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Biomedical subjects

M Yagi

Publications and source records attributed to M Yagi.

At least 55 records · Page 3Linked to original sources

Key factors influencing bowel function after ileal W-pouch anal anastomosis: a spectral analysis of W-pouch motor activity.

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard surgical procedure for ulcerative colitis (UC). The purpose of this study was to determine which factors are important to achieve good anal continence after IPAA in terms of the motor activity and pressure-volume relationship. A total of 17 patients with UC who underwent IPAA were evaluated. The internal ileal pouch pressure was transanally measured with and without volume-loading of the pouch which induces the urge to evacuate. The maximum tolerable volume (MTV), first urge volume (FUV), and ileal pouch compliance were calculated and the internal ileal pouch pressure records were subjected to spectral analysis for intensive evaluation of the intraluminal pressure waves. The FUV, correlation of the compliance of the FUV with MTV, and the remaining volume up to the MTV (RVMTV) were analyzed. Compliance of the FUV was significantly correlated with the RVMTV (r = 0.736, P < 0.01). The frequency of the phasic waves in the pouch decreased with length of follow up, reflecting improved function (r = -0.588, P < 0.05). The findings of this intensive analysis of manometric measurement indicate that the key factors in postoperative pouch function are RVMTV and the frequency of phasic waves in the W-pouch.

Adult↗

Spiral ganglion neurons are protected from degeneration by GDNF gene therapy.

Perceptual benefits from the cochlear prosthesis are related to the quantity and quality of the patient's auditory nerve population. Multiple neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have been shown to have important roles in the survival of inner ear auditory neurons, including protection of deafferented spiral ganglion cells (SGCs). In this study, GDNF gene therapy was tested for its ability to enhance survival of SGCs after aminoglycoside/diuretic-induced insult that eliminated the inner hair cells. The GDNF transgene was delivered by adenoviral vectors. Similar vectors with a reporter gene (lacZ) insert served as controls. Four or seven days after bilateral deafening, 5 microl of an adenoviral suspension (Ad-GDNF or Ad-lacZ) or an artificial perilymph was injected into the left scala tympani of guinea pigs. Animals were sacrificed 28 days after deafening and their inner ears prepared for SGC counts. Adenoviral-mediated GDNF transgene expression enhanced SGC survival in the left (viral-treated) deafened ears. This observation suggests that GDNF is one of the survival factors in the inner ear and may help maintain the auditory neurons after insult. Application of GDNF and other survival factors via gene therapy has great potential for inducing survival of auditory neurons following hair cell loss.

Animals↗

Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer.

Cochlear gene transfer is a promising new approach for inner ear therapy. Previous studies have demonstrated hair cell protection with cochlear gene transfer not only in the inoculated, but also in the uninoculated ear. To characterize the kinetics of viral spread, we investigated the extent of transgene expression in the contralateral (uninoculated) cochlea after unilateral adenoviral cochlear gene transfer. We used a lacZ reporter gene vector, and demonstrated spread of the adenovirus into the cerebrospinal fluid (CSF) after cochlear inoculation of 25 microl viral vector. Direct virus application into the CSF resulted in transduction of both cochleae, whereas virus inoculation into the bloodstream did not. The cochlear aqueduct was identified as the most likely route of virus spread to the contralateral cochlea. These data enhance our understanding of the kinetics of virus-mediated transgene expression in the inner ear, and assist in the development of clinical applications for inner ear gene therapy. Our results showed a functional communication between the CSF and the perilymphatic space of the inner ear, that is not only of importance for otological gene transfer, but also for CNS gene transfer. Gene Therapy (2000) 7, 377-383.

Adenoviridae↗

Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity.

Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated overexpression of GDNF against gentamicin ototoxicity. An adenovirus vector expressing the human GDNF gene (Ad.GDNF) was administered into the scala vestibuli as a rescue agent at the same time as gentamicin, or as a protective agent, 7 days before gentamicin administration. Animals in the Rescue group displayed hearing thresholds that were significantly better than those measured in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group, Ad.GDNF afforded significant preservation of utricular hair cells. The data demonstrated protection of the inner ear structure, and rescue of the inner ear structure and function against ototoxic insults. These experiments suggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.

Adenoviridae↗

The role of endoscopic retrograde cholangiopancreatography in infants with cholestasis.

BACKGROUND/PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP) was assessed in the diagnosis of cholestatic liver disease in infants. METHODS: ERCP was performed in 50 infants who had prolonged cholestasis. Their ages ranged from 25 to 274 days (mean, 69 days), and their weight ranged from 2.6 to 6.7 kg (mean, 4.7 kg). Incomplete visualization of the biliary tree or visualization of only the pancreatic duct was followed by exploratory laparotomy. In those in whom the biliary tree was visualized completely, the caliber of the bile duct was compared with that of the pancreatic duct. RESULTS: ERCP was completed in 43 patients (success rate, 86%) without complications. In the 7 patients in whom ERCP failed, 6 had biliary atresia (BA) diagnosed by exploratory laparotomy. The other patient had congenital biliary dilatation (CBD). In 29 of the 43 patients, the biliary tree was seen partially or only the pancreatic duct was visualized. These patients had BA diagnosed by laparotomy. Complete visualization of the biliary tree was obtained in 14 patients. Of these, 9 had neonatal hepatitis (NH), 2 had a paucity of intrahepatic bile ducts (PIBLD), and 3 had CBD. In all of the patients with NH, cholestasis improved spontaneously. The 2 patients with PIBLD had biopsy-proven disease. The caliber of the bile duct was larger than that of the pancreatic duct in NH. This relationship was not observed in PIBLD. CONCLUSIONS: ERCP is safe in infants. It is useful in the diagnosis of prolonged cholestasis.

Cholangiopancreatography, Endoscopic Retrograde↗

Measurement of serum hyaluronic acid as a sensitive marker of liver fibrosis in biliary atresia.

PURPOSE: The aim of this study was to clarify whether serum hyaluronic acid level (SHA) can reflect the degree of liver fibrosis in biliary atresia (BA). METHODS: SHA was measured in 44 postoperative BA patients at 7 months to 22 years of age, with sandwich enzyme method (Hy-A 100 kit). SHA was compared with T.Bil (group 1, T Bil < 2; group 2, 2 < or = T Bil < 5; group 3, T Bil > or = 5 mg/dL), fibrosis score (0-6, the number of abnormal values among Alb, PT, ChE, T Chol, Fischer's ratio, prealbumin), and histologic grading (0-IV). RESULTS: SHA was 499.8 +/- 332.5 in group 3, significantly higher than in the control, group 1, or group 2. As fibrosis score rose, SHA became higher, and SHA in Score 6 (430.1 +/- 366.1 ng/mL) and score-5 (172.9 +/- 141.8 ng/mL) was significantly higher than in the control and other scores, respectively. As the histologic grade rose, SHA became higher, and SHA in grade IV (444.8 +/- 323.5 ng/mL) and grade III (166.0 +/- 70.3 ng/mL) was significantly higher than in the control or other Grades. Serial change of SHA since before HPE was parallel to the clinical course in 8 patients. CONCLUSION: SHA may be a useful serum marker reflecting the degree of liver fibrosis in BA.

Adolescent↗

Motor function of the esophagus and the lower esophageal sphincter in children who undergo laparoscopic nissen fundoplication.

BACKGROUND/PURPOSE: To define the clinical role of laparoscopic Nissen fundoplication (LNF) in children with gastroesophageal reflux (GER), an appropriate understanding of its functional effects is required. The aim of this study was to investigate the motor function of the esophageal body and the lower esophageal sphincter (LES) with special reference to the effects of caloric nutrients in children undergoing LNF. METHODS: Studies were performed in 12 children with GER (age, 6 months to 13 years) before and a month after LNF. Continuous manometric examination was performed with an infusion system using a sleeve sensor for an hour each before and after the administration of apple juice (AAJ; 10 mL/kg). RESULTS: AAJ increased postoperative basal LES pressure from 15 +/- 7 to 20 +/- 6 mm Hg, whereas it decreased the preoperative values from 13 +/- 5 to 10 +/- 4 mm Hg (P < .05). Significant residual pressure was noted at the nadir of swallow-induced LES relaxation after LNF, which was increased by AAJ from 7 +/- 3 to 11 +/- 4 mm Hg. A child with a high nadir LES pressure showed postoperative dysphagia. Significant changes in the patterns of esophageal contractions were not noted after LNF. CONCLUSIONS: Characteristics of the effect of LNF on the LES were a postprandial increase of basal LES pressure and significant residual LES pressure at the nadir of LES relaxation. The motor function of the esophageal body was not affected by LNF.

Adolescent↗

Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25 years' experience.

BACKGROUND/PURPOSE: There are few long-term chronological reviews examining the incidence of total parenteral nutrition (TPN)-associated intrahepatic cholestasis (TPNAC) in infants. The authors therefore reviewed TPNAC in their 25-year series, and also looked at the current problems associated with TPN in infants. METHODS: Two hundred seventy-three surgical neonates who received TPN for more than 2 weeks were divided into 3 groups chronologically: group A (1971 through 1982, n = 77), group B (1983 through 1987, n = 72), and group C (1992 through 1996, n = 124). TPNAC was defined as serum direct bilirubin (DB) level greater than 2.0 mg/dL during the neonatal period. RESULTS: The incidence of TPNAC in groups A, B and C was 57%, 31%, and 25% (P< .01), respectively, and the mortality rate from TPN-associated complications was 13%, 3%, and 3% (P< .05), respectively. Over the last 5 years, severe TPNAC developed in 20 patients (16%). Four of 20 died of TPN-associated sepsis with hepatic failure; 2 had hypoganglionosis with intractable stagnant enteritis and subsequent sepsis, and 2 had fatal respiratory or cardiac disease. CONCLUSIONS: The incidence of TPNAC in surgical neonates and TPN-associated mortality rates have decreased significantly. The mortality rate, however, still remains at 3%. Two of 4 fatal cases had hypoganglionosis, which were totally dependent on TPN. In patients who require long-term TPN, TPN still has unsolved problems, and small bowel transplantation may be indicated.

Cholestasis, Intrahepatic↗

Screening of wound-responsive genes identifies an immediate-early expressed gene encoding a highly charged protein in mechanically wounded tobacco plants.

In order to identify genes that are temporally and spatially regulated during wound response, a cDNA population in mechanically wounded tobacco leaves was screened by the fluorescence differential display method. Of 28 clones initially identified to have altered levels of transcripts within 3 h of wounding, eight were characterized. Although each clone showed a unique pattern of transcript accumulation, one distinct clone was further characterized because of its immediate-early response. Its transcripts began to accumulate 10 min after wounding, reached a maximum level within 1 h and disappeared after 2 h. The response, which occurred repeatably and systemically, was observed by the treatment with propionic acid or erythrosin B, indicating that cytosolic acidification could be one of the signals for immediate-early response of this gene. The cDNA encodes a polypeptide of 513 amino acids with a relative molecular mass of 60,952. The putative polypeptide is rich in lysine (K), glutamic acid (E) and aspartic acid (D), which constitute up to 70% of total amino acids, and was therefore designated as KED. The KED polypeptide is composed of a highly hydrophilic N-terminal region and a relatively hydrophobic C-terminal region, suggesting that KED may function through electrostatic interactions with cellular components.

Amino Acid Sequence↗

The prevalence of dental caries and fluorosis in Japanese communities with up to 1.4 ppm of naturally occurring fluoride.

OBJECTIVES: The purpose of this study was to determine the relationship between the concentration of fluoride in drinking water and the prevalence of dental caries and fluorosis in seven Japanese communities with different concentrations of fluoride occurring naturally in the drinking water. METHODS: A total of 1,060 10- to 12-year-old lifetime residents were examined to determine the prevalence of dental caries and fluorosis in communities with trace amounts to 1.4 ppm fluoride in the drinking water in 1987. Systemic fluorides (drops or tablets) have never been available in Japan and the market share of fluoride-containing toothpaste was 12 percent at the time of the study. RESULTS: The prevalence of dental caries was inversely related and the prevalence of fluorosis was directly related to the concentration of fluoride in the drinking water. The mean DMFS in the communities with 0.8 to 1.4 ppm fluoride was 53.9 percent to 62.4 percent lower than that in communities with negligible amounts of fluoride. Multivariate analysis showed that water fluoride level was the strongest factor influencing DMFS scores. The prevalence of fluorosis ranged from 1.7 percent to 15.4 percent, and the increase in fluorosis with increasing fluoride exposure was limited entirely to the milder forms. CONCLUSIONS: The findings of this study conducted in 1987 in Japan parallel those reported by Dean et al. in the early 1940s.

Analysis of Variance↗

Effects of trimebutine on intestinal motility after massive small bowel resection.

Effects of trimebutine maleate (TM) on intestinal motility in short bowel syndrome (SBS) were studied in conscious canines in both acute and chronic phases following 80% massive distal small bowel resection (MSBR). TM was administered orally to beagles with MSBR or as controls in the postprandial and fasting states, and given simultaneously with meals. Intestinal motility was measured using bipolar electrodes for approximately 1 month after the electrodes were implanted in each beagle and the data compared between treatment groups. When TM was given with meals, the postprandial period without duodenal migrating myoelectric (or motor) complexes (MMCs) was shorter than in those given meals only. When TM was given in the postprandial state in short bowel beagles, the initial duodenal MMCs occurred earlier, i.e. the postprandial period was shorter. Diarrhea did not occur in these beagles. When TM was given in the fasting state, duodenal MMCs occurred and propagated to the distal intestine. In conclusion, oral TM administration can produce a more appropriate intestinal condition for the next food intake and make enteral nutrition possible even in the acute phase after MSBR. Such feeding can be carried out without overloading gut function as a result of the modulation of gastrointestinal motility by TM.

Anastomosis, Surgical↗

Effects of intestinal muscular wrapping on remnant intestinal motility after massive small bowel resection in conscious canines.

We searched the effect of the muscular valve on the management of short bowel syndrome. The motility of the remnant intestine with a special muscular valve after 80% massive distal small bowel resection (MSBR) was evaluated in conscious dogs. The valve (muscular ring) was made by the autointestinal muscle layer holding vascular pedicle. Interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gauge force transducers 2-4 weeks after the surgery, and data of this group (Group I) were compared to the motility in dogs after MSBR without valve construction (Group II) and in controls (Control). Results; Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) in Group I occurred at longer intervals than in Control and almost similarly to those in Group II. MMCs arising from the duodenum were often interrupted before the jejunum above the valve and the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment including that from the duodenum to the proximal jejunum, and to the jejunum above the anastomosis. Transit time in MSBR group (I and II) from the duodenum to the terminal ileum was extremely shorter than in Control, but there were no differences between in Groups I and II. The duration of the postprandial period without duodenal MMCs in Group I was significantly prolonged than in Control, but was shorter than that in Group II. The muscular valve was frequently activated, and the jejunum covered with the valve was contracted frequently which synchronized with the valve activity. It seemed the valve worked as sphincter. However, intestinal obstruction was not occurred through the jejunum covered by the valve. In conclusion, changes in gut motility after MSBR with the valve construction compensate for the shortened intestine and maintain the bowel content earlier postoperatively in comparison with the MSBR alone, and also contribute to the adaptive increase in the remnant intestinal absorption.

Animals↗

Successful manual reduction of locked metacarpophalangeal joints in fingers.

BACKGROUND: Many studies on the etiology and operative treatment of locked metacarpophalangeal joints in fingers have been reported, but there have been few investigations on manual reduction. The rate of success of manual reduction in previous reports has been low, and no consensus has been reached with regard to the best method of manual reduction. On the basis of our experience with operative treatment, we devised a safe method of manual reduction. METHODS: Between January 1987 and December 1995, we reduced a locked metacarpophalangeal joint in twelve female patients; every locked finger was successfully reduced, and complications such as fracture did not occur during manual reduction. The average duration of follow-up was five years and nine months (range, three years and two months to nine years and three months). RESULTS: Six patients had no recurrence of the locking. Four of the six remaining patients had one or two incidents of locking, had no alteration in the activities of daily living, and did not want operative treatment. The two remaining patients reported that they had incidents of locking several times a day, and they requested operative treatment as they were afraid of additional recurrences. One patient had an open reduction fifteen months after the initial episode of locking, and the other patient elected not to have an operation for personal reasons. CONCLUSIONS: We believe that our method of manual reduction should be used to treat a locked metacarpophalangeal joint in a finger and that operative treatment should be limited to patients in whom manual reduction is unsuccessful or the reduction is unstable.

Adult↗

Sustained ex vivo expansion of hematopoietic stem cells mediated by thrombopoietin.

The hematopoietic stem cell (HSC) is defined as a cell that can either self-replicate or generate daughter cells that are destined to commit to mature cells of different specific lineages. Self-replication of the most primitive HSC produces daughter cells that possess a long (possibly unlimited) clonal lifespan, whereas differentiation of HSC produces daughter cells that demonstrate a progressive reduction of their clonal lifespan, a loss of multilineage potential, and lineage commitment. Previous studies indicated that the proliferation of HSC ex vivo favors differentiation at the expense of self-replication, eventually resulting in a complete loss of HSC. In contrast, transplantation studies have shown that a single HSC can repopulate the marrow of a lethally irradiated mouse, demonstrating that self-renewal of HSC occurs in vivo. Thrombopoietin (TPO) has been shown to function both as a proliferative and differentiative factor for megakaryocytes and as a survival and weakly proliferative factor for HSC. Our studies focused on the effects of exogenous TPO on HSC in mouse long-term bone marrow cultures (LTBMC). Previous results indicate that HSC decline in LTBMC in the absence of TPO. In contrast, the continuous presence of TPO resulted in the generation of both long- and short-term repopulating HSC as detected by an in vivo competitive repopulation assay. HSC were generated over a 4-month period at concentrations similar to normal bone marrow. Our results demonstrate that TPO can mediate the self-replication of HSC in LTBMC, and provide proof that HSC can self-replicate ex vivo.

Animals↗

Inner ear transgene expression after adenoviral vector inoculation in the endolymphatic sac.

Gene transfer has been performed in a variety of organs. In the mammalian inner ear, viral vectors have been used to introduce exogenous reporter genes via the scala tympani into the cochlea. While scala tympani inoculation is clinically feasible, it is not without risks. Moreover, transgene expression has so far been restricted to the cochlear tissues in the perilymphatic spaces that are contiguous with the scala tympani. To achieve gene transfer of vestibular organs and cells surrounding the endolymphatic space, and to extend the clinical utility of inner ear gene therapy, we developed a new surgical approach for vector inoculation. A replication-deficient adenoviral vector, Ad.RSVntlacZ, was injected into the guinea pig endolymphatic sac. A large number of blue (LacZ-positive) cells was observed in the endolymphatic sac and duct, the vestibule, and the ampulla. Blue cells were also detected in the cochlea, mainly in cells bordering the endolymphatic space: marginal cells in the stria vascularis and supporting cells in the organ of Corti. These findings indicate that inoculation of viral vectors into the endolymphatic sac can provide efficient gene transfer into a variety of cell types that are not accessible via scala tympani inoculation.

Adenoviridae↗

Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor.

Aminoglycosides are commonly used antimicrobial drugs that often have ototoxic side effects. The ototoxicity often involves permanent loss of cochlear hair cells (HCs). Neurotrophic factors have been shown to protect a variety of tissues, including HCs, from toxic trauma. To determine if glial cell line-derived neurotrophic factor (GDNF) can protect cochlear HCs from trauma, we inoculated an adenoviral vector encoding the human GDNF gene into guinea pig cochleae via the round window membrane 4 days prior to injection of aminoglycosides. Control groups showed little or no negative influence of the viral inoculation on cochlear structure and function. In contrast, ears that were inoculated with the GDNF vector had better hearing and fewer missing HCs after exposure to the ototoxins, as compared with controls. Our results demonstrate the feasibility of gene therapy for cochlear application and suggest that virus-mediated overexpression of GDNF may be developed as a valuable prevention against trauma-induced HC death.

Adenoviridae↗