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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 145 records · Page 8Linked to original sources

A new neurological mutant rat with symmetrical calcification of Purkinje cells in cerebellum.

A new neurological mutant has been found in the inbred F344 strain of rats. The mutation is inherited as an autosomal recessive trait and is manifest clinically by a hesitant and wobbling gait with asynergic limbs and slight tremor. These symptoms begin at 16-18 days of age and remain essentially constant thereafter. Histologic examination revealed severe degeneration of the Purkinje cells and symmetrical calcification in these and in their dendritic branches in the cerebellar cortex. Such calcified Purkinje cells were intensely stained with the periodic acid-Schiff (PAS) method. PAS-positive substances in the Purkinje cells and extending diffusely over the lesioned sites in the molecular layer were also evident before calcification took place. We have named this neurological mutant the Cerebellar Calcification (CC) rat with the gene symbol cc. This offers a new animal model for the study of the Purkinje cell degeneration and intracranial calcification.

Animals↗

Increased urinary phosphate excretion in pseudohypoparathyroidism type II with long-term treatment with phosphodiesterase inhibitor.

A 58-year-old woman was diagnosed to have pseudohypoparathyroidism (PHP) type II because of the absence of an increase of urinary phosphate secretion, despite a marked increase in urinary cAMP excretion on the Ellsworth-Howard test. We treated the patient with a cyclic-nucleotide phosphodiesterase inhibitor, theophylline, resulting in increased urinary phosphate and cAMP excretions. Dibutyl cAMP administration induced the increase in the urinary phosphate excretion. In this case, the unresponsiveness of the urinary phosphate secretion to cAMP was recovered by a high dose of cAMP or long-term administration of a phosphodiesterase inhibitor. These data imply that cAMP responsiveness to renal tubular phosphate reabsorption should be more strictly elucidated in the patient with PHP type II.

Bucladesine↗

Effect of vitamin E eye drops on naphthalene-induced cataract in rats.

The effect of vitamin E acetate (VEA) eye drops on naphthalene-induced cataract in rats was investigated by Scheimpflug image analysis. The control group was administered only naphthalene (1 g/kg), while the other group was additionally given 1% VEA eye drops into both eyes 5 times a day every day for 9 weeks from the start of naphthalene treatment. During those 9 weeks, the changes of the crystalline lens were documented by an anterior eye segment analysis system (EAS-1000, NIDEK) once a week in mydriasis (Mydrin-P, Santen Pharmaceutical Co., Ltd.). The characteristic density values of the anterior deeper cortex regions were measured. The light scattering intensity of lenses from VEA eye drop-treated animals was significantly lower than that of animals without VEA treatment. This difference was found 1 week, 4 weeks, and from 7 to 9 weeks after the start of naphthalene application. VEA eye drops may have the potential to delay the progression of naphthalene-induced cataract in rats.

Animals↗

Transformation of fibrolamellar carcinoma to common hepatocellular carcinoma in the recurrent lesions of the rectum and the residual liver: a case report.

A 21-year-old man had undergone central bisegmentectomy of the liver due to fibrolamellar carcinoma (FLC). Twice, 24 and 30 months after the first operation, lymph node metastases were removed. We have reported this case previously and this is the second report of the same case. Forty-two months after the second operation to remove lymph node metastases, a recurrence occurred in the rectum and was excised. However, the tumor also recurred in the residual liver. The patient underwent hepatectomy for a palliative purpose but died 16 months after the last operation. Histopathologically, the primary tumor was diagnosed as pure FLC, but the lymph node metastases had foci of the common hepatocellular carcinoma (HCC) mixed with FLC. In contrast, the recurrent tumors in the rectum and the residual liver showed the histopathological features of common HCC. Thus, during repeated recurrences, histopathological features changed from pure FLC to common HCC.

Adult↗

Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas.

To investigate the contribution of the beta-catenin gene to the development of ovarian carcinomas, mutational analysis of exon 3 of the beta-catenin gene was conducted. We analyzed 61 primary ovarian carcinomas, consisting of 49 non-endometrioid-type and 12 endometrioid-type tumors, for genetic alteration of the beta-catenin gene. Five carcinomas showed beta-catenin mutations (S37C, T41I, T41A), including 4 (33%) of 12 endometrioid-type tumors and 1 (14%) of 7 mucinous-type tumors. All of these mutations altered at the serine/threonine residues that are potential sites of GSK3-beta phosphorylation. We detected no carcinomas with interstitial deletion involving exon 3 of beta-catenin. Furthermore, we immunohistochemically studied 27 of the 61 ovarian carcinomas. Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 4 of the 27 ovarian carcinomas for which tissue samples were available for examination. All 4 cases exhibited mutations in exon 3 of beta-catenin, including a mucinous carcinoma. Our results suggested that beta-catenin gene mutation at potential GSK3-beta phosphorylation sites results in accumulation of beta-catenin protein within the cells and its translocation to nuclei. Accumulated beta-catenin protein may be involved in the development of endometrioid-type ovarian carcinomas, and some mucinous-type ovarian carcinomas.

Adult↗

Mutational analysis of STK11 gene in ovarian carcinomas.

Recently STK11, the causative gene of Peutz-Jeghers syndrome (PJS) was identified on chromosome 19p13.3. PJS is often accompanied by several malignancies, including breast tumor, adenoma malignum of the uterine cervix, and ovarian tumor. To investigate the involvement of STK11 gene in the development of ovarian carcinomas, we analyzed 30 ovarian carcinomas for loss of heterozygosity (LOH) and STK11 gene mutations. We found one missense mutation (codon 281, Pro to Leu) with heterozygous and somatic status. This mutation occurred at codon 281, which lies within the mutational hot spot (codon 279-281) of STK11 gene previously reported in PJS. We also detected LOH in 2 (11%) of 19 informative ovarian carcinomas. Our results suggest that mutations of the STK11 gene may play a limited role in the development of ovarian carcinomas.

AMP-Activated Protein Kinase Kinases↗

[Microbiological and clinical studies with Streptococcus pneumoniae isolated in 5 Kitakyushu municipal hospitals].

Epidemiological and microbiological studies were carried out using 200 strains of pneumococci isolated from clinical specimens in 5 Kitakyushu municipal hospitals, between October 1994 and July 1995. Eighty nine percent of pneumococci were detected in the specimens from the respiratory tract. Pneumococci were isolated mainly from infants under 3-years of age and adults over 50-years of age, and the rates of isolation were 40.5% and 39.5%, respectively. MICs of 8 antimicrobial agents, such as PCG, NFLX, CPFX, LFLX, FLRX, TFLX, SPFX, LVFX, were determined using broth microdilution methods. According to NCCLS standard (1997), recovery rates of PSSP, PISP and PRSP were 48.0%, 39.5% and 12.5%, respectively. Among 7 quinolones, TFLX, SPFX and LVFX were effective so far examined, except for a few resistant strains. Four cases in which quinolones resistant pneumococci were isolated were reviewed retrospectively. Among them 3 cases had been given quinolones before the strains were detected.

Adolescent↗

Regulatory mechanisms of eosinophil adhesion to and transmigration across endothelial cells by alpha4 and beta2 integrins.

To participate in allergic airway inflammation, it is necessary for blood eosinophils (Eos) to adhere to and migrate across pulmonary vascular endothelial cells (EC). Accumulating evidence has established that Eos adhesion molecules, such as alpha4 and beta2 integrins, play central roles in these processes. We have reported that Eos spontaneously adhere to recombinant human (rh)-VCAM-1, while adhesion to rh-ICAM-1 requires a second stimulus such as GM-CSF. Furthermore, our study employing human pulmonary microvascular endothelial cells (HPMEC) revealed that although the alpha4 integrin/VCAM-1 pathway is crucial for the firm adhesion of Eos, subsequent transendothelial migration occurred dependent on the beta2 integrin/ICAM-1 pathway. We also discuss secretagogues that would affect Eos recruitment to the airways via regulation of alpha4 and beta2 integrins.

Animals↗

Glucose transporter 2 concentrations in hyper- and hypothyroid rat livers.

The deterioration of glucose metabolism frequently observed in hyperthyroidism may be due in part to increased gluconeogenesis in the liver and glucose efflux through hepatocyte plasma membranes. Glucose transporter 2 (GLUT 2), a facilitative glucose transporter localized to the liver and pancreas, may play a role in this distorted glucose metabolism. We examined changes in the levels of GLUT 2 in livers from rats with l-thyroxine-induced hyperthyroidism or methimazole-induced hypothyroidism by using Western blotting to detect GLUT 2. An oral glucose tolerance test revealed an oxyhyperglycemic curve (impaired glucose tolerance) in hyperthyroid rats (n=7) and a flattened curve in hypothyroid rats (n=7). GLUT 2 levels in hepatocyte plasma membranes were significantly increased in hyperthyroid rats and were not decreased in hypothyroid rats compared with euthyroid rats. The same results were obtained with a densitometric assay. These findings suggest that changes in the liver GLUT 2 concentration may contribute to abnormal glucose metabolism in thyroid disorders.

Animals↗

[Psychogenic lower urinary tract dysfunction in women: patho-physiological investigation for psychogenic frequency-urgency syndrome and psychogenic urinary retention].

PURPOSE: Psychogenic lower urinary tract dysfunction (PLUTD) is composed of two syndromes; psychogenic frequency-urgency syndrome (PFUS) and psychogenic urinary retention (PUR). We evaluated the patho-physiology of PFUS and PUR, and explored the different pathogenesis in these syndromes. MATERIAL AND METHODS: Forty five patients with PLUTD, consisting of 23 patients with PFUS and 22 patients with PUR were investigated by using the psychological tests: CMI (Cornell Medical Index) and TEG (Todai's Egogram), a quantitative perspiration test in 45 females (23 patients with PFUS and 22 patients with PUR), and simultaneous measurements of voiding cysto-urethrography and urodynamic studies using the Life-Tech 6 channel polygraph in 35 patients (17 patients with PFUS and 18 patients with PUR). RESULTS: The prevalence in ages revealed two peaks, 20 years and 50 to 60 years. Over 25% of them had pyuria more than 10/hpf of WBC. Peak flow rate measured by uroflowmetry showed normal range in PFUS group and decreased in PUR group. The functional vesical volume was less than 100 ml in most patients with PFUS. Residual urine in PUR group was significantly greater. Capacity of the PFUS group were able to hold over 400 ml of contrast instilled through the urethral catheter, despite increased desire to void. Over 15% of the study group with PFUS showed uninhibited systolic contraction of detrusor (> 15 cm H2O) during filling phase. The measurement value of urodynamic parameters demonstrated that a periodic follow-up survey of the upper urinary tract should be performed because of the low compliance bladder in the patients with PLUTD. During voiding phase, the women with PFUS had a tendency to be divided into two groups, hypercontractile or acontractile detrusor. The voiding cysto-urethrography (VCUG) showed a tendency of bladder neck opening on patients with PFUS during filling phase. Most of PLUTD cases demonstrated a round to triangle shape on vesical configuration, which led to a spastic condition of detrusor muscle. We attempted to measure the quantitative perspiration using 3 kinds of loading tests; respiratory, arithmetic and psychological load. In the psychological loading test, we asked 98 questions about their daily lives including occupation, living condition, family relationship and sexual activities. Arithmetic loading test consisted of counting in reverse, subtraction and multiplication. The quantitative perspiration rate resulted in a "positive" in many patients with PFUS. Respiration loading test was performed to measure the respiration volume during 3 large inhales. Most patients with PUR tested within the normal range for respiration except for those patients with decreased or no perspiration during the psychiatric loading test. These results may reflect the psychological elements including suppression and subconscious defense mechanism. Neurosis which was diagnosed as having type III to type IV of the Cornell Medical Index was demonstrated in less than under 40% of patients with PFUS and more than 55% patients with PUR. There was no significant trend or difference between PFUS and PUR detected from Todai's Egogram. CONCLUSIONS: Due to the reflection of many psychological responses, it is necessary to investigate from various examinations including psychological, autonomical and classical urological studies for accurate diagnosis of PLUTD.

Adolescent↗

[A trial of new protocol of rush immunotherapy with standardized mite antigen].

The objective of the present study was (1) to establish a new protocol of rush immunotherapy (IT) using a purified mite antigen for the treatment of house-dust-mite-sensitive bronchial asthma. Ten adult asthmatics were enrolled in the initial trial which was based on a 7-day protocol using a house-dust antigen, to determine the optimal maintenance dose of mite antigen. No systemic side effects were observed when the antigen dose was lower than 50 AU. Consequently, the duration of rush IT was shortened to 5 days, and the maintenance dose was determined as 50 AU in the new protocol. To confirm its safety, another ten asthmatics were enrolled in a second trial. Rush IT using the new protocol was able to be performed without any systemic side effects in all patients except one who showed urticaria at 40 AU. These results suggest that the 5-day protocol of rush IT using the mite antigen is safe in patients with house-dust-mite-sensitive asthma.

Adolescent↗

[A significance of the washout of 123I-BMIPP in patients with vasospastic angina].

We investigated the washout of 123I-BMIPP from early and delayed SPECT in 28 patients with vasospastic angina from the standpoint of the intervals from the last angina attack. We divided myocardial wall into 13 segments from the early and delayed SPECT, and visually classified into four grades of defect score ranged from 0 (normal) to 3 (severe defect). Early and delayed severity scores were calculated as a total of defect scores in 3 vessel territories, and washout scores (WS) as (delayed severity score-- early severity score)/number of segments. WS of the group within 1 month from last angina attack was compared with the groups more than 1 month. In the territory of the right coronary artery, the group within 1 month showed significantly higher WS than groups more than 1 month (p < 0.05). In the other two territories, the group within 1 month showed higher WS than one of the groups more than 1 month, but the difference was not statistically significant. We considered that the washout of 123I-BMIPP may reflect the clinical course of vasospastic angina.

Adult↗

[Epidemiological survey of ocular diseases in K Island, Amami Islands: prevalence of cataract and pterygium].

PURPOSE: An epidemiological survey of ocular disease was performed in a town of the Amami Islands in southwestern Japan. OBJECT AND METHODS: A total of 339 participants over 40 years joined the survey. Among the 339 participants, the lens findings of 602 eyes of 301 subjects were analyzed. RESULTS: The prevalence of lens opacification was 32.0, 54.0, 83.1, 96.9% and 100% among subjects in their 40, 50, 60, 70 s, and over 80 years. Lens opacification over grade II was 4.0, 12.7, 26.2, 60.0% and 83.3%. The cataract type most frequently seen was cortical (96.1%), followed by 48.5% with nuclear opacity and 14.7% with subcapsular type. A high prevalence was seen of pterygium at 25.4%. Although the prevalence of lens opacification was higher in the group with pterygium in their 70 s, no significant difference was noticed in persons in their 40, 50, 60 s, and over 80 years old between the pterygium and non-pterygium groups. CONCLUSIONS: Similarly to the results of a previous survey in Okinawa, Noto, and Hokkaido, the main type of lens opacification was cortical in Amami. The prevalence of nuclear opacification and pterygium was higher than in Noto and Hokkaido, and close to that seen in Okinawa.

Adult↗

Clinical significance of apolipoprotein (a) deposition in kidney diseases of children.

AIM AND METHOD: To address the clinical significance of lipoprotein (a) (Lp(a)) deposition in renal diseases of children, we examined renal localization of apolipoprotein (a) (apo(a)), which is the major apoprotein of Lp(a), using a new monoclonal antibody as a probe, and compared histological changes and clinical courses between the cases with and without apo(a) accumulation. Our study comprised 78 cases with various renal diseases. RESULTS: Of the 78 cases, 45 showed apo(a) deposition (group A) and the other 33 did not (group B). Nephrotic syndrome was similarly presented in groups A and B (46.7% vs 36.3%). Histological findings were analyzed in 62 proliferative and 16 non-proliferative original diseases separately. In the cases with proliferative diseases, severe histological changes were observed in group A more than in group B, severe proliferation (50.9% vs 26.1%: p < 0.01) and crescent formation (11.9% vs 5.1%: p < 0.01) were observed in group A over that of group B. However, the clinical status at the latest follow-up were quite similar, there was no difference of favorable (60.5% vs 62.5%) and unfavorable outcome (15.9% vs 16.7%) in groups A and B. In the cases with non-proliferative diseases, global sclerosis was more often encountered in group A than in group B (28.3% vs 6.5%). Group A carried poorer prognosis than group B in non-proliferative diseases. CONCLUSION: These results suggest that apo(a) deposits just passively follow the histological injury, and they do not always accelerate it.

Adolescent↗

[Renal glucosuria and membranous glomerulonephritis in chronic inflammatory demyelinating polyradiculoneuropathy: CIDP].

Glucosuria was detected in a 7-year-old boy by a routine school mass examination in April 1991. The diagnosis of renal glucosuria was made in the affiliated hospital of the University of Tsukuba. The patient developed muscle weakness and gait disturbance in February 1993. Spinal fluid examination revealed a protein level of 62 mg/dl and a cell count of 4/3. Under the diagnosis of Guillain-Barré syndrome, he was treated with i.v. immunoglobulin and oral prednisolone. Although the therapy somewhat improved the symptoms, his muscle strength had not fully recovered at the end of the treatment. In November 1995, the muscle weakness became worse; he could not go up stairs, nor stand upright on one leg. In April 1996, proteinuria was detected in a school mass examination. He was referred to the University Hospital of Tsukuba for a full renal study in March 1997. Renal biopsy revealed global sclerosis in 16 of 19 glomeruli with extensive interstitial fibrosis and mononuclear cell infiltration. A diagnosis of membranous glomerulonephritis was established based on the findings of spikes in PASM staining, weak IgG deposition in the glomerular capillary and subepithelial deposits by electron microscopic study. Additionally, pituitary growth hormone deficiency was found by endocrinological examination. The diagnosis of CIDP was established by fibulal neuron biopsy, which revealed neuronal degeneration and profound demyelinization. The clinical course of the present case was unlike that of the few reported cases of MGN associated with CIDP described in the literature. The initial renal symptom was glucosuria, which started 5 years prior to the onset of proteinuria. Second, glomerulosclerosis was more extensive than that seen in the literature. We surmise that chronic interstitial nephritis of insidious onset was followed by MGN which developed subsequently, probably at the time of the start of proteinuria.

Adolescent↗