Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 235 records · Page 13Linked to original sources

PubMed1996

Functional assessment of patients with spinal cord injury: measured by the motor score and the Functional Independence Measure.

There is some information about the Functional Independence Measure (FIM) score of patients with spinal cord injury (SCI), but there are a few publications dealing with the relationship between the FIM score and the motor score of the American Spinal Injury Association (ASIA). We have studied the relationship of all FIM items with the motor score, and reviewed the disability of patients with spinal cord injury in greater detail. The purpose of this study was to describe the characteristics of impairment and disability in patients with SCI, using the FIM and motor score of the ASIA. The subjects were 100 inpatients with SCI (Frankel A, B). Neurological level, days from the onset, and the FIM were examined. In addition to these items, the ASIA motor scores were calculated for 22 tetraplegic patients. We investigated the relationships among these various respects. We also examined the changes of the physical items of the FIM score (physical FIM) over time for 18 patients. The mean FIM scores of those with tetraplegia with C4, C5, C6, C7, C8 lesions, and those with paraplegia with above T5 levels, and those below T6 were 35, 61, 82, 90, 116, 114 and 114 respectively. The FIM score reached the plateau in approximately 10 months, 6 months and 3 months post-injury, in tetraplegia, paraplegia above T5 and that below T6 respectively. The FIM scores in C6 patients were widely distributed from 56 to 104. On the other hand, the ASIA motor score could subdivide C6 patients and related well to the FIM score. The mean FIM scores for each neurological level were similar to those previously reported, thus they appeared to be plateau scores. With regard to the motor score, we feel that it could reflect the disability of the patients better than considering the neurological levels alone. Also considering the changes in the physical FIM score over time within a year from the onset of the injury, there were differences in the ADL improvement patterns among patients with different neurological levels. It appears that timing of the highest physical FIM improvement for each neurological level can exist. Thus it is important not to delay the start of the rehabilitation of patients with spinal cord injury in proper time.

Activities of Daily Living↗

PubMed1996

Increases in calcium absorption with ingestion of soluble dietary fibre, guar-gum hydrolysate, depend on the caecum in partially nephrectomized and normal rats.

Effects of feeding soluble dietary fibre on apparent Ca absorption and the contribution of the caecum to Ca absorption were examined in five-sixths nephrectomized (NPX) and normal rats with or without caecectomy in four experiments. It is known that Ca absorption is lowered by renal failure. In the first experiment the amounts of femur Ca increased linearly with increasing dietary Ca up to 3.0 g Ca/kg diet in intact rats. Partial nephrectomy decreased apparent Ca absorption in rats fed on diets containing 3-0 and 4.5 g Ca/kg diet. In the NPX groups, Ca absorption in rats fed on the diet containing guar-gum hydrolysate (GGH; 50 g/kg diet; 3.0 g Ca/kg diet) was significantly higher than that in rats fed on a fibre-free diet, and the increase in Ca absorption with GGH feeding was completely abolished by caecectomy. Also, ingestion of GGH increased Ca absorption in normal rats, but not in normal, caecectomized rats. Mg absorption was also increased with GGH feeding and was decreased with caecectomy in NPX and normal rats. In experiments which used caecectomized rats, coprophagy was prevented with an anal cup to avoid re-ingestion of faecal Ca. We conclude that ingestion of the soluble dietary fibre, GGH, increased apparent Ca absorption in NPX and non-NPX rats, and the caecum was responsible for these increases in Ca absorption.

Animals↗

PubMed1996

Detection of apoptosis by in situ labeling in pilomatricoma.

Pilomatricoma is a benign epidermal appendage tumor with differentiation toward hair cortex cells. It is composed of varying percentages of basophilic cells, shadow cells, and transitional cells. Transitional cells seem to be apoptotic cells as evidenced by their morphological and ultrastructural characteristics. We investigated apoptosis in ten specimens of pilomatricoma by the transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. TUNEL-positive structures were detected in both transitional cell and amorphous debris zones, but not in either basophilic cell or shadow cell zones. In the transitional cell zone, apoptotic cells were found either in groups or bands, while in the amorphous debris zone, apoptotic bodies of varying sizes were seen diffusely. These findings indicate that transitional cells, due to the fact that they are dying cells, may not differentiate into the shadow cells. This view is supported by the facts that the transition of basophilic cells into the shadow cells is abrupt in some areas and that tumor cells, with or without ultrastructural characteristics of apoptosis, are found in the transitional cell zone. Furthermore, ultrastructural nuclear changes in shadow cells are different from those seen in apoptosis. Therefore, we propose that the name of transitional cells should be changed to "condensed cells." Although it has been conventionally though that basophilic cells in pilomatricoma differentiate directly and/or via transitional cells into shadow cells, we demonstrate that basophilic cells undergo two different processes. The first is differentiation directly into shadow cells, an the second is passage, via "condensed cells" (transitional cells), into the amorphous debris that results from tumor kinetics.

Apoptosis↗

PubMed1996

Cloning, expression, and mapping of UBE2I, a novel gene encoding a human homologue of yeast ubiquitin-conjugating enzymes which are critical for regulating the cell cycle.

From a human fetal-brain cDNA library we isolated a novel gene sharing significant homology with two yeast genes, UBC9 and hus5, which encode ubiquitin-conjugating enzyme 9 (UBC9). In yeast this protein is critical for normal mitosis, and seems to be closely involved in progression of G2 to M phase of the cell cycle. The human UBC9 (h-UBC9) cDNA, (gene symbol UBE2I), contained an open reading frame of 474 nucleotides encoding 158 amino acids. Its predicted peptide showed respectively 56% and 66% identity (75% and 82% similarity) with the products of UBC9 and hus5. Northern-blot analysis revealed expression of three transcripts, 6.4 kb, 3.3 kb, and 1.35 kb, in all human tissues examined. This gene, UBE2I, was mapped to chromosome band 16p13.3 by FISH.

Amino Acid Sequence↗

PubMed1996

Cloning, expression, and mapping of CKAPI, which encodes a putative cytoskeleton-associated protein containing a CAP-GLY domain.

From a human fetal-brain cDNA library we isolated a novel cDNA clone encoding a protein containing a CAP-GLY domain that is highly conserved among several cytoskeleton-associated proteins. The CAP-GLY domain is thought to be essential for their association with microtubules. The cDNA, designated CKAPI (for cytoskeleton-associated protein I, glycine motif) contained an open reading frame of 579 nucleotides encoding 193 amino acids. Northern-blot analysis revealed expression of three transcripts, 1.0, 3.4, and 4.6 kb in size, in all tissues examined. The 1.0-kb transcript was significantly higher in brain and heart than in other tissues. This gene was mapped by FISH to chromosome bands 19q13.11-->q13.12.

Amino Acid Sequence↗

PubMed1996

Cloning, expression and chromosomal mapping of a novel cyclophilin-related gene (PPIL1) from human fetal brain.

We isolated a human cDNA clone encoding a novel protein homologous to cyclophilins, specific cellular targets of cyclosporin A, which are conserved in species ranging from human to prokaryotes. This cDNA, designated hCyPX, contained an open reading frame of 498 nucleotides encoding 166 amino acids. Computer analysis indicated that its predicted amino acid sequence had 41.6%, 40.4%, and 39.2% homology to those of human, bovine, and Drosophila cyclophilins, respectively. Northern blot analysis indicated ubiquitous expression in adult human tissues, but most abundant expression in heart. Fluorescence in situ hybridization to human metaphase chromosomes localized this gene (PPIL1, peptidylprolyl isomerase [cyclophilin]-like 1) to chromosome bands 2p23.3-->p23.1.

Amino Acid Isomerases↗

PubMed1996

Cloning, expression pattern and mapping to 12p 13.2 --> p13.1 of CLAPS3, a gene encoding a novel clathrin-adaptor small chain.

From a human fetal-brain cDNA library we isolated a novel gene encoding a peptide homologous to clathrin-adaptor small chains in rat, mouse, and yeast. The cDNA, designated CLAPS3 (clathrin-associated/assembly/adaptor protein, small 3, 22 kDa), contained an open reading frame of 579 nucleotides encoding 193 amino acids. Northern-blot analysis revealed expression of a 1.35-kb transcript in all human tissues examined. This gene was mapped to chromosome bands 12p13.2 --> p13.1 by FISH.

Adaptor Protein Complex 3↗

PubMed1996

A frequent pathway to glomerulosclerosis: deterioration of tuft architecture-podocyte damage-segmental sclerosis.

Lesions in glomerular architecture include mesangial expansion, capillary ballooning, capillary unfolding and microaneurysm formation. Such lesions appear to develop in response to mechanical overextension. A frequent pathway to segmental glomerulosclerosis starts from capillary ballooning and unfolding. Podocytes supporting those deranged capillaries are exposed to increased mechanical stress. This may lead to podocyte injury terminating in detachments from the GBM. Naked GBM areas at peripheral capillary loops allow the attachment of parietal cells to the GBM, i.e. the formation of a tuft adhesion to Bowman's capsule. An adhesion has a strong tendency to progress to segmental sclerosis.

Animals↗

PubMed1996

Distributional change of alpha-tocopherol in the rat lens with age.

Concentration of alpha-tocopherol (alpha-Toc.) in the rat lens (1, 4 and 12 months old) was determined in single lenticular layers using gas chromatography and mass spectrometry. The highest concentration of alpha-Toc. in lens was found in the nucleus, followed by the deeper anterior and deeper posterior cortices, the shallow anterior and shallow posterior cortices, and the equatorial region. The topographic alpha-Toc. distribution in the lens did not differ between lenses of 1-, 4- and 12-month-old rats. A significant decrease of alpha-Toc. concentration was seen in lenses of 4- and 12-month-old rats compared to those 1 month old. Concentration and distribution in 4- and 12-month-old rat lenses were almost the same. The concentration of alpha-Toc. in the lens changes in relation to age.

Aging↗

PubMed1996

Effect of substrate on indirect immunofluorescence test for canine pemphigus foliaceus.

The effect of substrate on indirect immunofluorescence (IIF) tests for the detection of circulating autoantibodies was studied by examining sera from 14 canine pemphigus foliaceus patients, six sera with non-pemphigus dermatoses and ten normal dog sera against five different substrates from three species. These substrates included bovine esophagus, bovine nose, bovine tongue, monkey esophagus, and canine nose skin. Nine out of 14 (64.3%) sera from patients with canine pemphigus foliaceus showed intercellular space staining by indirect immunofluorescence using bovine esophagus as substrate. However, sera from nonpemphigus dermatoses and normal dog did not react with bovine esophagus. In other substrates, only bovine tongue showed 1/8 (12.5%) positive reaction at the intercellular space by sera from canine pemphigus foliaceus. Dog nose skin showed the intercellular space staining against ten of ten (100%) normal dog serum. Monkey esophagus showed the fluorescent deposit at the intercellular space in four of nine (44.4%) of pemphigus foliacues dog sera, however, four of ten (40%) of normal dog sera revealed nonspecificity intercellular staining. These results indicate that the sensitivity and the specifity of IIF test in canine pemphigus foliaceus depend on the substrate. The best substrate for detecting circulating autoantibody in canine pemphigus foliaceus patients among five different substrates was bovine esophagus because of its sensitivity and high specificity. The diagnosis of canine pemphigus foliaceus should be made on the basis of a combination of clinical signs, histopathology, direct immunofluorescence, and the detection of circulating autoantibody.

Animals↗

PubMed1996

[Single dose toxicity studies of calcipotriol (MC903) in rats and dogs].

A single dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, administered subcutaneously (s.c.) and percutaneously (p.c.) was studied in Slc:SD rats (s.c. and p.c.) and beagle dogs (s.c.). The LD50 values of MC903 were as follows: rats, 2.19 mg/kg in males and 2.51 mg/kg in females by s.c., and more than 15 mg/kg in both sexes by p.c.; dogs, more than 1.5 mg/kg in males by p.c. No sexual difference was noted in LD50 values of rats. Death of rats was observed from 1 to 3 days after administration by both routes. Dead animals showed decreases in body weight and locomotor activity, reddish tear, abnormal gait and dirty hair by both routes. Furthermore, dead animals administered by s.c. showed salivation, nasal discharge, piloerection, ptosis, diarrhea, urorrhea, nasal and vaginal bleeding, subnormal temperature, loose stool, cyanosis, irregular and deep respirations, clonic and tonic convulsions. Survival of rats showed similar signs to those of dead animals except for nasal discharge, nasal and vaginal bleeding, cyanosis, agonal respiration and convulsion. Discoloration of the kidney, white patch of the heart and a dilatation of the stomach wall were observed on macroscopic examinations. No mortalities were observed in dogs which showed vomiting, conjunctival congestion, circumoral and auricular reddenings, periblepharal purplish reddening, decreases in locomotor activity and defecation, emaciation, eye discharge, skin desquamation of treated area and an increase in respiration. On macroscopic examination, desquamation of the skin, reddening of the circumoral mucosa, pale gray yellow striations in renal tubules of the cortex and discoloration of the thyroid were observed. Histopathological findings revealed epidermal thickening with parakeratosis, fibrocytes, hypertrophy and hypersecretion of the sebaceous and sweat glands, formation of epitheloid glanulomas and infiltration of neutrophils in the subcutaneous tissues. Furthermore, moderate calcium deposits in the renal tubules, fatty cells and slight calcium deposits in interstitial tissues of the thyroid, and a cystic nest of an ectopic intestinal epithelium between muscle layers of the duodenum were observed at the highest dose. On the basis of results obtained in the present study, rats administered MC903 by s.c. or p.c. died probably due to the circulatory and renal disturbance resulted from effects of this drug on the heart and kidney.

Administration, Cutaneous↗

PubMed1996

[A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in rats].

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 4 weeks was studied in Slc:SD rats at doses of 4, 20 and 100 micrograms/kg/day as low, mid and high dose levels. 1. One male and female at high dose died probably due to stress and circulatory failure. One female at mid dose died with clonic convulsion considered to be results in attached error of a neck collar. Survival of rats showed reddish tear, reddening and desquamation of the skin at application site, and vocalization at all groups including control. Furthermore, abnormal gait, dirty hair, emaciation and opacity of the eyeball surface in both sexes were observed at high dose. 2. A decreased body weight and a slight increased water consumption in both sexes, and a decreased food consumption in males were observed at high dose. 3. An increased incidence of corneal opacity was noted significantly in both sexes as compared with control at high dose. Urinalysis revealed an increased Ca excretion in both sexes at more than mid dose, and lower pH in females at mid dose and in both sexes at high dose, and a decreased urinary volume in males at high dose. The increases of neutrophil and serum beta-globulin ratios in females, and serum Ca level in both sexes were observed at high dose. The increased mineralization of the cornea in males at mid dose and in both sexes at high dose, and of the Kidney in males at high dose were observed. At the skin of application site, cellular infiltration in the epidermis and dermis in both sexes at more than mid dose was observed. Furthermore, hyperplasia of the squamous cell in females, and hyperkeratosis in the epidermis and hypertrophy of the sebaceous gland in both sexes were observed at high dose. 4. After a 4-week recovery period, the changes related with application disappeared except for opacity of the eyeball surface and cornea, and mineralization of organs. 5. On the basis of results obtained in the present study, it is considered that 4 micrograms/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

Administration, Cutaneous↗

PubMed1996

A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in dogs.

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a 4-week recovery was studied in beagle dogs at doses of 0.04, 0.4 and 4 micrograms/kg/day. 1. In general conditions, reddening, desquamation, rash, and wet and hot skin were observed at the skin of application site at 4 micrograms/kg/day. 2. In urinalysis, a tendency to an increase in Ca level, was observed at 4 micrograms/kg/ day. In hematology, an increase in the segmented neutrophils and tendency to a decrease in the lymphocyte counts were observed at 4 micrograms/kg/day. In biochemistry of serum, an increase in gamma-globulin ratio, and decreases in A/G and albumin ratios were observed at 4 micrograms/kg/day. 3. In organ weights, tendency to decreases of the absolute and relative weights in the thymus was observed at 4 micrograms/kg/day. 4. Histopathological examination revealed squamous cell hyperplasia and hyperkeratosis at the skin of application site at 4 micrograms/kg/day. 5. The above changes disappeared after the 4-week recovery period and suggested that they were reversible. 6. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.

Administration, Cutaneous↗

PubMed1996

[A 26-week repeated subcutaneous dose toxicity study of calcipotriol (MC903) followed by a 5-week recovery test in rats].

A 26-week repeated subcutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 5 weeks was studied in Slc:SD rats at doses of 0.4, 2 and 10 micrograms/kg/day as low, mid and high dose levels. 1. No mortality during the experimental period was observed in both sexes of all groups including control. An increased incidence of opacity of the eyeball surface in males was noted at high dose. There were no difference in body weight and food consumption between control. An increased water consumption in both sexes was observed at high dose. 2. An increased incidence of the corneal opacity was noted significantly at high dose in both sexes compared with that observed in control. Urinalysis revealed the increased excretions of Ca at more than mid dose, and Na, Cl and IP in males at high dose, and an decreased urinary volume in females and lower pH in both sexes at high dose. An increased serum Ca level in males at mid dose and in both sexes at high dose, and an elevated ALP activity in males at high dose were observed. The increased weights of the kidney in males at more than mid dose and adrenal gland in both sexes at high dose were observed. The increased incidence of mineralization of the cornea and kidney was noted significantly in males at more than mid dose as compared with control. Dilatation of endoplasmic reticulum of distal tubular cells of the kidney in both sexes was observed at high dose on electron microscopic examination. 3. After a 5-week recovery period, the changes related with the treatment of MC903 almost disappeared except for mineralizations of the cornea and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 administered subcutaneously in both sexes of rats.

Adrenal Glands↗

PubMed1996

[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in rats].

A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in Slc:SD rats at doses of 0.8, 4 and 20 micrograms/kg/day as low, mid and high dose levels. 1. No mortality were observed in both sexes of all groups including control. An increased water consumption was observed in females at mid dose and in both sexes at high dose. 2. An increased incidence of the corneal opacity in males at mid dose and in both sexes at high dose was noted significantly as compared with that observed in control. Urinalysis revealed a slight increased urinary volume, increased excretions of Ca and IP, and lower pH in both sexes at more than mid dose. Levels of the serum IP in females and Ca in both sexes were elevated at high dose. 3. The increased weights of the kidney in males and adrenal gland in females were observed at high dose. The kidney in females at mid dose and in both sexes at high dose showed a higher incidence of mineralization than in control. Furthermore, osteosclerosis of the sternum and femur in both sexes, and hyperkeratosis of the skin at application site in females at high dose were observed. Electron microscopic examination revealed no abnormality in the liver and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.8 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

Administration, Cutaneous↗

PubMed1996

[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in dogs].

A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in beagle dogs at doses of 0.04, 0.4 and 4 micrograms/kg/day. 1. In general conditions, reddening, rash, desquamation, pruritus, wet and hot skin at 4 micrograms/kg/day, reddening, rash and desquamation at 0.4 microgram/kg/day, pruritus and desquamation at 0.04 microgram/kg/day, were observed at the skin of application site. 2. In urinalysis, an increase or a tendency to an increase in Ca level, were observed at 4 micrograms/kg/day. 3. Histopathological examinations revealed squamous cell hyperplasia and parakeratosis at the skin of application site in both sexes at 4 micrograms/kg/day. However, these findings were not shown at the skin of application site at 0.4 and 0.04 microgram/kg/day. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of beagle dogs.

Administration, Cutaneous↗

PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (1)--A fertility study in rats by subcutaneous administration].

Calcipotriol (MC903), an anti-psoriasic agent, was given subcutaneously at dose levels of 1, 5 and 25 micrograms/kg/day during the pre-pairing period (9 weeks prior to pairing in males and 2 weeks prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (day 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. 1. In the male 25 micrograms/kg group, opacity of the eyeball surface was observed, and depression of body weight gain, and decreases of body weight and food consumption, and increases in the weight of the kidney were statistically significant in comparison with vehicle controls. 2. In the female 25 micrograms/kg group, depression of body weight gain and food consumption were statistically significant in comparison with vehicle controls. 3. No changes in parameters of reproductive performance were seen in any dosed groups. 4. No changes in parameters of implantation performance were seen. There were no treated-related abnormalities in fetal mortality, weights of fetuses, and external, visceral and skeletal examinations. Based on there results, it is considered that in the present study the no-toxic dose levels of MC903 were 5 micrograms/kg/day for parents, 25 micrograms/kg/day for reproductive performance and fetal development.

Animals↗

PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (2)--A teratogenicity study in rats by subcutaneous administration].

Teratogenicity of calcipotriol (MC903), an anti-psoriasic agent, was studied. MC903 at doses of 6.25, 12.5 and 25 micrograms/kg/day were subcutaneously administered to pregnant Slc:SD rats from day 7 to 17 of gestation. 1. In animals administered 25 micrograms/kg/day MC903, food consumption decreased significantly and body weight gains lowered marginally. MC903 administered at any doses did not adversely affect female animals in regard to pregnancy, delivery and maternal behavior. 2. In fetuses, suppression of growth were noted at 25 micrograms/kg group. However, fetotoxicity and teratogenicity were not noted at all groups administered MC903. 3. In F1 pups, the postnatal growth, development, responses, behaviors, learning ability and reproductive ability were not influenced. Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were detected. 4. On the basis of results obtained in the present study, it is considered that the no-toxic doses level of MC903 are 12.5 micrograms/kg/day for pregnant animals and fetuses, 25 micrograms/kg/day for pups.

Abnormalities, Drug-Induced↗