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Biomedical subjects

I Murakami

Publications and source records attributed to I Murakami.

At least 37 records · Page 2Linked to original sources
PubMed2000

p53 gene mutations are associated with shortened survival in patients with advanced non-small cell lung cancer: an analysis of medically managed patients.

Mutations in the p53 gene are common in many cancers. Nevertheless, the relationship between mutations of this tumor suppressor gene and patient survival in non-small cell lung cancer (NSCLC) remains unclear. Interpretation of prior studies of patient outcomes are complicated by the inclusion of both surgical and nonsurgical patients. To better isolate the potential effects of p53 gene mutations per se on tumor progression, we chose to examine patients with advanced disease in whom surgery was not performed (stages IIIA, IIIB, and IV). We have used PCR-denaturing gradient gel electrophoresis, a sensitive and specific method for the detection of a variety of p53 mutations in cytology or biopsy specimens, to evaluate the prognostic significance of p53 gene mutations in nonsurgical patients with advanced NSCLC. In 70 consecutive medical patients, p53 mutations were found in 29 cases (41%) at the time of initial diagnosis. Followed prospectively, patients with p53 mutations had a significantly reduced survival time after diagnosis than those without mutations (median survival, 17 versus 39 weeks; P = 0.0003) independent of other clinical factors. This abbreviated survival occurred in both patients who received chemotherapy (n = 39, P = 0.002) or best supportive care (n = 31, P = 0.018). These results indicate that mutations of the p53 gene in patients with NSCLC who do not undergo surgical resection portends a significantly worse prognosis.

Adult↗
PubMed1999

The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin.

The integrin alpha(9)beta(1) mediates cell adhesion to tenascin-C and VCAM-1 by binding to sequences distinct from the common integrin-recognition sequence, arginine-glycine-aspartic acid (RGD). A thrombin-cleaved NH(2)-terminal fragment of osteopontin containing the RGD sequence has recently been shown to also be a ligand for alpha(9)beta(1). In this report, we used site-directed mutagenesis and synthetic peptides to identify the alpha(9)beta(1) recognition sequence in osteopontin. alpha(9)-transfected SW480, Chinese hamster ovary, and L-cells adhered to a recombinant NH(2)-terminal osteopontin fragment in which the RGD site was mutated to RAA (nOPN-RAA). Adhesion was completely inhibited by anti-alpha(9) monoclonal antibody Y9A2, indicating the presence of a non-RGD alpha(9)beta(1) recognition sequence within this fragment. Alanine substitution mutagenesis of 13 additional conserved negatively charged amino acid residues in this fragment had no effect on alpha(9)beta(1)-mediated adhesion, but adhesion was dramatically inhibited by either alanine substitution or deletion of tyrosine 165. A synthetic peptide, SVVYGLR, corresponding to the sequence surrounding Tyr(165), blocked alpha(9)beta(1)-mediated adhesion to nOPN-RAA and exposed a ligand-binding-dependent epitope on the integrin beta(1) subunit on alpha(9)-transfected, but not on mock-transfected cells. These results demonstrate that the linear sequence SVVYGLR directly binds to alpha(9)beta(1) and is responsible for alpha(9)beta(1)-mediated cell adhesion to the NH(2)-terminal fragment of osteopontin.

Amino Acid Sequence↗
PubMed1999

Motion-transparent inducers have different effects on induced motion and motion capture.

To assess the relationship among the underlying mechanisms of induced motion, motion capture, and motion transparency, directions of the former two illusions in the presence of motion-transparent inducers were examined. Two random-dot patterns (inducers) were superimposed upon a stationary disk (target), and moved in orthogonal directions. Either a high-contrast target (for induced motion) or a low-contrast target (for motion capture) was used. The task was to report the perceived direction of the target. The depth order of inducers was controlled either by adding binocular disparity or by asking the subject to report subjective depth order. For induced motion, the target appeared to move in the direction opposite to the inducer that had a disparity closer to the target; when there was no difference in disparity, induced motion occurred oppositely to the 'vector sum' of the inducers' directions. For motion capture, the target was captured by the inducer that subjectively appeared behind. These results suggest that the underlying mechanism of motion capture utilizes the output from the process for motion transparency, whereas induced motion has no clear relationship to the output of the process for motion transparency.

Contrast Sensitivity↗
PubMed1999

p53 mutations in tumor and non-tumor tissues of thorotrast recipients: a model for cellular selection during radiation carcinogenesis in the liver.

Concerns over cancer development from exposure to environmental sources of densely ionizing, high linear energy transfer (LET) radiation, such as alpha-particles from radon, is a current public health issue. The study of tumors attributable to high LET irradiation would greatly augment our insights into the biological mechanisms of carcinogenesis. Chronic low-dose-rate internal exposure to alpha-radiation from thorium dioxide deposits following intravascular administration of the radiographic contrast agent Thorotrast is known to markedly increase the risk of cancer development, especially that of hepatic angiosarcomas and cholangiocarcinomas. Although the mechanism is hypothesized to be via cellular damage, DNA being a major target, wrought by the high LET alpha-particles, the specific genes and the actual sequence of events involved in the process of transforming a normal cell into a malignant one are largely unknown. To shed some light on the molecular mechanisms of cancer development during a lifetime exposure to alpha-radiation, we analyzed the most commonly affected tumor suppressor gene in humans, p53, in 20 Thorotrast recipients who developed cancer, mostly of hepatic bile duct and blood vessel origin. Of the 20 cases, 19 were found to harbor p53 point mutations. Moreover, the accompanying non-tumor tissues from these patients also had p53 mutations, albeit at lower frequency. The distribution pattern of the point mutations was significantly different between the non-tumor and tumor tissues, with most mutations in malignant tissues located in the highly conserved domains of the p53 gene. Our results support the idea that p53 mutations are important in the genesis of Thorotrast-induced tumors but that these point mutations are a secondary outcome of genomic instability induced by the irradiation. Additionally, non-tumor cells harboring p53 mutations may gain some survival advantage in situ but mutations in the domains responsible for the formation of structural elements critical in binding DNA may be necessary for a cell to reach full malignancy.

Aged↗
PubMed1999

Is angiotensinogen gene polymorphism associated with hypertension in pregnancy?

OBJECTIVE: To determine whether a state of hypertension in pregnancy in the Japanese can be predicted in the early period based on detection of the M235T variant of the angiotensinogen gene, alone or with other factors. METHODS: A total of 313 Japanese pregnant women were divided into 3 groups on the basis of their angiotensinogen genotype: TT, MT, and MM. Hypertension in pregnancy was diagnosed for 33 patients in all. For each group, we sought to determine what factors increased the risk of the disease. MAIN OUTCOME MEASURES: The angiotensinogen M235T variant, mean arterial pressure (MAP) before the 12th gestational week, body mass index (BMI) before pregnancy, age at delivery, parity, a familial history of hypertension, and development of preeclampsia or gestational hypertension were considered. RESULTS: The frequencies of the allele T were the same among preeclampsia, gestational hypertension, and normal subjects. In TT subjects, a high incidence of gestational hypertension was found for women with MAP > or = 90 mm Hg, high or low BMI before pregnancy > or = 22.0 or < 18.0, and maternal history of hypertension. In MT subjects, women who showed MAP > or = 90 mm Hg or who were above 36 years old at delivery had a high incidence of gestational hypertension. Preeclampsia could not be predicted in either group. CONCLUSIONS: Hypertension in pregnancy cannot be predicted on the basis of the M235T variant of angiotensinogen gene alone. However, gestational hypertension is associated with combinations of other factors. In contrast, it is virtually impossible to predict the development of preeclampsia.

Adult↗
PubMed1999

[A case of Lyme disease with the triad of neurologic manifestations (meningitis, radiculoneuritis, facial nerve palsy) and dermatitis of the nail roots].

A 23-year-old man experienced dysesthesia of the distal parts of four limbs and spilling of drinking water from the right corner of his mouth. He also experienced low grade fever, headache, and nausea. Neurological examination showed weakness of the right frontal, orbicularis oculi and orbicularis oris muscles, atrophy and weakness of the interosseous muscles in both upper limbs and dysesthesia in the distal parts of four limbs. Laségue's sign was also positive on the left side. Examination of CSF showed lymphocytic pleocytosis and an increase of total protein. Serum antibody against Borrelia garinii was positive as determined by ELISA. The patient was diagnosed as a case of Lyme disease. His symptoms were not alleviated by administration of ceftriaxone (2 g/day) for 15 days, and dermatitis of nail roots appeared. Following administration of penicillin G at a high dose (12 million units/day) for 20 days, both neurologic symptoms and dermatitis were alleviated. Since B. garinii was reported to move preferentially toward the sites of low temperature, dermatitis of nail roots may be one of the characteristic features of Lyme disease caused by B. garinii.

Adult↗
PubMed1999

[A Japanese case of Poland-Möbius syndrome].

We herein report a Japanese case of Poland-Möbius syndrome. The patient was a 19-year-old female. She was the product of a full-term forceps delivery. Birth weight was 2500 g. She had a defect of the right pectoral muscle, and syndactyly of the right hand. When she was 10 days old, facial diplegia, bilateral abducens nerve palsy, and bilateral ptosis were also noted. She was admitted to our hospital at 19 years of age. On physical examination, she had microsyndactyly of the right hand, and her right pectoralis major muscle was absent. Neurological examination revealed bilateral abducens nerve paresis, mild impairement of the upward and adducting movement of both eyes and bilateral facial weakness and atrophy of the left side of her tongue. Her karyotype was normal. Neither R 1 nor R 2 response was evoked in the blink reflex on either side. Brain MRI disclosed thin facial nerves and atrophy of the pons and medulla. Therefore, she was diagnosed as a case of Poland-Möbius syndrome. In this case, the facial nerves were considered to be hypoplastic.

Adult↗
PubMed1998

A jitter after-effect reveals motion-based stabilization of vision.

A shaky hand holding a video camera invariably turns a treasured moment into an annoying, jittery momento. More recent consumer cameras thoughtfully offer stabilization mechanisms to compensate for our unsteady grip. Our eyes face a similar challenge in that they are constantly making small movements even when we try to maintain a fixed gaze. What should be substantial, distracting jitter passes completely unseen. Position changes from large eye movements (saccades) seem to be corrected on the basis of extraretinal signals such as the motor commands sent to the eye muscle, and the resulting motion responses seem to be simply switched off. But this approach is impracticable for incessant, small displacements, and here we describe a novel visual illusion that reveals a compensation mechanism based on visual motion signals. Observers were adapted to a patch of dynamic random noise and then viewed a larger pattern of static random noise. The static noise in the unadapted regions then appeared to 'jitter' coherently in random directions. Several observations indicate that this visual jitter directly reflects fixational eye movements. We propose a model that accounts for this illusion as well as the stability of the visual world during small and/or slow eye movements such as fixational drift, smooth pursuit and low-amplitude mechanical vibrations of the eyes.

Adaptation, Ocular↗
PubMed1998

Identification of the ligand binding site for the integrin alpha9 beta1 in the third fibronectin type III repeat of tenascin-C.

The integrin alpha9 subunit forms a single heterodimer, alpha9 beta1 that mediates cell adhesion to a site within the third fibronectin type III repeat of tenascin-C (TNfn3). In contrast to at least 3 other integrins that bind to this region of tenascin-C, alpha9 beta1 does not recognize the common integrin recognition motif, Arg-Gly-Asp (RGD). In this report, we have used substitution mutagenesis to identify a unique ligand recognition sequence in TNfn3. We introduced mutations substituting alanine for each of the acidic residues in or adjacent to each of the exposed loops predicted from the solved crystal structure. Most of these mutations had little or no effect on adhesion of alpha9-transfected SW480 colon carcinoma cells, but mutations of either of two acidic residues in the B-C loop region markedly reduced attachment of these cells. In contrast, cells expressing the integrin alphav beta3, previously reported to bind to the RGD sequence in the adjacent F-G loop, attached to all mutant fragments except one in which the RGD site was mutated to RAA. The peptide, AEIDGIEL, based on the sequence of human tenascin-C in this region blocked the binding of alpha9-transfected cells, but not beta3-transfected cells to wild type TNfn3. This sequence contains a tripeptide, IDG, homologous to the sequences LDV, IDA, and LDA in fibronectin and IDS in VCAM-1 recognized by the closely related integrin alpha4 beta1. These findings support the idea that this tripeptide motif serves as a ligand binding site for the alpha4/alpha9 subfamily of integrins.

Amino Acid Sequence↗
PubMed1998

Assay of 222Rn in water samples by a modified integral counting method.

22Rn activity concentrations in water collected from 163 private wells and 14 springs in Tokyo were measured with a liquid scintillation spectrometer using a modified integral counting method. The activity concentrations of 222Rn range from 0.2 to 22.9 Bq/L and average 4.8 Bq/L. The errors due to the air luminescence counts and the interferences from 220Rn and 219Rn are discussed and evaluated. 222Rn samples of 0.2 Bq/L can be assayed within an overall uncertainty of 3.1%. The liquid scintillation method involving agitation of the sample water directly with a liquid scintillation cocktail was compared with the present method and evaluated.

Fresh Water↗
PubMed1998

Effects of diabetes and hyperglycemia on disaccharidase activities in the rat.

BACKGROUND AND METHODS: To elucidate the effect of hyperglycemia on disaccharidase activities, the specific and total activities of the disaccharidases were measured in the intestinal mucosa and kidney cortex of diabetic and hyperglycemic rats. The diabetes was induced with an intraperitoneal injection of streptozotocin (60 mg/kg). The rats were made hyperglycemic with an intravenous instillation of a solution containing 40% dextrose monohydrate at a rate of 1.5 ml/h for 24 h. RESULTS: The blood glucose level was 387+/-45 mg/dl and 382+/-35 mg/dl (mean +/- standard deviation) in diabetic and hyperglycemic rats, respectively. In diabetic rats the intestinal maltase, sucrase, and lactase activities were significantly higher than those in control rats. Similarly, disaccharidase activities in hyperglycemic rats were significantly higher than those in control rats. The renal maltase activity in diabetic rats was significantly lower than that in control rats. The maltase activity in hyperglycemic rats, however, was not significantly different from that in control rats. CONCLUSIONS: These results suggest that 1) hyperglycemia directly increases the activities of intestinal maltase, sucrase, and lactase; 2) hyperglycemia does not influence renal maltase activity; and 3) hyperglycemia is partly responsible for increased activities of intestinal disaccharidases in diabetes mellitus.

Animals↗
PubMed1998

Use of new magnetic attachments for implant-supported overdentures.

A newly designed magnetic attachment system for external hexed implants with a standard abutment platform has been developed. This system has certain definite advantages over bar attachments and ball attachments, which are frequently utilized for implant-supported overdentures. Especially, it can be applied to cases with reduced vertical dimension of occlusion because the total height of the magnet and the keeper is only 2.3 mm when assembled. In addition, detrimental lateral stresses to the fixture are greatly alleviated due to very low attractive forces horizontally. Favorable clinical results using this new magnetic attachment system have been obtained, and it may be considered a useful addition to overdenture therapy using any external hexel implant with a standard abutment platform, such as the Brånemark implant system.

Aged↗
PubMed1998

Deletion of Epstein-Barr virus latent membrane protein 1 gene in Japanese and Brazilian gastric carcinomas, metastatic lesions, and reactive lymphocytes.

A 30-bp deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Information on this deletion in EBV-associated gastric carcinoma (EBVaGC) is limited. The association of gastric carcinoma (GC) with EBV was examined by EBV-encoded RNA (EBER) in situ hybridization in 510 patients from Japan and 80 patients from Brazil. We studied the prevalence of 30-bp LMP1 gene deletion in EBVaGC in Japan (29 cases) and Brazil (four cases) in comparison with the corresponding EBER1-positive metastatic lesions in lymph nodes (10 cases) and EBV-infected reactive lymphocytes from dissected nonmetastatic lymph nodes (22 cases), microdissected non-neoplastic gastric mucosa of EBVaGC (five cases), and EBV-nonassociated GC (25 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction products obtained after amplification with primers flanking the site of the deletion. We also performed EBV typing and LMP1 protein immunohistochemistry. EBV DNA was amplified by polymerase chain reaction in 30 of 33 EBVaGC cases, 8 of 10 metastatic carcinomas, 14 non-neoplastic tissues from 27 EBVaGC cases, and 12 of 25 non-EBV-associated GC cases with EBER1-positive lymphocytes. The 30-bp LMP1 gene deletion was observed in 23 of 26 (88.5%) cases of EBVaGC from Japan and two of four (50%) cases of Brazilian EBVaGC as compared with EBER1-positive reactive lymphocytes from 11 of 14 (78.6%) EBVaGC cases and 9 of 12 (75%) cases of non-EBV-associated GC. The variant type (the 30-bp deletion variant or nondeleted wild type) of LMP1 gene was the same among reactive lymphocytes, primary and secondary lesions of EBVaGC in all cases for which all three tissue types were studied (six of six). There was no correlation between the presence of the 30-bp deletion with depth of cancer invasion or presence of metastasis. Type A was detected in all available EBV-positive cases. The similar high incidence of 30-bp deletion in LMP1 gene in both carcinoma cells and reactive lymphocytes in EBVaGC cases suggests that this deletion may not be relevant to the pathogenesis of EBVaGC.

Adult↗
PubMed1998

[A case of early-onset cortical cerebellar atrophy with rhythmic skeletal myoclonus in the left upper limb].

A 19-year-old man developed progressive unsteady gait and speech disturbance two years ago. He recently noticed muscle twitches in the left limb. Neurological examination revealed scanning speech, saccadic ocular movement, ataxia of trunk and limbs predominant on the left side. Rhythmic myoclonus was present at rest around the left shoulder and arm, and amplified by raising the left arm. There was no myoclonus in the soft palate. MRI revealed only a cerebellar atrophy. This patient was diagnosed as having cortical cerebellar atrophy with rhythmic skeletal myoclonus (RSM). Tc-99m ECD SPECT showed a decrease in the blood flow of the right thalamus when the myoclonus was enhanced by raising the left upper limb, which suggests that the cerebello-thalamo-cortical system as well as Guillain-McIlaret triangle is involved in the development of RSM.

Adult↗
PubMed1997

Motion transparency in superimposed dense random-dot patterns: psychophysics and simulation.

To determine the mechanism underlying motion transparency, representative examples of motion transparency are listed and possible mechanisms are suggested. Those are feature tracking, multiple spatial-frequency channels, luminance-based transparency rules, and motion energy. Next, an interesting stimulus for motion transparency is introduced, namely superimposed dense random-dot patterns, which is not explained by feature tracking or multiple spatial-frequency channels. A psychophysical experiment reveals that the occurrence of motion transparency in this stimulus depends on three luminance levels assigned to three possible combinations of component dots: (1) white dots superimposed upon white dots, (2) white dots upon black dots, and (3) black dots upon black dots. However, physical rules of luminance-based transparency fail to explain the results. Finally, a computer simulation reveals that a computational model based on motion energy quantitatively predicts the human psychophysical performance. All the results support the idea that motion-energy detection followed by spatial integration is a likely candidate for the mechanism underlying motion transparency.

Computer Simulation↗