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Biomedical subjects

T Imai

Publications and source records attributed to T Imai.

At least 415 records · Page 23Linked to original sources

Hyaluronic acid is increased in the skin and urine in patients with amyotrophic lateral sclerosis.

We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

Adult↗

Lipid peroxidation and antioxidant activities in regenerating liver after partial hepatectomy in splenectomized rats.

Lipid peroxidation, antioxidant activities, and total fatty acids were investigated in the regenerating liver after partial hepatectomy in splenectomized male Wistar rats. The lipoperoxide levels were significantly lower in the splenectomized rats than in the non-splenectomized rats. The hepatic superoxide dismutase (SOD) activity was significantly higher in the splenectomized rats than in the controls, whereas the alpha-tocopherol content, and the activities of glutathione (GSH) peroxidase and catalase did not differ so widely between splenectomized and nonsplenectomized rats. In both groups, the fatty acid composition of the total lipids was not so different in the early stages of hepatic regeneration after partial hepatectomy, but it was noted that in the later stages of hepatic regeneration, polyunsaturated fatty acids tended to increase in the splenectomized rats. These results suggest that splenectomy attenuates lipid peroxidation, and tends to increase in polyunsaturated fatty acids in the remnant liver after partial hepatectomy, which may be attributable to high SOD activity, the maintenance of alpha-tocopherol, and the remaining activities of GSH peroxidase and catalase.

Animals↗

Change in plasma endotoxin titres and endotoxin neutralizing activity in the perioperative period.

PURPOSE: To elucidate whether endotoxaemia detected during major surgery was a specific or non-specific reaction. METHODS: Prospective clinical study in the operating theatre and multidisciplinary intensive care unit in a university hospital. A series of plasma samples was obtained from 21 patients, including eight after cardiopulmonary bypass (CPB), until 48 hr after surgery. The endotoxin titres in these samples were compared by the two chromogenic limulus amebocyte lysate (LAL) assays; one is factor G containing and the other factor G-free, endotoxin-specific test. The endotoxin neutralizing activity of the plasma was determined by adding the endotoxin to the plasma (1,000 pg.ml-1), and by assaying how much the potency of the endotoxin to activate LAL was lost during incubation for 120 min at 37 degrees C. RESULTS: Although endotoxin titres measured using the test including factor G showed a marked elevation during and after surgery, which were 3 +/- 5 (4 +/- 10), 14 +/- 13 (20 +/- 17**), 133 +/- 13* (46 +/- 29*), 89 +/- 72* (48 +/- 35*), 62 +/- 40** (37 +/- 29*), 50 +/- 54 (39 +/- 36) pg.ml-1 in patients with CPB (without CPB), mean +/- SD, at 0, 3, 6, 9, 24, and 48 hr after start of surgery (*P < 0.01, **P < 0.05 compared with 0 hr), those measured by the endotoxin-specific test did not show any changes. Plasma neutralized 95% of endotoxin potency after five minutes incubation at 37 degrees C. CONCLUSION: Using an endotoxin-specific assay, endotoxin could not be detected in the blood stream during or after major surgery.

Adult↗

Adrenalectomy for treatment of Cushing syndrome: results in 122 patients and long-term follow-up studies.

Patients with Cushing syndrome (n = 122) who underwent adrenalectomy from 1957 through 1993 were reviewed for survival and complications. Of the 122 patients, 70 had adrenocortical adenoma, 30 Cushing's disease, 6 primary pigmented nodular adrenocortical disease (PPNAD), 7 other types of primary nodular hyperplasia, 5 adrenocortical carcinoma, and 4 ectopic ACTH syndrome. Sixty-five patients with adrenocortical adenoma are alive, and the survival rate was equal to the age-matched control population, when patients who died of the postoperative complication were excluded. Of the patients with Cushing's disease, 20 are alive; and 10 of 16 patients (63%) who were followed-up and evaluated had skin pigmentation. Four of sixteen patients (25%) developed Nelson's syndrome. Four PPNAD patients and five with other types of nodular hyperplasia are alive. Most of these patients underwent bilateral total adrenalectomy, but some patients remitted after unilateral adrenalectomy. All of five adrenocortical carcinoma patients and four with ectopic ACTH syndrome died within 2 years after operation. The prognosis for patients with adrenocortical adenoma after unilateral adrenalectomy is excellent, though it is important to avoid operative complications. The rapid cure of signs and symptoms of glucocorticoid excess after total adrenalectomy is ensured, and prognosis is satisfactory under careful glucocorticoid replacement, making total adrenalectomy an alternative treatment for Cushing's disease.

ACTH Syndrome, Ectopic↗

Golgi apparatus and intraneuronal inclusions of anterior horn cells in amyotrophic lateral sclerosis: an immunohistochemical study.

We applied immunohistochemical techniques to study alterations of the Golgi apparatus, and to determine possible relationships between this complex and the intraneuronal inclusions of lower motor neurons of patients with the sporadic form of amyotrophic lateral sclerosis (ALS). Spinal cords from normal individuals served as controls. Monoclonal antibodies to the Golgi zone and to Golgi beta-COP protein were used. Immunoreactivity with these antibodies was seen in frozen sections of paraformaldehyde-fixed spinal cord tissue, but not in formalin-fixed, paraffin-embedded specimens. The immunoreaction products were seen as granular structures, diffusely distributed in neurons and glial cells. Although immunostaining of some ALS neurons was reduced, fragmentation of the Golgi apparatus was not evident with either antibody. Bunina bodies and skein-like inclusions, characteristically found in spinal anterior horn cells of ALS patients, were not stained by these antibodies to epitopes of the Golgi apparatus, nor were Lewy body-like hyaline inclusions, present in some cases of sporadic ALS and reported to be characteristic to familial ALS with posterior column degeneration. These results suggest that components of the Golgi apparatus are not directly incorporated into intraneuronal inclusions. However, the possibility that abnormal proteinaceous material of the Golgi apparatus may be involved in their genesis cannot be ruled out.

Adult↗

Studies on the cytogenetic and endocrinologic background of spontaneous abortion.

OBJECTIVE: To determine whether chronic menstrual irregularity with elevated LH levels has a role in spontaneous abortion. DESIGN: In 41 consecutively examined women with spontaneous abortions occurring within 11 complete gestational weeks, fetal chromosomal analyses were performed. The differences of endocrinologic background in relation to the result of fetal chromosomal analyses were investigated. MAIN OUTCOME MEASURES: Endocrinologic profiles, including menstrual history, basal hormone levels (LH, FSH, and PRL), ovarian morphology on ultrasound, and fetal chromosomal karyotypes. RESULTS: The women with normal fetal karyotypes compared with those with abnormal fetal karyotypes showed higher frequency of menstrual irregularity (47.1% versus 8.3%), elevated basal LH levels (7.42 +/- 5.12 versus 4.41 +/- 1.39 mIU/mL; conversion factor to SI unit, 1.00), and higher frequency of polycystic ovary (41.2% versus 8.3%). CONCLUSION: Elevated LH-polycystic ovary may be involved in the genesis of spontaneous abortions that are not explainable by fetal chromosomal abnormality.

Abortion, Spontaneous↗

Development of a quantitative sampling method for periapical exudates from human root canals.

A quantitative method for collection of periapical exudates on endodontic paper points is described. In a pilot study, it was revealed that the relationship between fluid volume and wetted length of paper points had a highly significant curvilinear relationship (p < 0.0001), and a highly significant positive linear relationship was found to describe eluted and absorbed interleukin (IL)-1 beta activities from paper points. Periapical exudates from 29 root canals with apical periodontitis were collected using this method, and IL-1 beta activities in clinical specimens were measured. Periapical exudates (0.15 to 26.7 microliters) were recovered, and the range of IL-1 beta concentration was 0.1 to 179.5 ng/ml. These results showed that this sampling method was useful to analyze immunological changes in periapical lesions.

Dental Pulp Cavity↗

Widespread pruritic plaques in a patient with subacute cutaneous lupus erythematosus and hypocomplementemia: response to dapsone therapy.

We describe a patient with subacute cutaneous lupus erythematosus, widespread pruritic papulosquamous plaques, and hypocomplementemia. Skin biopsy specimens revealed liquefaction degeneration and colloid bodies and dyskeratotic cells in basal and suprabasal layers. An immunofluorescence study revealed deposits of IgG, IgM, and C3 at the dermalepidermal junction in a bandlike pattern, and particulate IgG deposition in the basal and suprabasal layers. Treatment with prednisolone (15 mg/day), chloroquine phosphate (200 mg/ day), cyclosporine (5 mg/kg daily), and gold (10 mg/day) failed to reduce pruritic plaque formation, and pulse methylprednisolone therapy led to only a transient remission. Clinical exacerbations correlated with a decrease in complement levels. The disease was successfully controlled with dapsone (75 mg/day) and prednisolone (25 mg/day).

Adult↗

Evaluation of stereoselective transdermal transport and concurrent cutaneous hydrolysis of several ester prodrugs of propranolol: mechanism of stereoselective permeation.

PURPOSE: The purpose of this study was to evaluate the stereoselective permeation and concurrent cutaneous hydrolysis of a series of ester prodrugs of propranolol (PL). METHODS: In vitro studies were performed across full-thickness, stripped and diisopropylfluorophosphate (DFP) treated skins of hairless mouse with flow-through diffusion cells at 37 degrees C. RESULTS: The permeability coefficients (Kp), which were dependent on partition coefficients (PC), of all the prodrugs were markedly increased compared to the parent drug. In full-thickness skin, the (R) caproyl-PL (CR-PL) showed the highest Kp, which was about 52-fold greater than that of PL. Most of the more lipophilic prodrugs showed stereoselectivity in Kp (R > S). All the prodrugs underwent stereoselective hydrolysis (R > S) during penetration. The prodrugs which showed stereoselectivity in permeation were comparatively lipophilic and showed great differences in hydrolysis percentages between the enantiomers. Permeation studies with stripped skin revealed that prodrugs were more permeable across stratum corneum compared to PL, whereas reverse was happened across viable skin. Although CR-PL showed high stereoselectivity in permeation across full-thickness skin and underwent higher percent of concurrent stereoselective cutaneous hydrolysis, the prodrug showed no stereoselectivity in permeation across DFP, an esterase inhibitor, treated skin and the concurrent cutaneous hydrolysis was also stopped. CONCLUSIONS: Lipophilic prodrugs may readily pass the stratum corneum but may not be able to penetrate so easily through the deeper tissues. Unlike the (S) isomers, the (R) isomers of lipophilic prodrugs almost completely converted to propranolol in epidermis and can easily pass through the dermis layer, resulting in stereoselective penetration.

Administration, Cutaneous↗

Elevated serum interferon gamma and interleukin-6 in patients with necrotizing lymphadenitis (Kikuchi's disease).

We investigated serum levels of interferon alpha, interferon gamma, tumour necrosis factor alpha, interleukin-2 (IL-2) and interleukin-6 (IL-6) in patients with necrotizing lymphadenitis (Kikuchi's disease) (NL). Four male patients, diagnosed as having NL following biopsy of the affected lymph nodes and by the clinical course, were included in this study. All four patients had higher than normal serum interferon gamma and IL-6 levels during the acute phase, which returned to normal levels during the convalescent phase. Interferon alpha, tumour necrosis factor alpha and IL-2 were, however, within the normal ranges. Our findings indicate the possibility that interferon gamma and IL-6 may play an important role in the pathogenesis of NL.

Child↗

Expression of hepatocyte growth factor and c-met mRNAs during rat chemically induced hepatocarcinogenesis.

The receptor for hepatocyte growth factor (HGF), a potent hepatocyte mitogen, is the product of the protooncogene c-met. In order to cast light on their significance for hepatocarcinogenesis, levels of both HGF and c-met mRNA were evaluated in rat livers during development of 2-acetylaminofluorene (2-AAF)-selected preneoplastic nodules and carcinomas following diethylnitrosamine (DEN) initiation. Rats were given a single i.p. injection of 200 mg/kg body wt DEN and, starting 2 weeks later, were administered 0.015% 2-AAF in the diet for up to 6 weeks. All rats were subjected to partial hepatectomy (PH) at week 3. Additional animals undergoing the DEN, 2-AAF and PH regimen were sacrificed at week 40 to allow evaluation of carcinomas. Oval cell proliferation, glutathione S-transferase placental form (GST-P)-positive preneoplastic lesion development and HGF and c-met mRNA levels were sequentially analyzed after PH. Numerous oval cells were observed 1 week after PH, but were remarkably reduced 2 weeks thereafter. The areas of GST-P-positive foci and nodules rapidly increased with time not only during 2-AAF feeding, but also to the same degree for at least 2 weeks after cessation of carcinogenic insult. Dot blot analysis showed HGF transcripts to be elevated after PH and during the selective growth conditions of 2-AAF feeding, dropping after cessation of carcinogenic insult. In the c-met transcript case transient increases were observed after PH, followed by a decrease. c-met over-expression in nodular livers did not correlate with the presence of 2-AAF or lesion development. In most hepatocellular carcinoma samples expression of both HGF and c-met mRNAs was below levels in non-neoplastic regions. These data suggest that HGF and c-met are directly involved in a paracrine growth pathway controlling proliferation in normal hepatocytes and oval cells, but not in preneoplastic and neoplastic cells.

2-Acetylaminofluorene↗

Identification and characterization of a new gene physically linked to the ATM gene.

Ataxia telangiectasia (AT) is an autosomal recessive disease of unknown etiology associated with cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and hypersensitivity to ionizing radiation. Although AT has been divided into four complementation groups by its radioresistant-DNA synthesis phenotype, the ATM gene has been isolated as the candidate gene responsible for all AT groups. We identified a new gene, designated NPAT, from the major AT locus on human chromosome 11q22-q23. The gene encoded a 1421-amino-acid protein containing nuclear localization signals and phosphorylation target sites by cyclin-dependent protein kinases associated with E2F. The messenger RNA of NPAT was detected in all human tissues examined, and its genomic sequence was strongly conserved through eukaryotes, suggesting that the NPAT gene may be essential for cell maintenance and may be a member of the housekeeping genes. Analysis of the genomic region of NPAT surprisingly revealed that the gene existed only 0.5 kb apart from the 5' end of the ATM transcript with opposite transcriptional direction. It may be possible to propose the idea that the promoter region could be shared by both housekeeping genes and that each gene could influence the expression of the other.

Amino Acid Sequence↗

Cerebral energy metabolism in insulin induced hypoglycemia in newborn piglets: in vivo 31P-nuclear magnetic resonance spectroscopy.

The effect of insulin induced hypoglycemia on cerebral energy metabolism was examined in four newborn piglets. Cerebral energy metabolism was assessed using in vivo 31P-nuclear magnetic resonance spectroscopy. It was demonstrated that the normal level of phosphocreatine/inorganic phosphate (PCr/Pi), an indicator of phosphorylation potential, was maintained at a blood glucose level of 40 mg/dL or above, whereas when blood glucose was reduced to less than 40 mg/dL, PCr/Pi rapidly decreased in parallel with this. Below the critical blood glucose level of 40 mg/dL, a positive correlation (y = 0.02x + 0.632; r = 0.668; P < 0.001) existed between blood glucose and PCr/Pi. In the present investigation, a reduction of blood glucose level to 20 mg/dL or lower resulted in a PCr/Pi of less than 1, indicating a state of cerebral energy failure. The intracellular pH (pHi) was 7.08 +/- 0.05 at the onset and 7.15 +/- 0.07 in the hypoglycemic state, indicating no significant difference between the two groups. The present study has clarified that cerebral energy failure occurs when the blood glucose level is about 20 mg/dL or lower. The critical point of blood glucose exists to maintain brain energy metabolism.

Animals↗

[Basic and clinical studies of pazufloxacin on infectious enteritis research group of T-3761 on infectious enteritis].

A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.

4-Quinolones↗

Proliferating cell nuclear antigen expression in papillary thyroid carcinoma.

AIMS: To correlate the expression of proliferating cell nuclear antigen (PCNA) with various clinicopathological features of papillary thyroid carcinoma. METHODS: Sections from 131 formalin fixed, paraffin wax embedded papillary thyroid carcinomas were stained with a monoclonal antibody (PC10) directed against PCNA using the avidin-biotin immunoperoxidase (ABC) method. PCNA immunoreactivity was based on the PCNA labelling index (LI) following evaluation of at least 1000 tumour cells, and expressed as follows: grade A (LI < 10%), grade B (10% < or = LI < 25%), and grade C (LI > or = 25%). The relation between PCNA expression in these three groups and other clinicopathological factors, such as sex, age, tumour size, nodal metastases, and histological differentiation, were examined. RESULTS: Based on the labelling index, 57 (43.5%) cases were graded as A, 46 (35.1%) as B, and 28 (21.4%) as C. The female-:male ratios were 6.13:1 for group A, 2.83:1 for group B, and 2.11:1 for group C. The mean (SD) ages of the patients were 39.0 (16.1) in group A, 53.5 (14.4) in group B, and 55.8 (13.3) years in group C. The correlation between age and PCNA grade was strongest in women. CONCLUSIONS: PCNA immunoreactivity is correlated with sex and age in patients with papillary thyroid tumours.

Adolescent↗

Aluminum potentiates P(i) transport stimulation induced by fluoride in osteoblast-like cells.

The effect of aluminum (AI) on inorganic phosphate (P(i)) transport stimulation induced by fluoride (F) was investigated in MC3T3-E1 osteoblast-like cells. Al potentiated the increase in P(i) transport activity induced by F in a dose- and time-dependent manner. Results obtained with deferoxamine mesylate, an Al chelator, suggest that a fluoroalumino complex is probably the active F molecule responsible for the change in P(i) transport observed in this study. The signaling pathway responsible for the stimulation of P(i) transport by F+Al likely involves a tyrosine phosphorylation process but neither a protein kinase C nor a mitogen-activated protein kinase pathway. As previously found in UMR-106 cells for F alone, F+Al potentiated the change in P(i) transport induced by fetal calf serum. A similar interaction was found between F+Al and thrombin acting through a G protein-coupled receptor. These observations are compatible with the hypothesis that F+Al could interact with G protein-coupled receptors associated with a signaling tyrosine phosphorylation process involved in the regulation of P(i), transport in osteoblast-like cells.

3T3 Cells↗

Bromocriptine therapy in early-stage Parkinson's disease.

We evaluated bromocriptine monotherapy during the early stage of Parkinson's disease (Hoehn and Yahr stage I or II). Of the 120 patients registered as participants in this trial, 96 were studied. The follow-up period was 48 weeks. For the first 24 weeks they were all placed on bromocriptine with or without anticholinergic drugs; for the second 24 weeks, 75 of them were still kept on the same medication, with 21 requiring additional levodopa. Clinically, the former group showed a good response to the bromocriptine monotherapy, while the latter responded poorly to it (requiring in addition levodopa). We think that Parkinson's disease encompasses a heterogeneous group of patients of whom about 75% are well treated by bromocriptine alone at the early stages of the illness.

Antiparkinson Agents↗

Oxyphil cell function in secondary parathyroid hyperplasia.

Oxyphil cell function in secondary parathyroid hyperplasia due to chronic renal failure was evaluated using in situ hybridization and heterotransplantation of parathyroid tissue. In situ hybridization and histologic analysis were performed on continuous frozen sections using 22 parathyroid tissues. A restricted area composed exclusively of oxyphil cells was observed in 10 specimens, and an area of only chief cells was found in 12 specimens. Silver grains demonstrating the existence of parathyroid hormone (PTH) mRNA were 18.8 +/- 7.8 (mean +/- SD) in oxyphil cells while those in chief cells were 17.2 +/- 7.5. PTH mRNA was abundant in both the oxyphil and chief cells. Further analysis of oxyphil cell function was assessed by the heterotransplantation of parathyroid nodules, consisting exclusively of oxyphil or chief cells, into nude mice. The function of these implants was assessed by measuring the concentration of human intact PTH which did not cross-react with mouse PTH. Serum PTH concentrations were correlated with the volume of implanted tissue. Elevations of PTH concentrations were similar in the mice transplanted with oxyphil or chief cells, indicating that both cell types had similar PTH secretory activity. The basic histologic characteristics of both cell types were not altered following transplantation. These results demonstrate that oxyphil cells in secondary parathyroid hyperplasia synthesize and secrete PTH, and that this secretion contributes to the pathophysiology of hyperparathyroidism.

Alkaline Phosphatase↗