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T Naito

Publications and source records attributed to T Naito.

At least 145 records · Page 8Linked to original sources
PubMed1996

Hepatic bile acid synthesis and DNA synthetic rate after partial hepatectomy.

The relationship between hepatic DNA synthetic rate and activity of cholesterol 7 alpha-hydroxylase, the rate limiting enzyme for bile acid synthesis, was examined in regenerating liver after partial hepatectomy or sham operation in rats. Hepatic cholesterol 7 alpha-hydroxylase activity was significantly (P < 0.001) suppressed on days 1 and 2, returned to the control level on day 3, and was significantly raised on day 7 after hepatectomy. The rate of DNA synthesis was significantly (P < 0.001) activated during the first 3 days after hepatectomy and returned to the control level on day 7. Enzyme activities regulating hepatic bile acid synthesis and DNA synthesis change inversely during liver regeneration after hepatectomy.

Animals↗
PubMed1996

Dysregulated transforming growth factor-beta in neonatal and adult autoimmune MRL-lpr mice.

Transforming growth factor- beta (TGF- beta) is a cytokine that promotes inflammatory processes and prevents tissue injury. Autoimmune destruction of the kidney in MRL-lpr mice is spontaneous, rapid, fatal and consists of glomerular damage and an influx of lymphocytes surrounding vessels and in the interstitium. In MRL-lpr mice, cytokine dysregulation is apparent in neonates and continues throughout the life span. Circulating levels of tumour necrosis factor (TNF- alpha) and colony stimulating factor-1 (CSF-1) are detected in neonatal mice and progressively increase in proportion to the loss of renal function. We now report elevated intracellular expression of distinct isoforms of TGF- beta (TGF- beta 3, TGF- beta 2, and TGF- beta 1) detected immunohistochemically in MRL-lpr kidneys and other tissues including the liver and thymus. Enhanced TGF- beta 3 and TGF- beta 2 isoforms are detectable in neonatal mice within the renal tubular epithelial cells (TEC) and vascular smooth muscle cells (VSMC). In MRL-lpr mice 4-6 months of age, TGF- beta 2 and TGF- beta 1 are detected in TEC, VSMC, glomerular epithelial cells (GEC) and in perivascular infiltrating cells. By comparison, TGF- beta is minimally detectable in the normal kidneys of age and sex matched MRL(-)+2 or C3H/Fej mice. Paradoxically, in vitro cultured TEC and VSMC from MRL-lpr mice secrete less TGF- beta than TEC and VSMC isolated from MRL(-)+2 or C3H/FeJ mice. TNF- alpha, but not IL-6, CSF-1, or IFN- gamma stimulated the secretion of TGF- beta in TEC and VSMC. Our data demonstrate the dysregulation of TGF- beta isoforms in neonatal and adult MRL-lpr mice prior to and after the onset of autoimmune renal disease. We suggest that TNF- alpha and/or other molecules increase TGF- beta expression in MRL-lpr mice. We speculate that enhanced expression of TGF- beta promotes autoinmune renal injury in MRL-lpr mice.

Aging↗
PubMed1996

Sequential changes of energy charge, lipoperoxide level, and DNA synthesis rate of the liver following biliary obstruction in rats.

To clarify the effects of obstructive jaundice on the liver, sequential changes of hepatic energy charge, the concentrations of adenine nucleotides and malondialdehyde, DNA synthesis rate, and histology of the liver were examined on the day before and Days 1, 2, 4, 7, and 14 after biliary obstruction in rats and compared with those of sham-operated controls. Foci of necrotic hepatocytes were present on Days 1 and 2 and mitoses of the hepatocytes were frequently observed with a peak on Day 2 in the jaundiced liver. Marked proliferation of bile ductules were subsequently observed on Days 7 and 14, resembling biliary cirrhosis. The DNA synthesis rate was significantly activated after bile duct obstruction with its peak on Day 2, more than nine times higher than the control value and returned to the control level on Day 14. Hepatic ATP concentration and energy charge gradually declined with prolonged jaundice and significantly lower levels persisted after Day 7 compared with the controls. The malondialdehyde level in the jaundiced liver gradually increased and became significantly higher on Day 14. We conclude that obstructive jaundice decreases hepatic energy charge and increases the lipoperoxide level. In the initial stage of obstructive jaundice, the hepatocytes proliferate associated with activated DNA synthesis probably to compensate hepatic damage; however, prolonged obstructive jaundice induces functional hepatic injury possibly necessitating biliary drainage.

Adenosine Triphosphate↗
PubMed1996

Bile acid synthesis and biliary hydrophobicity during obstructive jaundice in rats.

Hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, is regulated by bile acid returning to the liver. In the bile duct-ligated rats, however, cholesterol 7alpha-hydroxylase activity is known to increase in spite of the elevated serum bile acids. The aim of this study was to investigate the relationship between the bile acid synthesis and biliary hydrophobicity to solve the paradoxical phenomenon. Male Wister rats (250-350 g) were divided into two groups, bile duct-ligated group and sham-operated group. Rats were sacrificed on the Days 1, 2, 4, 7, and 14 after the operation. Cholesterol 7alpha-hydroxylase activity, biliary bile acid composition, and biliary hydrophobicity were analyzed. Hepatic and serum total bile acid concentrations and serum 7alpha-hydroxycholesterol levels were also determined. Bile duct ligation caused significant increases in hepatic and serum bile acid concentrations on Day 1, which persisted for 14 days after the bile duct ligation. Activities of hepatic cholesterol 7alpha-hydroxylase increased to 3.2-fold of the preoperative value on Day 2, remained significantly high until Day 7, and then decreased to the basal value on Day 14. The serum 7alpha-hydroxycholesterol level essentially behaved in a similar fashion to that of hepatic cholesterol 7alpha-hydroxylase activity with a significant (P < 0.01) positive correlation. beta-Muricholic acid was predominant in bile until Day 7 (71 vs 10% in the controls on Day 4; P < 0.05) with a concomitant decrease in the proportion of cholic acid. Biliary bile acid became less hydrophobic and hepatic cholesterol 7alpha-hydroxylase activity significantly correlated with the hydrophobicity of biliary bile acids (n = 55, r = 0.54, P < 0.01). There were no significant correlations between the activity of cholesterol 7alpha-hydroxylase and total bile acid concentrations in serum, liver, or bile. The increased cholesterol 7alpha-hydroxylase activity is accompanied by the decreased biliary hydrophobicity, which may be a rationale for the paradoxical increase in bile acid synthesis in spite of the accumulation of bile acids in the serum and liver during obstructive jaundice in rats.

Animals↗
PubMed1996

Oxysterols found in opacified cornea of fish.

We describe a new concept implicating oxidized cholesterol derivatives and very long-chain fatty acids as possible factors in the development of corneal opacification after death. Corneal tissues, removed from both fresh and stale fish eyes, were examined for cholesterol derivatives and fatty acids after methanolysis of lipids. Cholesta-3,5-dien-7-one, cholest-4-en-3-one, hexacosenoic acid, and hexacosenoic acid were identified via gas chromatography/mass spectrometry in opacified corneas, but not in significant amounts in fresh ones. The present study confirmed the presence of lipid hydrolysis and a peroxidation process in the opacified cornea.

Animals↗
PubMed1996

Transplant approach establishes that kidneys are responsible for serum CSF-1 but require a stimulus in MRL-lpr mice.

Colony stimulating factor-1 (CSF-1) is a chemoattractant and growth factor for macrophages. In autoimmune MRL-lpr mice, CSF-1 is detected in the circulation and there is an increase in CSF-1 transcripts and macrophages in the kidney. The purpose of this study was to establish whether the MRL-lpr kidney is responsible for increasing serum CSF-1, and to determine if the expression of CSF-1 requires a circulating component in MRL-lpr mice. We transplanted a MRL-lpr kidney with nephritis [serum CSF-1 = 32.6 +/- 5.1 colony forming units (CFU)] into a bilaterally nephrectomized normal MRL-++ recipient. Circulating CSF-1 increased from 1.2 +/- CFU to 14.1 +/_ 5.6 CFU in recipients by one week. Continuous production of CSF-1 required a stimulating component since: (1) CSF-1 in the kidney and circulation disappeared several weeks after engraftment into MRL-++ mice and (2) isolated glomeruli from MRL-lpr required stimulation to express CSF-1. In the transplanted MRL-lpr kidney, hypercellularity in the glomerulus and interstitium (predominantly macrophages) returned to normal as rapidly as two weeks after engraftment into MRL-++. Thus, this study establishes that the kidney is responsible for circulating CSF-1 in MRL-lpr mice. Without the autoimmune environment CSF-1, macrophages, but not T cells, disappear and nephritis resolves.

Animals↗
PubMed1996

Some problems in wrist reconstruction after tumor resection with vascularized fibular-head graft.

Restoration of wrist function was attempted in six patients with aggressive or malignant bone tumor of the distal end of the radius with free vascularized fibular graft including the fibular head, and following wide resection of tumor. There was no local recurrence in all six cases. In one case, pulmonary metastasis occurred, but was successfully treated. Secondary bone graft was necessary in two cases for non-union. Additional procedures, such as partial or total wrist fusion, were necessary in three cases due to collapse of the grafted fibular head. Corrective osteotomy or a Sauve-Kapandji procedure were also needed in two cases for improvement of forearm rotation. Grip strength ranged from 41 to 68 percent of the contralateral side, with an average of 54.6 percent in five cases; it was only 6 percent in one patient because of flexion contracture at the wrist joint. Final functional results, evaluated by a modified system of Enneking, ranged from 73 to 92 percent, with an average of 83.2 percent. Indications for this procedure seem to be limited to patients engaged in non-heavy manual work, in whom the proximal carpal row can be preserved during tumor resection, and who have given consent for additional secondary procedures, if they prove necessary.

Adult↗
PubMed1996

Identification of cholesta-3,5-dien-7-one by gas chromatography-mass spectrometry in the erythrocyte membrane of alcoholic patients.

Lipids and oxidized lipids were analyzed by gas chromatography-mass spectrometry in the erythrocyte membranes of alcoholic and control subjects. Cholesta-3,5-dien-7-one and cholesta-trienes were detected in alcoholic samples examined, but not in significant amounts in controls. Levels of polyunsaturated fatty acids (arachidonic acid, 20:4; docosahexaenoic acid, 22:6; and docosatetraenoic acid, 22:4) in alcoholic samples declined significantly, whereas cholesta-3,5-dien-7-one levels increased. A high level of total bilirubin was observed in most patients. A possible mechanism of the accumulation of cholesta-3,5-dien-7-one in the erythrocyte membrane of alcoholics is discussed.

Adult↗
PubMed1996

Clinical evaluation of carbocyclic oxetanocin G eyedrops in the treatment of herpes simplex corneal ulcers.

BACKGROUND: Acyclovir (ACV) ophthalmic ointment is effective in the treatment of herpetic keratitis. However, when applied, the ointment has an unpleasant feeling and some cases are resistant to ACV. A new antiviral compound, carbocyclic oxetanocin G (C.OXT-G) has potent anti-herpes simplex virus activity and high water solubility, so the clinical effect of C.OXT-G eyedrops on ulcerative herpetic keratitis was evaluated. METHODS: Studies were conducted on the corneal ulcers in 37 eyes of 27 patients. Patients with typical dendritic or geographic corneal ulcers were treated with 0.1% C.OXT-G eyedrops, applied five times a day, together with eyedrops of an antibiotic applied four times a day. The eyes were examined at least twice a week until the ulcers healed, and thereafter at intervals for up to 3 months. RESULTS: All of the ulcers healed, their average healing time being 4.9 (SD 2.2) (range 2 to 9) days. The ulcers in 20 of the 37 eyes were induced by the use of corticosteroid or immunosuppressive drugs, and their average healing time was 4.8 (2.3) days. No adverse drug reactions were seen during the observation period in this trial. CONCLUSION: Eyedrops containing 0.1% C.OXT-G are excellent and safe for treatment of herpes simplex corneal ulcers in humans.

Administration, Topical↗
PubMed1996

A gene transfer system establishes interleukin-6 neither promotes nor suppresses renal injury.

Conflicting reports claim that circulating interleukin (IL)-6 promotes or suppresses renal disease. Although autoimmune MRL-lpr mice have an increase in serum IL-6, and kidneys can produce IL-6, the relevance of systemic and local exposure remains undefined. To investigate the impact of IL-6 on kidney disease, we constructed a gene transfer approach to deliver sustained, stable IL-6 into the kidney and circulation. We infused syngeneic genetically modified tubular epithelial cells (IL-6-TEC) under the renal capsule of autoimmune and nonautoimmune mice. IL-6-TEC did not incite renal injury in any strain. Furthermore, serum IL-6 levels, which were increased three- to fivefold by IL-6-TEC, did not alter the contralateral kidney. Therefore, neither local nor systemic exposure to IL-6 promoted renal injury. As opposed to IL-6, we previously established that granulocyte macrophage (GM)-colony-stimulating factor (CSF) initiates renal injury in autoimmune mice. To determine whether IL-6 could suppress GM-CSF-incited damage, we infused GM-CSF-TEC TEC along with IL-6-TEC. Local production of IL-6 into the kidney did not alter the tempo or severity of GM-CSF-induced injury. Thus neither local nor systemic delivery of IL-6 promotes or suppresses kidney disease.

Animals↗
PubMed1996

Hepatic adenine nucleotides and DNA synthesis during the regenerative and atrophic process of the liver lobes after selective portal vein ligation.

Selective portal vein occlusion prior to aggressive hepatic resection is now an alternative way to decrease postoperative morbidity and mortality rates. However, the detailed changes in the hepatic energy status and DNA synthesis rate in both portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear. In rats, the portal branch that supplies 70% of the liver volume was ligated, and changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared with those in sham-operated rats. The weight of the PVL lobes decreased, while that of the PVNL lobes increased depending on time. The DNA synthesis rates of the PVNL lobes were significantly higher than those in sham-operated control liver during the first 4 days with the maximal value on the 2nd day, while those of PVL lobes were essentially similar to the control values. Energy charge (EC) in both PVL and PVNL lobes significantly decreased on day 1 and recovered gradually, but with less extent in the regenerating PVNL lobes. The concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes were essentially similar during the first 2 days, but became significantly lower in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on day 2 and subsequently enlarged lobules with an increased number of hepatocytes were histologic features in the PVNL liver. The AKBR was not correlated with hepatic energy charge of the liver. In conclusion, PVNL liver regenerates preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping TAN constant, while PVL liver becomes atrophic, with a similar change in EC of the PVNL liver but ultimately decreased TAN without any change in DNA synthesis. AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

Adenine Nucleotides↗
PubMed1996

Pulsed Doppler echocardiographic assessment of changes in pulmonary artery pressure during oxygen breathing.

To validate the use of pulsed Doppler echocardiography in detecting changes in pulmonary artery pressure (PAP), several parameters of flow velocity profiles of the right ventricular outflow tract were compared with changes in PAP and pulmonary vascular resistance measured directly by cardiac catheterization. The study was performed in 33 patients with chronic pulmonary disease (chronic obstructive pulmonary disease or pulmonary fibrosis) or pulmonary thromboembolism, during room air and 100% oxygen breathing. Inhalation of 100% oxygen for 15 min significantly reduced PAP in patients with mild pulmonary hypertension (20 < or = mean PAP < or = 24 mm Hg; control: 21.3 +/- 1.3, O2: 17.9 +/- 2.2 mm Hg, p < 0.05) and those with severe pulmonary hypertension (mean PAP > or = 25 mm Hg; control 44.9 +/- 16.8, O2: 35.4 +/- 13.5 mm Hg, p < 0.05). It also significantly reduced the pulmonary vascular resistance and cardiac output in both groups. The ratio of acceleration time to right ventricular ejection time (AT/RVET), a parameter measured by Doppler echocardiography, correlated significantly with mean PAP during room air (r = 0.73, p < 0.0001) and oxygen breathing (r = 0.64, p < 0.0001). Furthermore, AT/RVET increased significantly in patients with mild pulmonary hypertension and those with severe pulmonary hypertension. Our results suggest that the Doppler technique provides a clinically useful, noninvasive index for assessing changes in PAP during oxygen breathing in patients with pulmonary hypertension complicating chronic pulmonary disease or pulmonary thromboembolism.

Administration, Inhalation↗
PubMed1996

Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.

BACKGROUND: Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known. METHODS AND RESULTS: A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved. CONCLUSION: Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.

Aged↗
PubMed1996

[Limy bile].

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Calcium Carbonate↗
PubMed1996

Iodine-123-metaiodobenzylguanidine myocardial imaging in patients with right ventricular pressure overload.

UNLABELLED: Iodine-123-metaiodobenzylguanidine ([123I]MIBG) has been used to evaluate the cardiac sympathetic nervous system, particularly that of the left heart. To clarify whether the right ventricular (RV) sympathetic neuronal function could be evaluated by [123I]MIBG myocardial imaging, we applied the technique in patients with pulmonary hypertension that was associated with either chronic pulmonary diseases or pulmonary vascular diseases. METHODS: All patients underwent right heart catheterization, and right heart hemodynamics were determined during a clinically stable state. SPECT was performed in the resting state 15 min (early imaging) and 4 hr (delayed imaging) postadministration of [123I]MIBG. Seven regions of interest (ROI) were selected on the delayed short-axis images on the RV free wall, left ventricular (LV) free wall and interventricular septum (IVS). We calculated the IVS-to-LV uptake ratio from the scintillation counts of the ROI. Thallium-201 myocardial imaging was also performed within 1 wk after [123I]MIBG imaging. RESULTS: Images obtained with these techniques were analyzed for the RV-to-LV uptake ratio. The IVS-to-LV ratio on [123I]MIBG correlated negatively and significantly with the mean pulmonary arterial pressure (PAm). The RV-to-LV uptake ratio on 201Tl images correlated significantly with PAm. CONCLUSION: Our results suggest that the uptake ratio of [123I]MIBG in the IVS is a useful index for evaluating the severity of pulmonary hypertension, and that chronic RV pressure overload contributes to disturbances of the cardiac sympathetic nervous system.

3-Iodobenzylguanidine↗