR expression associated with diseases such as allergic diseaes and IgA nephropathy.

Antigens, CD↗

PubMed2000

A first-passage-time analysis of the periodically forced noisy leaky integrate-and-fire model.

We present a general method for the analysis of the discharge trains of periodically forced noisy leaky integrate-and-fire neuron models. This approach relies on the iterations of a stochastic phase transition operator that generalizes the phase transition function used for the study of periodically forced deterministic oscillators to noisy systems. The kernel of this operator is defined in terms of the the first passage time probability density function of the Ornstein Uhlenbeck process through a suitable threshold. Numerically, it is computed as the solution of a singular integral equation. It is shown that, for the noisy system, quantities such as the phase distribution (cycle histogram), the interspike interval distribution, the autocorrelation function of the intervals, the autocorrelogram and the power spectrum density of the spike train, as well as the input-output cross-correlation and cross-spectral density can all be computed using the stochastic phase transition operator. A detailed description of the numerical implementation of the method, together with examples, is provided.

Action Potentials↗

PubMed2000

Positional relationships between the masticatory muscles and their innervating nerves with special reference to the lateral pterygoid and the midmedial and discotemporal muscle bundles of temporalis.

For an accurate assessment of jaw movement, it is crucial to understand the comprehensive formation of the masticatory muscles with special reference to the relationship to the disc of the temporomandibular joint. Detailed dissection was performed on 26 head halves of 14 Japanese cadavers in order to obtain precise anatomical information of the positional relationships between the masticatory muscles and the branches of the mandibular nerve. After complete removal of the bony elements, the midmedial muscle bundle in all specimens and the discotemporal muscle bundle in 6 specimens, derivatives of the temporalis, which insert into the disc were observed. On the anterior area of the articular capsule and the disc of the temporomandibular joint, the upper head of the lateral pterygoid, the midmedial muscle bundle of temporalis and the discotemporal bundle of temporalis were attached mediolaterally, and in 3 specimens the posterosuperior margin of the zygomaticomandibularis was attached to the anterolateral area of the disc. It is suggested that these muscles and muscle bundles contribute to various mandibular movements. Although various patterns of the positional relationships between the muscles and muscle bundles and the their innervating nerves are observed in the present study, relative positional relationships of the muscles and muscle bundles and of nerves of the mandibular nerve are consistent. A possible scheme of the developmental formation of the masticatory muscles based on the findings of the positional relationships between the muscles and the nerves is presented.

Female↗

PubMed2000

Colon delivery efficiencies of intestinal pressure-controlled colon delivery capsules prepared by a coating machine in human subjects.

Large quantities of pressure-controlled colon delivery capsules (PCDCs) were prepared by a Hicoater-mini pharmaceutical coating machine and colon delivery efficiencies were evaluated in man. Caffeine powder as a model drug was suspended with a polyethylene glycol (PEG) 1000 suppository base at 50 degrees C, and was hardened in no. 0- and no. 2-sized capsular shapes. The capsule-shaped suppositories were coated with 5% w/v ethanolic ethylcellulose (7G grade) solution using the coating machine. By increasing the coating weight of ethylcellulose from 28.6 +/- 1.1 mg to 45.3 +/- 0.2 mg, the mean coating thickness of no. 0 PCDCs increased from 56 +/- 1 microm to 64 +/- 1 microm. With no. 2 PCDCs, the mean coating thickness increased from 50 micro +/- 1 microm to 57 +/- 1 microm by increasing the coating weight of ethylcellulose from 8.1 +/- 0.5 mg to 11.2 +/- 0.3 mg. The no. 0 PCDCs, having a mean ethylcellulose coating membrane thicknesses of 56 +/- 1 microm (type 1) and 64 +/- 1 microm (type 2), as well as no. 2 PCDCs, having thicknesses of 50 +/- 1 microm (type 3) and 57 +/- 1 microm (type 4), were used for in-vivo evaluation in man. After oral administration of test preparations containing 75 mg of caffeine, saliva samples were obtained and salivary caffeine levels were measured by an HPLC method. The first appearance time, Ti, of caffeine in the saliva was used as a parameter for the estimation of the release time of caffeine from PCDCs in the gastrointestinal tract. The mean Ti values of no. 0 PCDCs were 3.3 +/- 0.3 h for type- 1 and 5.3 +/- 0.3 h for type-2 preparations while the mean Ti values of no. 2 PCDCs were 4.3 +/- 0.5 h for type 3 and 5.3 +/- 0.3 h for type 4. There were good correlations between ethylcellulose coating membrane thicknesses and in-vivo Ti values. A colon arrival time of 5 h was reported in our subjects by gastrointestinal magnetomarkergraphy. PCDCs having a mean coating thickness of 64 +/- 1 microm for no. 0 capsules and of 57 +/- 1 microm for no. 2 capsules were thought to deliver caffeine to the human colon efficiently.

Adult↗

PubMed2000

[A case of heart surgery without homologous transfusion for complete atrioventricular septal defect associated with tetralogy of Fallot].

We performed intracardiac repair in an 11-month-old infant, weighing 5.1 kg, with complete atrioventricular septal defect and tetralogy of Fallot, who had been on a respirator, preoperatively, because of congestive heart failure due to severe common atrioventricular valve regurtitation. The preoperative angiogram revealed a very narrow and hypoplastic left pulmonary artery. Autologous blood donation after induction of anesthesia and minimalization of the cardiopulmonary bypass circuit (priming volume: 230 ml) made it possible to perform open-heart surgery without homologous blood transfusion in this case. The perioperative hemodynamics and respiratory status were satisfactory. An angiogram taken 1 year after surgery showed a well-developed left pulmonary artery.

Blood Transfusion, Autologous↗

PubMed2000

[Surgical treatment for mitral regurgitation: mid-term outcome following mitral valve repair].

Mid-term results of mitral valve repair for mitral regurgitation were evaluated in 173 consecutive patients (mean age 53 years, 107 males, 66 females) treated from July 1991 to March 1998. Pathological causes of the mitral valve disease were degenerative in 118 patients, infective endocarditis in 25, rheumatic in 13, and ischemic in 8 (ischemic cardiomyopathy in 7). The principal technique was chordal replacement with expanded polytetrafluoroethylene sutures for prolapse of the anterior leaflet, and Carpentier's sliding leaflet technique for prolapse of the posterior leaflet. Most patients received ring annuloplasty with a rigid ring and flexible band (physiological remodeling annuloplasty). Intraoperative transesophageal echocardiography was used after 1993. There were 7 operative deaths (4%) and 7 mitral valve replacements (4%) during the same operation. Successful repair was achieved in 96% of patients with mitral regurgitation. Mean follow-up was 35 months (range 2 to 78 months). Survival at 6 years was 85 +/- 10% of all patients, 98 +/- 2% in degenerative cases. Six patients required reoperation (1.2%/patient-year) and mean time interval between initial operation and reoperation was 33.1 months. Four patients with atrial fibrillation had thromboembolic events (0.8%/patient-year). There were no anticoagulant-related complications. Freedom from reoperation and all valve-related event at 6 years was 88 +/- 6% and 84 +/- 6%. Late postoperative Doppler echocardiography revealed satisfactory results in 93% of the patients. Mitral valve repair using chordal replacement, sliding plasty and ring annuloplasty provides excellent mid-term results.

Disease-Free Survival↗

PubMed1999

Increased uncoupling protein2 mRNA in white adipose tissue, and decrease in leptin, visceral fat, blood glucose, and cholesterol in KK-Ay mice fed with eicosapentaenoic and docosahexaenoic acids in addition to linolenic acid.

The effects of n-3 polyunsaturated fatty acids (n-3PUFA) on obesity and diabetes were examined using KK-Ay mice fed with perilla oil (P), soybean oil (S), or lard (L), and those containing 30% fish oil (PF, SF, or LF), containing eicosapentaenoic acid (EPA = 9.9%) and docosahexaenoic acid (DHA = 18.0%). Perilla oil contained the largest proportion of linolenic acid (LNA = 61.9%). Computerized tomography (CT) scans showed narrower areas of visceral fat in the abdominal cross sections of groups given fish oil (PF, SF, and LF) and lower leptin levels (p < 0.05-p < 0.001) compared with controls (P, S, and L), without significant changes in energy intake and body weight. The highest plasma n-3PUFA content (21.31 +/- 0.35%) was attained with PF. This group contained 2.6-fold more plasma DHA (p < 0.001), and expressed 2.7-fold more UCP2 mRNA in white adipose tissue (p < 0.01) than in the P group. The epididymal fat pad (p < 0.05) weighed less, and levels of blood glucose (p < 0.05) and total cholesterol (p < 0.01) were reduced in PF compared with P.

Adipose Tissue↗

PubMed1999

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Acute Disease↗