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Biomedical subjects

Y Furuta

Publications and source records attributed to Y Furuta.

At least 55 records · Page 3Linked to original sources

Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS.

Antigens, Nuclear↗

[Effects of low dose pimobendan in patients with cor-pulmonale].

The acute and chronic efficacy of low dose pimobendan (1.25 mg x 2/day) was evluated in patients with cor-pulmonale. Fifteen patients (12 men, 3 women, mean age 73 +/- 5 yr) with right ventricular dysfunction judged by Tei's Doppler index (> or = 0.4) and poor working capacity (exercise tolerance: 2.2-6.6 MET) were studied. Mean pulmonary artery pressure, cardiac output, total pulmonary resistance using Swan-Ganz catheter, and arterial oxygen and carbon dioxide pressure (PaO2, PaCO2) were measured before and 24 hr after pimobendan administration. Maximal oxygen intake (MET), saturation of arterial blood oxygen at rest and desaturation by treadmill stress test were measured before and 1 month after pimobendan administration. Pulmonary artery pressure decreased (17.6 +/- 4.7 to 10.2 +/- 2.3 mmHg, p < 0.001) and cardiac output increased (3.5 +/- 0.6 to 5.1 +/- 0.9 l/min, p < 0.001), resulting in decreased total pulmonary resistance (5.0 +/- 1.3 to 2.1 +/- 0.7 U, p < 0.001), and a mild decrease in PaO2 (74 +/- 8 to 70 +/- 10 mmHg, p < 0.05). Exercise tolerance improved significantly (4.8 +/- 1.7 to 6.8 +/- 2.2 MET, p < 0.001), without deterioration of PaO2 and desaturation. These results indicate that low dose pimobendan is useful for the treatment of patients with cor-pulmonale.

Aged↗

Genomic structure and chromosomal mapping of the human and mouse hippocalcin genes.

In an attempt to elucidate the possible relationship of hippocalcin to neurological disorders, we isolated and analyzed the human and mouse hippocalcin genes. The human and mouse hippocalcin genes contain three exons and two introns, and span approximately 7 and 8kb, respectively. The exon/intron splice junctions of the human and mouse genes are all situated in exactly the same position and are not consistently placed with respect to the coding regions of the tandemly repeated EF-hand motifs. The amino acid sequences of human and mouse hippocalcins deduced from the genes are 100% identical. Within the 2-kb 3'-flanking sequences of the human and mouse genes, one conserved polyadenylation signal was identified at positions 762 and 823bp downstream from TAG, respectively. Within the 2.6-kb 5'-flanking sequences of the human and mouse genes, neither a canonical 'TATA' box nor a 'CAAT' box was found. Southern blot analysis of the human and mouse genomic DNAs demonstrated that the positive bands coincide exactly with those expected from the sequence of the cloned genes, indicating that the human and mouse hippocalcin genes are present as a single-copy gene. Fluorescence in-situ hybridization revealed that the human hippocalcin gene is located at chromosome 1 p34.2-35 and the mouse hippocalcin gene at chromosome 4 D2-D3.

Animals↗

BMP4 is essential for lens induction in the mouse embryo.

Vertebrate lens development is a classical model system for studying embryonic tissue interactions. Little is known, however, about the molecules mediating such inductive events. Here, we show that Bmp4, which is expressed strongly in the optic vesicle and weakly in the surrounding mesenchyme and surface ectoderm, has crucial roles during lens induction. In Bmp4(tm1) homozygous null mutant embryos, lens induction is absent, but the process can be rescued by exogenous BMP4 protein applied into the optic vesicle in explant cultures. This is associated with rescue of ectodermal expression of Sox2, an early lens placode marker. Substituting the optic vesicle in explant cultures with BMP4-carrying beads, however, does not lead to lens induction, indicating that other factors produced by the optic vesicle are involved. BMP4 appears to regulate expression of a putative downstream gene, Msx2, in the optic vesicle. No change in Pax6 expression is seen in Bmp4(tm1) mutant eyes, and Bmp4 expression appears unaffected in the eyes of homozygous Pax6(Sey-1Neu), suggesting that PAX6 and BMP4 function independently. Based on these results we propose that BMP4 is required for the optic vesicle to manifest its lens-inducing activity, by regulating downstream genes and/or serving as one component of multiple inductive signals.

Animals↗

Reactivation of herpes simplex virus type 1 in patients with Bell's palsy.

Reactivation of herpes simplex virus type 1 (HSV-1) has been implicated in the pathogenesis of idiopathic peripheral facial palsy (Bell's palsy). The present study used the polymerase chain reaction (PCR) to analyze the saliva of patients with Bell's palsy for the presence of shed HSV-1. The study involved 47 patients with Bell's palsy, 24 patients with Ramsay Hunt syndrome, and 16 healthy HSV-seropositive volunteers. HSV-1 DNA was not detected in the saliva samples from HSV-seronegative patients. The prevalence of shed HSV-1 in patients with Bell's palsy (50%) was significantly higher than that in healthy volunteers (19%, p<0.05). When saliva samples were tested within 7 days after the onset of palsy, the prevalence of shed HSV-1 in patients with Bell's palsy (40%) was significantly higher than that in patients with Ramsay Hunt syndrome (7%, p<0.05). Furthermore, HSV-1 usually became undetectable by the second week after the onset of Bell's palsy when HSV-1 was detected during the acute phase of the disease. These findings strongly suggest that reactivation of HSV-1 is involved in the pathogenesis Bell's palsy, and indicate that PCR is a useful tool for early diagnosis of HSV-1 reactivation in patients with Bell's palsy.

Antibodies, Viral↗

Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo.

In mammals, 16 members of the Fgf family have so far been described with diverse roles in embryonic cell growth and differentiation. Here, we report the expression from early streak stage to midgestation of two newly-identified murine genes, Fgf17 and Fgf18, that are most closely related to Fgf8 (63.7% and 56.8% identical, respectively, at the amino acid level). Fgf17 is expressed during gastrulation but at lower levels than Fgf8, while Fgf18 RNA is not expressed until later, in paraxial mesoderm. In the developing tail bud, each Fgf gene shows a different pattern of transcription. Distinct and overlapping expression patterns are also described in the developing brain and limbs.

Animals↗

Use of intraperitoneal vessels in reconstructive microsurgery: an account of 117 cases.

The purpose of this study was to evaluate our experience of microvascular anastomosis of intraperitoneal vessels. Between 1985 and 1994, 117 microsurgical reconstructions were done using intraperitoneal vessels. These included oesophageal reconstruction (n = 106), reconstruction of the hepatic arterial, superior mesenteric arterial, or portal venous system (n = 8), and reconstruction of the chest or abdominal wall (n = 3). We used 129 intraperitoneal arteries and 117 intraperitoneal veins. Of a total of 246 intraperitoneal vessels, five hepatic arteries, seven splenic, 14 gastroepiploic, six superior mesenteric, 178 jejunal, 30 ileocolic, four middle colic arteries or veins, and two portal veins were used for microvascular anastomosis. The overall successful rate for these reconstructive cases was 97% (114/117). Microsurgical use of intraperitoneal vessels is a safe and developing procedure in plastic and reconstructive surgery.

Adult↗

Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.

We report here the isolation, functional characterization, tissue distribution, and membrane localization of rat renal Na+-dicarboxylate transporter (rNaDC-1). rNaDC-1 consists of 2,245 nucleotides, and the deduced amino acid sequence showed 73% and 75% identity to rabbit and human NaDC-1, respectively. When expressed in Xenopus laevis oocytes, rNaDC-1 mediated sodium-dependent uptake of di- and tricarboxylates. Substrates of rNaDC-1 evoked inward currents in oocytes expressed with rNaDC-1; succinate, alpha-ketoglutarate, and glutarate were relatively high-affinity substrates, and citrate was a low-affinity substrate of rNaDC-1. The coupling ratio of citrate to charge was determined to be 1:1 at pH 7.4; influx of one positive charge per citrate molecule suggests a symport of three Na+ with a divalent citrate. Expression of rNaDC-1 mRNA was detected in the kidney and the small and large intestines. Immunohistochemistry using polyclonal antibodies raised against the 14 amino acids at the COOH terminus of rNaDC-1 revealed that rNaDC-1 is localized exclusively in the luminal membrane of S2 and S3.

Amino Acid Sequence↗

Formation of Rathke's pouch requires dual induction from the diencephalon.

Targeted disruption of the homeobox gene T/ebp (Nkx2.1, Ttf1, Titf1) in mice results in ablation of the pituitary. Paradoxically, while T/ebp is expressed in the ventral diencephalon during forebrain formation, it is not expressed in Rathke's pouch or in the pituitary gland at any time of embryogenesis. Examination of pituitary development in the T/ebp homozygous null mutant embryos revealed that a pouch rudiment is initially formed but is eliminated by programmed cell death before formation of a definitive pouch. In the diencephalon of the mutant, Bmp4 expression is maintained, whereas Fgf8 expression is not detectable. These data and additional genetic and molecular observations suggest that Rathke's pouch develops in a two-step process that requires at least two sequential inductive signals from the diencephalon. First, BMP4 is required for induction and formation of the pouch rudiment, a role confirmed by analysis of Bmp4 homozygous null mutant embryos. Second, FGF8 is necessary for activation of the key regulatory gene Lhx3 and subsequent development of the pouch rudiment into a definitive pouch. This study provides firm molecular genetic evidence that morphogenesis of the pituitary primordium is induced in vivo by signals from the adjacent diencephalon.

Animals↗

Isolation of two human cDNAs, HLP3 and HLP4, homologous to the neuron-specific calcium-binding protein genes.

We have cloned and sequenced two types of human cDNA, HLP3 and HLP4, encoding a protein of 191 amino acid residues with four EF-hand calcium-binding motifs. The HLP3 and HLP4 proteins are homologous to the neuron-specific calcium-binding proteins and are likely human counterparts of the neural visinin-like protein(NVP) 1 and NVP2 identified in the rat brain (Kajimoto et al. 1993), displaying 98% and 99% amino acid identities with these sequences, respectively. The human HLP3 and 4 mRNAs are detected only in the brain and found at high amount in the cerebral cortex and cerebellum by Northern blot analysis.

Amino Acid Sequence↗

Functional reconstruction of the tongue and deglutition muscles following extensive resection of tongue cancer.

The authors describe their experience with functional restoration of tongue and deglutition muscles at the floor of the mouth after an extensive resection of tongue cancer. Five patients underwent immediate tongue reconstruction using a reinnervated rectus abdominis myocutaneous free flap in which the included tenth intercostal nerve was coapted to the remaining hypoglossal nerve. The rectus sheath strips attached on both cut ends of the muscle were used to create the firm tendinous insertions between the mandible and hyoid bone based on the anatomic findings of the extrinsic tongue and suprahyoid muscles. The postoperative course was uneventful in all patients. All patients presented with good tongue bulk without obvious atrophy. Three patients with subtotal glossectomy demonstrated good cooperative mobility of the reconstructed and remaining tongue and had solid or semisolid/soft diet. However, two patients with total glossectomy did not show satisfactory rehabilitation of the reconstructed tongue. Postoperative electromyographic assessment in two patients showed good functional recovery of the grafted muscle. The cine-magnetic resonance imaging deglutition study in one patient with 80-percent tongue resection demonstrated sufficient elevation of the dorsal base of the reconstructed tongue, contraction of the reconstructed deglutition muscles, complete glossopalatal closure, and elevation of the hyoid bone and larynx during the deglutition. This reconstructive technique is strongly recommended for the patients who have undergone subtotal glossectomy to provide physiological functional recovery of the reconstructed tongue synchronizing with the remaining tongue.

Adult↗

Detection of latent varicella-zoster virus infection in human vestibular and spiral ganglia.

Varicella-zoster virus (VZV) becomes latent in the sensory ganglia after primary infection and VZV DNA has been found in human trigeminal, thoracic, and geniculate ganglia. In this study, human vestibular and spiral ganglia, which do not received innervation from the skin, were examined for VZV DNA using the polymerase chain reaction. VZV DNA was detected in 2 of 10 (20%) vestibular ganglia and in 2 of 10 (20%) spiral ganglia from five adults. VZV DNA was undetectable in either type of ganglion from a newborn and from two of the five adults. These two adults were VZV seronegative. The results indicate that VZV becomes latent in several types of sensory ganglion after primary infection and suggest the possibility that reactivation of the virus from the vestibular and spiral ganglia may cause disorders in the labyrinth.

Adult↗

Ductoplasty for an aberrant hepatic duct in a choledochal cyst.

The confluence of the right and left hepatic ducts at the hepatic hilum frequently shows normal anatomic variations. Choledochal cysts (CC) are also accompanied by similar variations, and devices for free drainage of bile are occasionally required in biliary reconstruction. We present a CC that had an aberrant posterior branch of the right hepatic duct draining into the distal common hepatic duct. A capacious hepaticoduodenostomy at the hilum was performed after joining the hilar and aberrant ducts.

Child, Preschool↗

Reconstruction following total laryngopharyngoesophagectomy and extensive resection of the superior mediastinum.

Our experience with four patients who underwent immediate reconstruction following total laryngopharyngoesophagectomy and extensive resection of the superior mediastinum is presented. The reconstructive procedures included free jejunal graft or microvascularly augmented gastric pedicle for esophageal reconstruction, pectoral fasciocutaneous or myocutaneous flap for tracheal reconstruction, and mesenteric flap connected with jejunal graft omental flap, or pectoral flap for protection of the great vessels and obliteration of the dead space in the cervical and superior mediastinal region. The reconstructive procedures were successful, and no pharyngocutaneous fistula, mediastinitis, or great vessel rupture was noted in any patient. There was one patient who developed lung edema and liver dysfunction postoperatively. Combinations of reconstructive procedures using well-vascularized soft tissues can be expected to provide well-tolerated reconstruction following extensive cervical and superior mediastinal resection.

Aged↗

Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis.

Branching morphogenesis of the embryonic lung requires interactions between the epithelium and the mesenchyme. Previously, we reported that Sonic hedgehog (Shh) transcripts are present in the epithelium of the developing mouse lung, with highest levels in the terminal buds. Here, we report that transcripts of mouse patched (Ptc), the homologue of a Drosophila gene encoding a putative transmembrane protein required for hedgehog signaling, are expressed at high levels in the mesenchyme adjacent to the end buds. To investigate the function of SHH in lung development, Shh was overexpressed throughout the distal epithelium, using the surfactant protein-C (SP-C)-enhancer/promoter. Beginning around 16.5 dpc, when Shh and Ptc RNA levels are normally both declining, this treatment caused an increase in the ratio of interstitial mesenchyme to epithelial tubules in transgenic compared to normal lungs. Transgenic newborn mice die soon after birth. Histological analysis of the lungs at the light and electron microscope level shows an abundance of mesenchyme and the absence of typical alveoli. In vivo BrdU labeling indicates that Shh overexpression results in increased mesenchymal and epithelial cell proliferation at 16.5 and 17.5 dpc. However, analysis of CC-10 and SP-C expression reveals no significant inhibition in the differentiation of proximal and distal epithelial cells. The expression of genes potentially regulated by SHH was also examined. No difference could be observed between transgenic and control lungs in either the level or distribution of Bmp4, Wnt2 and Fgf7 RNA. By contrast, Ptc is clearly upregulated in the transgenic lung. These results thus establish a role for SHH in lung morphogenesis, and suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo.

Animals↗