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Biomedical subjects

A Ishikawa

Publications and source records attributed to A Ishikawa.

At least 127 records · Page 7Linked to original sources

A deficiency of coproporphyrinogen III oxidase causes lesion formation in Arabidopsis.

We isolated an Arabidopsis lesion initiation 2 (lin2) mutant, which develops lesion formation on leaves and siliques in a developmentally regulated and light-dependent manner. The phenotype of the lin2 plants resulted from a single nuclear recessive mutation, and LIN2 was isolated by a T-DNA tagging approach. LIN2 encodes coproporphyrinogen III oxidase, a key enzyme in the biosynthetic pathway of chlorophyll and heme, a tetrapyrrole pathway, in Arabidopsis. The lin2 plants express cytological and molecular markers associated with the defense responses, usually activated by pathogen infection. These results demonstrate that a porphyrin pathway impairment is responsible for the lesion initiation phenotype, which leads to the activation of defense responses, in Arabidopsis. Lesion formation was not suppressed, and was even enhanced when accumulation of salicylic acid (SA) was prevented in lin2 plants by the expression of an SA-degrading salicylate hydroxylase (nahG) gene. This suggests that the lesion formation triggered in lin2 plants is determined prior to or independently of the accumulation of SA but that the accumulation is required to limit the spread of lesions in lin2 plants.

Amino Acid Sequence↗

Comparative FISH mapping of human cDNA clones to chromosomes of the musk shrew (Suncus murinus, Insectivora).

Forty-one cDNA clones of human functional genes were newly mapped to chromosomes of the musk shrew (Suncus murinus, Insectivora) by fluorescence in situ hybridization, and a comparative cytogenetic map of 51 genes, including 10 genes reported in our previous study, was constructed between human (HSA) and musk shrew (SMU) chromosomes. In this comparative map, the 51 genes localized to human autosomes, except HSA 8, 16, and 20, were mapped to 15 shrew autosomes, except SMU 4, 16, 17 and 18. Twelve conserved segments were identified between human and shrew chromosomes, and six segments among the musk shrew, human, and mouse. Our results defined the presence of at least one inversion and several interchromosomal rearrangements that occurred during evolution after the two species diverged from a common ancestor. Localization of three major histocompatibility complex (MHC) genes to shrew chromosome 3 suggested that the MHC genes of the musk shrew are located in a cluster on chromosome 3. The cytogenetic map constructed in this study is the first cytogenetic map with many functional genes in insectivore species. This approach provides clues for clarifying the chromosomal evolution in this order.

Animals↗

In vitro growth of mouse ovarian preantral follicles and the capacity of their oocytes to develop to the blastocyst stage.

Two groups of mouse preantral follicles with diameters of 125-150 and 151-175 microm were cultured individually for 6 days in a medium supplemented with FSH and fetal calf serum to determine their in vitro growth characteristics. Their oocyte capacity for maturation and development to the blastocyst stage following in vitro fertilization was also assessed. Antral formation rate at the end of culture was higher in the follicles of 151-175 microm (89%) than 125-150 microm (76%). The timing of antrum formation was different between the two follicle categories: most 151-175 microm follicles formed antra earlier than 125-150 microm follicles (days 4 and 5 vs. 5 and 6). However, follicle diameters at the time of antrum formation were the same regardless of the initial size and the culture period. Maturation rates of the oocytes derived from both categories of in vitro grown follicles (70 and 62%) were not different from those of oocytes from in vivo grown follicles (74%). The in vitro derived oocytes, however, showed less cleavage (30 and 35%) than the in vivo derived oocytes (89%). Although the oocytes from both follicle categories developed to the morula stage after in vitro fertilization, blastocysts were only obtained from oocytes derived from the 151-175 microm category. These results demonstrate that an individual follicle culture system using a medium with FSH and fetal calf serum supports in vitro growth of mouse preantral follicles with diameters of 151-175 microm to the preovulatory stage, and that their oocytes have the capability to develop to the blastocyst stage.

Animals↗

Quantitative trait loci for body weight in the intercross between SM/J and A/J mice.

We performed a genome-wide quantitative trait locus (QTL) analysis of body weight at 10 weeks of age in a population of 321 intercross offspring from SM/J and A/J mice, progenitor strains of SMXA recombinant inbred strains. Interval mapping revealed two significant QTLs, Bwq3 (body weight QTL3) and Bwq4, on Chromosomes (Chrs) 8 and 18 respectively, and five suggestive QTLs on Chrs 2, 6, 7, 15 and 19. Bwq3 and Bwq4 explained 6% of the phenotypic variance. The SM/J alleles at both QTLs increased body weight, though the SM/J mouse was smaller than the A/J mouse. On the other hand, four of the five suggestive QTLs detected had male-specific effects on body weight and the remainder was female-specific. These suggestive QTLs explained 5-6% of the phenotypic variance and all the SM/J alleles decreased body weight.

Alleles↗

Osteoporosis, bone turnover and hypogonadism in elderly men with treated leprosy.

In male hypogonadism associated with bone loss, it is important to determine whether bone loss continues with ageing and an increased risk of fracture. We studied bone metabolism in 86 male leprosy patients, who were classified according to the presence or absence of osteoporosis. Osteoporosis was present when men had lumbar compression fractures or a mean BMD-2SD that of normal Japanese men in each age decade. Four men had fractures. Serum concentrations of 1,25-dihydroxyvitamin D and high-sensitivity parathyroid hormone were almost normal in both groups, whereas free testosterone and oestradiol were significantly lower in the osteoporosis group than in the non-osteoporosis group (free testosterone: P < 0.01, oestradiol: P < 0.05). The urinary concentrations of pyridinoline and deoxypyridinoline, as a marker of bone absorption, were significantly higher in the osteoporosis group than in the non-osteoporosis group (pyridinoline: P < 0.01, deoxypyridinoline: P < 0.01). The serum concentration of osteocalcin, a marker of bone formation, was significantly higher in the osteoporosis group than in the non-osteoporosis group (P < 0.01). Elevated concentration means that bone repair is increased possibly because of compensation mechanisms for increased bone loss. In the osteoporosis group, hypogonadism occurred, and high bone turnover continued even in older men. We recommend clinical studies of treatment such as replacement therapy to prevent bone loss and increasing risk of fractures in older men with leprosy.

24,25-Dihydroxyvitamin D 3↗

[A case of pheochromocytoma with von Recklinghausen's and review of 67 Japanese cases].

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.

Adrenal Gland Neoplasms↗

Relationship among growth, steroid production and immunolocalization of transforming growth factor-beta 1 in the normally developing mouse follicles cultured in vitro.

This study examined the relationship among growth, steroid production and transforming growth factor-beta 1 (TGF-beta 1) immunolocalization in the mouse follicles cultured in vitro to evaluate the hypothesis that normally developing follicles should express TGF-beta 1 in the granulosa cells around the time of antrum formation. Preantral follicles with 151-175 microns (large category) and 125-150 microns (small category) of initial diameters were used as models for normal and retarded follicles, respectively. Growth rate and timing of antrum formation in both categories were comparable to those of in-vivo grown follicles. At the time of antrum formation, follicular diameters were similar between the two follicle categories; however, antral follicles from the large category showed larger number of granulosa cells, higher estradiol production and proportion of follicles with TGF-beta 1 positive granulosa cells. Two days after antrum formation, there were no differences in the number of granulosa cells and the proportions of follicles with TGF-beta 1 positive granulosa or theca cells between the two categories. Temporal association in large follicles between the increase in estradiol production and proportion of follicles with TGF-beta 1 positive granulosa cells at the time of antrum formation supports our hypothesis. Furthermore, this study demonstrated the usefulness of the follicle culture system in the investigations of follicular physiology.

Animals↗

[A case of suprasellar hemangioblastoma with thoracic meningioma].

Supratentorial hemangioblastoma is encountered very rarely, with only about 110 cases reported. This report concerns a case of a suprasellar hemangioblastoma associated with thoracic meningioma. A 62-year-old man was admitted with visual disturbance of the left eye. T2-weighted magnetic resonance imaging (MRI) showed a high signal intensity mass in the suprasellar region without perifocal edema. T1-weighted MRI with gadolinium showed a homogeneously enhanced mass. The angiogram revealed remarkable tumor staining originating from the right and left internal carotid arteries (ICA) and the left external carotid artery (ECA). On the basis of the pre-operative diagnosis of tuberculum sellae meningioma, total tumor removal was performed. Photomicrographs of the specimen showed numerous capillaries divided by stroma cells. Positive immunostaining for factor VIII related antigen (F VIII RAg) was observed in endothelial cells, but immunostaining for epithelial membrane antigen (EMA) was not observed in any cells. A diagnosis of suprasellar hemangioblastoma was made on the basis of these findings. The patient suffered paraparesis on the postoperative seventh day. Since MRI showed a thoracic tumor, a second total tumor removal was performed. The tumor was diagnosed as a meningothelial meningioma. The patient was discharged without evidence of new neurological deficits. Our experience shows that, when a mass is vascularized in the cerebral hemisphere, the possibility of hemangioblastoma needs to be taken into consideration.

Hemangioblastoma↗

Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti.

The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.

ATP-Binding Cassette Transporters↗

Anomalous substituent effects in the bischler-napieralski reaction of 2-aryl aromatic formamides

Treatment of some 1-naphthylformamides (or formanilides) possessing a 2,4,5-trioxygenated phenyl substituent at the 2-position with POCl(3) caused an unprecedented carbon insertion reaction into a benzene ring, producing 7-5 ring (azaazulene) systems as valence isomers of isoquinoline skeletons. Precise examination of this abnormal Bischler-Napieralski reaction (BNR) using various substrates led to the following scope and limitations: (i) the 7-5 ring systems were constructed when either 2-alkoxy-4, 5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a starting substrate; (ii) in the former case the formyl carbon was inserted into the C(1)-C(6) bond of the 2-phenyl group, and normal isoquinoline cyclization competed with an abnormal carbon insertion reaction; (iii) the presence of a hydroxy group at the 2'-position as in the latter cases caused exclusive carbon insertion, in which alternative C(1)-C(2) insertion products were quantitatively formed; (iv) 3, 6-dimethoxy-2-hydroxyphenyl-substituted formanilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produced an indole-pyrone as an abnormal BNR product. Theoretical approaches using the PM-3 method indicated that these abnormal BNRs could be triggered by ipso attack at the 1'-position yielding spiro intermediates. Ring cleavege of the six-membered ring in the spiro intermediates to a ketene function followed by recyclization was proposed for the 2'-hydroxy-directed abnormal BNRs leading to the C(1)-C(2) insertion product or the indole-pyrone derivative.

Journal Article↗

Learning deficiency and alterations in acetylcholine receptors and protein kinase C in the brain of senescence-accelerated mouse (SAM)-P10.

The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. A novel inbred SAMP10 has shown age-related brain atrophy and learning deficiency. In the present study, we investigated the changes in learning ability and in ligand binding with muscarinic acetylcholine (mACh) receptors, alpha adrenoceptors and protein kinase C in SAMP10. In Morris's water maze task, in a control strain of SAMR1 at 9 months, the escape latency and path length decreased with increasing trial days, in contrast, escape latency and path length did not decrease in SAMP10. These results indicate that SAMP10 exhibits learning deficiency. The ligand binding activity of mACh receptors decreased in the hippocampus of SAMP10 and the protein kinase C level in the hippocampus of SAMP10 was lower than that of SAMR1. On the other hand, there was no significant difference between SAMR1 and SAMP10 regarding ligand binding activity of alpha(1) and alpha(2) adrenoceptors. Thus, a reduction of mACh receptors and protein kinase C in the brain seems to underlie dysfunction of learning and memory in SAMP10.

Aging, Premature↗

Expression of lbx1 involved in the hypaxial musculature formation of the mouse embryo.

Somites are the source of hypaxial musculature including skeletal muscles of the limb, tongue, and trunk. To get insight into the function of mouse Lbx1 homeobox gene in early somitic mesoderm differentiation, in situ hybridization analyses were performed. At the 4-6 somite stage (8 dpc), Lbx1 was first expressed in the lateral portion of the epithelial somite and dermomyotomal epithelium. This was in contrast to the expression of myf-5 in the medial region of the somite. The lateral expression of Lbx1 in somitic mesoderm then occurred regionally along the anterior-posterior body axis. Later, at 10 dpc (stage 1 of limb bud development), Lbx1-positive migrating cells originated in the lateral dermomyotomal lips at occipital, forelimb, and hindlimb levels. They also expressed Pax-3 and c-met, known as markers of the migrating limb muscle precursor cells. In stage 4 hindlimb bud (11.5 dpc), the dorsal and ventral muscle precursor populations expressed Lbx1. In stage 8 forelimb buds (12.5 dpc), Lbx1 expression was reduced in the proximal muscle masses, where the high expression of myogenin accompanying muscle differentiation was detected. These results suggest that mouse Lbx1 might be involved in the commitment or determination of a muscle cell subpopulation during hypaxial musculature development. J. Exp. Zool. 286:270-279, 2000.

Animals↗

An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene.

We report the neuropathologic and genetic features of a 70-year-old man with autosomal-recessive juvenile parkinsonism (AR-JP). At the age of 32 years, he developed a dystonic gait, followed by hand tremor, rigidity, bradykinesia, and impaired postural reflex. Levodopa was effective in ameliorating these symptoms. Pathologic examination of autopsy specimens from this patient revealed loss of pigmented neurons and gliosis in the substantia nigra pars compacta (SNPC), being most pronounced in the medial and ventrolateral regions, and locus ceruleus (LC). The melanin content of the remaining SNPC neurons was low. This feature was less marked in the LC. There were no Lewy bodies, as confirmed by immunostaining for alpha-synuclein. An additional, significant finding in this patient was neuronal loss and fibrillary gliosis in the substantia nigra pars reticulata; this feature has not been reported previously in AR-JP. Gene analysis revealed that this autopsied patient and his siblings had the parkin gene mutation (homozygous exon 4 deletion) that is responsible for the disease.

Aged↗

Lipoblastoma with aberration in the long arm of chromosome 8.

We report a case of lipoblastoma in a 6-month-old girl with a new chromosomal aberration, 46, XX, der (2) add (2) (p23) del (2) (q33), add (8) (q1?). In addition to the patient's age and pathological features, aberration of long arm of chromosome 8 in lipoblastoma can assist the differential diagnosis from myxoid or well differentiated liposarcoma.

Biopsy↗