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Biomedical subjects

Y Kuroda

Publications and source records attributed to Y Kuroda.

At least 451 records · Page 25Linked to original sources
PubMed1995

Initial depolarizing potentials in Wolff-Parkinson-White syndrome using signal-averaged electrocardiograms: correlation with reciprocating tachycardia.

Initial depolarizing potentials were examined in patients with Wolff-Parkinson-White (WPW) syndrome using signal-averaging techniques. In all, 25 WPW patients and 21 age-matched healthy children were studied. Ten of the patients were symptomatic and 15 were asymptomatic. Symptomatic patients with supraventricular tachycardias had longer durations of low-amplitude signals (LAS) < 40 mu V in the initial portion of the QRS complex (initial LAS, 49 +/- 7 ms vs. 37 +/- 9 ms, p < 0.01) and lower root-mean-square (RMS) voltage in the initial 40 ms of the QRS complex (initial RMS, 12 +/- 4 mu V vs. 23 +/- 8 mu V, p < 0.01) compared with asymptomatic patients. When a symptomatic patient was defined as having an initial LAS of > 46 ms or an initial RMS of < 15 mu V, the sensitivity and specificity for predicting documented supraventricular tachycardia were 100 and 67%, respectively. These SA-ECG findings may reflect instability of conduction in symptomatic patients through an accessory pathway and may identify those at high risk for supraventricular tachycardia.

Adolescent↗
PubMed1995

Quantitative and qualitative comparative analysis of gradient-separated hematopoietic cells from cord blood and chemotherapy-mobilized peripheral blood.

Some of the uncertainty regarding the use of cord blood (CB) in transplant settings includes the suspected relative rarity of hematopoietic stem cells (SC) in CB and the feasibility of incorporating a cell separation protocol to remove red blood cells, which may result in an unacceptable loss of SC. To address this uncertainty, we isolated a SC fraction by Percoll or Ficoll gradients from CB and peripheral blood (PB), which had been mobilized by chemotherapy. The frequencies of mononuclear cells (MNC), CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and the output of colony-forming cells (CFC) after five weeks in long-term culture (LTC) assay were then evaluated. The mean numbers of these cells per ml of CB sample before gradient separation were, respectively, 4.9 x 10(6), 13.8 x 10(4), 3.0 x 10(3) and 681 (n = 37). In the recovery phase of PB, these numbers were, respectively, 2.0 x 10(6), 14.9 x 10(4), 3.5 x 10(3) and 270 per ml of processed blood at apheresis (n = 35). After Percoll separation, the recovery rates of these cells were, respectively, 29%, 92%, 97% and 95% in CB, and 65%, 87%, 123% and 102% in PB. After Ficoll separation of CB, the rates were, respectively, 55%, 107%, 92% and 105%. These results suggest that CB contains an adequate number of more immature progenitors which can be retained after cell separation with Percoll or Ficoll, thereby making it feasible to incorporate a cell processing procedure into a CB transplant protocol. Percoll separation provided a greater enrichment of cells than Ficoll.

Adolescent↗
PubMed1995

Role of [Ca2+]i in lethal oxidative injury in rat cultured inner medullary collecting duct cells.

Reactive oxygen metabolites have been implicated in the pathogenesis of toxic, ischaemic and immunologically mediated renal injury. An increase in the cytosolic free Ca2+ concentration ([Ca2+]i) has been proposed as a mechanism of oxidative stress-induced cell injury. We used a fluorescence spectrometer and a fluorescence probe to measure the [Ca2+]i and viability of rat primary cultured inner medullary collecting duct (IMCD) cells during oxidative stress induced by 5 mM tert-butyl hydroperoxide (TBHP). Initially, this oxidative stress evoked a small increase in [Ca2+]i which was followed by a slower sustained increase from the resting level of 170.8 +/- 38.8 nM to 1490.5 +/- 301.7 nM after 60 min, and this preceded the loss of plasma membrane integrity, measured by the propidium iodide fluorescence method. The elimination of extracellular Ca2+ from the culture medium prevented the TBHP-induced [Ca2+]i increase and improved cell viability. Restoration of extracellular Ca2+ resulted in an immediate and large increase in [Ca2+]i and extensive cell death. Verapamil, a Ca2+ channel blocker, inhibited the [Ca2+]i increase and afforded significant protection against cellular injury following exposure to TBHP-induced oxidative stress. Extracellular acidosis also prevented the increase in [Ca2+]i and cell death caused by this oxidative stress. These results are consistent with the hypothesis that oxidative stress-induced IMCD cellular injury may be the result of increased [Ca2+]i caused, in part, by activation of voltage-dependent Ca2+ channels.

Animals↗
PubMed1995

Carmofur-induced leukoencephalopathy: MRI.

Carmofur, a derivative of 5-fluorouracil, has recently been noted to have an infrequent but serious association with leukoencephalopathy. To our knowledge, there has been no report of early MRI findings in this leukoencephalopathy. We describe a case in which diffuse high signal intensity of the entire cerebral white matter, including the corpus callosum, was seen on T2-weighted magnetic resonance images. Although similar findings can be seen in many other diseases, carmofur-induced leukoencephalopathy should be suspected in a patient treated with carmofur. It is important to know the clinical and MRI characteristics of this condition, for early diagnosis and better prognosis.

Antineoplastic Agents↗
PubMed1995

Echocardiographic evaluation of the development of aortic valve prolapse in supracristal ventricular septal defect.

UNLABELLED: The development and timing of aortic valve prolapse (AoVP) and aortic regurgitation (AR) was studied by two-dimensional echocardiography in 99 consecutive patients with supracristal ventricular septal defect (VSD). Thirty patients (30%) had aortic valve prolapse (VSD + AoVP group), and 31 patients (31%) had AoVP with AR (VSD + AoVP + AR group). In the VSD + AoVP group, AoVP was detected first by echocardiography at the age of 6.8 +/- 4.2 years (mean +/- SD). In the VSD + AoVP + AR group, the interval from detection of AoVP to the appearance of AR was 3.4 +/- 2.0 years. The configuration of the prolapsed aortic valve was echocardiographically classified into two types: tear-drop type (small) prolapse and box type (large) prolapse. The frequency of tear-drop type prolapse was not significantly different between VSD + AoVP and VSD + AoVP + AR groups (43% versus 32%, respectively), indicating that even minor AoVP can result in AR. Four infants (4%) had AoVP at the ages of 1, 5, 7, and 11 months, respectively. All infants had tear-drop type prolapse. Two infants developed AR by colour flow mapping at the ages of 3 and 11 months, and the interval from prolapse to AR was only 2 and 4 months, respectively. CONCLUSION: Aortic valce involvement can develop under the age of 1 year in supracristal VSD. Regular evaluation by two-dimensional echocardiography with colour flow mapping is important in the follow-up of children with supracristal VSD.

Age of Onset↗
PubMed1995

Anomalous inferior vena cava in association with omphalocele: a case report.

We present the case of a 6-year-old boy who had an omphalocele repaired at day 1 of life. He had a secundum atrial septal defect and an anomalous inferior vena cava of a type which has not been previously reported. Cine-MRI was a useful noninvasive tool for diagnosing the anomalous subaortic innominate vein and four immature vessels which make up the venous drainage systems of the lumbar region. The recognition of this malformation is important in planning and executing surgical repair or cardiac catheterization for postoperative patients with omphaloceles.

Child↗
PubMed1995

Development of the brainstem and cerebellum in autistic patients.

Studies of magnetic resonance images have revealed morphological disorders of the brainstem and cerebellum in autistic children and adults. When we studied development of the brainstem and cerebellum in autistic patients, we found that although the brainstem and cerebellum significantly increased in size with age in both autistic patients and controls, these structures were significantly smaller in autistic patients than in controls. The speed of development of the pons, the cerebellar vermis I-V and the cerebellar vermis VI-VII was significantly more rapid in autistic patients than in the controls. However, the speed of development of the other brain structures in the posterior fossa did not differ between autistic patients and controls. The regression intercepts of the brainstem and cerebellum as well as those of their components were significantly smaller in autistic patients than in controls. Results suggest that brainstem and vermian abnormalities in autism were due to an early insult and hypoplasia rather than to a progressive degenerative process.

Adolescent↗
PubMed1995

DNA diagnosis of pyruvate dehydrogenase deficiency in female patients with congenital lactic acidaemia.

The diagnosis of pyruvate dehydrogenase (PDH) E1 alpha deficiency, which is an X-linked inborn error of metabolism, is usually established by the measurement of PDH complex activity in cultured cells. However, heterozygous female patients with PDH E1 alpha deficiency may be misdiagnosed when the normal X chromosome is predominantly expressed in the cultured cells. Therefore, in female patients with convincing clinical presentations of PDH E1 alpha deficiency and the normal enzyme activity, the X-inactivation pattern should be analysed and the PDH E1 alpha gene screened for mutations. For this screening, we applied the method of single-strand conformational polymorphism (SSCP) and DNA sequencing and examined 11 female patients with congenital lactic acidaemia whose PDH complex activity was normal in cultured cells. In 2 of the 11 female patients, we found distinct pathogenic missense mutations in the PDH E1 alpha gene (G89S and G291R). Both affected patients showed a similar clinical presentation and had been diagnosed as West syndrome. In 3 of the 11 patients, we found a polymorphic base-pair substitution in exon 9 of the PDH E1 alpha gene which resulted in a changed amino acid residue (M282L). We conclude that PCR-SSCP analysis of the PDH E1 alpha gene, followed by DNA sequencing, is a useful method to screen for mutations of the PDH E1 alpha gene in female patients with congenital lactic acidaemia who have normal enzyme activities in available samples, normal ratio of lactate to pyruvate, and predominantly raised lactate concentration in cerebrospinal fluid.

Base Sequence↗
PubMed1995

Molecular genetic analysis of a female patient with pyruvate dehydrogenase deficiency: detection of a new mutation and differential expression of mutant gene product in cultured cells.

A new 18 bp insertion mutation in the gene for the alpha subunit of pyruvate dehydrogenase (E1 alpha) was found in a female patient with congenital lactic acidaemia. Cultured skin fibroblasts and Epstein-Barr virus-transformed lymphoblastoid cells from this patient showed decreased and normal pyruvate dehydrogenase complex (PDHC) activity, respectively. This 18 bp insertion was a de novo mutation, because it was not present in her parents. Although this female patient was heterozygous for the normal and the mutant alleles, 97% of cultured skin fibroblasts expressed the mutant allele, while 100% of cultured lymphoblastoid cells, 94% of peripheral blood lymphocytes and 98% of IL-2-activated T-cells expressed the normal allele. These results suggest that in this patient the X chromosome containing the normal allele was predominantly inactivated in fibroblasts and the X chromosome containing the mutant allele was predominantly inactivated in lymphocytes. The diagnosis of E1 alpha deficiency is usually established by measurement of PDHC activity and the level of immunoreactive proteins. However, these methods are not sufficient to diagnose the disorder in female patients with E1 alpha deficiency due to differential inactivation of the X chromosome. Therefore, it is necessary to develop a new method to firmly establish the diagnosis of E1 alpha deficiency.

Alleles↗
PubMed1995

Characterization of humoral and cellular immunity in the central nervous system of HAM/TSP.

In HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) immunopathological processes in the central nervous system (CNS) have not been clarified. We compared the humoral and cellular immunity within the CNS and in the systemic circulation of 24 patients with HAM/TSP (8 men and 16 women) to 6 asymptomatic HTLV-I carriers, 7 patients with active multiple sclerosis, 6 patients with acute viral encephalitis, and 39 patients with other non-inflammatory neurological diseases. Significant differences were observed between the HAM/TSP patients and one or more of the control groups: HAM/TSP cerebrospinal fluids (CSF) exhibited higher levels of IgG, IgG index, de novo IgG synthesis rate, and beta 2-microglobulin, and also a predominance of CD8+ cells that expressed CD11a and CD45RO but lacked CD28 antigens. Results in the 6 patients with acute viral encephalitis suggested that the CD8+ population in the CSF which is positive for CD28 and CD45RO is important for the elimination of virus from infected CNS tissues. Therefore, potentially cytotoxic T cells of a unique CD8+CD11a+CD45RO+CD28- phenotype may play a key role in the CNS pathogenesis of HAM/TSP.

Adult↗
PubMed1995

A follow-up study on spastic paraparesis in Japanese HAM/TSP.

We followed 24 patients with HTLV-I-associated myelopathy (HAM) for 4-12 years (mean 7 years) and assessed longitudinal changes of their spastic paraparesis by Kurtzke's Disability Status Scale (DSS). The DSS score of spastic paraparesis was unchanged in 18 patients (75%), advanced (worsened) by two in 1 patient and by one in 3 patients, and declined (improved) by one in 2 patients during the follow-up period. The results demonstrated that HAM presents with a variety of clinical courses including spontaneous improvement.

Adult↗
PubMed1995

Seronegative myasthenia gravis associated with atonic urinary bladder and accommodative insufficiency.

We report a 20-year-old female with generalized myasthenia gravis (MG) who developed atonic urinary bladder and accommodative insufficiency. Although her sera did not contain antibodies to either nicotinic acetylcholine receptor (AChR) or voltage-gated calcium channels, a positive intravenous edrophonium test and a waning phenomenon on electromyographic studies indicated a diagnosis of seronegative MG. Myasthenic symptoms as well as urinary incontinence and impaired near vision disappeared with slight sequelae after corticosteroid therapy and total removal of the hyperplastic thymus. These symptoms recurred during a tapering course of corticosteroids, and improved again with an increased dose. Therefore, in this patient, the neuromuscular transmission of muscarinic type of AChR in the smooth muscles was also affected. This patient provides insight into the mechanisms by which some smooth muscles are involved in MG.

Accommodation, Ocular↗
PubMed1995

Proton magnetic resonance spectroscopy of brain in congenital myotonic dystrophy.

Volume selective proton magnetic resonance spectroscopy of brain was performed on a 1.5 T magnet in 5 patients with congenital muscular dystrophy and compared to the results in 46 healthy children and 1 healthy adult. Peaks of N-acetyl aspartate, choline, and creatine but not lactate, were observed in both groups on proton magnetic resonance spectroscopy. Spectroscopy of controls revealed an increase with advancing age in the ratio of N-acetyl aspartate/choline and N-acetyl aspartate/creatine and a decrease in the choline/creatine ratio. In patients with congenital myotonic dystrophy, the N-acetyl aspartate/choline ratio did not increase with advancing age, but the N-acetyl aspartate/creatine ratio did. The choline/creatine ratio decreased with advancing age, which matched the results of controls. At any age older than 4 years, the N-acetyl aspartate/choline and N-acetyl aspartate/creatine ratios were lower in patients with congenital myotonic dystrophy than in controls. The choline/creatine ratio did not differ between congenital myotonic dystrophy and controls. These results suggest that in patients with congenital myotonic dystrophy N-acetyl aspartate decreases and there exists a developmental disorder of neurons in brain.

Adolescent↗
PubMed1995

Reduced N-acetylaspartate in the brain observed on in vivo proton magnetic resonance spectroscopy in patients with mental retardation.

Volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain was performed with a 1.5T magnet in 28 patients with unclassified mental retardation (MR) and in 25 age-matched healthy children. Peaks of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), but not of lactate, were observed in both groups on 1H-MRS. In all our subjects of this age range, 1H-MRS revealed an increase with advancing age in the ratio of NAA/Cho (P = .0031), but no developmental change in the NAA/Cr and Cho/Cr ratios. The NAA/Cho ratio was lower in patients with MR than in controls (P = .0016). The NAA/Cr ratio tended to be lower in the MR group, and the Cho/Cr ratio did not differ between patients with MR and controls. These results suggest that in patients with MR, NAA decreases and a disorder and/or dysfunction of neurons in the brain exists.

Adolescent↗
PubMed1995

Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma.

BACKGROUND: We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. METHODS: Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. CONCLUSIONS: This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

Adult↗
PubMed1995

A strategy for the de novo design of helical proteins with stable folds.

This paper describes peptide analogs and the design strategy that were used to facilitate the final construction of a de novo-designed protein (ALIN) whose stable tertiary fold has been determined recently by NMR spectroscopy. Previous studies have suggested that the main problem in the de novo design of proteins is the attainment of a protein with a defined fold. To effectively overcome this mainchain multiconformation problem, three related steps, with experimental evaluation of the design hypotheses for each step, were pursued in the design process. Firstly, 15-residue sequences with experimentally verified high helicites were selected for the helical regions. Secondly, hydrophobic and electrostatic interhelical interactions as well as an interhelical disulfide bridge were designed to favor an antiparallel configuration of the helix axis. Finally, a loop with sufficient flexibility was inserted to stabilize the helices in the desired orientation. To assess the design strategy, peptides corresponding to each design step were synthesized and their structures verified experimentally by far-UV CD. As anticipated, ALIN was the most helical, and the SS-bridged dimeric peptides were more helical than their monomeric counterparts. The van't Hoff enthalpy change for ALIN computed from the CD denaturation curve and assuming a two-state model was 50 kJ/mol, a value close to that observed for helical coiled-coils. Overall, this report shows that small, simple proteins can be built using the current knowledge of protein structures.

Amino Acid Sequence↗
PubMed1995

Myelodysplastic syndrome in two young brothers.

We report the youngest cases of myelodysplastic syndrome (MDS) in two brothers aged 7 and 2 years. The maternal grandfather and maternal grandmother had been exposed to radioactive fallout after the atomic bomb attack on Hiroshima in 1945. The elder brother demonstrated pancytopenia with < 1% blast cells in his peripheral blood and < 5% in his bone marrow at diagnosis. The younger brother was thrombocytopenic without increased blasts. The karyotype of bone marrow cells from the elder brother was 46,XY, -7, +der (7), t(1:7) (lqter-lq11::7q11-7pter), but the younger brother's karyotype was normal. Immature myeloid cells in the bone marrow from both brothers were morphologically abnormal. A diagnosis of refractory anaemia (RA) was made in both brothers. Atavism due to radioactive poisoning was suspected in the development of MDS in these two cases.

Anemia, Refractory↗