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Biomedical subjects

Ken Inoue

Publications and source records attributed to Ken Inoue.

47 records · Page 3Linked to original sources

A prospective pancreatographic study of the prevalence of pancreatic carcinoma in patients with diabetes mellitus.

BACKGROUND: The correlation between diabetes mellitus and pancreatic carcinoma is well documented, but no criteria have been established for the efficient selection of a high-risk group among patients with diabetes mellitus. METHODS: Eighty-seven patients were selected prospectively from outpatients with diabetes and underwent endoscopic retrograde pancreatography (ERP) according to the authors' original criteria, including the onset of diabetes after age 55 years, deterioration of diabetes or loss of body weight despite strict medical control, elevation of serum amylase and/or CA19-9 levels, and pancreatobiliary abnormalities on routine ultrasonography. The patients were divided into two groups according to the time from the onset of diabetes to ERP: Patients in Group A had recent-onset diabetes (within 3 years), and Group B patients had diabetes for > 3 years. RESULTS: A total of 86 patients (excluding 1 patient with unsuccessful ERP who had undergone previous Billroth-2 gastrectomy) were enrolled. There were 33 males and 53 females, age 40-90 years, with a mean age of 65.1 years. ERP demonstrated pancreatic carcinoma, although it was advanced disease in all patients, at an extremely high rate of 7.0% (6 of 86 patients) with no serious complications. The prevalence of pancreatic carcinoma in Group A (13.9%; 5 of 36 patients) was significantly greater compared with Group B (2.0%; 1 of 50 patients; P = 0.0442). ERP with an indwelling balloon catheter and subsequent pancreatic juice sampling was performed in 49 patients, yielding positive cytology in 1 patient with pancreatic tail carcinoma, whereas measurements of carcinoembryonic antigen and CA19-9 levels in pancreatic juice were of no use in the diagnosis of pancreatic carcinoma. CONCLUSIONS: Selective ERP in patients with diabetes who were at high risk did not lead to the early diagnosis of pancreatic carcinoma, although this study showed that the 3-year period after the onset of diabetes was critical. A more aggressive diagnostic approach within this period in diabetic patients with the authors' criteria may contribute to the earlier diagnosis of pancreatic carcinoma.

Adult↗

Molecular mechanisms for genomic disorders.

Genomic rearrangements play a major role in the pathogenesis of human genetic diseases. Nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) that flank unique genomic segments results in changes of genome organization and can cause a loss or gain of genomic segments. These LCRs appear to have arisen recently during primate speciation via paralogous segmental duplication, thus making the human species particularly susceptible to genomic rearrangements. Genomic disorders are defined as a group of diseases that result from genomic rearrangements, mostly mediated by NAHR. Molecular investigations of genomic disorders have revealed genome architectural features associated with susceptibility to rearrangements and the recombination mechanisms responsible for such rearrangements. The human genome sequence project reveals that LCRs may account for 5% of the genome, suggesting that many novel genomic disorders might still remain to be recognized.

Animals↗

Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg-Hirschsprung disease: phenotypes linked by SOX10 mutation.

A unique phenotype of Waardenburg-Hirschsprung disease (WS4) accompanied by peripheral neuropathy and central dysmyelination has been recognized recently in association with SOX10 mutations. We report an infant boy with lethal congenital hypomyelinating neuropathy and WS4 who had a heterozygous SOX10 mutation (Q250X). Histopathological studies showed an absence of peripheral nerve myelin despite normal numbers of Schwann cells and profound dysmyelination in the central nervous system. These observations suggest that some SOX10 mutations such as Q250X may allow Schwann cells and oligodendrocytes to proliferate but interfere with further differentiation to form myelin. In contrast with the SOX10 loss-of-function mutations causing only WS4, mutations associated with both peripheral and central dysmyelination may affect pathology through a dominant-negative mechanism.

DNA-Binding Proteins↗

The human secretin gene: fine structure in 11p15.5 and sequence variation in patients with autism.

Secretin is a peptide hormone involved in digestion that has been studied as a potential therapeutic agent in patients with autism. We characterized the human secretin locus to determine whether mutations in this gene might play a role in a fraction of autism patients. While the secretin gene (SCT) was not found to be mutated in the majority of autistic patients, rare heterozygous sequence variants were identified in three patients. We also investigated length variation in a variable number of tandem repeats (VNTR) immediately upstream of SCT and found no significant differences in length between patients with autism and normal controls. SCT is located on 11p15.5, adjacent to DRD4 and HRAS. This region has been reported to be associated with both autism and attention deficit hyperactivity disorder (ADHD). Although imprinting is a characteristic of some genes in the vicinity, we could find no evidence for methylation of SCT in lymphoblast cells from patients or control individuals.

Amino Acid Sequence↗

Role of human SII cortices in sensorimotor integration.

OBJECTIVES: To elucidate the functional properties of neurons in the human primary (SI) and ipsilateral and contralateral secondary (iSII or cSII) cortices in response to stimuli during finger movement. METHODS: We measured somatosensory evoked fields (SEFs) produced by electric stimuli delivered to the median nerve at 0.2 Hz in 6 healthy subjects. RESULTS: The amplitudes of evoked fields from both iSII and cSII were gradually attenuated with time. Consecutive blocks of trials were obtained to assess the habituation of each evoked field. Complex finger movements with attention (gating session) increased the amplitude of evoked fields from the iSII cortices but reduced the amplitudes of evoked fields from the cSII cortices (P<0.01). In contrast, the amplitude of P30 m from the SI did not show habituation effects but decreased significantly in the gating session (P<0.01). CONCLUSIONS: The enhanced iSII as well as suppressed cSII cortices during complex finger movements with attention are not only considered to be result of gating effect but also attention.

Analysis of Variance↗

Biliary sphincter motility after neural isolation of the pancreatoduodenal region in conscious dogs.

BACKGROUND: Several neural and hormonal factors are known to affect the motility of the sphincter of Oddi. However, the precise mechanisms of the control of sphincter motility have not been completely explored. We investigated the relationship of canine biliary sphincter motility when it is extrinsically denervated by neural isolation of the pancreatoduodenal region. METHODS: Interdigestive and postprandial sphincter motility in a denervated pancreatoduodenal segment and effects of cholecystokinin-octapeptide were studied in 7 conscious dogs. Data were compared with those of 7 neurally intact control dogs. RESULTS: After extrinsic denervation of the pancreatoduodenal region, sphincter motility exerted a cyclic change in concert with the duodenal myoelectric cycles; this change involved short cyclic bursts of motor activity, which gradually increased in intensity. The increase in the cyclic bursts of motor activity was also cyclic and associated with an increase in the plasma motilin concentration. Neural isolation of the pancreatoduodenal region increased sphincter basal pressure and motility index (integral per minute). In the denervated biliary sphincter, the feeding pattern and temporary inhibitory effect of feeding, as seen in controls, were absent, which suggests the role of extrinsic nerves in delivering bile into the duodenum after feeding. In the denervated dogs, cholecystokinin-octapeptide caused excitation of the sphincter activity, instead of relaxation observed in controls. CONCLUSIONS: Extrinsic innervation to the pancreatoduodenal region has an inhibitory effect on biliary sphincter motility. Abnormalities in extrinsic innervation to the biliary sphincter might increase the resistance of the sphincter to the bile flow and induce bile stagnation.

Animals↗

Effect of truncal vagotomy on sphincter of oddi cyclic motility in conscious dogs.

OBJECTIVE: To evaluate the effects of truncal vagotomy at the diaphragmatic level on the sphincter of Oddi (SO) motility. SUMMARY BACKGROUND DATA: Cholelithiasis is a well-known late complication after gastrectomy and/or vagotomy. The mechanism of gallstone formation is only partly understood, and few studies address the effects of vagotomy on SO cyclic motility in conscious subjects. METHODS: In conscious dogs, SO motility was recorded by retrograde infusion manometry through a duodenal cannula before and after bilateral truncal vagotomy at the diaphragmatic level. Effects of cholecystokinin-octapeptide and feeding were also evaluated before and after vagotomy. RESULTS: SO cyclic motility and the gastroduodenal migrating motor complex continued to occur during postvagotomy fasting. Intermittent inhibitions of the SO and duodenal contractions disappeared during phase 3 of the migrating motor complex. SO basal pressure significantly decreased, whereas the amplitude significantly increased. Cholecystokinin-octapeptide inhibited SO contractions before and after vagotomy. The amplitude of SO contractions increased and their frequency decreased after feeding; however, these effects disappeared after vagotomy. CONCLUSIONS: SO cyclic motility and the effects of feeding change after truncal vagotomy at the diaphragmatic level. These facts may at least partly explain gallstone formation after gastric surgery and/or vagotomy.

Animals↗

N10 potential as an antidromic motor evoked potential in a median nerve short-latency somatosensory evoked potential study.

When stimulating the mixed nerve to record evoked potential, both sensory and motor fibers are activated before entering the spinal cord. The N10 potential has been described as an antidromic motor evoked potential based on results obtained by recording at the anterior midneck. In the present study, we examined the changes in latencies of Erb's potential, N10, and N13 by stimulating the median nerve distally at the wrist and proximally at the elbow. The conduction velocity of N10 calculated by the difference between N10 latencies at the two stimulation points was consistent with motor conduction velocity, although N13 conduction velocity estimated by the same method reflected a sensory conduction velocity. A positive relation was also observed between the indirect latency from the stimulation point to the anterior root as calculated using the equation (F - M - 1) / 2 (ms) and the direct latency to the negative peak of the N10 potential. Our data support the notion that N10 represents antidromic motor potential originating in the spinal entry zone of the anterior root.

Adolescent↗

Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse.

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same approximately 4 Mb interstitial genomic deletion within chromosome 17p11.2. To investigate the molecular bases of the SMS phenotype, we constructed BAC/PAC contigs covering the SMS common deletion interval and its syntenic region on mouse chromosome 11. Comparative genome analysis reveals the absence of all three approximately 200-kb SMS-REP low-copy repeats in the mouse and indicates that the evolution of SMS-REPs was accompanied by transposition of adjacent genes. Physical and genetic map comparisons in humans reveal reduced recombination in both sexes. Moreover, by examining the deleted regions in SMS patients with unusual-sized deletions, we refined the minimal Smith-Magenis critical region (SMCR) to an approximately 1.1-Mb genomic interval that is syntenic to an approxiamtely 1.0-Mb region in the mouse. Genes within the SMCR and its mouse syntenic region were identified by homology searches and by gene prediction programs, and their gene structures and expression profiles were characterized. In addition to 12 genes previously mapped, we identified 8 new genes and 10 predicted genes in the SMCR. In the mouse syntenic region of the human SMCR, 16 genes and 6 predicted genes were identified. The SMCR is highly conserved between humans and mice, including 19 genes with the same gene order and orientation. Our findings will facilitate both the identification of gene(s) responsible for the SMS phenotype and the engineering of an SMS mouse model.

Abnormalities, Multiple↗

[A case of Guillain-Barré syndrome complicated with severe autonomic failure and presented elevated anti-GD1b and anti-GQ1b antibody].

We report a 30-year-old woman who presented symptoms of oropharyngeal palsy and glove-stocking type sensory disturbance followed by acute cerebellar ataxia, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), gastroenteric symptoms, urinary disturbance and orthostatic hypotension. She did not have any preceding infection. She was diagnosed as having Guillain-Barré syndrome with autonomic failure. Autonomic failure such as sinus tachycardia and nocturnal ventricular arrhythmia in addition to motor and sensory dysfunction was palliated by immunoadsorption. During the course of her illness, there were elevations of antiganglioside antibodies to GT1a and GQ1b in the IgG subclass, and to GD1b and GQ1b in the IgM subclass. The elevation of anti-GD1b antibody and anti-GQ1b antibody may be pathologically related to autonomic failure, cerebellar ataxia and SIADH.

Adult↗

Comparison of quality of life after pylorus-preserving pancreatoduodenectomy and Whipple resection.

BACKGROUND/AIMS: There have been many supportive data that the postoperative changes in nutritional status are more favorable after pylorus-preserving pancreatoduodenectomy than after Whipple resection; however, few reports are available on the postoperative changes in subjective quality of life after pancreatoduodenectomy. The aim of this study was to compare the postoperative change in quality of life after pylorus-preserving pancreatoduodenectomy and Whipple resection. METHODOLOGY: A total of 36 patients (31 with pylorus-preserving pancreatoduodenectomy and five with Whipple resection) were studied regarding quality of life before and at short term (within two months) and at long term (six months to one year) after surgery, using a questionnaire. The questionnaire consisted of 13 physical and 10 psychosocial items. The medical records were also reviewed to evaluate their objective nutritional status. Postoperative changes in quality of life and nutritional status were compared between the pylorus-preserving pancreatoduodenectomy and Whipple groups. RESULTS: Overall and physical quality of life scores dropped at short term and then recovered at long term in the pylorus-preserving pancreatoduodenectomy group, but showed a persistently low value even at long term in the Whipple group. The change in physical quality of life showed almost parallel changes with the nutritional status in both groups. However, the scores of psychosocial quality of life, which reflected the patient's mental status, remained low even at long term in both pylorus-preserving pancreatoduodenectomy and Whipple groups. CONCLUSIONS: Quality of life is more favorable after pylorus-preserving pancreatoduodenectomy than after Whipple resection, but long-standing mental health care is necessary in patients with pyloruspreserving pancreatoduodenectomy and Whipple resection.

Activities of Daily Living↗