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Biomedical subjects

A Ishikawa

Publications and source records attributed to A Ishikawa.

At least 163 records · Page 9Linked to original sources

Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism is a hereditary neurodegenerative disorder, usually beginning before the age of 40. We found three exonic deletions and two novel point mutations (Arg33Stop and Cys431Phe) in six families with autosomal recessive juvenile parkinsonism. In 1 family, in which an autosomal dominant mode of inheritance was suspected, multiple mutant alleles were identified. Although a wide range of ages at onset was observed, there was no correlation between age at onset and genotype.

Adolescent↗

[Penile metastasis from renal cell carcinoma: a case report].

Penile metastasis is rare. It occurs in the advanced stage of genitourinary cancer, with many other metastases in various organs. All 7 patients with penile metastasis of renal cell cancer, reported in the Japanese literature, died within a year. Our case was not the exception. A 69-year-old male presented with right flank pain and penile induration. Right renal cancer with liver invasion and multiple pulmonary metastases were found. Microscopic examination revealed a sarcomatous pattern. He died 4 months later.

Aged↗

Detection of small round structured viruses in stool specimens from outbreaks of gastroenteritis by electron microscopy and reverse transcription-polymerase chain reaction.

In testing 60 stool specimens small round structured virus (SRSV) particles were detected in 35 (58%) specimens from all 17 outbreaks of gastroenteritis by electron microscopy (EM), while SRSV genes were found in 36 (60%) specimens from 15 outbreaks by reverse transcription-polymerase chain reaction (RT-PCR) by use of 2 primer pairs. Specimens from 2 outbreaks were found SRSV particles-positive by EM but SRSV genes-negative by RT-PCR. EM remains the basic examination method for diagnosis of SRSV agents.

Caliciviridae Infections↗

[Wearing-off phenomenon--neurological approach].

The mechanism of the wearing-off phenomenon and the method of how to control it by means of anti-parkinsonian medications is described. To control the wearing-off phenomenon, it is useful to administer L-dopa before eating because absorption of L-dopa is less when competing with amino acids. Administration of L-dopa four or five times a day is also useful. Dopamin agonists(e.g., bromocriptine, pergolide, talipexole, and cabergoline), and monoamine oxidase inhibitors(e.g., selegiline) control the wearing-off phenomenon, and may also suppress its occurrence. As a specific method for controlling the wearing-off phenomenon, continuous administration of anti-parkinsonian drugs by the intra-alimentary tract or a subcutaneous injection is useful. It is important to avoid early wearing-off phenomenon when treating patients with Parkinson's disease.

Antiparkinson Agents↗

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.

Aged↗

Cell death by 1-chloro-2,4-dinitrobenzene, an inhibitor of thioredoxin reductase and its dual regulation by nitric oxide in rats.

Thioredoxin (Trx), the oxidized form of which is converted to a reduced form by Trx reductase, regulates cell proliferation and survival. We investigated the effect of 1-chloro-2,4-dinitrobenzene (DNCB), an inhibitor of Trx reductase, on cell death in neuronal PC12 cells and rat glial cells. In both types of cells, culture with DNCB for 4 h stimulated lactate dehydrogenase (LDH) leakage. LDH leakage by DNCB was inhibited by an inhibitor of caspases. Addition of 2,2-(hydroxynitrosohydrazino)bis-ethanamine, of which 50% decays and releases nitric oxide (NO) in 21 h, inhibited DNCB-induced LDH leakage. Addition of 10 microM N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC-12), of which 50% decays and releases NO in 100 min, inhibited DNCB-induced LDH leakage, although 0.2 mM NOC-12 enhanced the leakage in PC12 cells. These findings suggest that DNCB induces cell death of neuronal and glial cells accompanied by caspase(s) activation. NO inhibits DNCB-induced cell death in both types of cells, although excess NO showed a toxic effect.

Amino Acid Chloromethyl Ketones↗

Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome.

BACKGROUND: Acute rejection (AR) of the transplanted kidney has been identified as the major risk factor for the development of chronic rejection and immunological graft loss. However, the clinical presentation and response to AR therapy can vary considerably between recipients. METHODS: We studied the first AR episode in 201 kidney-only recipients transplanted between January 1987 and June 1998 who were biopsied between April 1993 and June 1998 and were graded using the Banff schema. All patients received cyclosporine-based immunosuppression. There were 134 cadaver donor (66.7%) and 67 live donor (33.3%) recipients followed for a mean of 46.2 (range 4-128) months. All Banff grade 1-3 and 40/78 borderline (BL) cases were treated for rejection after biopsy. These patients were compared with a contemporaneous control population who did not experience AR. Demographic risk factors associated with graft loss were identified in both univariate and multivariate analysis. Daily (0-18) serum creatinine (SCr) values during and after the AR were plotted for each patient to generate curves and calculate area under the serum creatinine versus time curve (mg/dl/day). Four response patterns to treatment were identified according to the velocity of % increase (V1) and decrease (V2) of serum creatinine. These were identified as rapid rise and fall (n=62); rapid rise and slow fall (n=43); slow rise and fall (n=55); and slow rise and rapid fall (n=41). Kaplan-Meier graft survivals were compared between the groups. RESULTS: Any Banff grade was associated with increased risk for graft loss (P=0.0001). However, no significant differences were observed between the Banff BL and B1-3 groups, or among those BL patients who were treated or remained untreated for AR. Multivariate analysis identified a black recipient (P=0.03, risk ratio 2.0) and area under the serum creatinine versus time curve (P=0.0001, risk ratio 3.2) as significant risk factors for graft loss. The AR response pattern RS resulted in a significantly (P=0.0072) diminished 5-year graft survival (45%) compared with the other groups. Serum creatinine pattern, but not Banff grade, was also a significant (P=0.025) predictor of re-rejection. CONCLUSIONS: These data suggest that all Banff grades, including BL, carry a significant risk for graft loss, and the initial response to antirejection therapy can predict long-term graft outcome. They support the practice of treating AR promptly and definitively and suggest that the RS subgroup of rejecting grafts could be targeted for additional antirejection therapy. This subgroup can be identified by 10 days of AR therapy, and should be the subject of further study.

Acute Disease↗

Suppression of the heterotrimeric G protein causes abnormal morphology, including dwarfism, in rice.

Transgenic rice containing an antisense cDNA for the alpha subunit of rice heterotrimeric G protein produced little or no mRNA for the subunit and exhibited abnormal morphology, including dwarf traits and the setting of small seeds. In normal rice, the mRNA for the alpha subunit was abundant in the internodes and florets, the tissues closely related to abnormality in the dwarf transformants. The position of the alpha-subunit gene was mapped on rice chromosome 5 by mapping with the restriction fragment length polymorphism. The position was closely linked to the locus of a rice dwarf mutant, Daikoku dwarf (d-1), which is known to exhibit abnormal phenotypes similar to those of the transformants that suppressed the endogenous mRNA for the alpha subunit by antisense technology. Analysis of the cDNAs for the alpha subunits of five alleles of Daikoku dwarf (d-1), ID-1, DK22, DKT-1, DKT-2, and CM1361-1, showed that these dwarf mutants had mutated in the coding region of the alpha-subunit gene. These results show that the G protein functions in the formation of normal internodes and seeds in rice.

Base Sequence↗

Osteoporosis in male and female leprosy patients.

We measured the bone mineral density (BMD) of 353 leprosy patients (197 males 50-89 years old, average age 70.2; and 156 females 53-90 years old, average age 72.9) and serum levels of free testosterone (FT) in 81 males. The BMD of the lumbar vertebrae (L2-L4), diaphysis of the radius (1/3 radius), and the neck of the femur (neck) was measured using DXA (QDR 4500). The BMD of -2.5 SD YAM (young adult mean) in Japanese men and women was used as the cutoff value for osteoporosis in the respective genders: BMD of L2-L4, 0.751 g/cm2 (male), 0.747 g/cm2 (female); 1/3 radius, 0.655 g/cm2 (male), 0.550 g/cm2 (female); neck, 0.581 g/cm2 (female). The percentages of males with osteoporosis were 31.3% in the 50th, 32.9% in the 60th, 44.9% in the 70th, and 40.7% in the 80th decade at L2-L4. Similarly, the percentages were 33.3%, 58.3%, 74.3%, and 75.0%, respectively, at 1/3 radius. Among females, the percentages were 22.2%, 41.3%, 44.9%, and 68.8%, respectively, at L2-L4; 0%, 42.9%, 89.5%, and 78.6%, respectively, at 1/3 radius; and 11.1%, 38.6%, 67.7%, and 84.6% respectively, at neck. FT in men ranged from almost 0 to normal at each decade and BMD levels were significantly correlated with FT in all three regions of the skeleton (P < 0.0001). More than 30% of osteoporosis was found at each decade and FT may be one of the main factors affecting BMD in male leprosy patients.

Aged↗

A preventive effect of a selective endothelin-A receptor antagonist, S-0139, on the erythropoietin-induced reduction of the renal cortical blood flow.

We have confirmed that renal cortical blood flow (RCBF) is significantly decreased by recombinant human erythropoietin (EPO). Endothelin-1 (ET(1)) is thought to be a mediator because its level increased significantly when EPO was administered. The present study was performed to clarify the effect of a selective ET-A receptor antagonist, S-0139, on EPO-induced RCBF reduction. Ten-week-old male Wistar rats, weighing about 250 g, were divided into five groups. Group 1 (n = 5), a control group, received normal saline solution (NSS). Group 2 (n = 5) received 200 U/kg body weight (BW) per hour of EPO. Group 3 (n = 5) received 400 U/kg BW per hour of EPO. Group 4 (n = 5) received both 200 U/kg BW per hour of EPO and 4 mg/kg BW per hour of S-0139. Group 5 (n = 5) received both 200 U/kg BW per hour of EPO and 40 mg/kg BW per hour of S-0139. Drugs were administered intravenously via the right femoral vein using a microinfusion pump for 4 h under urethane anesthesia. The RCBF was measured every 30 min by the hydrogen gas clearance method. When the 4 h had elapsed, the concentrations of plasma creatinine (Cr), ET1 and renin activity (RA) were measured. Compared with group 1, groups 2 and 3 showed significant (P < 0.001) decreases of RCBF, while the ET1 levels of these two groups increased significantly (P < 0.03). The ET1 of groups 4 and 5 also increased significantly (P < 0.03), however, the RCBF of these two groups did not decrease. No significant differences were observed in either Cr or RA between the five groups. EPO induces ET(1) secretion. The reduction of RCBF is due to ET(1)-derived vasoconstriction. S-0139 has potential for preventing EPO-induced and ET(1)-mediated RCBF reduction.

Animals↗

Quantitative trait loci for growth traits in C57BL/6J x DBA/2J mice.

Quantitative trait loci (QTLs) for body weight and tail length are mapped in an F2 population of 927 C57BL/6J x DBA/2J mice. We test the concordance between the locations of the mapped QTLs with those detected by changes of marker frequency under artificial selection in a previous experiment with the same base population. The directions of effects of the QTLs are generally in agreement, and in many cases significant QTLs are found in similar map positions, but there are also discrepancies between the two experiments. There are indications of age-specific QTL effects on growth. For body weight traits, the genetic variation in the F2 appears to result from many loci with relatively small effects. For tail length at 10 weeks, however, a single QTL on Chromosome (Chr) 1 with a peak LOD score of approximately 33 contributes most of the genetic variation detected, changes the trait value by about 6%, and explains about 20% of the phenotypic variance of the trait.

Animals↗

A non-familial Huntington's disease patient with grumose degeneration in the dentate nucleus.

We report a non-familial Huntington's disease (HD) patient presenting with increased levels of protein and IgG in his cerebrospinal fluid (CSF), antineuronal antibody in his serum and CSF, Purkinje cell and granule cell degeneration in the cerebellum, and grumose degeneration in the dentate nucleus, in addition to typical HD findings. This patient showed an expanded CAG repeat in the HD gene, and provides new information on the clinical and neuropathologic varieties of HD.

Aged↗

Efficacy of sulfamethoxazole-trimethoprim administration in the prevention of Pneumocystis carinii pneumonia in patients with connective tissue disease.

The efficacy and adverse effects of prophylactic administration of Sulfamethoxazole-Trimethoprim (ST) for Pneumocystis carinii Pneumonia (PCP) were assessed in patients with connective tissue diseases (CTD). Eighty-four patients who were receiving more than 40 mg/day of prednisolone were entried in the present study. Patients with at least one of the two PCP risk factors (interstitial pulmonary fibrosis and lymphopenia), were administered either one (11 patients) or two (26 patients) ST tablets/day. The remaining 47 patients who did not receive ST served as the controls. Although PCP was detected in 4.3% of the patients in the no-ST group, none of the patients who received ST developed PCP. Five of these 26 patients who received two tablets of ST/day, experienced adverse reactions. However, no adverse reactions were detected in the patients who received one tablet of ST/day (p < 0.05). Abnormal laboratory data were obtained for 10 (38.5%) of the patients who received two tablets of ST/day and for 4 (36.4%) of the 11 patients who received one tablet of ST/day. The results of the present study suggest that the prophylactic administration of one tablets of ST in patients with CTD that have at least one of the two PCP risk factors is effective in preventing PCP.

Adult↗

In vivo and in vitro trimethadione oxidation activity of the liver from various animal species including mouse, hamster, rat, rabbit, dog, monkey and human.

Trimethadione (TMO) has the properties required of a probe drug for the evaluation of hepatic drug-oxidizing capacity and, in this study, we have summarized the in vivo and in vitro metabolism of TMO in various animal species including mouse, hamster, rat, rabbit, dog, monkey and human. In the in vivo study, the plasma TMO level was measured after intravenous or oral (human) administration of TMO at a dose of 4 mg/kg to various animal species. The rate of TMO metabolic clearance in these animal species in vivo was in the order mouse > hamster > rat > rabbit > dog > monkey > human. In the in vitro study, species differences were observed in the cytochrome P450 (P450) content and drug-oxidizing enzyme activity. The content of P450 was monkey> mouse > dog > rabbit > hamster > rat > human. On the other hand, TMO N-demethylation was in the order mouse > hamster > rat > rabbit > dog > monkey > human. There was a good correlation between the mean total body clearance of TMO (in vivo) and the mean TMO N-demethylase activity (in vitro) (y=1.7 x +0.11, r=0.965, P < 0.001). These results show that TMO is a probe agent with metabolic and pharmacokinetic characteristics making it attractive for the in vivo and in vitro characterization of metabolic activity in various animal species.

Animals↗

Delayed development of reflexes and hyperactive locomotion in the spontaneous mutant "waltzing" of the musk shrew, Suncus murinus.

The autosomal recessive mutation waltzing (wz), displaying abnormal circling and head-shaking behavior, has previously been reported in the musk shrew (Suncus murinus). Postnatal development of reflexes and locomotor patterns in an open arena were examined in wz/wz mutant shrews. The wz/wz shrews showed extreme developmental delays in surface-righting reflex and negative geotaxis until 10-16 days after birth, but both reflexes eventually recovered to the levels of +/wz normal. Nevertheless, the wz/wz adults exhibited bi-directional circling behavior 59 times, head-tossing behavior 22 times and horizontal head-shaking behavior 6 times more frequent than in the +/wz controls. Although the wz/wz adult shrews were extremely hyperactive with daily spontaneous locomotor activity exceeding 4-7 times control shrew activity, they appeared to have a normal circadian rhythm. This shrew mutant may therefore be useful as a model for hyperactivity syndromes in humans.

Animals↗

An odontometrical difference in the mandibular molars of two laboratory strains of the musk shrew, Suncus murinus, derived from Bangladesh and Tokunoshima Island of Japan.

We investigated an odontometrical difference in the mandibular molars (M1, M2, and M3) of two laboratory strains of the musk shrew (Suncus murinus) originating in Bangladesh (BAN strain) and Tokunoshima Island of Japan (TKU strain). We used skulls from two strains of shrews that were maintained under identical laboratory conditions. Mesiodistal and buccolingual crown diameters in the trigonid and talonid of the mandibular molars were measured with a measuring microscope, calibrated to 0.001 mm. The crown proportion was expressed by the crown indices calculated from the measurements. Size reduction was analyzed quantitatively according to the reduction index. All crown dimensions were significantly larger in BAN shrews than in TKU shrews (P < 0.01). Sexual differences were noted in the talonid dimensions, while interstrain differences were clearly evident in the trigonid dimensions. The crown indices in M1 showed the least interstrain difference of the three molars. The crown indices showed that TKU shrews had relatively larger buccolingual diameters and talonid diameters than BAN shrews, and the reduction indices showed that TKU shrews had relatively larger M2 and M3 than BAN shrews. To extract the variance components of tooth shape, a principal component analysis was performed after the variables were standardized. After Varimax rotation, each factor was interpreted. The first three factors accounted for 79.9% of all variances. The first component represented the mesiodistal crown proportion of the trigonid-to-talonid crown component. The second and third components represented the relative size of buccolingual diameters in the distal molars for M1. The principal component scores showed that TKU shrews had relatively larger talonids and distal molars than BAN shrews.

Animals↗

[A case of seronegative spondylarthropathy with iritis and retroperitoneal fibrosis].

In 1985 a 41-year old male visited a local hospital because of congestion in the bulbar conjunctiva, which was diagnosed as iritis. In August 1990, right coxalgia and arthralgia of metatarsophalangeal joints appeared, with recurrence of iritis. In October, stiffness in the hands and arthralgia of proximal interphalangeal joints also started. In July 1991, the right coxalgia worsened, resulting in walking difficulty. He was admitted to the Kitasato University Hospital. He presented with bilateral iritis, polyarthritis with limited ranges of motion and sacroilitis. The Schober's test was positive at 3 cm. Serological tests for rheumatoid factor and HLA-B 27 were negative. Abdominal computer tomographic scan revealed low density lesion around the aorta. PSL 10 mg was initiated, and iritis and arthritis remitted. Progression of the periaortic lesion was not observed during the subsequent 5 years. In this case, iritis preceded limited ranges of motion in the vertebrae and sacroilitis. From these findings, seronegative spondylarthropathy with peripheral arthritis was diagnosed. The periaortic lesion seen in this case probably corresponds to chronic periaortitis recently reported as a subset of idiopathic retroperitoneal fibrosis. The two lesions observed in the present case may be interpreted as caused by inflammation of the connective tissue initially either at the vertebrae or around the aorta, which had advanced to involve the other lesion.

Adult↗