Clonality analysis of nodular fasciitis by HUMARA-methylation-specific PCR.
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Biomedical subjects
Publications and source records attributed to M Tadokoro.
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The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are considered first-line therapeutic agents for the prevention of coronary heart disease and atherosclerotic disorders related to hypercholesterolemia. Statins inhibit lipid deposition in the aortic endothelium. Although it has been accepted that the statins are potent inhibitors of cholesterol biosynthesis in the liver and that they lower circulating cholesterol levels, several cholesterol-independent (pleiotropic) effects have been reported. The cholesterol-independent effects of statins involve normalization of the nitric oxide (NO)-NO synthase system, anti-inflammatory effects through the inhibition of cytokine/chemokine production, inhibition of vascular smooth muscle cell proliferation and migration, and inhibition of platelet thrombus formation/reduction of the thrombotic response. Some pleiotropic effects of statins may depend on the inhibition of the biosynthesis of farnesyl- and geranylgeranyl-nonsterol compounds from mevalonate in the cells. The Rho/Rho kinase pathway and the phospatidylinositol-3 kinase/Akt pathway mediate the pleiotropic effects of statins. As variations occur in absorption, metabolism, and excretion mechanisms due to the characteristics of specific statins including their hydrophilicity and lipophilicity, there are differences in the transfer mechanisms of statins into tissues. However, the pleiotropic effects occur regardless of statin hydrophilicity and lipophilicity. This review summarizes the pleiotropic effects of statins on lipid deposition in blood vessels.
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A new series of ester-armed cyclens nicely accommodated a Na+ ion in their quadruplicated helical binding spheres and effectively discriminated the cation from Li+ and K+ ions. Crystallographic studies revealed that four ester-functionalized sidearms provided effective coordination with the Na+ ion trapped in the 12-membered cyclen ring. Log K values for their Na+ complexes were estimated as 9-11 in CD3CN or C2D5OD, which were comparable to those of common bicyclic cryptands. FAB-MS, liquid-liquid extraction, and NMR binding experiments demonstrated that the cooperative action of the parent cyclen ring and ester-functionalized sidearms offered stable and selective encapsulation of the Na+ ion based on unique quadruplicated helical geometry.
In patients with cerebral tumors, high accumulations of L-methyl-11C-methionine (11C-Met) have been reported in some cases of cerebral ischemic disease, but no high accumulations of 11C-Met in areas where only transient arterial occlusions are most likely to occur have been reported. Herein we present a case of a high accumulation of 11C-Met in an area of frontal interhemispheric cerebral infarction and a moderately high accumulation with an unclear margin in a distant frontal convexity area. A craniotomy revealed a subacute stage of cerebral infarction in the interhemispheric lesion, and an ischemic change in the distant convexity area. Sixteen months after onset, CT scans demonstrated an infarction area in the interhemispheric lesion only, and no atrophic changes were observed in the distant convexity area indicating that no serious tissue damage had occurred.
A 68-year-old man was admitted to St Marianna University Hospital on account of loss of consciousness with left hemiplegia. During the hospital recovery course with a rehabilitation procedure, the patient's blood pressure was very unstable, fluctuating between high (210/110 mmHg) and low (110/70 mmHg) values accompanied by a fainting sensation. A second stroke of left hemiplegia took place 1 month later. Afterwards, his condition worsened to tetraplegia with dysarthria. Three months later, lung cancer with multiple metastasis including his left neck was found and he died from adynamic ileus 6 months after the onset of the present illness. Autopsy revealed nearly complete atheromatous obstruction and more than 50% stenosis, respectively, of his right common and internal/external carotid arteries. His intracranial arterial trunks and main branches were all patent with localized atherosclerosis of only moderate degree. The pathology of the brain existed predominantly in the right hemisphere in the border zone area between the anterior and middle cerebral arteries systematically with numerous disseminated foci of complete or incomplete necrosis, white matter and gray matter being involved independently. Involvement of centrum semiovale white matter is more extensive and intensive than that of gray matter. Of the gray matter, cerebral cortex as well as striatum, periventricular (the third ventricle) gray and cerebellar cortex was involved. The specific characteristic topography and distribution of the lesions together with their histopathology are described in detail with illustration. It is concluded that this case represents an outstanding example of hemodynamic cerebral circulatory insufficiency doubly caused by hemilateral carotid artery stenosis and repeated episodes of systemic hypotension.
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We present 4 patients undergoing hemodialysis in whom thoracic computed tomography (CT) suggested a diagnosis of rounded atelectasis (RA) with pleural effusion. The clinical setting and follow-up CT of all 4 patients confirmed this diagnosis. The pleural fluid of each appeared serosanguineous or hemorrhagic and predominantly consisted of lymphocytes. Biochemical analysis of this fluid revealed high levels of total protein, lactate dehydrogenase and glucose. Bacterial culture and polymerase chain reaction for Mycobacterium tuberculosis DNA was negative. Pleural biopsy specimens from 2 of the 4 patients showed evidence of fibrinous change and mesothelial cell hyperplasia. Pleural effusion from all 4 patients did not respond to either fluid restriction or aggressive hemodialysis-induced dehydration. The subsequent clinical course and thoracentesis were repeated, and in 1 patient, this was followed by tetracycline pleurodesis. However, 2 patients died during pre-pleurodesis and 1 died during post-pleurodesis, all due to respiratory failure. We propose that the clinical setting and follow-up thoracic CT and thoracentesis of patients receiving long-term hemodialysis confirmed a diagnosis of rounded atelectasis with uremic pleural effusion. We also propose that the prognosis of patients with refractory pleural effusion receiving long-term hemodialysis would be improved by early pleurodesis.
The impairments of learning and memory function and of the cholinergic system were examined in rats with microsphere embolism. Microsphere embolism was induced by injection of 900 microspheres with a diameter of 48 microm into the right internal carotid artery. The retention latency of a passive avoidance test was shortened and the escape latency of a water maze test was prolonged, when the animals were tested on the 5th to 10th day after the embolism, suggesting learning and memory dysfunction. Cholinergic parameters of the striatum and hippocampus, such as acetylcholine (ACh) content (67 and 60% decrease, respectively), choline acetyltransferase (ChAT) activity (45 and 56% decrease, respectively), and Bmax of muscarinic acetylcholine M1-receptor (43 and 37% decrease, respectively), were reduced on the 11th day after the embolism, suggesting attenuation of ACh synthesis and a decrease in the number of muscarinic acetylcholine M1-receptors mainly in the striatum and hippocampus. Areas not stained with triphenyltetrazolium chloride, an indication of infarction, were detected mainly in the striatum and hippocampus and partly in the frontal cortex on the 11th day after the embolism. The results suggest that an animal with microsphere embolism may be a good ischemic model with relatively sustained impairments of learning and memory function and of the striatal and hippocampal cholinergic system.
BACKGROUND: Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome. OBJECTIVE: The aim of this study was to investigate the genotype-phenotype correlations of PDS. METHODS: Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient. RESULTS: A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles. CONCLUSION: The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R.
KL-6 is a glycoprotein antigen derived from the cell line of human lung adenocarcinoma. Although KL-6 is known to be a serum marker of interstitial pneumonia, elevated KL-6 serum levels have also been reported in some cases of pulmonary tuberculosis. To elucidate the mechanism of KL-6 elevation in pulmonary tuberculosis, we stained pulmonary tissue samples from five clinical cases for immunohistochemical analyses. In the two cases showing productive changes, KL-6 immunoreactivity was localized in the area of type II pneumocytes showing strong interstitial changes surrounding caseous necrosis. In the two cases showing exudative changes, KL-6 immunoreaction was observed not only to surround caseous necrosis but also to appear within it, particularly in the remaining alveolar lumen septa. On the other hand, the one patient with old pulmonary tuberculosis that showed slight interstitial changes presented with weak KL-6 immunoreactivity on the surface of the alveolar lumen surrounding the tuberculotic region. These results suggest that serum elevation of KL-6 in pulmonary tuberculosis originates from the proliferation of type II pneumocytes along with interstitial changes that surround the tuberculous region.
We report here a novel family of G-protein coupled receptor (GPCR) which is extraordinarily conserved among vertebrate species. This family, designated SREB (Super Conserved Receptor Expressed in Brain), consists of at least three members, termed SREB1, SREB2, and SREB3. SREB members share 52-63% amino acid identity with each other and show relatively high similarity to previously known amine amine GPCRs (approximately 25% identity). Amino acid sequence identity between human and rat orthologues is 97% for SREB1 and 99% for SREB3, while the SREB2 sequence is surprisingly completely identical between the species. Furthermore, amino acid sequence of zebrafish SREB2 and SREB3 are 94 and 78% identical to mammal orthologues. Northern blot analysis revealed that SREB members are predominantly expressed in the brain regions and genital organs. Radiation hybrid analysis localized SREB1, SREB2, and SREB3 genes to different human chromosomes, namely 3p21-p14, 7q31 and Xp11, respectively. The high sequence conservation and abundant expression in the central nervous system suggest the existence of undiscovered fundamental neuronal systems consisting of SREB family members and their endogenous ligand(s).
PURPOSE: The aim of this study was to determine how extensive resection affects operative morbidity, mortality, and long-term survival in elderly patients with colorectal cancer. METHODS: A total of 119 patients 80 years of age or older were given a diagnosis of colorectal carcinoma at our hospital between 1985 and 1997. Eleven patients who did not undergo surgery were excluded. The remaining 108 patients underwent laparotomy and were reviewed. Serum levels of interleukin-6 were measured perioperatively in 22 patients to assess the degree of operative stress. RESULTS: Potentially curative resection was performed in 64 (88.9 percent) of the 72 patients in the active performance status group and 13 (36.1 percent) of the 36 patients in the sedentary performance status group (P < 0.001). The in-hospital mortality rate was 8.3 percent in group the active performance status group and 38 percent in the sedentary performance status group (P = 0.007). Patients in the sedentary performance status group and those who underwent emergency operations had higher levels of IL-6 than patients in the active performance status group or those who underwent elective operations. CONCLUSIONS: Preoperative performance status, operative curability, and tumor stage have a significant impact on outcome in patients with colorectal cancer who are 80 years of age or older. Knowledge of early postoperative response of IL-6 is useful in predicting postoperative mortality and morbidity in this subgroup of patients.
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A 50-year-old male presented with benign intracranial hypertension (BIH). He was admitted to our hospital for headache and papilledema. The diagnosis was BIH as continuous monitoring of lumbar cerebrospinal fluid pressure (CSFP) showed high basal pressure with intermittent plateau waves. Ten months after successful ventriculoperitoneal shunting, he presented with headache again due to shunt malfunction. CSFP monitoring showed the same findings as before. Regional cerebral blood flow (rCBF) was measured by positron emission tomography (PET) using the 15O-labeled water autoradiographic method with simultaneous recording of lumbar CSFP. The rCBF values of the cerebral cortex, white matter, thalamus, cerebellar cortex, and pons were evaluated during both the plateau waves and the intervals. In spite of severely reduced cerebral perfusion pressure, rCBF during the plateau waves was not reduced when compared with the rCBF of normal volunteers in all regions. This result might explain why patients with BIH show no impairment of consciousness or focal signs during the plateau waves.
A 57 year-old man visited our hospital with general fatigue and a sensation of abdominal fullness. He had lost 10 kg in body weight during the previous 3 months. Between admission and the time the diagnosis of AFP-producing gastric carcinoma with multiple liver metastases was made, his condition deteriorated quickly due to the rapid growth of the liver metastases. Combined chemotherapy consisting of cisplatin and 5-FU was given, and was so effective that the patient recovered well and both serum AFP level and the size of the swollen liver decreased markedly. However, about a month after being discharged, he experienced a relapse and was readmitted. After obtaining informed consent, chemotherapy consisting of methotrexate and 5-FU was started. Though the level of tumor markers and LDH decreased significantly, he died of hepatic failure. We think that this case is worthy of notice because it shows the effectiveness and limitations of chemotherapy in a situation where the condition of a patient is deteriorating quickly due to rapid extension of an AFP-producing gastric carcinoma.
A 29-year-old male who had a past history of mild ECG abnormality of arrhythmia at the age of 14 years, was referred to our hospital because of elevated serum creatine kinase (CK) level. He had never been aware of muscular weakness nor cardiac symptoms. Neurological examination revealed normal muscle strength of all extremities except marked back muscle weakness. He had normal intelligence. On laboratory examination, serum AST, ALT, LDH, aldolase, CK and myoglobin levels were elevated. Both lactate and pyruvate levels were normally responded after an ischemic exercises test. Acid maltase activity was normal in white blood cells. A muscle biopsy obtained from rectus femoris muscle revealed vacuolar myopathy with mildly increased PAS positive material. On electron microscopy, there were autophagic vacuoles scavenging glycogen particles and cytoplasmic debris, and sarcolemmal indentation, compatible with the findings of lysosomal glycogen storage disease with normal acid maltase. This patient had unusual clinical features of absent mental retardation and no apparent cardiomyopathy. Accordingly, mental retardation is probably not necessary to see later onset of cardiac muscle involvement.
We reported a 64-year-old woman in the early stage of progressive supranuclear palsy presenting as pure akinesia syndrome who showed marked improvement with tandospirone citrate. She revealed bradykinesia, severe frozen gait and disturbance of postural reflex without rigidity or tremor. Treatment with L-dopa and L-threo DOPS was not effective, but tandospirone citrate at a daily dosage of 30 mg significantly lessened the severity of frozen gait. Activation single photon emission computed tomography study with 99mTc-ethyl cysteinate dimer during gait revealed a significant increase in brain activity in the right cingulate cortex after tandospirone citrate treatment. The effect lasted ten months until neck rigidity and ventricular supranuclear palsy were evident.