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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 505 records · Page 28Linked to original sources

Coronary heart disease mortality is actually low in diabetic Japanese by direct comparison with the Joslin cohort.

OBJECTIVE: To identify the mortality rate from coronary heart disease (CHD) in diabetic Japanese by directly comparing the Tokyo University Hospital cohort and the Joslin cohort using identical protocols. RESEARCH DESIGN AND METHODS: Five hundred thirty-eight diabetic patients who were treated at Tokyo University Hospital with a 35- to 62-year age range at entry and with a diabetes duration of < 5 years were followed retrospectively for more than 24 years. RESULTS: The percentage of patients who survived at the end of the 24-year period was higher in the Tokyo University cohort (42%) than in the Joslin cohort (12%). The percentage of patients who died from CHD was remarkably lower in the Tokyo University cohort (11%) than in the Joslin cohort (39%). The CHD mortality rate was lower in the Tokyo University cohort than in the Joslin cohort, regardless of the duration of diabetes. CONCLUSIONS: Our study confirmed the previous finding that the CHD mortality is lower in diabetic Japanese than in diabetic Caucasians.

Adult↗

Expression of c-fms on smooth muscle cells isolated from experimental arteriosclerosis.

In the present study, we demonstrated gene transcription of c-fms in smooth muscle cells isolated from an experimental rabbit model of arteriosclerosis (intimal smooth muscle cells), although there was no gene transcription of c-fms detected in medial smooth muscle cells. On immunocytochemical analysis, both types of smooth muscle cells similarly reacted with an antibody specific to muscle cells (HHF 35), but did not react with an antibody specific to rabbit macrophages (RAM 11). Intimal smooth muscle cells bound to acetylated LDL and resulting foam cell formation was observed. In response to M-CSF, an increased rate of cell proliferation was observed in intimal smooth muscle cells, but not in medial smooth muscle cells. These results indicated that intimal smooth muscle cells have monocyte-macrophages characteristics such as the expression of c-fms and scavenger receptor gene.

Animals↗

[Morphological atypism and clinicopathological factors in colorectal adenoma and cancer using nuclear DNA content, p53 and PCNA].

Cytofluorometric analysis of DNA content and immunohistochemical examination of p53 and PCNA were performed in colorectal adenomas, mainly borderline lesions, and cancers. Nuclear DNA content revealed aneuploidy and polyploid cells in severely atypical adenomas and cancers. Mutated p53 protein was also observed in severely atypical adenomas, especially tortuous and villous lesions and cancers. PCNA labeling index (P-I) was significantly increased in proportion to cell atypism and P-I over 50% was noted in half of severely atypical adenomas. Among infiltrating cancers, poorly differentiated adenocarcinoma showed high P-I. However, well differentiated adenocarcinoma infiltrating beyond the tunica muscularis propria showed various P-I values depending on the presence of metastasis to lymph node or blood vessel invasion. Furthermore, P-I in the metastatic lesion was significantly higher than that of primary lesion. These results suggest that severely atypical adenomas showing morphological features such as an increased N/C ratio, loss of polarity, roundish nucleus, tortuous and villous change of gland have malignant potentiality. So severely atypical adenomas have the clinical indication for polypectomy. In addition, poorly differentiated adenocarcinoma shows high proliferative ability and metastatic lesions or poorly differentiated components existing in infiltrating cancers may affect cancer development as productive clones.

Adenocarcinoma↗

[A case of ruptured hepatocellular carcinoma with rapid growth after the interferon therapy in chronic hepatitis].

A 75-year-old man who had had a long history of chronic hepatitis C virus liver disease underwent interferon (IFN) therapy for three months. After three months of the last IFN injection, he presented with a sudden attack of epigastralgia. Abdominal US and CT revealed a tumor about 9 x 10 cm in the right lobe of the liver. Serum AFP level was 8,499 ng/ml. Spontaneous hemoperitoneum due to ruptured hepatocellular carcinoma (HCC) was suspected. Hepatectomy was carried out on 35 days postembolization. Pathological examination revealed HCC of trabecular type. Although the relation between the rapid growth and IFN is not clear, US examination should be performed once a month for the patient.

Aged↗

[Perspective of gene therapy in hyperlipoproteinemia].

Several experimental trials are under way to correct the deficiency of LDL receptor function known as Familial Hypercholesterolemia (FH) that develops devastating atherosclerosis leading to premature fatal coronary occlusion. Recently, a 28-year-old FH homozygous woman has received ex vivo autologous liver transplantation after transduction with retroviral vector expressing functional LDL receptors. The outcome is partially successful but is still controversial because of an argument that the apparent small decrease in the total plasma cholesterol level is not necessarily caused by the correction of the LDL receptor expression. In addition to retrovirus, adenovirus vector and non-viral methods are being employed as potential tools for FH gene therapy.

Adenoviridae↗

[Establishment and characterization of a human breast cancer cell line, OCUB-1].

We established new human breast cancer cell line, OCUB-1 derived from the pleural effusion of 53-year old female with recurrent breast cancer. Two sub-cell lines were also established with cloning technique from OCUB-1. Investigating the differences of characteristics between OCUB-1M and 1F, OCUB-1M shows a monolayered growing and OCUB-1F grows in floating. OCUB-1M and 1F revealed Modo 84 and 41 by chromosomal analysis and flow cytometric analysis showed OCUB-1M had twice amount of DNAs as -1F. OCUB-1M revealed higher expression of E-cadherin and laminin receptor against-1F, and activity of 92kDa type IV collagenase could be seen only in OCUB-1M. Estorogen and progesteron receptor were negative in either OCUB-1M and -1F, and no production of tumor markers in the spent media (CEA, CA19-9, CA15-3 and NCC-ST439) was detected in both cells. Both cells could be hetero-transplanted in nude mice, but they showed different histology.

Animals↗

[A case of lobar atrophy with stereotypic unusual laughing].

We report a case of a Pick's disease (frontal predominant type) with unusual laughing. The patient was a 54-year-old, right handed, female. The patient began to show low activity and inappropriate laughing at about 51 years. She did not speak at all and showed weird laughing with a voice "hi hi hi hi hi hi" frequently at first presentation. When asked some questions, she sometimes answered with a nod. Almost all of her laughing did not match with the situation and seemed to lack a relationship between affective change and observed expressions. The laughing could be elicited by non specific and varied stimuli. She often interrupt laughing voluntarily unlike pathological laughing. Neurological examination revealed visual rooting reflex and forced grasping reflex but there was no signs of pseudobulbar palsy often observed in patients with pathological laughing. Her electromyogram of facial expression during the laughing showed that electric discharge of M. corrugator supercilii was over 4 times as much as that in normal laughing. And it showed also that the duration of her laughing was several seconds as normal laughing. CT and MRI scans demonstrated atrophy in the fronto-temporo-parietal lobe bilaterally (L > R), most prominent in the frontal lobe. SPECT scan showed a significant diminution of blood flow in the atrophic region. An EEG was normal. We consider that the laughing of the present case is not due to an emotional disturbance but rather a disorder of affective expression as pathological laughing.

Dementia↗

[Increased levels of circulating hyaluronate in the sera of patients with rheumatoid arthritis with special reference to joint destruction].

We sought to assess whether serum levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) are elevated and correlated with grade of joint destruction and with laboratory data. Circulating HA levels were determined by protein binding assay of serum from 236 patients and 19 healthy controls. The greatest elevations of HA were seen in RA patients (350.7 +/- 689.5 ng/ml) than controls (33.7 +/- 24.2 ng/ml). Their levels showed only weak correlation values of CRP in laboratory data. Although HA levels of sera in stage III and IV in Steinbrocker's classification revealed significantly higher on average than ones in stage I and II (p < 0.01), there were many cases with low HA levels even in stage III and IV. Comparing HA levels between the cases with progressive and non-progressive type of hip or knee joint destruction within a year, the former (1143.6 +/- 1746.0 ng/ml median 480.1 ng/ml) presented significantly higher HA levels than the latter (245.3 +/- 255.8 ng/ml median 140.0 ng/ml) (p < 0.01). Further, one of 7 cases followed by 4 years with extremely high levels of HA showed progression of joint destruction from grade III to IV in Larsen Grade in bilateral knee joints during these times, though there were no significant correlations between HA levels and laboratory data. From above results, levels of circulating HA in the sera of patients with RA correspond to the joint destruction, not to a result of one.

Aged↗

[Biological rhythm disturbances in affective disorders].

Affective disorders are characterized by rhythmic disturbances: early morning awaking, diurnal variations in mood, and periodic and seasonal recurrence of episodes. Therefore, biological rhythm disturbances are considered as an etiology of affective disorders. The free-running hypothesis of cyclic mood disorders, or the phase advanced hypothesis, phase instability hypothesis, and reduced amplitude hypothesis of depression were formulated to explain a variety of clinical and physiological phenomena found in affective disorders. A new therapy such as chronotherapy has been developed according to the hypothesized mechanisms of biological disturbances. Furthermore, antidepressant effects of antidepressants, sleep deprivation, and phototherapy have been discussed from a chronobiological point of view.

Biological Clocks↗

Pharmacological profile of the novel, potent and selective peptide leukotriene antagonist (E)-2,2-diethyl-3'-[2-[2-(4-isopropyl)thiazolyl]ethenyl]succinanilic acid.

In this report, the in vitro and in vivo pharmacological profile of MCI-826 ((E)-2,2-diethyl-3'-[2-[2-(4-isopropyl) thiazolyl]ethenyl]succinanilic acid, CAS 121230-22-6) is described. In isolated guinea pig ileum, MCI-826 inhibited LTD4 (a peptide leukotriene, 10(-9) mol/l)-induced contraction in a concentration-dependent manner with an IC50 of 6.8 x 10(-12) mol/l. It had no effect on histamine (10(-5) mol/l)-, serotonin (2.5 x 10(-5) mol/l)-, or acetylcholine (5.5 x 10(-6) mol/l)- induced contractions in isolated guinea pig ileum. In isolated guinea pig trachea, MCI-826 demonstrated competitive antagonism of the contractile activity of LTD4 and LTE4 with pA2 values of 9.0 and 8.8, respectively. MCI-826 inhibited LTC4-induced contraction in a concentration-dependent manner. However, in the presence of an inhibitor of the metabolism of LTC4 to LTD4, MCI-826 (10(-6) mol/l) produced no effect on LTC4 concentration-response curves in guinea pig trachea. In the in vivo study, the oral administration of MCI-826 caused a dose-dependent inhibition of LTC4- and LTD4-induced bronchoconstrictions in guinea pigs with an ED50 of 0.049 and 0.013 mg/kg, respectively. However, MCI-826 (3 mg/kg p.o.) showed no effect on histamine-induced bronchoconstriction in guinea pigs. The pharmacological half-life of orally administered MCI-826 as assessed by LTD4-induced bronchoconstriction was more than 12 h in guinea pigs. MCI-826 also inhibited antigen-induced bronchoconstriction in a dose-dependent manner with a MID (minimum dose that causes significant inhibition) of 0.1 mg/kg p.o. in guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

[A case of venous angioma complicated by unruptured aneurysm with TIA as the initial manifestation].

Venous angioma is a relatively rare vascular malformation of the brain. It is usually asymptomatic and may be an incidental finding at autopsy or on cerebral angiography. We report a very rare case in which TIA-like attack occurred as the initial manifestation. A 59-year-old woman was hospitalized because of a TIA-like attack about 5 months after left putaminal bleeding. Detailed examination allowed us to make a diagnosis of subcortical venous angioma of the left parietal lobe and multiple cerebral aneurysms. The cerebral aneurysms were treated surgically. Since the angioma was localized in an eloquent area, radiotherapy was chosen first. Angioma giving rise to TIAs is very rare. The ischemia may have been caused by transient venous thrombosis or a steal phenomenon due to a decrease in blood circulation in the left cerebrum caused by the putaminal bleeding.

Brain Neoplasms↗

Technetium-99m-HMPAO as a marker of chemical and irradiation lung injury: experimental and clinical investigations.

UNLABELLED: We evaluated the ability of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) to serve as a sensitive marker of lung injury. METHODS: Two experimental rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, we clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of 99mTc-HMPAO in the lungs. RESULTS: Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of 99mTc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of 99mTc-HMPAO activity in the patients who received chemotherapy (0.649 +/- 0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387 +/- 0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. CONCLUSION: These findings suggest that 99mTc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury.

Adult↗

[Difference of thallium-201 kinetics between VX-2 tumors and inflammatory lesions in rabbits].

To evaluate the difference of thallium-201 chloride (201Tl) kinetics between malignant tumors and inflammatory lesions, 201Tl scintigraphy was performed in the 30 rabbits with variable sized VX-2 tumors; and in the 27 rabbits with variable sized inflammatory lesions induced by turpentine oil and the solution of auto-feces. The degree of 201Tl uptake was expressed as the count ratios of the lesions over the contralateral normal muscle tissue, and the early uptake ratio (1 min after the injection) and the delayed uptake ratio (30 min) were acquired. The retention index derived from these ratios was used to assess the degree of 201Tl washout from the lesions. When dividing both the tumors and inflammatory lesions into the large lesions (more than 40 mm in diameter) and smaller ones, different 201Tl kinetics according to the size of the lesions were demonstrated. In the small lesions, the VX-2 tumors showed higher early and delayed uptake ratios and a faster washout than the inflammatory lesions. In contrast, in the large lesions, both the early and delayed uptake ratios were not significantly different; however, the retention index in the tumors was higher compared to the inflammatory lesions. Thus, our animal study indicates that 201Tl kinetics are different according to the size of the tumor and inflammatory lesions, and that in the small lesions the higher tumor uptake compared to the inflammatory lesions may be available to differentiate. However, in the large sized lesions, assessment of the 201Tl washout from the lesions is necessary for differentiation.

Animals↗

Immunotherapy for Stewart-Treves syndrome. Usefulness of intrapleural administration of tumor-infiltrating lymphocytes against massive pleural effusion caused by metastatic angiosarcoma.

We describe a 56-year-old woman with Stewart-Treves syndrome who had severe dyspnea from a pleural effusion caused by metastatic angiosarcoma in the right lung. Tumor-infiltrating lymphocytes (TIL) in the pleural effusion were cultured and expanded in vitro in the continuous presence of recombinant interleukin 2 with periodic stimulation by CD3 antibody. The expanded TIL were administered intrapleurally seven times at 1- to 4-week intervals in combination with intravenous infusion of recombinant interleukin 2. A panel of T-cell clones was also obtained from TIL. Immunotherapy dramatically improved the patient's dyspnea and pleural effusion. A CD4+ T-cell clone and a CD8+ T-cell clone established from TIL had specific cytotoxicity to the tumor cells.

Breast Neoplasms↗

A randomized, controlled trial of human lymphoblastoid interferon in patients with compensated type C cirrhosis.

OBJECTIVE: To determine the efficacy of human lymphoblastoid interferon (L-IFN) in the treatment of compensated type C cirrhosis, 30 patients were assigned randomly to three groups, consisting of 10 patients each, who were treated as follows. METHODS: The 1- and 3-megaunit (MU) groups received 1 or 3 MU of L-IFN, respectively, daily for 2 wk, and three times weekly for 24 wk thereafter. The control group received no treatment. All of the patients had positive C100-3 hepatitis C virus antibody (anti-HCV) titers. RESULTS: The serum alanine aminotransferase (ALT) levels decreased 26 wk after L-IFN treatment was began, in both treatment groups. In the 3-MU group, the ALT levels became normal [complete response (CR)] in 40%, improved to less than twice the upper limit of the normal value [partial response (PR)] in 10%, and remained unchanged [no change (NC)] in 50%. In the 1-MU group, a PR occurred in 30%. There was NC in 70%, and NC occurred in the control group. Twenty-four weeks after stopping L-IFN, the CR and NC rates in the 3-MU group were 10% and 90%, respectively, and NC was observed in all of the 1-MU and control patients. 2',5'-Oligoadenylate synthetase activities increased in both treatment groups (p < 0.05), but not in the control group. The anti-HCV titers decreased in the 3-MU group (p < 0.05), but not in the 1-MU and control groups. Higher doses of L-IFN were more effective. No serious side effects occurred. CONCLUSIONS: These findings suggest that IFN administration can be effective and safe in patients with compensated type C cirrhosis, and that it would be worthwhile to evaluate IFN therapy for cirrhotic patients further.

2',5'-Oligoadenylate Synthetase↗