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T Nagata

Publications and source records attributed to T Nagata.

At least 325 records · Page 18Linked to original sources
PubMed1995

Study on the DNA synthesis of pulmonary cells in aging mice by light microscopic radioautography.

The DNA synthesis and morphological changes of the pulmonary cells of 11 groups of mice from fetal day 16 to 22 months after birth were studied by light microscopic radioautography after 3H-thymidine incorporation. A detailed investigation was first carried out to determine the localization and the frequency of 3H-thymidine incorporation with the age-related change of pulmonary cells in the mouse lung. The results showed that the DNA synthesis of pulmonary cells changed with aging. The examination of radioautograms demonstrated that the activity of DNA synthesis of type 1 epithelial cells was very low, which reached the peak on the third day after birth, decreased gradually with aging, and lost the ability from postnatal 6 months onwards. On the other hand, the labeling indices of type 2 epithelial, interstitial and endothelial cells were the highest on the fetal day 16, then fell down with the developing of the lung, but increased again on the third postnatal day, and decreased gradually with age. These data provided the evidence that the DNA synthesis of type 2 epithelial, interstitial and endothelial cells were the largest on fetal day 16, then decreased with the developing of the lung due to aging.

Aging↗
PubMed1995

[A case of biopsy-proven sarcoid meningoencephalitis presented with hallucination, nominal aphasia and dementia].

Here we report a 36-year-old male with sarcoid meningoencephalitis who initially presented with hallucination, nominal aphasia and disturbance of consciousness. After the onset, his symptoms fluctuated. He had no meningeal signs, and his cranial nerves were normal except for bilateral papapilledema. Muscle power and tone was normal, and there was no gait disturbance. Deep tendon reflexes were slightly exaggerated in lower extremities, but no pathological reflexes were noted. There was no impairment in extrapyramidal system, cerebellar system and sensory system. The cerebrospinal fluid revealed increased opening pressure, mild lymphocytic pleocytosis, slightly decreased glucose, increased protein to 87mg/dl and increased IgG index to 1.11. Cerebrospinal fluid culture was negative. Marked meningeal thickening and contrast enhancement was shown by CT and MRI. The meningeal biopsy demonstrated characteristic sarcoid nodules and confirmed the diagnosis of neurosarcoidosis. His manifestations were alleviated by oral administration of corticosteroid. Since neurosarcoidosis is a disorder treatable with corticosteroid, it is important to consider the possibility of this disorder in mind when a patient is presenting with psychiatric manifestations and chronic meningitis.

Adult↗
PubMed1995

[Histochemistry of the organs--application of histochemistry to anatomy].

Histochemistry has been developed as a science to localize chemical components of cells and tissues on histological sections by using chemical, physical and biological techniques. Many textbooks are available dealing with the methodology of histochemistry, consisting of fixation of tissues, demonstration of biochemical components such as nucleic acids, proteins, sugars, lipids, enzymes, pigments, inorganic substances and amines by means of chemical reactions (Fig. 5) or application of physical (Figs. 1-3, 6-13) and biological (Fig. 4) methods such as spectrophotometry, X-ray microanalysis, radioautography and immunohistochemistry. The methodology has been well developed to form a new science which should be given a designation "general histochemistry" as similar to general histology. On the other hand, these techniques should be applied to all the organ systems, i.e. the skeletal, muscular, circulatory, digestive (Figs. 1-6), respiratory (Figs. 7, 8), urinary (Fig. 9), genital (Fig. 10), endocrine (Fig. 11), nervous (Fig. 12), and sensory organs (Fig. 13). The results of these applications to all the organs should be collected and construct a new field of histochemistry of the organs like "histology of the organs". These results now form a new field of science which should be designated as "special histochemistry". Since the present author started the career as an anatomist and histologist in 1955, the author first aimed at the study of histochemistry by developing new chemical, physical and biological techniques such as enzyme histochemistry (Fig. 5), microspectrophotometry, autoradiography (Figs. 1-3, 6-13), cryo-techniques, immunohistochemistry (Fig. 4) and lectins in the 1950s, 1960s and 1970s. However, the author and coworkers made efforts to apply these techniques to various organ systems of humans and animals since the 1970s to the present time and collected data from all the organs including the aging process from embryos, neonates, sucklings, weanlings, adults and to senescence. The data include not only 3-dimensional structures of the organs but also the 4-dimensional features taking the time dimension into account using the radioautographic techniques by labeling cells and tissues in connection with the time lapse. The original papers published from our laboratory during these 40 years were reviewed and compiled to form a new field of science, which should be designated as histochemistry of the organs or, alternatively, special histochemistry. It is hoped that this new prospect would be well developed to form a novel system in medical science.

Aging↗
PubMed1994

The mouse Rxrb gene encoding RXR beta: genomic organization and two mRNA isoforms generated by alternative splicing of transcripts initiated from CpG island promoters.

Two major isoforms of retinoid X receptor beta (RXR beta; H-2RIIBP), encoded by the Rxrb gene, have been identified in the mouse. Northern analysis of Rxrb mRNA showed two close bands of 2.8 and 2.6 kb in many tissues and cell lines. They are designated as mRxr beta 1 and mRxr beta 2, respectively. Some rapidly growing cell lines and spleen tissue had about twofold more Rxr beta 1 mRNA than Rxr beta 2 whereas most adult tissues had similar amounts of both beta 1 and beta 2. Amino acid (aa) sequences deduced from cDNAs show an extra N-terminal domain of 72 aa for RXR beta 1 that is well conserved between mouse and human, but not found in RXR beta 2. These isoforms are generated from separate exons transcribed from different CpG island promoters and spliced into the common acceptor site in the transactivation domain by an alternative splicing. The Rxrb gene contains an intron in the midst of the first zinc-finger coding region. This is different from the retinoic acid receptor (RAR) and other nuclear receptor superfamily genes that contain an intron between the first and the second zinc-finger coding regions. These results, together with their unique ability to form heterodimers with other members of the superfamily, suggest a distinct phylogenic position for the Rxr genes.

Alternative Splicing↗
PubMed1994

Thyroid hormone suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances functional activities of mature osteoblasts in cultured rat calvaria cells.

The effects of thyroid hormone on osteoblastic differentiation and activity were studied in fetal rat calvaria (RC) cells cultured for up to 30 days in medium supplemented with thyroid hormone-depleted serum. In this condition, the cells proliferated and differentiated to form mineralized bone nodules (BN) and expressed osteoblastic markers such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). The continuous presence of triiodothyronine (T3) at 10(-9)-10(-8) M in the medium inhibited the osteoblastic differentiation: 34% decrease in ALP activity on day 12 and 60% decrease in BN formation on day 15 at 10(-8) M. T3 at these doses had no effect on the DNA content of RC cells at confluence (day 6). Short-term (48-h) exposure of T3 at 10(-9) M or higher decreased ALP activity when RC cells were differentiating (days 7-11). However, when BN formation by the cells had already reached a plateau (day 28), the activity was increased by treatment with T3 at 10(-7)-10(-6) M. OCN production was increased dose dependently by this treatment with T3 (2.1-fold and 1.3-fold of control at 10(-8) M on days 11 and 28, respectively). Similar increases were observed in the levels of OCN mRNA. In addition, increases in phosphorylated OPN in the medium (day 11) and mineralized matrix (day 28) were observed (1.5-fold at 10(-8)-10(-6) M), while OPN synthesis and the level of its mRNA were depressed by T3 (60-70% of control at 10(-8) M). These results suggest that T3 regulates osteoblastic differentiation and activity depending on the state of cell differentiation: T3 suppresses the differentiation of osteoprogenitor cells to osteoblasts, but enhances the functional activity of mature osteoblasts.

Alkaline Phosphatase↗
PubMed1994

Effect of prostaglandin E2 on mineralization of bone nodules formed by fetal rat calvarial cells.

The effects of PGE2 on mineralized bone nodule formation were studied in fetal rat calvarial (RC) cells in vitro. Continuous exposure of RC cells to 3 x 10(-8) M PGE2 induced a twofold increase in mineralized bone nodule formation and a 1.5-fold increase in alkaline phosphatase (ALPase) activity without affecting RC cell growth. These stimulatory effects were evoked by concentrations of 3 x 10(-9)-3 x 10(-6) M PGE2 and the maximal effect was observed with 3 x 10(-8) M PGE2. The in vitro effects of PGE2 were evident when RC cells were exposed to it on days 8-14 and 8-21, which correspond to the post-confluent culture stage, but no effects were observed when the cells were exposed on days 1-7, the growth stage. The ALPase activity was also higher (1.2-1.4-fold) when 3 x 10(-8) M PGE2 was added during the post-confluent stage. In order to determine the effect of PGE2 during the mineralization phase of bone nodules in the presence of a large population of osteoprogenitor cells, RC cells were exposed to dexamethasone for 7 days before PGE2 was added during the post-confluent stage. A significantly higher percentage of nodules mineralized were observed with 3 x 10(-8)-3 x 10(-9) M PGE2 (1.6- and 1.4-fold, respectively), than in control cultures. Analysis of the mineral-related proteins by EDTA extraction of bone nodules followed by electrophoresis and Stains-All staining revealed an increased total amount of osteopontin extracted from the mineralized matrix after PGE2 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1994

Changes of colon epithelium proliferation due to individual aging with cyclin proliferating cell nuclear antigen (PCNA/cyclin) immunostaining compared to [3H]-thymidine radioautography.

We report a change in the proliferative activity of mouse colonic epithelium due to development and aging. In order to measure the proliferative activity, colonic epithelium was immunostained for cyclin proliferating cell nuclear antigen (PCNA/cyclin), which appears from the Gl to the S phase of the cell cycle, and compared with labeling obtained by [3H]-thymidine radioautography. Litter mice of six age groups from the fetal period (embryonic day 19), newborn period (postnatal day 1), suckling period (postnatal day 5), weaning period (postnatal dy 21), adult period (2 month old) to the senescent period (11 month old) were examined by immunohistochemistry. The descending colons were fixed in methacarn (method-Carnoy) and embedded in paraffin. Sections were stained for PCNA/cyclin activity using 19A2 monoclonal antibody and the avidin-biotin peroxidase complex (ABC) technique. For radioautography, litter mice of nine age groups using in vivo intraperitoneal administration of [3H]-thymidine. The labeling indices of colonic epithelial cells in the proliferative zone were then analyzed and compared between the two investigative methods. Our results show that the proliferative activity of mice colon was high in the fetal and newborn periods and almost constant from the suckling period to senescence, as demonstrated by both PCNA/cyclin immunohistochemistry and [3H]-thymidine radioautography. The labeling index seen by PCNA/cyclin immunohistochemistry was, however, higher than that seen by [3H]-thymidine radioautography.

Aging↗
PubMed1994

How to diagnose polysulphide poisoning from tissue samples.

We carried out animal experiments to toxicologically verify polysulphide poisoning by analyzing tissue samples. A bathing agent containing calcium polysulphides was administered orally to rats, and then polysulphides and sulphide, the decomposed product of polysulphides, were analyzed by GC and GC/MS. The concentrations of polysulphides (mumol/ml or g) were found to be highest in blood (0.196), followed by the liver (0.051), the lungs (0.018) and kidneys (0.013), but were below the detection limit (0.005 mumol/g) in the other tissues tested. Sulphide was detected in all the tissue samples and was found to be highest in the blood (0.518 mumol/ml), this being 40 times higher than that required for fatal poisoning in the case of hydrogen sulphide. Polysulphide poisoning was considered to be confirmatively diagnosed by detecting and measuring polysuphides and supplementarily sulphide in body tissues, most pertinently in the blood. Two practical cases of suspected poisoning by polysulphides are briefly described.

Animals↗
PubMed1994

Simultaneous determination of nicotine and cotinine in various human tissues using capillary gas chromatography/mass spectrometry.

A reliable and sensitive method for the simultaneous determination of nicotine and cotinine concentrations in various human tissues was developed using capillary gas chromatography/mass spectrometry. Nicotine and cotinine were extracted using a 3-step solvent extraction procedure and quinoline as an internal standard. Quantification was carried out by single ion monitoring using ions of m/z 133 for nicotine, m/z 176 for cotinine and m/z 129 for quinoline. The lower limit of detection was 5 ng/g for nicotine and 10 ng/g for cotinine, in each tissue sample. The calibration curves of various tissues were linear in the concentration range from 5-1,200 ng/g for nicotine and 10-1,500 ng/g for cotinine. The accuracy and precision of this method were examined using human tissues and the results were satisfactory. The distribution of nicotine and cotinine was measured in tissues from 10 human autopsies. Nicotine was detected in every tissue examined at a level seen in habitual smokers. The nicotine concentration was high in the liver, kidney, spleen and lung, and low in adipose tissue. The cotinine level was highest in the liver. The tissue/blood concentration ratios of nicotine and cotinine were most stable in skeletal muscle, where the level of these drugs was close to that in whole blood. Skeletal muscle is, therefore, considered to be the most suitable tissue sample for toxicological examination, when acquisition of blood samples is not feasible.

Adipose Tissue↗
PubMed1994

Recovery of antitumor CD4+ T cell responsiveness, suppressed in the tumor-bearing state, by release from tumor burden.

The present study investigates the recovery of antitumor CD4+ T cell responsiveness, suppressed in the tumor-bearing state, following release of tumor burden. Spleen cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 1-3 weeks after the inoculation with CSA1M cells produced interleukin-2 (IL-2) and IL-4 upon in vitro cultures without addition of exogenous tumor antigens. This lymphokine production was achieved through collaboration between anti-CSA1M CD4+ T cells and antigen-presenting cells (APC) that has been pulsed with CSA1M tumor antigens in vivo in the tumor-bearing state. The lymphokine-producing capacity gradually decreased as the tumor-bearing period increased, and spleen cells from mice at late (8-10 week) tumor-bearing stages produced reduced levels of lymphokines. Because APC in these cells exhibited enhanced capacities to present tumor antigens, the reduced responsiveness was ascribed to the dysfunction of CD4+ T cells themselves. However, removal of a tumor after 8 weeks resulted in a remarkable recovery of the lymphokine-producing capacities of whole spleen cells. In contrast to the reduction in CSA1M-antigen-presenting activity of APC following tumor resection, CD4+ T cells exhibited a reciprocal increase in their responsiveness to CSA1M antigens. The recovery of antitumor responsiveness was also observed in the in vitro cultures free from tumor burden; when spleen cells from mice at late tumor-bearing stages were pre-incubated for 1-2 days and re-cultured in fresh medium, they produced potent amounts of IL-2 and IL-4. These results indicate that the immunodysfunction of antitumor CD4+ T cells induced in the tumor-bearing state is not irreversible, and release from tumor burden results in almost complete recovery of the potent antitumor responsiveness they previously expressed.

Animals↗
PubMed1994

Squamous cell carcinoma of the splenic flexure of the colon: report of a case.

A 51-year-old Japanese man underwent resection of a tumor in the splenic flexure of the colon, which proved to be squamous cell carcinoma. At the time of presentation, the liver was found to have multiple metastases. On the 39th postoperative day, the patient died of liver failure. An autopsy demonstrated metastatic nodules on the pleura and parenchyma of both lungs, as well as in the liver, but failed to show any other primary squamous cell carcinoma. We emphasize that a meticulous search to disprove adenosquamous carcinoma is mandatory before a diagnosis of squamous cell carcinoma of the colon can be confirmed.

Carcinoma, Squamous Cell↗
PubMed1994

1 alpha,25-dihydroxyvitamin D3 stimulation of osteopontin expression in rat clonal dental pulp cells.

Osteopontin (OPN) is a major phosphorylated non-collagenous protein isolated from bone. Rat clonal dental-pulp cell lines RPC-C2A and RDP4-1 produce and secrete OPN as a principal phosphoprotein. 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a potent calcitropic hormone which regulates calcified tissue metabolism including the synthesis of extracellular matrix proteins. The effects of 1,25(OH)2D3 on the expression of OPN mRNA and the synthesis of OPN protein by pulp cells in vitro were investigated. In RPC-C2A cells, 1,25(OH)2D3 markedly stimulated synthesis of both [32PO4]- and [35S]-methionine-labelled OPN. Phosphorylated OPN synthesis increased dose-dependently and showed a maximum level at 48 h after addition of 10(-11)-10(-7) M 1,25(OH)2D3. Similar stimulation was also observed in RDP4-1 cells. Northern hybridization analysis revealed that 1,25(OH)2D3 greatly increased the level of OPN mRNA in both pulp cell lines. Examination of the time course of the effects of 1,25(OH)2D3 on the level of OPN mRNA in RPC-C2A cells by dot-blot analysis showed that stimulation was detectable at 24 h and reached a maximum at 48 h after exposure to 10(-7)M 1,25(OH)2D3. These findings indicate that 1,25(OH)2D3 stimulates the production of dental-pulp OPN by a mechanism that involves de novo synthesis and transcriptional control.

Animals↗
PubMed1994

New dihydropyridine calcium channel antagonist, pranidipine, attenuates hypertensive renal injury in Dahl salt-sensitive rats.

Interest in the cardiovascular protective effects of calcium channel antagonists has increased in the past decade. We investigated prevention of vascular wall remodeling by the long-acting calcium channel antagonist pranidipine in 12-week-old Dahl salt-sensitive (SS) rats with high-salt-induced (4% NaCl) hypertension. Six-week pranidipine treatment (60 mg/kg chow) decreased systolic blood pressure (SBP) by 22% in SS rats. This BP reduction was associated with decreases in cardiac mass and weight of the aortic wall. Glomerular filtration rate (GFR) was increased by 33%, but this did not lead to a decrease in urinary protein or NAG excretion. Morphologic investigation demonstrated striking resolution of arterial injury (medial necrosis and/or hyperplasia, inflammatory cell infiltration, and thrombus formation) by 87% after pranidipine treatment. Glomerular sclerosis was also attenuated by 61%, whereas tubular injury was improved by only 28%. These morphologic changes were reflected in the findings that the capacity of kidney homogenate for generating lipid peroxides was significantly decreased and that collagen levels and pattern type became similar to those of normotensive salt-resistant (SR) rats. Pranidipine also attenuated hypertensive vasculopathy in small arteries of the middle cerebral arteries. Thus, the calcium channel antagonist pranidipine can attenuate the vascular injury that occurs in salt-induced hypertension, a promising property that implicates its clinical usage, particularly in essential hypertension with cardiovascular complications.

Animals↗
PubMed1994

Clinical evaluation of a potassium nitrate dentifrice for the treatment of dentinal hypersensitivity.

The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double-blind study in 36 Japanese subjects who complained of cold and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 x a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by all 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks' examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.

Adult↗
PubMed1994

Distribution and elimination of sulphadimethoxine and its metabolites in treated chicken.

Sulphadimethoxine (SDM), and its metabolites, N4-acetyl SDM, N1-(2-methyl-6-hydroxy-4-pyrimidinyl) sulphanilamide (6-OH-SDM), N1-(6-methyl-2-hydroxy-4-pyrimidinyl) sulphanilamide (2-OH-SDM), N1-(2,6-dihydroxy-4-pyrimidinyl) sulphanilamide (2,6-diOH-SDM) and SDM N1-glucuronide in chicken tissues were extracted, partially purified by Bond Elute SCX cartridges, and assayed and identified by HPLC/LC-MS after administration of SDM to chickens. During the administration and 24 h after withdrawal, SDM and 6-OH-SDM were observed in almost all tissues and excreta. N4-Acetyl SDM and 2,6-diOH-SDM were observed in some tissues, but 2-OH-SDM and SDM N1-glucuronide were observed in a few limited tissues. Twenty four hours after withdrawal, SDM and its metabolites, except 6-OH-SDM, decreased. SDM and its metabolites were eliminated from all tissues within 48 h of withdrawal.

Animals↗
PubMed1994

Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene regulation in embryonal carcinoma cells.

Retinoid X receptors (RXRs) heterodimerize with multiple nuclear hormone receptors and are thought to exert pleiotropic functions. To address the role of RXRs in retinoic acid- (RA) mediated gene regulation, we designed a dominant negative RXR beta. This mutated receptor, termed DBD-, lacked the DNA binding domain but retained the ability to dimerize with partner receptors, resulting in formation of nonfunctional dimers. DBD- was transfected into P19 murine embryonal carcinoma (EC) cells, in which reporters containing the RA-responsive elements (RAREs) were activated by RA through the activity of endogenous RXR-RA receptor (RAR) heterodimers. We found that DBD- had a dominant negative activity on the RARE reporter activity in these cells. P19 clones stably expressing DBD- were established; these clones also failed to activate RARE-driven reporters in response to RA. Further, these cells were defective in RA-induced mRNA expression of Hox-1.3 and RAR beta, as well as in RA-induced down-regulation of Oct3 mRNA. Gel mobility shift assays demonstrated that RA treatment of control P19 cells induces RARE-binding activity, of which RXR beta is a major component. However, the RA-induced binding activity was greatly reduced in cells expressing DBD-. By genomic footprinting, we show that RA treatment induces in vivo occupancy of the RARE in the endogenous RAR beta gene in control P19 cells but that this occupancy is not observed with the DBD- cells. These data provide evidence that the dominant negative activity of DBD- is caused by the lack of receptor binding to target DNA. Finally, we show that in F9 EC cells expression of DBD- leads to inhibition of the growth arrest that accompanies RA-induced differentiation. Taken together, these results demonstrate that RXR beta and partner receptors play a central role in RA-mediated gene regulation and in the control of growth and differentiation in EC cells.

Animals↗
PubMed1994

Antihypertensive property and renal protection by shichimotsu-koka-to extract in salt-induced hypertension in Dahl strain rats.

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsukoka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Animals↗