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Biomedical subjects

H Ando

Publications and source records attributed to H Ando.

At least 127 records · Page 7Linked to original sources

Possible involvement of proteolytic degradation of tyrosinase in the regulatory effect of fatty acids on melanogenesis.

The purpose of this study was to investigate the mechanism of fatty acid-induced regulation of melanogenesis. An apparent regulatory effect on melanogenesis was observed when cultured B16F10 melanoma cells were incubated with fatty acids, i.e., linoleic acid (unsaturated, C18:2) decreased melanin synthesis while palmitic acid (saturated, C16:0) increased it. However, mRNA levels of the melanogenic enzymes, tyrosinase, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2), were not altered. Regarding protein levels of these enzymes, the amount of tyrosinase was decreased by linoleic acid and increased by palmitic acid, whereas the amounts of TRP1 and TRP2 did not change after incubation with fatty acids. Pulse-chase assay by [35S]methionine metabolic labeling revealed that neither linoleic acid nor palmitic acid altered the synthesis of tyrosinase. Further, it was shown that linoleic acid accelerated, while palmitic acid decelerated, the proteolytic degradation of tyrosinase. These results suggest that modification of proteolytic degradation of tyrosinase is involved in regulatory effects of fatty acids on melanogenesis in cultured melanoma cells.

Animals↗

[Treatment of solid tumor by a direct electric current].

This is a case report of a 37-year-old Japanese married female with laryngeal sarcoma, treated by direct electric current so as to obtain remission for more than 4 years without signs of recurrence. Due to her hoarseness and laryngeal numb feeling she underwent a laryngeal examination including a biopsy, resulting in a diagnosis of sarcoma. She refused a total laryngectomy and was given Cobalt treatment of 40 Grey. In the following several months, no improvement was observed, objectively or subjectively. In Nagoya University Hospital the patient then received direct electric current therapy of 36 Coulombs through two platinum electrodes inserted into the tumor under a CT guide, pericutaneously. Two months later, as the hoarseness remained in spite of some improvement, she underwent another session of direct electric current therapy of 14.4 Coulombs through the platinum electrodes by bronchoscope-guided direct insertion. Her hoarseness soon disappeared thereafter and there was a regression of the tumor in 6 months. She did well thereafter without any signs of recurrence for 4 years. Clinical treatment of solid tumors with electric treatment with direct electric current has been done in more than 8,000 cases with CR in 25% of all cases and PR in 50%. Its mechanism, however, remains unclear. In our experimental animal studies, apoptosis was observed. It is considered that this electric therapy using direct electric current will be recognized as one method to treat solid tumors.

Adult↗

A new operation for noncorrectable biliary atresia.

An improved operative technique to transect the fibrous cord by dividing the ligamentum venosum (Arantius' canal) is described for noncorrectable biliary atresia. The Arantius' canal is situated cranial and posterior side to the bifurcation of the umbilical portion and the portal branch of the Quinous' segment 3. The portal vein is fully mobile and the porta hepatis can be widely exposed by dividing the Arantius' canal. The fibrous cord of the porta hepatis can easily be dissected posteriorly and laterally where there is an extensive number of bile ducts. Eight patients with biliary atresia underwent this procedure. Jaundice resolved completely (serum total bilirubin concentration: < or = 1 mg/dl) in 7 patients within 40 days. Postoperative cholangitis did not occur. By dividing the Arantius' canal, the portal vein comes free from the portal fissure to make the hepatic hilum wider, and surgeons are able to work within a larger porta hepatic space without causing portal vein compression. Free drainage of the bile from the porta hepatis may prevent postoperative cholangitis and promote resolution of jaundice.

Animals↗

Efficient mutagenesis of zebrafish by a DNA cross-linking agent.

We developed a novel procedure for efficient mutagenesis of zebrafish using a DNA cross-linking agent 4,5',8-trimethylpsoralen (TMP), which is known to frequently induce small deletions in Escherichia coli and Caenorhabditis elegans. A specific-locus test and pilot screenings indicated that the TMP mutagenesis procedure was efficient. To confirm the successful mutagenesis by TMP, we characterized mutants with selective impairments in the nervous system. The no tectal neuron mutation hindered the development of the tectal neurons, while the edawakare mutation resulted in the enhancement of the extension and branching of the peripheral axons of trigeminal ganglion and Rohon-Beard sensory neurons. These results suggest that the TMP mutagenesis will provide an efficient method to isolate and characterize zebrafish mutants at molecular level.

Animals↗

Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin.

This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the skin. An efficient lightening effect was observed following topical application of linoleic acid or alpha-linolenic acid to UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes. In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by alpha-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by alpha-linolenic acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and alpha-linolenic acid are, at least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment from the epidermis.

Administration, Topical↗

Localization of the gene responsible for Peutz-Jeghers syndrome within a 6-cM region of chromosome 19p13.3.

Patients with Peutz-Jeghers syndrome (PJS), an autosomal dominant disease characterized by hamartomatous polyposis of the gastrointestinal tract, are thought to be predisposed to malignancies of the digestive tract, genital tract, and other organs. Using microsatellite markers on chromosome 19p, we have closely defined the region containing the gene responsible for this disorder through linkage analysis in seven affected families. The lack of obligate recombinants at two of these loci, D19S883 and D19S878, with maximum LOD scores of 2.88 and 3.75, confirmed the localization of the PJS locus to chromosome 19. Furthermore, haplotype analysis placed the PJS locus within a 6-cM telomeric region of chromosome 19p, between D19S886 and D19S565.

Centromere↗

Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome.

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disease characterized by hamartomatous polyposis involving the entire bowel. Recently STK11, a gene bearing a mutation responsible for PJS, was isolated. We investigated the entire coding region of STK11 in 15 unrelated PJS families by the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method and PCR-direct sequence analysis, and found nine different, novel mutations among ten of those families. One nonsense mutation and five different frameshift mutations (two families carried the same mutation), all of which would cause truncation of the gene product, were found in seven families; mutations found in five families were clustered within exon 6. Among these five mutations, three occurred at the mononucleotide-repeat region (CCCCCC) of codons 279-281, suggesting that this region is likely to be a mutational hotspot of this gene. One of the remaining three families carried a 3-bp in-frame deletion that would eliminate an asparagine residue within a kinase domain of the product; the other two carried intronic mutations at or adjacent to the consensus dinucleotide sequences of splice-acceptor or -donor sites, which were likely to lead to aberrant splicing.

AMP-Activated Protein Kinase Kinases↗

Heart rate variability during the first month of smoking cessation.

BACKGROUND: Heart rate variability (HRV) is known to increase after smoking cessation. However, no work has been performed concerning HRV immediately after smoking cessation. METHODS AND RESULTS: We studied HRV before and from 1 day to 1 month after smoking cessation and also determined whether there is a relation between HRV and the withdrawal syndrome immediately after smoking cessation. We determined HRV by using a two-channel 24-hour ambulatory ECG system before and 1, 2, 3, 7, 14, 21, and 28 days after smoking cessation in 20 healthy male volunteers who had smoked one or more packs per day for 2 or more years. One day after smoking cessation, heart rate decreased significantly, and all 24-hour time and frequency domain indices of HRV increased except the standard deviations of the normal R-R intervals and the 5-minute mean R-R. The magnitude of increase in these indices peaked 2 to 7 days after smoking cessation and gradually decreased thereafter. The increase in HRV persisted 1 month after smoking cessation. In the 16 subjects with signs of withdrawal syndrome and in the four subjects without evidence of withdrawal before and immediately and 1 month after smoking cessation, HRV increased immediately after smoking cessation and remained elevated after 1 month. CONCLUSIONS: HRV increases immediately after smoking cessation and gradually declines thereafter, which suggests that the effect of smoking on autonomic activity rapidly disappears immediately after smoking cessation. HRV remained unaffected by the presence or absence of the withdrawal syndrome.

Adult↗

Assessment of left atrial appendage function after cardioversion of atrial fibrillation: relation to left atrial mechanical function.

Although several flow patterns in the left atrial appendage have been described, mechanical determinants of its function have not been elucidated in human beings. We attempted to investigate changes in left atrial appendage function after cardioversion of atrial fibrillation and examine the potential relation between appendage function and left atrial mechanical function. Twenty patients without mitral valvular disease underwent transesophageal and transthoracic echocardiography at 24 hours and 1 week after cardioversion of atrial fibrillation. Left atrial appendage function was assessed by the pulsed Doppler measurements of left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively. Left atrial mechanical function was evaluated by the transmitral A-wave velocity, percent atrial contribution of the total left ventricular filling (percent atrial filling), and the pulmonary venous A-wave velocity. Left ventricular function was also estimated with conventional M-mode echocardiography. The late appendage emptying and filling velocities markedly increased during 1 week after cardioversion (p < 0.0001, respectively). This finding was associated with an increase in left atrial mechanical function. Changes in the late emptying and filling velocities significantly correlated with changes in the transmitral A-wave velocity (r = 0.59, p < 0.01), percent atrial filling (r = 0.61, p < 0.005), and the pulmonary venous A-wave velocity (r = 0.56, p < 0.05). In contrast, little change was observed in the early emptying and filling velocities. There was no relation between the indexes of left ventricular function and those of appendage function. In conclusion, unless there was an alteration of the loading conditions, left atrial appendage function improved over several days after cardioversion, and its function was related to left atrial mechanical function.

Adult↗

Extrinsic nerve strands in the aganglionic segment of Hirschsprung's disease.

BACKGROUND/PURPOSE: The distributions and pathways of the extrinsic enteric nerves in the aganglionic segment in Hirschsprung's disease (HD) have not been delineated completely. The authors have clarified the major pathways and the details of fine distribution of the extrinsic nerves in the aganglionic segment of a congenital aganglionosis rat. Further investigation was extended to apply those findings in human materials. METHODS: Five HD patients, eight fetuses, and two postmortem neonates with normally innervated colon were examined. Specimens were observed by histochemical technique using light microscopy in whole-mount preparations. RESULTS: Two sets of extrinsic nerve strands were observed in the distal aganglionic colon; one consisted of a continuous network located between the longitudinal and circular muscle coats, and the other involved branches that mainly coursed along the blood vessels in the submucosal layer originating from the nearby mesentery. These two sets of nerve strands were similar to those of aganglionosis rats. Also, thick nerve strands were found running longitudinally in the myenteric layer in the normally ganglionated colon of 18- and 21-week-old fetuses. These nerve strands were unclear in a 32-week-old fetus. CONCLUSIONS: This study showed the following: (1) the origin of the nerve strands in the myenteric layer is mainly the pelvic nerve plexus and (2) the number of ascending extrinsic nerve strands decreases from the proximal colon in cases of long-segment aganglionosis, which may be caused by the same process that occurs in the normally innervated bowel.

Colon↗

Surgical removal of protein plugs complicating choledochal cysts: primary repair after adequate opening of the pancreatic duct.

BACKGROUND/PURPOSE: Recently, pancreaticoduodenectomies have been performed for choledochal cysts complicated by protein plugs. The authors describe a new surgical procedure for removal of protein plugs or pancreatic stones that does not involve pancreatectomy. METHODS: Protein plugs were detected in 43 (34.1%) of 126 pediatric patients with choledochal cysts. The plugs disappeared spontaneously in 26 patients and were removed using nonsurgical methods in seven. The 10 patients treated surgically are considered here. RESULTS: Protein plugs were removed with the residual cyst in one patient. The plugs in the common channel were flushed into the duodenum by irrigation with saline through the narrow segment beneath choledochal cyst in another. The plugs were removed through the narrow segment using a blunt spoon in four. In the other four patients, the plugs that were too large or too hard to be removed through the narrow segment were taken away through an incision in the main pancreatic duct. This was followed by primary closure of the main pancreatic duct using the narrow segment as a flap to prevent stricture formation. All of the patients have done well. CONCLUSIONS: Protein plugs complicating choledochal cysts can be removed without pancreatectomy. Particularly, primary repair of the pancreatic duct using a flap made of the narrow segment beneath the choledochal cyst is a safe and feasible method to remove large or hard protein plugs.

Adolescent↗

Combined resection of abdominal aorta and inferior vena cava for retroperitoneal rhabdomyosarcoma invading the aortoiliac bifurcation.

The authors report on an 11-year-old boy with retroperitoneal alveolar rhabdomyosarcoma at the aortoiliac bifurcation. The tumor was resected en bloc together with the infrarenal abdominal aorta and the inferior vena cava. The aortic defect was repaired successfully with a Y-shaped Dacron graft. The authors conclude that tumor resection with aortic reconstruction can be a choice for unresectable retroperitoneal tumors in children.

Aorta, Abdominal↗

Lack of adenosine causes myocardial refractoriness.

OBJECTIVES: This study sought to investigate the myocardial mechanisms causing refractoriness to ischemic preconditioning in pigs. BACKGROUND: Ischemic preconditioning in the pig vanishes after 60 min and cannot be reinstated by a second cycle of brief coronary occlusions at this time point. Ischemic preconditioning has been shown to be mediated by adenosine A1-receptors. Because myocardial adenosine production during ischemia ceases as the number of repeated brief ischemic episodes increases, we hypothesized that this lack of adenosine may cause this myocardial refractoriness. METHODS: In open chest pigs, ischemic preconditioning was achieved by repeated brief coronary occlusions. Myocardial adenosine content was assessed by high performance liquid chromatographic analysis of serial myocardial biopsy samples; infarct size (percent infarcted area of the area at risk) was determined using tetrazolium salts. RESULTS: Ischemic preconditioning by two cycles of occlusion of the left anterior descending coronary artery (10 min) and reperfusion (30 min) decreased infarct size ([mean +/- SEM] 40.4+/-2.9%; control: 76.9+/-1.8%, p < 0.001). Prolonging the second reperfusion period to 60 min caused ischemic preconditioning to vanish (79.0+/-0.5%) and caused refractoriness to a second cycle of preconditioning (70.0+/-2.0%). Myocardial adenosine content increased only during the first coronary occlusion (baseline: 110.9+/-42.0 nmol/g dry weight; first coronary occlusion: 1,686.2+/-244.1, p < 0.001) but not during subsequent coronary occlusions. In refractory myocardium, intramyocardial microinfusion of the adenosine A1-receptor agonist N6-cyclohexyladenosine (CHA [0.3 mmol/liter]) again decreased infarct size (27.4+/-7.0%, p < 0.001 vs. control). CONCLUSIONS: Myocardial refractoriness may be caused by the inability to produce adenosine endogenously. In refractory myocardium, application of CHA reinduces cardioprotection.

Adenosine↗

Effect of coronary bypass grafting onto the site of old myocardial infarction and the recovery of cardiac function.

This study investigated whether or not revascularization to the site of old myocardial infarction can bring beneficial effects on postoperative cardiac function. Thirty-two patients without a history of old myocardial infarction and 71 with a history of old myocardial infarction were included. The mean number of grafts bypassed were 2.7 and 2.8, and the mean duration of aortic clamping was 99 min and 105 min in non-old myocardial infarction and old myocardial infarction patients, respectively. All the patients underwent simple coronary artery bypass grafting electively. The left ventricular stroke work index in non-old myocardial infarction and old myocardial infarction were 40.8 g-m/m2 and 38.9 g-m/m2 preoperatively, and this was recovered to 41.4 g-m/m2 and 38.7 g-m/m2, respectively, at 24 hours after reperfusion (NS). Subgroups of old myocardial infarctions had high ejection fractions of more than 50% (49) and low ejection fractions of less than 50% (22). The left ventricular stroke work index in high and low ejection fractions was 39.7 g-m/m2 and 36.7 g-m/m2 preoperatively (NS). Recovery rates in both high and low ejection fractions were reduced to 74.2% and 84.3% at 3 h after reperfusion (P < 0.001 and P < 0.05 versus preoperative value), but were increased in the low ejection fraction by up to 102.7% and 108.5% at 6 and 12 h after reperfusion, while still remaining reduced in the high ejection fraction at 88.8% and 88.2%, respectively (P < 0.01). At 24 h after reperfusion, left ventricular stroke work index in the low ejection fraction was improved to 44.3 g-m/m2 or 130% of the preoperative value, and the high ejection fraction was 37.5 g-m/m2 or 100% (NS). This showed that a chief cause of reduced cardiac function in the low ejection fraction was mainly reversible myocardial damage or hibernation. Preoperative mean left ventricular ejection fractions in non-old myocardial infarctions and old myocardial infarctions were 73.1% and 55.9%, and these returned to 73.7% (NS) and 61.8% (P < 0.001) at 1 month post-coronary artery bypass grafting. A similar trend towards a significant improvement was shown in both end-diastolic volume indices and end-systolic volume indices of patients with an old myocardial infarction (P < 0.001). Regional wall motion according to AHA classification in patients with old myocardial infarctions was estimated from biplane left ventriculogram as normal, reduced, none, dyskinetic and aneurysmal, and scored as 0, 1, 2, 3 and 4, respectively. Summated scores in old myocardial infarctions was improved from 5.2 to 4.1 after coronary artery bypass grafting (P < 0.05). There was a significant improvement of summated scores from 8.17 to 6.28 in the low ejection fraction (P < 0.05); however, this was not reflected in the high ejection fraction (3.76 to 3.0; NS). The regional wall motion in the old myocardial infarctions that were heart bypassed to the left anterior ascending artery (n = 67) or to the circumflex artery (n = 40) were significantly improved at regions 2 (P < 0.05), 3 (P < 0.05) and 7 (P < 0.05), and that bypassed to right coronary artery (n = 50) was also improved at regions 3 (P < 0.05), 5 (P < 0.05) and 7 (P < 0.001). This shows that augmentation of regional blood flow by coronary artery bypass grafting will contribute to awakening the hibernated myocardium even in the old myocardial infarction.

Case-Control Studies↗

Nine-year follow-up study of heart rate variability in patients with Duchenne-type progressive muscular dystrophy.

OBJECTIVES: The purpose of this study was to investigate the progression of autonomic dysfunction in patients with Duchenne-type progressive muscular dystrophy (DMD) over time by using heart rate variability. BACKGROUND: Although previous studies suggest the presence of autonomic dysfunction in patients with DMD, the precise cause is not known. On the other hand, it is well known that analysis of heart rate variability provides a useful, noninvasive means of quantifying autonomic activity. High frequency power is determined predominantly by the parasympathetic nervous system, whereas low frequency power is determined by both the parasympathetic and sympathetic nervous systems. METHODS AND RESULTS: Frequency and time domain analyses of heart rate variability during ambulatory electrocardiographic monitoring were performed in 17 patients with DMD over a 9-year period. At the time of entry, the mean patient age was 11 years and the mean Swinyard-Deaver stage was 4. In the first year, high frequency power was significantly lower and the ratio of low frequency to high frequency was significantly higher in patients with DMD than in the normal control subjects. These differences become significantly greater as the disease progressed. At the time of entry, low and high frequency powers increased at night in both groups. However, over time, high and low frequency powers at night tended to decrease. All of the time domain parameters were significantly lower in the patients with DMD at all time points compared with the normal control subjects. CONCLUSIONS: We concluded that DMD patients have either a decrease in parasympathetic activity, an increase in sympathetic activity, or both as their disease progresses.

Adolescent↗