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Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 343 records · Page 19Linked to original sources
PubMed1993

Subchronic oral toxicity study of captafol in B6C3F1 mice.

The effects of subchronic administration of captafol were studied in B6C3F1 mice given dose levels of 0, 0.3, 0.625, and 1.25% in the diet for 12 wk. There was a dose-related decrease in body weight gain during the 12-wk experiment and a loss of body weight in the 1.25% group of both sexes. Whiles the mice given captafol consumed less diet than the control mice, this was not directly dose-related. The relative weights of liver demonstrated a tendency for dose-dependent increase. Light-microscopic examination revealed cytoplasmic vacuolar degeneration, depending in severity on the dosage, in the livers of both sexes given captafol. In conclusion, the findings obtained from the present subchronic toxicity study indicated the liver to be a primary target organ.

Administration, Oral↗
PubMed1993

No enhancing effects of calcium/magnesium salts of L-glutamate and L-ascorbate on tumor development in a rat medium-term multiorgan carcinogenesis bioassay.

Calcium/magnesium salts of L-glutamate and L-ascorbate were tested for modification potential using a rat multiorgan carcinogenesis bioassay. Following sequential treatment with three different carcinogens (diethylnitrosamine, N-methylnitrosourea, and dihydroxydi-N-propylnitrosamine) over a 4-wk period, rats were given diet containing 5% monocalcium di-L-glutamate tetrahydrate (Ca-glutamate), 2.5% monomagnesium di-L-glutamate tetrahydrate (Mg-glutamate), 5% L-glutamic acid, 5% monocalcium di-L-ascorbate dihydrate (Ca-ascorbate), 2.5% monomagnesium di-L-ascorbate dihydrate (Mg-ascorbate), or 5% L-ascorbic acid for 16 wk. Body weight increase was slightly suppressed in the groups receiving Ca-ascorbate, Mg-ascorbate, and ascorbic acid supplementation after the carcinogen treatments. While administration of Ca-glutamate or Ca-ascorbate raised urinary pH, ascorbic acid values were decreased. Concentrations of calcium and magnesium ions in the urine increased after ingestion of Ca-glutamate or Ca-ascorbate, and Mg-glutamate or Mg-ascorbate, respectively, but phosphorus levels decreased in all groups given calcium and magnesium salts. No consistent treatment-related changes in the concentrations of sodium or potassium ions in the urine were detected. Histopathological investigation at wk 20 did not demonstrate any modification of tumorigenesis with regard to the incidence of frequency of lesions developing in the various target organs/tissues. The present results thus revealed no apparent enhancement of carcinogenesis at any site, including the urinary system, by calcium or magnesium salts using the present rat multiorgan carcinogenesis bioassay.

Animals↗
PubMed1993

Dose-dependence of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) carcinogenicity in rats.

The dose-dependence of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) carcinogenicity was investigated in F344 rats of both sexes administered the heterocyclic amine in the diet at concentrations of 25 or 100 p.p.m. for up to 104 weeks. Incidences of mammary adenocarcinomas were 7% (2/30) for 25 p.p.m. and 47% (14 of 30 rats) for 100 p.p.m. in females and those of colon adenocarcinomas were 43% (13/30) for males and 13% (4/30) for females of the 100 p.p.m. groups. No mammary adenocarcinomas were induced in males and no colon carcinomas were observed in the 25 p.p.m. groups of either sex. Furthermore, development of lymphocytic leukemia was apparently enhanced by PhIP in males. In a separate experiment, dose-dependent induction of aberrant crypts in the large intestine, considered as preneoplastic lesions, was evident after 8 weeks feeding of PhIP-supplemented diet at doses of 25, 100 or 400 p.p.m. Thus a clear dose-dependency was demonstrated for both colon and mammary carcinogenesis. Since PhIP is a particularly abundant heterocyclic amine and its carcinogenic organotropism overlaps with the types of neoplasias most commonly observed in western countries, the compound may be extremely important with respect to human cancer development.

Adenocarcinoma↗
PubMed1993

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). I. Study design, cohort description, and intersite comparisons.

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The "Predictors Study," a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.

Activities of Daily Living↗
PubMed1993

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). II. Neurological, psychiatric, and demographic influences on baseline measures of disease severity.

The "Predictors Study" is a prospective cohort study of the natural history of Alzheimer disease (AD), the aim of which is to identify milestones in disease progression and to develop a model to predict disease course in individual patients. The empirical background to this study is based on previous reports that the presence of extrapyramidal signs (EPS), myoclonus, and psychosis in AD may signify greater disease severity at any given stage and a more rapid course of the disease over time. The present analyses were conducted to determine whether these independent "predictor" variables were associated with greater disease severity at baseline within a new cohort of 224 mild AD patients recruited from three different medical centers (in New York, Baltimore, and Boston). Measures of disease severity were provided by the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale (BDRS), which measures functional capacity. Independent variables were EPS, delusions, and slowing of the posterior dominant EEG rhythm. The frequency of myoclonus and hallucinations was too low to permit adequate statistical assessment of their effects at this time. EPS and EEG slowing were associated with low mMMSE scores, whereas delusions were primarily associated with impaired functional capacity. These effects were independent of the influence of age and disease duration. These results indicate that the effects of these independent variables can be detected at mild stages of AD and that these effects can be generalized across different geographical regions.

Aged↗
PubMed1993

Safety and efficacy of oral physostigmine in the treatment of Alzheimer disease.

Results of therapeutic trials with physostigmine in the treatment of Alzheimer disease (AD) have been inconsistent and controversy persists concerning safety and efficacy. In a double-blind, placebo-controlled, crossover study, patients received 6 weeks of oral physostigmine (OP) and placebo in random order. Twenty-nine patients with AD received as much as 16 mg/day of OP and were assessed with neuropsychological and functional measures. No significant cardiac side effects were noted, though other systemic adverse effects were noted, requiring dose reduction in four patients. There was a slight but significant improvement (12%) in performance on the selective reminding test with physostigmine and the memory performance was correlated with dosage. This improvement compares favorably with the 15% decrease in scores seen in an untreated comparison cohort followed for an equivalent time period. There was a trend toward an improvement in communication and a reduction in memory complaint. These results suggest that oral physostigmine is safe and may improve memory in AD.

Administration, Oral↗
PubMed1993

Immunohistochemical localization of calmodulin in the testes of patients with idiopathic male infertility.

The localization of calmodulin in testes of patients with idiopathic male infertility was studied using the indirect immunoperoxidase method. Specimens were obtained by testicular biopsy from 55 patients. They were divided into 26 cases of hypospermatogenesis, 11 cases of maturation arrest (8 of primary spermatocyte arrest and 3 of spermatid arrest) and 18 cases of Sertoli cell-only syndrome. Regardless of the type of testicular pathology, the types of immunoreactive cell and the intensities of staining were the same as those in the normal testis. That is, staining for calmodulin was first found to be positive in early pachytene primary spermatocytes. It became intense in late pachytene primary spermatocytes and round spermatids. By contrast, elongated spermatids and spermatozoa were not stained. Sertoli cells were stained slightly or not at all. A calmodulin-staining index (CaM-S index) was defined as the proportion of primary spermatocytes that were stained intensely for calmodulin relative to the total number of primary spermatocytes. The indices for the testes of men with complete spermatocyte maturation arrest were significantly lower than those for the testes of normal controls and of men with hypospermatogenesis. Degenerating late pachytene spermatocytes observed in the testes of men with spermatocyte arrest showed low calmodulin-specific immunoreactivity. Such a decrease in numbers of normal late pachytene spermatocytes might be responsible for the low CaM-S index in cases of complete spermatocyte arrest.

Adult↗
PubMed1993

Bone lesions of multiple myeloma in three dogs.

Three cases of canine multiple myeloma that showed monoclonal IgA gammopathy and bone lesions were examined. One dog was associated with Bence-Jones proteinuria as well. Radiographic examination revealed extensive skeletal involvement of flat bones such as scapula, pelvic bone, costa, and epiphysis of long bones where the hematopoiesis was active throughout the life. Histopathologically, small osteolytic lesions occurred from periosteum and Haversian canal as well as endosteum, and larger lesions were formed by gradual expansion or fusion of small lesions. Osteolytic lesions did not necessarily involve tumor growth, explaining the inconsistent confirmation of tumor cells in biopsy specimens for diagnosis of multiple myeloma and suggesting the possible mechanism for osteolysis by some other humoral factors.

Animals↗
PubMed1993

Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment.

We obtained data from 111 gay men who entered a longitudinal study of the natural history of human immunodeficiency virus (HIV) without clinical evidence of acquired immunodeficiency syndrome (AIDS), and examined them regularly over a 36-month period. Using a Cox proportional-hazard regression model to compare cumulative risk of mortality in subjects with and without cognitive impairment and several putative risk factors present at baseline, we found that the mortality risk ratio (RR) associated with poor neuropsychologic test performance was significantly increased (RR = 2.9; 95% confidence interval [CI], 1.1 to 7.8), and increased further (RR = 4.1; 95% CI, 1.3 to 12.5) when adjusted for other factors associated with mortality (a history of a disturbance in movement or gait, CD4-lymphocyte and red blood-cell counts, and age). A significant increase in symptoms related to cognitive impairment and gait, a decline in neuropsychologic test performance, and declines in CD4-lymphocyte and red-cell counts occurred over the study period. A second model was constructed to adjust for changes in CD4-lymphocyte and red-cell counts, age, medical stage, and motor symptoms over the study period, but the mortality RR for poor neuropsychologic test performance at baseline changed very little (RR = 4.7; 95% CI, 1.5 to 14.9). We conclude that the presence of cognitive impairment, manifest by poor neuropsychologic test performance in both asymptomatic and symptomatic gay men with HIV infection, is associated with a significantly increased risk of death. This effect progresses in parallel with the immunologic and systemic effects of HIV.

Adult↗
PubMed1993

Enzyme immunoassay of anti-human acetylcholine receptor autoantibodies in patients with myasthenia gravis reveals correlation with striational autoantibodies.

Anti-acetylcholine receptor (AChR) autoantibodies are a marker of acquired myasthenia gravis (MG). Some of these antibodies cause muscle weakness. Striational autoantibodies (StrAb) also are a marker of MG. They are most prevalent in older patients and patients with thymoma. Here we describe a reproducible enzyme immunoassay (AChR-EIA) for detecting antibodies reactive with human muscle AChR, using antigens concentrated on plastic by prior sequential application of a biotinylated carrier, avidin, and biotinylated monoclonal IgG against AChR. There was significant correlation between values for antibodies assayed by AChR-EIA and by immunoprecipitation of AChR complexed with 125I-alpha-bungarotoxin. Unexpectedly, AChR-EIA and StrAb values also were significantly correlated. Further studies revealed a significant and unprecedented correlation for StrAb and AChR precipitating antibodies. A plausible explanation for these findings is that some StrAb may react with cytoskeletal proteins that associate and copurify with AChR. The AChR-EIA offers a nonradioactive method for detecting two autoantibodies that are relatively restricted to patients with acquired MG.

Antibodies, Monoclonal↗
PubMed1993

Patterns of neuropsychological performance in Alzheimer's disease patients with and without extrapyramidal signs.

We investigated the relationship between extrapyramidal signs (EPS) and the cognitive function in 90 patients meeting NINCDS-ADRDA criteria for probable Alzheimer's disease (AD) by dividing them into those showing no evidence of EPS and those showing at least one EPS on the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of verbal memory, orientation, abstract reasoning, language, and construction. Patients with EPS were significantly more impaired than patients without EPS on tests of short-term learning and memory, orientation, naming, verbal fluency, and construction, but not on tests of long-term memory, abstract reasoning, or verbal comprehension. These results could not be explained by any differences in age, education, or disease duration between the groups. Since this pattern of neuropsychological impairment resembles that of patients with Parkinson's disease and other EPS syndromes, we hypothesize that EPS are associated with neuropathologic and neuropsychological changes that are superimposed over the classic features of AD.

Aged↗
PubMed1993

Accumulation of (E)-4-hydroxy-2-nonenal and n-hexanal, degradation products of lipid peroxides, in mouse lung and liver.

Effects of lipid peroxide breakdown products, (E)-4-hydroxy-2-nonenal (4-HN) and n-hexanal, on mouse lung lesion were examined. When 4-HN was injected i.v., the plasma level of 4-HN increased just after the injection and then decreased immediately. The amounts of 4-HN increased in the liver and lung were ca. 0.085 and 0.43% to the dose administered, respectively, 5 min after the injection. Reduced glutathione (GSH) content and both GSH peroxidase (GSH-Px) and GSH reductase (GSSGR) activities in the lung were decreased significantly by 4-HN treatment. On the other hand, in the case of i.v. injection of n-hexanal into mice, the amount of n-hexanal detected in the lung was 5.0% to that of 4-HN, and no effect on the activities of GSH-Px and GSSGR and the content of GSH was observed. These results suggest that 4-HN generated from lipid peroxides would be transferred into the lung and cause the lung lesion through the inhibition of GSH-dependent antioxidative defense systems.

Aldehydes↗
PubMed1993

Acute effects of alcohol on regional cerebral blood flow in man.

Acute effects of alcohol in a low (0.7 g/kg) and a high dose (1.5 g/kg) on regional cerebral blood flow (rCBF) were measured with 133Xe inhalation technique at resting conditions in 13 normals. Mean hemisphere CBF increased globally by 12% at the lower dose and 16% at the higher dose. A normal hyperfrontal flow pattern was seen in both alcohol conditions. There were, however, significant regional differences in response to alcohol. The largest rCBF increase was observed in prefrontal regions at the lower dose, and in temporal regions at the higher. Expressed in relative values (% of the whole brain CBF), the temporal rCBF increased linearly with increasing alcohol dosage, while the prefrontal rCBF showed a increase at the lower dose followed by a decrease at the higher dose. It is concluded that alcohol has two types of acute effects on rCBF, a global vasodilatory effect and some regional effects, most clearly seen in prefrontal and temporal regions. The prefrontal flow augmentation following acute alcohol intake may be related to a transient arousal reaction, which has been reported by others. The temporal flow increase may be related to effects of alcohol on emotions and mood.

Adult↗
PubMed1993

Measurement of anaphylatoxin activity during surgery.

We studied whether or not anaphylatoxins (ATs) are related to stress-related surgery by examining AT measurement in 51 patients undergoing operation. C3a plasma levels in patients who underwent the Caldwell-Luc operation increased from a pre-surgery concentration of 129 +/- 19 (mean +/- SD) ng/ml to 293 +/- 91 ng/ml during surgery under local anesthesia. However, pre- and post-surgery values were almost the same. No significant change occurred in the C5a plasma concentration at any time in patients undergoing the Caldwell-Luc operation, tonsillectomy or partial glossectomy. The mechanism underlying elevation in C3a during surgery is discussed.

Adult↗
PubMed1993

IgG-kappa-type plasmacytoma secreting salivary-type amylase in adult T-cell leukemia.

A IgG-kappa-type plasmacytoma secreting salivary-type amylase ectopically is reported in a patient with smouldering adult T-cell leukemia(ATL). The patient had plasmacytomas in the distal region of the right femur, the proximal region of left tibia, and the left paranasal sinus. Both his serum and urine contained high levels of amylase. The presence of IgG-kappa and S-type amylase in the plasmacytoma cells was confirmed immunocytochemically. In addition, he was also positive for the antibody against the human T-cell leukemia virus type I (HTLV-I), and had abnormal lymphocytes with convoluted nuclei (ATL cells) in the peripheral blood. The monoclonal integration of HTLV-I proviral DNA was demonstrated in the leukemic cells of the peripheral blood, but not in the plasmacytoma cells. Our case suggested that not only can HTLV-I infection play a role in the development of ATL, but may also induce a B-cell malignancy in an indirect manner, and even an ectopic amylase producing plasmacytoma.

Amylases↗
PubMed1993

Unique T-helper leukaemia with cytoplasmic granules and convoluted nuclei.

An unusual case of CD4+ helper T-cell lymphocytic leukaemia is reported in a 67-year-old Japanese woman. CD4+ cells showed convoluted nuclei and dense cytoplasmic granules, features usually present in CD8+ large granular lymphocytes and disorders of this particular cell type. Serum did not show antibodies to HTLV-I and HTLV-I proviral DNA integration was not evident by Southern blot analysis or after PCR. A monoclonal rearrangement of the TCR-beta chain gene was evident when hybridization methods were used. The patient died 11 months after diagnosis. No skin involvement, or splenomegaly was evident. Serum LDH levels were markedly elevated but serum calcium levels were within normal limits. The case is discussed and compared to other T-cell lymphoid leukaemias. The heterogeneity in the morphology of CD4+ T cell leukaemias is stressed.

Aged↗
PubMed1993

Pathological specimens of rat temporal bone--comparison between different fixative solution.

We investigated the difference in temporal bone specimens fixated by three sorts of fixative solution (10% formalin fixative, Wittmaack's fixative and Heidenhein-SuSa fixative). 1. 10% Formalin's fixative solution We found many pinkish precipitates, which are stained by hematoxy-eosin, in the scala media of the cochlea. Same substance is found in the perilymphatic space and endolymphatic space in the vestibulum. The fusion of the cells is indicated in the tectorial membrane, inner sulucus cell, outer sulucus cell especially in the apical turn of the cochlea. 2. Wittmaack's fixative solution The detachment of inner and outer sulucus cells are found from basilar membrane at the basal turn of the cochlea. The tendency in convex and concave form of the Reissner's membrane is most remarkable in these three fixative solution. 3. Heidenhein-SuSa fixative solution In this solution, no precipitates, no fusion of cells are found. No detachment of the inner or outer sulucus cells is also found. This study indicates that Heidenhein-SuSa fixation is most excellent fixative method.

Animals↗