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Biomedical subjects

A Shimada

Publications and source records attributed to A Shimada.

At least 199 records · Page 11Linked to original sources
PubMed1994

Increase in neutral cholesteryl ester hydrolase activity produced by extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (H-35).

The metabolism of high-density lipoprotein-associated cholesteryl esters (HDL-CE) in liver cells is not well understood. We studied the possible role of lysosomal and extralysosomal pathways on such metabolism by measuring the uptake and hydrolysis of HDL-CE in H-35 rat hepatoma cells. Incubation of cells with [3H]cholesteryl ester-labeled HDL led to the intracellular accumulation of both 3H-free cholesterol and [3H]cholesteryl ester. The ratio of 3H-free cholesterol/[3H]cholesteryl ester increased with an increase in incubation time even in the presence of chloroquine. Because chloroquine did not inhibit the conversion of cholesteryl ester to free cholesterol, the hydrolysis of HDL-CE may have been catalyzed by an extralysosomal enzyme, perhaps by neutral cholesteryl ester hydrolase (NCEH). When we incubated cells with increasing concentrations of HDL, NCEH activity increased. This increase in enzyme activity was not inhibited by the addition of chloroquine. A complex of dimyristoylphosphatidylcholine (DMPC)/apo HDL/cholesteryl ester enhanced the activity as well as native HDL. Neither the DMPC/apo HDL nor the DMPC/cholesteryl ester complex affected the activity, suggesting that apo HDL may be required for the uptake of HDL-CE. The present study demonstrated that the extralysosomal hydrolysis by NCEH is operating in the metabolism of HDL-CE in hepatoma cells.

Animals↗
PubMed1994

Spermidine potentiates dizocilpine-induced impairment of learning performance by rats in a 14-unit T-maze.

The NMDA receptor, a ligand-gated ion channel complex, has been reported to be involved in memory processes. Learning is impaired following administration of dizocilpine, a non-competitive antagonist of the NMDA receptor. Polyamines, such as spermine and spermidine, interact with the NMDA receptor to enhance binding of dizocilpine, which blocks the ion channel. The present study assessed action of polyamines as modulators of learning via NMDA receptor activation. Dizocilpine (0.05 mg/kg) was given i.p. before maze learning, at a dose that produced a slight, nonsignificant impairment of maze learning. Pretreatment with 80 mg/kg but not 15 or 40 mg/kg spermidine (i.p.) before dizocilpine impaired maze learning compared to saline controls. Administration of 80 mg/kg spermidine without dizocilpine did not impair maze learning. The results are consistent with the view that systemic injection of a polyamine can modulate learning processes involving the NMDA receptor.

Analysis of Variance↗
PubMed1994

Isolation of Mycoplasma hyorhinis and Mycoplasma arginini from the ears of pigs with otitis media.

Mycoplasmas were isolated from the middle ears and nasal cavities of clinically ill, young pigs that were slaughtered due to an unfavourable prognosis. The isolation rates of Mycoplasma hyorhinis were 27 of 43 (62.8 per cent) from the auditory tube, 22 of 43 (51.2 per cent) from the tympanic cavity, and 15 of 25 (60.0 per cent) from the nasal cavity. M arginini was also recovered at rates of 11 of 43 (25.6 per cent) from the auditory tube, 7 of 43 (16.3 per cent) from the tympanic cavity, and 9 of 25 (36.0 per cent) from the nasal cavity. Dual infections with M hyorhinis and M arginini occurred in these sites in some cases. M hyorhinis was isolated from 16 (80.0 per cent) of 20 pigs with otitis media diagnosed histologically, and from two (25.0 per cent) of eight pigs without this condition. The isolation rate was significantly different (P < 0.05) between the groups, suggesting either that the organism triggers development of the disease of the ear or that the agent(s) or factors responsible for otitis media in the pigs created favourable conditions at this site for colonisation by M hyorhinis.

Animals↗
PubMed1994

Analysis of MHC class II antigens in Japanese IDDM by a novel HLA-typing method, hybridization protection assay.

We examined HLA Class II antigens in 116 Japanese IDDM patients [84 typical IDDM (T-IDD); 32 slowly progressive IDDM (S-IDD)] by the hybridization protection assay (HPA) which is a novel HLA typing method based on hybridization of acridinium-ester-labeled DNA probes to amplified DNA. We detected HLA-DRB1, -DQA1 and -DQB1 genes by this method which is capable of analyzing over 50 samples within 4 h with high sensitivity. Positive associations were found in DRB1*0405, DRB1*0802, DRB1*0901, DQA1*0301, DQB1*0303 and DQB1*0401, negative correlations in DRB1*0403, DR2, DR12, DRB1*0801 or 03, DQA1*0101 or 02, DQA1*0501, DQB1*0301 and DQB1*0602 alleles. The absence of aspartic acid (Asp) at position 57 of the DRB1 chain and the presence of arginine (Arg) at position 52 of the DQA1 chain correlated positively with both types of IDDM. There were no significant differences in HLA between T-IDD and S-IDD. These results suggest that the absence of Asp at position 57 of the DRB1 chain and the presence of Arg at position 52 of the DQA1 chain are significant Japanese IDDM patients and that DRB1*0802, in which the amino acid at position 57 is aspartic acid, may play a role in the pathogenesis of IDDM. Also, T-IDD and S-IDD have common bases in the HLA gene.

Adolescent↗
PubMed1994

Acceleration of diabetes in young NOD mice with peritoneal macrophages.

To elucidate the roles of macrophages in the pathogenesis of NOD murine diabetes, peritoneal macrophages from NOD mice were injected into young NOD mice. We used 12 to 20 week-old NOD mice of both sexes as donors, and sex-matched 2-week-old NOD mice as recipients. Cyclophosphamide (CY), 200 mg/kg, was intraperitoneally injected into the donors. Two weeks later, peritoneal exudate cells (PEC) were collected from the diabetic donors. Macrophage-rich fractions (MRF) were collected by adherence. Then PEC(5-8 x 10(6)) or MRF(3-7 x 10(6)) were transferred, intraperitoneally, to the recipients. Two weeks later, some of the recipients were killed in order to perform immunofluorescent analysis of splenocytes and to assess pancreatic histology. Mac 1 positive splenocytes were increased in PEC- and in MRF-injected recipient mice. Insulitis was seen in PEC- and MRF-injected mice, but not in controls. Some of the recipients were injected with CY, 200 mg/kg, intraperitoneally, at two weeks post cell transfer. Two weeks after CY injection, the animals were examined for the presence of diabetes. The incidences of diabetes were 67% in PEC-injected mice, 40% in the MRF-injected group, and 3% in the controls. These results suggest that peritoneal macrophages accelerate the disease process in NOD mice.

Animals↗
PubMed1994

Localization of atrophy-prone areas in the aging mouse brain: comparison between the brain atrophy model SAM-P/10 and the normal control SAM-R/1.

Mouse inbred strain "SAM-P/10" (Senescence Accelerated Mouse) is a model of age-related brain atrophy. In this strain there is an earlier and more severe age-related deterioration in the conditional avoidance learning than the normal control inbred SAM-R/1 strain. The present study analysed age-related changes in brain area size using a computerized morphometric method. The region most vulnerable to age-related atrophy in SAM-P/10 was the frontal region of the cerebral cortex, including the prefrontal cortex. Other neocortical regions underwent diffuse atrophy. Posterior piriform cortex, entorhinal cortex, anterior olfactory nucleus, amygdala, caudate-putamen, nucleus accumbens and cerebellar cortex were atrophy-prone regions. The septum also underwent atrophy but other basal forebrain structures were intact. The hippocampus, diencephalon and brainstem structures showed no atrophic change. White matter structures did not change in size with aging except for the forceps minor of the corpus callosum, which showed age-related atrophy. On the contrary, SAM-R/1 showed a significant age-related atrophy only in a restricted part of the cerebral cortex, mainly in the parietal region. Other cortical regions, subcortical structures, diencephalon, brainstem structures, cerebellum and white matter were atrophy-resistant in SAM-R/1. The prefrontal cortex, entorhinal cortex, piriform cortex and striatum are closely interconnected and also connect with the amygdala which plays a key role in conditioning in the rodent. Age-related atrophy in all these structures in SAM-P/10 presumably accounts for the age-related deficits in conditional avoidance learning in this strain of mouse. Comparison between SAM-P/10 and SAM-R/1 or other well-known rodents indicates that SAM-P/10 is a unique rodent that spontaneously and rapidly develops progressive generalized cerebral atrophy, which is considered to be a pathological process rather than an accelerated aging process.

Aging↗
PubMed1994

Age-related hearing impairment in senescence-accelerated mouse (SAM).

The auditory brainstem response and histopathology of the cochlea were investigated in an accelerated senescence-prone strain, SAM-P/1 mice and a senescence-resistant strain, SAM-R/1 mice. Each strain displayed an age-related auditory loss expressed as elevated thresholds similar to human hearing loss in that high-frequency losses occurred earlier than middle- or low-frequency losses. SAM-P/1 showed a more rapid decline of hearing with age than did SAM-R/1. Interpeak intervals I-III and I-IV were prolonged with age in both strains, especially at high frequency. The prolongation was more marked in SAM-P/1 than in SAM-R/1. The decrease in amplitude of wave I observed in both strains was greater in SAM-P/1 than in SAM-R/1. The auditory function assessed by thresholds, interpeak intervals and amplitudes of wave I in SAM-P/1 at 12 months of age corresponded roughly to that in SAM-R/1 at 20 months of age. In morphological studies, there was an age-related decrease in the cell density as well as in the size of spiral ganglion neurons in both strains, but these changes were more pronounced in SAM-P/1 than in SAM-R/1. These results reveal that age-related hearing impairment associated with morphological changes in the cochlea is manifested earlier and progresses more rapidly in SAM-P/1 than in SAM-R/1. Thus, the SAM-P/1 strain should prove useful as a model of presbycusis.

Aging↗
PubMed1994

The Japanese medaka, Oryzias latipes, as a new model organism for studying environmental germ-cell mutagenesis.

The effects of genotoxic substances on ecosystems should be assessed using various test systems with multiple genetic end points. The most widely used test system has been the specific-locus test developed by W.L. Russell, using the mouse. We are developing a new, nonmammalian test system using the Japanese medaka, Oryzias latipes. We have examined 625,926 embryos that correspond to 1,586,649 loci. In the medaka test system, four genetic end points are evaluated: dominant lethals, total mutations, viable mutations, and malformations. Because the medaka is an oviparous experimental animal, we were able to determine that approximately 90% of spontaneous as well as gamma-ray-induced total mutants died during development, irrespective of spermatogenesis stages at the time of exposure. Exposure of sperm and spermatids to ethylnitrosourea (ENU) also resulted in embryonic death of approximately 90% of total mutants. In sharp contrast, approximately 90% of total mutants recovered from ENU-exposed spermatogonia became viable mutants. These results indicate that the quantitative relationship between induction of specific-locus mutations and dominant lethals remains the same among spermatogenesis stages for gamma-rays, while it is biased excessively to the induction of specific-locus mutations in ENU-exposed spermatogonia. Thus, the assessment should integrate at least two factors, agent-specific and species-specific effects.

Animals↗
PubMed1994

Radioimmunoassay detects the frequent occurrence of autoantibodies to the Mr 65,000 isoform of glutamic acid decarboxylase in Japanese insulin-dependent diabetes.

Glutamic acid decarboxylase antibodies (GAD65Ab) are common in new onset Caucasian insulin-dependent diabetic (IDDM) patients but it is unclear if this marker is also prevalent in patients of other ethnic backgrounds. We determined antibodies against human recombinant GAD in Japanese diabetic patients using a radioimmunoassay with competition between in vitro translated 35S-GAD65 and non-labelled recombinant human GAD65 (rhGAD65). GAD67 antibodies (GAD67Ab) were similarly analyzed but without antigen competition. In 73 Japanese diabetic patients, GAD65Ab were found in 11/16 (69%) of patients with short-duration (less than 5 yrs) IDDM, 6/23 (26%) with long-duration (5 or more yrs) IDDM and 10/20 (50%) with slowly progressive diabetes. High GAD65Ab levels were associated with concomitant autoimmune diseases (p = 0.021). GAD67Ab were found in 4/16 (25%) of patients with short-duration IDDM, 3/23 (13%) with long-duration IDDM and 2/20 (10%) with slowly progressive diabetes. In 14 non-insulin dependent diabetic (NIDDM) patients, GAD65Ab and GAD67Ab were not found (0/14) and 1/50 (2%) healthy controls were positive in either assay. Among the GAD67Ab-positive samples, 8/9 (88%) were also high level GAD65Ab positive, 7/9 (77%) were displaced by an excess of rhGAD65 and the antibody levels correlated (r2 = 0.573; p = 0.003). Our data are consistent with a strong association of GAD65Ab also in Japanese IDDM, and suggest that, when present, GAD67Ab are frequently directed to epitope(s) common to GAD65 and GAD67.

Asian People↗
PubMed1994

Resistance to cyclophosphamide-induced diabetes in transgenic NOD mice expressing I-Ak.

Transgenic expression of the MHC (major histocompatibility complex) class II I-Ak molecule was previously shown to effectively reduce the incidence of insulitis in non-obese diabetic (NOD) mice at the age of 20 weeks. We have further characterized the expression and function of the I-Ak molecule and examined its effects on the incidence of diabetes in NOD mice. The newly expressed I-Ak molecule was recognized as an alloantigen by the T lymphocytes of normal NOD mice as shown by mixed lymphocyte reaction (MLR). The levels of endogenous I-Ag7 expression on peripheral blood lymphocytes were not affected by the transgene expression. Transgenic NOD mice were completely resistant to spontaneous diabetes, but the treatment by cyclophosphamide, which effectively induces diabetes in normal NOD mice, caused diabetes, although at a much lower incidence than that of normal NOD mice. On the basis of these findings, we discuss the role of I-Ak in the prevention of diabetes in NOD mice.

Animals↗
PubMed1994

[A study of diagnostic scale in borderline personality disorder that was synthesis of symptomatic and personality structural element].

The diagnostic criteria for BPD such as the DSM-III(-R) and DCR, based on polythetic format for prototypal categories, has not always been able to result in accurate clinical diagnosis of BPD. Reasons posited for this were that DSM-III(-R) criteria consist of symptom items based on descriptive phenomenology, even for Axis II personality diagnosis, and that descriptions of the criteria were vague because of the standardization of vocabulary which aimed at improved inter-rater reliability. With the polythetic "yes/no" format, diagnosis was influenced by the determination of only one item; furthermore, different combinations of items yielding a heterogeneous membership might lead to the same diagnosis. It was, therefore, considered difficult to perform an accurate diagnosis of BPD in clinical practices using the existing general diagnostic criteria, and it was realized that the development of new diagnostic criteria for BPD was necessary. For those reasons, we generated a Clinical BPD Scale (CBS) as diagnostic evaluation scale of BPD with considering advantages for clinical use. This reconstituted some features of BPD which have been reported by many researchers, synthesizing symptomatic elements and personality structural elements. CBS is composed of four clusters, Two of these four clusters are evaluated by four grade anchor points which are provided for the rating of the severity of symptoms, and that are illustrated on the radarchart for comprehensive evaluation of the severity of the disorder. CBS was confirmed to have a high degree of validity, and achieved a satisfactory degree of inter-rater reliability by ANOVA ICC, and it has been found in application of CBS to several cases in the clinical practice that the degree of severity of each symptom could be clarified and differential diagnosis was possible with this diagnostic scale. Furthermore, the outcome of treatment could be confirmed at any time during the clinical follow up. In addition, through the dimensions, it is possible to grasp the severity, and further, through spectrum and hierarchy. We considered diagnostic area of BPD and its position by CBS correlating the other closely related disorders.

Borderline Personality Disorder↗
PubMed1993

Plasminogen-binding protein associated with the plasma membrane of cultured embryonic rat neocortical neurons.

To investigate the receptor-like molecule(s) for plasminogen (PGn) on the neuronal surface, the properties of binding of PGn to the plasma membrane of cultured embryonic rat neocortical neurons were investigated. [125I]PGn was found to specifically bind to the plasma membrane depending on the incubation temperature and time. The binding was also affected strongly by ionic strength and slightly by Ca2+. Furthermore, ligand blotting analysis revealed that [125I]PGn binds to a major protein with an apparent molecular weight of 45 kDa among plasma membrane proteins. These results suggest that the 45-kDa protein is a PGn receptor-like molecule on the neuronal surface.

Animals↗
PubMed1993

Age-related deterioration in conditional avoidance task in the SAM-P/10 mouse, an animal model of spontaneous brain atrophy.

A novel inbred strain of mouse 'SAM-P/10' (Senescence Accelerated Mouse) is a model of age-related brain atrophy characterized by age-related loss and shrinkage of neurons in the cerebral neocortex. Age-related changes in learning and memory skills of SAM-P/10 mice were investigated using a newly developed conditional avoidance task in a T-maze. Comparisons were made with findings in the SAM-R/1 strain which shows a little loss and no shrinkage of neocortical neurons. Four-month-old SAM-R/1 and SAM-P/10 performed well during a 10-day training schedule of the conditional avoidance task. SAM-R/1 mice over 17 months of age were slower learners than younger SAM-R/1 mice but reached nearly the same high percentage avoidance as seen in the 4-month-old mice during the last 4 days of the schedule. Performance of the SAM-P/10 mice gradually worsened with aging and 10- to 12-month-old SAM-P/10 mice could not reach the percentage avoidance seen with the 4-month-old mice, even after the 10-day training. When the mean percentage of successful avoidance or escape behavior on every training day was plotted, the curves were much the same for both SAM-R/1 and SAM-P/10 mice, of any age. These results show that aged SAM-P/10 mice retained the left-right turning discrimination in the T-maze and lost the ability to predict the forthcoming aversive shock by associating conditioned stimulus and unconditioned stimulus.

Aging↗
PubMed1993

Type C Niemann-Pick disease in a boxer dog.

Pathological and biochemical studies were performed on a 9-month-old boxer dog with progressive neurological abnormality. Histological examination revealed marked neuronal storage throughout the central nervous system and histiocytic storage in the reticuloendothelial system. Ultrastructurally, the neuronal storage consisted of accumulation of concentric membranous inclusions and clusters of dense bodies. The biochemically unesterified cholesterol content was high in the liver and spleen. The brain showed increased levels of lactosylceramide and two gangliosides, GM3 and GM2. These findings indicate that this dog was affected with a heterogeneous lipid storage disease similar to the human Niemann-Pick type C disease.

Animals↗
PubMed1993

Improvement of left ventricular function after renal transplantation in a patient with uremic cardiomyopathy: report of a case.

The improvement of heart function in a patient on hemodialysis with dilated cardiomyopathy by renal transplantation is herein reported. The patient was a 35-year-old woman. Hemodialysis had been initiated 3 months before, but she experienced difficulty with hemodialysis maintenance and exhibited congestive heart failure. The ejection fraction (EF) was decreased to 36.6% in the echocardiogram, and an intracardiac biopsy of the right ventricle showed myofiber degeneration and interstitial edema upon examination by light microscopy. She then underwent renal transplantation, and the postoperative recovery was almost uneventful. The cardiothoracic ratio decreased rapidly to around 40% after 1 month, although her body weight increased. The ejection fraction increased to 50% in the echocardiogram. An intracardiac biopsy of the right ventricle revealed disoriented myofibers, but myofiber degeneration improved, and no interstitial edema was present upon examination by light microscope. The electron microscopy showed that the intracellular edema had disappeared and other degenerative changes had also improved. The patient was discharged on the 44th postoperative day, with a serum creatinine of 1.3 mg/dl.

Adult↗