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Biomedical subjects

T Nagaoka

Publications and source records attributed to T Nagaoka.

At least 19 recordsLinked to original sources
PubMed1996

Magnetic resonance imaging and pathologic studies on lateral fluid percussion injury as a model of focal brain injury in rats.

In this study, morphologic changes in brain lesions initiated by moderate lateral fluid percussion injury in rats were investigated chronologically using high-resolution magnetic resonance imaging (MRI) and histopathologic methods. Rats were subjected to moderate fluid percussion injury (average 2.80 +/- 0.48 atmospheres) over the exposed dura overlying the right parietal cortex. MRI obtained in vivo were compared with corresponding pathologic findings at 1, 6, and 24 h and at 3, 6, 14 and 80 days after injury. T2-weighted images showed scattered low-signal intensity in the injured cortex within a few hours after injury, whereas histologic findings revealed intraparenchymal hemorrhages. T2-weighted images of the ipsilateral cerebral cortex and/or corpus callosum showed a high-signal-intensity area 4 h after injury. The high-signal-intensity area became largest in size between 6 and 24 h, then declined gradually, and almost disappeared 14 days after injury. Histologic examination revealed pyknosis, retraction of the cell body of neurons with vacuolated neuropil in the corresponding regions 6 and 24 h after injury, and cystic necrosis 14 days after injury. The location and extent of these pathologic changes were depicted accurately by MRI in vivo. In the hippocampus, pyknosis and retraction of the cell body of pyramidal neurons were observed on the injured side 24 h after injury, and the number of neurons in the CA1 and CA2-CA3 regions decreased significantly on the same side by 14 days after injury. It is concluded that morphologic changes in the brain following experimental traumatic brain injury in rats are detectable in vivo by high-resolution MRI, and that MRI may be useful for the evaluation of treatment effects in experimental brain injury.

Animals↗
PubMed1995

Influence of high-fat diets on the occurrence of spontaneous uterine endometrial adenocarcinomas in rats.

The effects of high-fat diets on the spontaneous occurrence of uterine endometrial adenocarcinomas were examined in the Donryu rat. Ninety females at 6 weeks of age were equally divided into 3 groups. Animals in group 1 were fed a basal diet, while those in groups 2 and 3 received powdered basal diets containing 10% and 20% corn oil until 15 months of age, when all survivors were sacrificed. For sequential serum steroid assay and histological examination of sex organs, additional rats were fed diets containing 20% corn oil or without supplement. Body weight gain in group 3 was significantly increased, while in group 2 it was similar to that in the control. In both high-fat groups, calorie intake and weight of fat deposits in the abdominal cavity were significantly increased. The incidences of uterine adenocarcinomas in groups 2 and 3 were 18% (P < 0.05) and 7%, respectively, as compared to 0% in group 1. Severe hyperplasia (hyperplasia+++) also showed a non-significant tendency for increase in incidence. In both high-fat groups, an elevated incidence of persistent estrus was generally observed until 8 months of age. Sequential assays of steroid hormones in rats fed a 20% fat diet showed a tendency for early elevation and continued high values for the serum estrogen: progesterone (E2:P) ratio. In these rats, histological changes in the ovary, uterus, and vagina also appeared at an early stage, as compared to rats fed the basal diet. These results suggest that a high-fat diet may exert a slight promoting effect on the spontaneous occurrence of uterine adenocarcinomas in Donryu rats, and this might be mechanistically related to hormonal imbalance and a high E2:P ratio in particular.

Adenocarcinoma↗
PubMed1995

Recurrent posterior dislocation of the head of the radius in post-traumatic cubitus varus.

Four patients who had injured the lower end of the humerus in childhood with resulting cubitus varus developed recurrent posterior dislocation of the head of the radius after further injury to the elbow. Dislocation occurred when the forearm was supinated and spontaneous reduction took place on pronation. At operation the lateral ligament complex was seen to be lax and elongated. After tightening of the ligament and with a supracondylar osteotomy of the humerus to correct the cubitus varus the recurrent dislocation was eliminated.

Elbow Joint↗
PubMed1994

Sequence of a 2.6-kb cryptic plasmid from a marine cyanobacterium Synechococcus sp.

We have shown previously that the copy number of plasmid pSY10 from the marine cyanobacterium Synechococcus sp. NKBG 042902 is dependent on the salinity of the growth medium. We report here the complete nucleotide sequence (2561 bp) of this plasmid. The longest open reading frame, ORF-B (1.08 kb), occurs on a 1.6-kb EcoRI fragment. This ORF encodes a putative protein which is 360 aa residues in length and is 37.8% homologous to the replication protein of plasmid pCA2.4 from Synechocystis sp. strain PCC 6803, 35.8% homologous to an ORF from the Nostoc plasmid pGL2, and 33.2% homologous to the ORF of a plasmid from Lactobacillus plantarum, pC30il. Highly conserved regions of amino acid sequence were also found between ORF-B and other bacterial plasmids.

Amino Acid Sequence↗
PubMed1994

Portal vein aneurysm in the liver associated with multiple vascular malformations.

Portal vein aneurysm (PVA) includes focal dilatation of the portal vein, and was formerly thought to be a rare disease. We report a 46-year-old man with chronic aggressive hepatitis and intrahepatic portal vein aneurysm communicating with the hepatic vein. Hemangiomas in the liver and intracranial arteriovenous malformation (AVM) were also found. To our knowledge, this is the first report of a case of PVA in a patient with congenital intracranial AVM. As the PVA in this patient communicated with the hepatic vein, and as hemangiomas in the liver and intracranial AVM were also present, the pathogenesis in this patient seems to have been congenital anomaly of the vasculature.

Aneurysm↗
PubMed1994

Levels of serum colony-stimulating factors (CSFs) in patients on long-term haemodialysis.

We measured the levels of colony-stimulating factors (G-CSF, M-CSF and GM-CSF) and several cytokines in paired sera obtained from 51 patients (33 males and 18 females; mean age: 53 years) on long-term haemodialysis (HD). The mean pre-HD G-CSF level was 22.7 +/- 21.7 pg/ml and the post-HD level was 40.3 +/- 54.4 pg/ml. The mean pre-HD M-CSF level was 2.4 times higher than normal at 1287 +/- 380 U/ml, and it increased to 1644 +/- 456 U/ml after HD (r = 0.83). GM-CSF was not detectable in any of the serum samples. IL-1 beta was detectable in 38 pre-HD sera at a mean level of 57.1 +/- 21.8 pg/ml, but was rarely detected after HD. TNF-alpha was not usually detected. When the CSF levels were divided by the product of the serum total protein concentration and body weight, the post-HD value for G-CSF was almost always greater than the pre-HD value and there was an improved pre-post correlation (r = 0.69). In the transformed pairs of M-CSF level, the post-HD value did not differ much from the pre-HD value, and a strong pre-post correlation was noted (r = 0.94). These results suggest that the serum G-CSF level is not affected by chronic renal failure, although HD may induce an increase of G-CSF. In the case of M-CSF, however, impaired renal metabolism and/or excretion may increase the serum concentration, but it is not modulated by haemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the fibronectin finger-like domain and the kringle 1 domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which is used to treat acute myocardial infarction. Pharmacokinetically, t-PA is characterized by a rapid clearance from the circulation. In a previous study, we constructed variant forms of t-PA with genetic modifications at the fibronectin finger-like domain (finger domain) or at the kringle 1 domain (K1 domain). The finger modified variant, t-PA N37S.S38V.G39V.R40E. A41F.Q42S had about a 6.0-fold higher plasma half-life in vivo than wild-type t-PA. Two variants with modifications in the K1 domain, t-PA G161R.K162R.S165W and t-PA N115P, showed an improved kinetic parameters and a 2.2-fold higher plasma half-life in vivo than wild-type t-PA, respectively. To create a recombinant variant of t-PA with a higher enzymatic activity and a further prolonged half-life in vivo, the genes containing each modifications were joined and expressed in animal cells. The two variants, t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G16 1R.K162R.S165W and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N11 5P, were purified from conditioned media and their biochemical, pharmacokinetic and thrombolytic profiles were investigated. Although the variant t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G16 1R.K162R.S165W demonstrated an impaired enzymatic activity compared to the wild-type t-PA, the half-life of the variant, t-PA N37S.S38V.G39V.R40E.A41F.Q42S. N115P, following intravenous bolus injection in rabbits was considerably longer than that of finger-domain modified variants.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Studies on production of anticollagen antibodies in silicosis.

Silicosis is characterized by pulmonary fibrotic changes which consist primarily of an increase in collagen. In this study, anticollagen antibodies in the serum of 134 silicosis patients versus 40 normal subjects were examined and their relationship with immunoglobulin, autoantibodies, and procollagen III peptide (PIIIP) was investigated by enzyme-linked immunosorbent assay (ELISA). The mean levels of anti-human type I collagen (HI) and anti-human type III collagen (HIII) antibodies were significantly higher in the silicosis patients versus the normal subjects (P < 0.001). However, no differences were observed in the mean levels of anti-human type IV collagen (HIV) antibodies in the silicosis patients versus the normal subjects. Anticollagen antibodies in the sera of silicosis patients appear to be formed at an early stage of the disease. We observed a correlation between anticollagen antibodies and immunoglobulin. There was a tendency toward high values of anticollagen antibodies in the sera of patients positive for antinuclear antibodies (ANA) and rheumatoid factor (RF), both of which are autoantibodies. However, no correlation was observed between serum PIIIP and anticollagen antibodies. These observations suggest that, in silicosis, there is a relationship between anticollagen antibodies and immunoglobulins, as well as between anticollagen antibodies and autoantibodies. Measurement of anticollagen antibodies in the sera of silicosis patients offers a useful index for evaluating the prognosis of pulmonary fibrosis and autoimmune abnormality in silicosis.

Aged↗
PubMed1993

Identification and biological activity of germination-inhibiting long-chain fatty acids in animal-waste composts.

Long-chain fatty acids in germination-inhibiting animal-waste composts were identified by gas chromatography-mass spectrometry as myristic, palmitic, stearic, oleic, linoleic, and linolenic acids. These acids were found at concentrations greater than 0.25 mg (g dry compost)-1. The identified acids, together with lauric acid, and five kinds of short- and medium-chain fatty acid, were tested for their effects on the germination process of sorghum seeds. The authentic long-chain fatty acids, which were dissolved in a 1:9 (v/v) mixture of methanol and distilled water at 40 mg liter-1, significantly reduced the alpha-amylase activity, physiological water uptake, and ATP content of the germinating seeds during the first 24 h of inhibition, as well as the rate of germination of seeds. Among the tested fatty acids, myristic and palmitic acids were the most potent inhibitors of germination. The inhibitory effects of long-chain fatty acids were stronger than those of the phenolic acids. The short- and medium-chain fatty acids did not have any significant germination-inhibitory effects at 40 mg liter-1. The results indicate that the long-chain fatty acids are the dominant inhibitors of germination in animal-waste composts, and that the inhibition of the alpha-amylase activity in germinating sorghum seeds is one aspect of the mode of action of these long-chain fatty acids.

Animals↗
PubMed1992

Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7-9, 10-14, 15-19, 28-33, and 37-42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37-42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37-42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37-42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37-42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

Amino Acids↗
PubMed1992

Promoting effects of 6-mercaptopurine on carcinogenesis in various organs of F344 rats.

Possible promoting effects of 6-mercaptopurine (6-MP) on carcinogenesis in various organs, including the hematopoietic system, were investigated in female F344 rats, using a 2-stage carcinogenesis model. 6-MP was given as a dietary supplement (50 ppm) for 35 weeks subsequent to wide-spectrum initiation with N-ethyl-N-nitrosourea (ENU). Various tumors were observed in the carcinogen-initiated groups. No significant influence of 6-MP on their development, including the occurrence of leukemia, was apparent. However, the incidences of some proliferative lesions in the lung, intestine and kidney were slightly higher in the ENU/6-MP group than the ENU group. Further studies may be needed on promoting effects of 6-MP, based on dose-effect relation using several 6-MP doses and/or other initiators.

Animals↗
PubMed1992

[A case of pseudohypoparathyroidism (PHP) type II associated with Bartter's syndrome--restoration of phosphaturic response to parathyroid hormone (PTH) by treatment for hypopotassemia].

We report a case of PHP Type II whose phosphaturic response to PTH was restored by treatment for complicated Bartter's syndrome. A 34-year-old woman was admitted to our hospital in July 1990 because of tetanic convulsion. The physical examination showed normal blood pressure (118/62mmHg), round face without shortness of metacarpal bones and positive Trousseau's sign. Although renal function was normal, hypocalcemia (6.5mg/dl) and hyperphosphatemia (4.8mg/dl) in association with high levels of serum PTH (942pg/ml) and 1.25 (OH)2D3 (86pg/ml) were disclosed. Ellsworth-Howard test revealed that there was no increase in the urinary secretion of phosphate despite an increase in urinary cAMP excretion. On the other hand, hypopotassemia (2.5mEq/l) and metabolic alkalosis with high plasma renin activity (22.8ng/ml/hr) and aldosterone concentration (22.7ng/dl) were coexistent. Pressor response to angiotensin II infusion was blunted. Although no glomeruli were obtained by renal biopsy specimen, vacuolar degeneration on proximal tubules were noted. These findings indicated that she had PHP Type II associated with Bartter's syndrome. By administration of potassium (24mEq/day), spironolactone (50mg/day) and only small doses of 1 alpha-hydroxyvitamin D3 (0.5mg/day), serum levels of potassium as well as calcium were normalized and tetanic attacks disappeared. In March 1991, she was re-examined by Ellsworth-Howard test in order to clarify the effects of hypopotassemia on renal tubular response to PTH. Interestingly, phosphaturic response to PTH was restored, and the degree of increase in urinary cAMP excretion was 4 times as high as that on the first admission. These results suggest that hypopotassemia changes the response of renal proximal tubular cells to PTH, particularly such as reabsorption of phosphate and cAMP response, although it is possible that hypocalcemia may contribute to the blunted phosphaturic response to PTH. The mechanism of hypocalcemia seen in this case remains to be elucidated.

Adult↗
PubMed1991

Increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary biliary cirrhosis.

The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001). These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes.

Adult↗
PubMed1991

The 'oral 1,25-dihydroxyvitamin D3 pulse therapy' in hemodialysis patients with severe secondary hyperparathyroidism.

Many hemodialysis patients are still suffering from secondary hyperparathyroidism although 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been used to treat renal osteodystrophy for the last two decades. The main reason for its failure to correct the secondary hyperparathyroidism is that in patients, hypercalcemia occurs before adequate parathyroid hormone (PTH) suppression is obtained when a large daily dose of 1,25(OH)2D3 is started. In this study, the oral dose of 1,25(OH)2D3 (4.0 micrograms) was administered only twice a week at the end of hemodialysis ('oral 1,25(OH)2D3 pulse therapy'), in 19 patients with severe secondary hyperparathyroidism. Serum immunoreactive PTH started to decrease after 6 weeks of therapy, and the original level of 41.2 +/- 7.24 was reduced to 24.4 +/- 6.12 ng/ml by the end of the 6-month therapy (p less than 0.001). Serum alkaline phosphatase also was reduced by 64.4%. Three out of 19 patients suffered from hypercalcemia during the 4th month of therapy. Calcium supplement given to 6 other patients with severe secondary hyperparathyroidism did not lower serum PTH levels significantly after 6 weeks of therapy, although serum calcium levels increased and were sustained above 10 mg/dl for the last 5 weeks. These findings strongly suggest that the suppressive effect of the oral 1,25(OH)2D3 pulse therapy was attained by a direct action of 1,25(OH)2D3 on the parathyroid gland rather than by its ability to elevate serum calcium levels. In conclusion, the oral 1,25(OH)2D3 pulse therapy effectively lowered PTH levels in hemodialysis patients who cannot tolerate large daily doses of 1,25(OH)2D3.

Administration, Oral↗
PubMed1991

The effect of stimulus rate upon common peroneal, posterior tibial, and sural nerve somatosensory evoked potentials.

We examined the effect of stimulus rate on somatosensory evoked potentials (SEPs) following stimulation of the common peroneal nerve (CPN) at the knee, and the posterior tibial nerve (PTN) and sural nerve (SN) at the ankle. We measured the amplitude of P40-N50 and N50-P60 in the PTN-SEP and corresponding amplitude of CPN-SEP and SN-SEP at the rate of 2.3, 3.4, 4.1, and 5.1 Hz. When the stimulation rate was increased from 2.3 to 5.1 Hz, the P40-N50 amplitude decreased by 50% for the CPN-SEP and 20% for the PTN-SEP. Also, the N50-P60 amplitude was reduced by 30% in the CPN-SEP and 20% in the PTN-SEP. In contrast, this change in stimulus rate produced no significant amplitude decline in the SN-SEP. Blocking the peroneal nerve with lidocaine just distal to the stimulating electrodes eliminated the descending peroneal nerve volley and abolished the amplitude attenuation observed with the faster stimulus rate. The findings suggest that at higher rates of stimulation, the afferent volleys induced by the movements that follow mixed nerve stimulation interfere with the SEP produced by electrical activation of the sensory afferents. The interference is greater when the more proximal site of the mixed nerve is stimulated.

Adult↗
PubMed1990

A heteromeric transcription factor required for mammalian RNA polymerase II.

A general transcription factor, FC, essential for specific initiation of in vitro transcription by mammalian RNA polymerase II was identified and a procedure developed to purify it to near homogeneity from HeLa cell nuclei. Purified FC is composed of two polypeptides of apparent molecular masses 80 kDa and 30 kDa, on SDS-PAGE, and has a native size of 280 kDa estimated by gel filtration column. Both polypeptides were shown to be essential for reconstituting in vitro transcription activity. Biochemical analysis showed that the 80 kDa and 30 kDa components were present in a 1:1 molar ratio. FC was also demonstrated to interact directly or indirectly with purified RNA polymerase II. Similarities between FC and transcription factors reported by others from human, rat or Drosophila cells are discussed.

Chromatography, High Pressure Liquid↗
PubMed1990

Two-year carcinogenicity study of 6-mercaptopurine in F344 rats.

The carcinogenicity of 6-mercaptopurine (6-MP), an anticancer drug, was examined in F344 rats of both sexes, administered the chemical at dietary levels of 0 (control), 25 ppm or 50 ppm for 2 years. Many tumors developed in all groups including the control group, the organ distribution and histological types being similar to those reported for spontaneous lesions. In males, there was no significant increase in the incidence of any tumor in the treated groups over that in the control group. In females, however, positive trends were noted in the occurrence of C-cell tumors, pheochromocytomas, uterine adenocarcinomas and gliomas, and the incidences of C-cell tumors and pheochromocytomas in the 50 ppm group were significantly higher than the values in the respective control group. In addition, the total numbers of malignant tumors increased significantly in the female 50 ppm group. However, most of the tumors demonstrating increase are frequently observed spontaneous lesions in this strain of rats, and their incidences in the present female control group were lower than in our historical data. In addition, there were no significant differences in the incidences of preneoplastic changes and induction times for the above-listed tumors between the female control and the 50 ppm groups. These results thus indicated that while the carcinogenic potential of 6-MP can not be precluded, it can be only very weak or marginal, after continuous administration in the diet at the 50 ppm level for 2 years. The leukemogenic action of 6-MP was negative under the present experimental conditions.

Animals↗