[Dihydropyrimidine dehydrogenase deficiency].
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Biomedical subjects
Publications and source records attributed to A Taniguchi.
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The authors report the initial results, between January 1998 and February 2001, of stenting utilizing the brachial approach in seven patients for total occlusions at the following locations: two right subclavian, one brachiocephalic, and five left subclavian arteries. All lesions were associated with subclavian steal syndrome. Indications for the treatment included ischemic symptoms in the affected arm (seven patients), and vertebrobasilar insufficiency (five patients). A total of eight stents were implanted in six occluded arteries, resulting in a 75% procedural success rate. Procedural complications encountered were two subintimal dissections by a 0.035-inch guide wire during recanalization, and one stent dislodgement with migration. There was no stroke, presumably because of the previously reported preventive effect of delayed reversal of a stealing vertebral artery. Follow-up over a mean duration of 11 months revealed no sign or symptom of recurrence in cases with initial technical success. The results of the current study, with a literature survey, indicated that percutaneous transluminal angioplasty with primary stent deployment in an occluded prevertebral segment of the subclavian or the brachiocephalic artery should be considered as an available choice for treatment. Further points, such as some remaining technical and clinical problems, will require more experience and consideration.
The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries.
We experienced two cases of malignant hyperthermia (MH) triggered by sevoflurane. Case 1 was a six-year-old girl, 15.8 kg, undergoing strabismus repair. She had flat back, elevated diaphragm and high arched palate. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Her trachea was intubated without the use of muscle relaxant. Thirty minutes after the induction of anesthesia, ETco2 was over 60 mmHg despite hyperventilation. Muscle rigidity of legs and the rise in temperature were noted. MH was diagnosed and dantrolene i.v. was administered. Her maximum esophageal temperature was 40.2 degrees C. ETco2 and temperature returned to baseline values after dantrolene administration. Creatine phosphokinase (CK) level was 252 U.l-1 preoperatively, and 1690 U.l-1 next day. Case 2 was a year-and-9-month-old boy undergoing accessory ear resection. Anesthesia was induced with sevoflurane and nitrous oxide in oxygen. His trachea was intubated with an aid of vecuronium. Forty minutes after administration of sevoflurane his temperature rose to 38.6 degrees C with heart rate 191 bpm and Spo2 93%, and muscle rigidity of legs. MH was diagnosed and dantrolene was administered. His highest temperature was 39.3 degrees C and was reduced promptly after dantrolene. Postoperatively he was noted to have downslanting palpebral fissures, micrognathia, low set ears, and a single crease of the fifth finger and diagnosed as King syndrome which is reported to have association with MH. Both patients had no history of anesthesia nor abnormal family history. Both of them were rescued with dantrolene and recovered without sequelae.
Chronic parenteral administration of beta-beta'-iminodipropionitrile (IDPN) in adult female rats induces large neurofilament-rich axonal spheroids (AXS) in spinal motor neurons closely resembling those AXS in early phases of amyotrophic lateral sclerosis. Immunohistochemistry of advanced glycosylation end-products (AGEs) in axonal spheroids was performed in the present study. Anti-AGE and anti-neurofilament antibodies strongly co-labeled IDPN-induced axonal spheroids, whereas motor neuron soma showed little AGE immunoreactivity. In an attempt to modify and intensify glycosylation, another group of IDPN rats was made hyperglycemic with streptozotocin after IDPN intoxication. These hyperglycemic rats showed AXS with striking AGE immunoreactivity. An additional group of rats made hyperglycemic before IDPN intoxication showed markedly diminished AXS formation, with a few small AGE-positive AXS in anterior horns. Findings suggest that AGEs are involved in neurofilament crosslinking as well as disassembly of neurofilament induced by IDPN with or without hyperglycemia. Hyperglycemia did not intensify neurofilament aggregation. Additional immunohistochemistry revealed not only aberrant phosphorylation, but also intense local production of Cu/Zn superoxide dismutase and nitrotyrosine in axonal spheroids, probably secondary to superoxide generation as a consequence of AGE production at neurofilament protein, impeding its assembly as hypothesized in motoneuron diseases.
In fucosyltransferase genes, mRNA expression is regulated in a cell-type-specific manner. The expression level of human fucosyltransferase 4 (FUT4) mRNA is high in both colon adenocarcinoma and myeloid cell lines. We will demonstrate here cell-specific expression and transcriptional regulation of the FUT4 gene. FUT4 has two different transcription initiation sites that respectively produce long- and short-form mRNAs. To determine the major FUT4 transcript in colon adenocarcinoma and myeloid cell lines, we analyzed the transcriptional starting sites of the FUT4 gene in myeloid and colon adenocarcinoma cell lines, using 5'-RACE, RT-PCR, and luciferase analysis. The results suggested that the expression level of short-form mRNA is higher than the long-form transcript in the colon adenocarcinoma cell lines and that the expression level of long-form mRNA is higher than the short-form transcript in the myeloid cell lines. Using a luciferase assay, we identified a functional DNA portion within FUT4 genomic DNA that confers a colon adenocarcinoma cell line-specific enhancer, located in nucleotide number (nt) -256 to -44, and a myeloid cell line-specific enhancer, located in nt -686 to -582. The present results suggest that these elements play a critical role in the colon adenocarcinoma and leukemia cell-specific transcriptional regulation of the FUT4 gene.
OBJECTIVE: To evaluate whether matrix metalloproteinase 3 (MMP-3), a proteinase that is expressed in rheumatoid synovial tissue and shows potent activity in degrading the proteoglycan of cartilage, plays a pivotal role in the joint destruction seen in early rheumatoid arthritis (RA). METHODS: In a prospective study of patients with early RA, the relationship between the serum concentration of MMP-3, as determined by a sandwich enzyme immunoassay system, and the progression of joint destruction in patients with early RA, as measured by the Larsen radiologic score, was investigated. RESULTS: Serum MMP-3 levels were elevated in the RA patients compared with healthy controls, not only in the late stage, but also in the early stage of the disease in patients whose duration of RA was <4 months. The serum MMP-3 level at entry into the study had a strong correlation with the Larsen score at 6 months and 12 months after entry (r = 0.58 and r = 0.49, respectively). Similarly, the serum MMP-3 level at 12 months and 24 months after entry showed a positive association with the Larsen score in the subsequent 6-12 months. Suppression of the serum MMP-3 level in the first year led to a decline in joint damage in the second year. CONCLUSION: The serum concentration of MMP-3 is a useful marker for predicting bone damage in the early stage of RA, and the suppression of MMP-3 production may be an effective therapeutic approach for patients with early RA.
The pathogenicity of a new neurotropic equine herpesvirus 9 (EHV-9) formerly designated gazelle herpesvirus 1 was evaluated using the goat as a representative of domesticated ruminants. Two goats inoculated intranasally with EHV-9 showed salivation, teeth grinding and other neurological disorders on day 8 post inoculation. One goat died 30 min after the onset of clinical signs and the other was sacrificed 3 h after the sudden onset of teeth grinding and foamy salivation. EHV-9 was recovered from peripheral white blood cells, the olfactory bulbs and brain, nasal swabs, concha, and lungs. Neuropathological lesions were located in the olfactory bulbs, cerebrum, midbrain and medulla oblongata with degeneration and necrosis of neurons, rarefaction, perivascular infiltration of mononuclear cells, and nodal glial reaction. EHV-9 antigen was detected in neurons in the lesions. These findings indicated that EHV-9 is highly pathogenic with high neurotropism for goats.
The present study investigated the mechanism underlying alterations of cell surface sugar chains of Jurkat cells by inducing apoptosis with etoposide, an inhibitor of topoisomerase II. Within 3 h of etoposide treatment, flowcytometric analysis revealed a decrease in Maackia amurensis agglutinin recognized alpha2,3-linked sialic acid moieties and an increase in Ricinus communis agglutinin recognized galactose. The results suggested that asialo-sugar chains on glycoconjugates were rapidly induced on the etoposide-treated cell surface. To clarify the desialylation mechanism, we studied alpha2,3-sialyltransferase mRNA expression and the activity of sialidase on the cell surface during etoposide-induced apoptosis. The expression of hST3Gal III and hST3Gal IV mRNAs were down-regulated and sialidase activity on the cell surface increased threefold within 2 h of etoposide treatment. Moreover, the decrease in alpha2,3-linked sialic acid levels was significantly suppressed in the presence of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid, an inhibitor of sialidase. These results suggested that activation or exposure of sialidase on the cell surface was induced by etoposide treatment and was the main cause of the decrease in sialic acids.
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. In addition, TNF-alpha can stimulate a variety of physiological, neuroendocrine and behavioural responses of the central nervous system. In experimental animals, TNF-alpha induces changes in physiological and behavioural parameters which have also been observed in eating disorders. The biological activities of TNF-alpha are mediated by two structurally related, but functionally distinct receptors, TNF-RI and TNF-RII. Since injection of TNF-alpha results in increased shedding of TNF-alpha receptors, it is likely that TNF-alpha release is reflected by soluble TNF-receptors (sTNF-Rs) levels. AIMS: We studied plasma concentrations of TNF-alpha and two sTNF-Rs (sTNF-RI and sTNF-RII) in female patients with bulimia nervosa. DESIGN AND PATIENTS: Twenty female patients with bulimia nervosa (BN) and 20 age-matched normal women (N) were studied. MEASUREMENTS: Plasma TNF-alpha concentrations were measured by enzyme immunoassay kit and plasma concentrations of sTNF-RI and sTNF-RII were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma TNF-alpha concentrations in BN were significantly higher than those in N (4.7+/- 0.5 ng/l vs. 1.6+/-0.1 ng/l; P<0.01). Although no significant difference was observed in plasma sTNF-RI concentrations between the two groups, plasma sTNF-RII concentrations in BN were significantly higher than those in N (2080.0+/-107.5 ng/l vs. 1569.5 +/-84.0 ng/l; P<0.01). Plasma TNF-alpha concentrations were significantly related to plasma sTNF-RI concentrations (r = 0.511, P<0.05) and to plasma sTNF-RII concentrations (r = 0.532, P<0.05) in bulimic patients. However, plasma TNF-alpha concentrations were not related to body fat mass or to bulimic behaviours in these patients. CONCLUSIONS: Our present findings suggest that the adipose tissue may not be the immediate source of TNF-alpha in bulimic patients but the increase in plasma TNF-alpha in these patients may be derived from the central nervous system sources. The elevated sTNF-RII may reflect different shedding kinetics compared with sTNF-RI in bulimic patients.
Seven patients (one man and six women) with a diagnosis of pulmonary thromboembolism (PTE) were examined by polysomnography in order to clarify the relationship between sleep-related breathing disorders and PTE. In the chronic stage of PTE, sleep apnea syndrome (SAS) was recognized in two patients (a man and a woman) among the subjects. Four of the five patients without SAS showed nocturnal hypoxemia. The female predominance was different from ordinary SAS without the disease background of PTE even though PTE is accompanied by hypoxemia and pulmonary hypertension like SAS. A pathophysiological relationship between PTE and SAS was not found in this study.
Using the minimal model approach shown by Bergman, our group had previously shown 2 variants among non-obese mildly diabetic patients, one with normal insulin sensitivity and the other with insulin resistance. The present study examines whether these 2 variants exist in the ordinary Japanese non-insulin-dependent diabetes mellitus (NIDDM) population and compares the clinical profile between the 2 discrete forms of NIDDM. In addition, we investigated the factors responsible for insulin resistance observed in Japanese NIDDM populations. One hundred eleven untreated Japanese NIDDM subjects (fasting glucose < 10 mmol/L) were assessed for insulin action (homeostasis model assessment [HOMA-IR] = fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5) and the fasting lipid profile. Sixty percent of these patients had normal insulin sensitivity (HOMA-IR < 2.5). The insulin-resistant patients had higher serum cholesterol (188.1 +/- 5.2 v 182.2 +/- 3.9 mg/dL, P> .05) and low-density lipoprotein (LDL) cholesterol (501.2 +/- 16.7 v 469.4 +/- 14.8 mg/dL, P > .05) than the insulin-sensitive patients, but the difference was not statistically significant. In contrast, the former group had a significantly higher body mass index ([BMI] 26.6 +/- 0.8 v 21.7 +/- 0.4 kg/m2, P < .0001) and higher serum triglycerides (181.0 +/- 16.4 (range, 79 to 545) v 95.1 +/- 4.1 (range, 36 to 204) mg/dL, P < .0001) and lower high-density lipoprotein (HDL) cholesterol (47.2 +/- 1.7 v 58.2 +/- 2.5 mg/dL, P < .005) than the latter group. HOMA-IR was related to the BMI. Fifteen of 17 (88%) NIDDM patients with a BMI greater than 27.0 were insulin-resistant, whereas 35 of 38 (92%) NIDDM patients with a BMI less than 21.5 were insulin-sensitive. In the midrange BMI (21.5 to 27.0 kg/m2), patients were equally likely to be insulin-resistant or insulin-sensitive. Analysis of the midrange BMI group showed that HOMA-IR was associated with serum triglycerides (P < .0001) but not with the BMI. These data suggest the following conclusions: (1) Japanese NIDDM patients can be classified into 2 populations, one with normal insulin sensitivity and the other with insulin resistance; (2) NIDDM patients with normal insulin action have a low cardiovascular disease risk factor, whereas those with insulin resistance have a markedly increased cardiovascular disease risk factor; and (3) the BMI and serum triglyceride level per se are associated with insulin action in Japanese NIDDM populations.
We have previously shown that the expression of beta-galactoside alpha2,6-sialyltransferase (hST6Gal I) mRNA decreases during HL-60 differentiation induced with dimethyl sulfoxide (DMSO) and that transcriptional regulation depends on the P3 promoter that exists 5'-upstream of exon Y (A. Taniguchi et al., FEBS Lett.,441, 191-194, 1998). The regulation of hST6Gal I may be important for the expression of sialyl-Le(x)in HL-60 cells. In the present report, we studied the transcriptional regulation of hST6Gal I gene during DMSO-induced differentiation of HL-60 cells. To elucidate the molecular basis of hST6Gal I gene expression, the genomic region containing the P3 promoter of hST6Gal I was isolated and functionally characterized. Using a luciferase assay, we identified a functional DNA portion that confers an enhancer, located at nucleotide number (nt) -317 to -174 within the P3 promoter of hST6Gal I genomic DNA. This element contains two sequences similar to Sp1 (GC-box) and one sequence similar to Oct-1 recognition motifs (octamer sequence). Site-directed mutagenesis of Sp1 and Oct-1 sites showed that two Sp1 motifs and one Oct-1 motif are essential for transcriptional activity in HL-60 cells. Enhancer activity is suppressed during HL-60 cell differentiation induced with DMSO. These results suggest that GC-box and octamer sequence may play a critical role in the transcriptional regulation of the hST6Gal I gene during HL-60 cell differentiation.
Our purpose is to directly measure mammographic x-ray spectra with collimators and a low-efficiency CdZnTe detector developed recently and to find out the best fit response function of CdZnTe detector to correct the measured spectra. Photon spectra (target Mo or Rh) produced by a mammographic x-ray unit at 25-32 kV and 240 mAs (= 3 times of 80 mAs) and transmitted through 0.03 mm Mo or 0.025 mm Rh filter and object (0.1 mm Al to 0.8 mm Al phantoms) have been analyzed. Since detected spectra were distorted by the response of CdZnTe detector and did not present the true photon spectra, the correction was applied by the stripping procedure. The response function of detector used in this procedure has been determined by the evaluation of interactions (K-escape, coherent scattering, and Compton scattering processes) and incomplete charge collection calculated using the Monte Carlo method. We have used Kalpha1, Kalpha2, Kbeta1, Kbeta2 radiations of Cd, Zn, and Te, respectively and have used the weight function for the incomplete charge collection and have considered Compton scattering. The Monte Carlo simulations were continued by changing the important factors (mean path length of hole lambda(h), dead layer of the CZT crystal and weight factor Wq) of incomplete charge collection until the best fit response function was found out. Corrected photon spectra were compared with the mammographic x-ray spectral data of Bureau of Radiological Health (BRH) measured using a Ge detector. Attenuation curves of aluminum for 25-32 kV were calculated from the corrected photon spectra and compared with the attenuation curves measured using an ionization chamber. These results obtained using the CdZnTe detector agreed with the mammographic x-ray spectral data of BRH and attenuation curves obtained by the ionization chamber.
Pathogenicity of equine herpesvirus 9 (EHV-9), a new type of equine herpesvirus isolated from Gazella thomsoni, in horses was investigated by intranasal inoculation of EHV-9 (10(7) pfu) to two conventionally reared 8-months old half-bred weanling horses. Fever higher than 39 degrees C was recorded. Virus was recovered from nasal swabs and peripheral blood mononuclear cells. Both horses developed neutralizing antibody to EHV-9. Perivascular infiltration of mononuclear cells and glial reaction were found in the olfactory and limbic systems. The results suggested that EHV-9 has a pathogenicity in horses.
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OBJECTIVE: The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. RESULTS: The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. CONCLUSIONS: These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.