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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 109 records · Page 6Linked to original sources
PubMed1998

Synthesis and antifungal activity of novel thiazole-containing triazole antifungals. II. Optically active ER-30346 and its derivatives.

A series of novel thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4- difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.

Animals↗
PubMed1998

Three-dimensional alveolar bone morphology analysis using computed tomography.

The purpose of the present study was to determine whether the use of 3-dimensional computed tomography (3DCT) is an effective method of imaging bone defect morphology caused by periodontal disease. A total of 186 sites from 9 patients were examined. Periodontal parameters were recorded after initial therapy. For the evaluation of bone resorption and root morphology, computed tomography (CT) scanning was performed and then CT images were reconstructed for 3-dimensional evaluation. Immediately prior to the surgery, bone sounding measurements were done under local anesthesia. The denuded bone measurement during periodontal surgery represented the true bone level. To compare the bone level obtained from 3DCT images with the true bone level, the examiner, without being informed of the patient's condition, traced the cemento-enamel junction (CEJ) and apical extent of the bone levels on the images of 3DCT, and measured the vertical distance between the CEJ and bone. The mean difference between 3DCT and the true bone level was 0.41+/-2.53 mm (mean+/-SD). The correlation between them showed a highly significant linear regression (R=0.75). However, the mean difference between the bone sounding level and the true bone level was 0.22+/-1.49 mm (R=0.91). Thus, bone sounding was slightly more accurate than 3DCT, but there was no significant difference between these two assessments (P >0.05). The results of present study indicate that 3DCT has the potential to allow precise assessment of bone defect caused by periodontal disease.

Adult↗
PubMed1998

Liddle's syndrome in an elderly woman.

A 78-year-old woman with hypertension was hospitalized with acute bronchitis. However, she was also found to have hypernatremia, hypokalemia, and metabolic alkalosis. Detailed examination showed a low plasma renin activity and plasma aldosterone concentration. A provisional diagnosis of Liddle's syndrome was established and the patient was successfully treated with triamterene. Although Liddle's syndrome is generally considered an inherited hypertensive disease found in young people, a review of the literature indicated that muscle weakness is an important clinical finding in elderly patients with this disease. Liddle's syndrome should be considered in the differential diagnosis of hypertension even in elderly individuals.

Aged↗
PubMed1998

[Intracranial aneurysms in autosomal dominant polycystic kidney disease detected by MR angiography: screening and treatment].

The association of intracranial aneurysm with ADPKD is well-known, and patients with ADPKD are at increased risk of subarachnoid hemorrhage from rupture of intracranial aneurysms. We prospectively performed three-dimensional time-of-flight magnetic resonance angiography (MRA) in 30 nonselective adult patients with ADPKD. Sixteen were women and 14 were men with a mean age of 51 yr (range 24 to 79 yr). The diagnosis of ADPKD was made on the basis of abdominal ultrasound or computed tomographic studies. Three patients were on maintenance hemodialysis, 8 patients were nondialysed patients with chronic renal failure (serum creatinine > or = mg/dl) and 25 patients had hypertension (BP > or = 140/90 mmHg). None of these patients have a previous diagnosis of intracranial aneurysm. Unruptured intracranial aneurysms were suspected in 5 patients by MRA, and 8 aneurysms were confirmed in 4 (13.3%) of 30 patients by conventional arteriography. These aneurysms were 3 approximately 10 mm in diameter and 3 aneurysms (3 approximately 4 mm in diameter) were newly detected by cerebral arteriography. After informed consent was obtained, neck clipping of the intracranial aneurysms were performed successfully in all the patients. These results suggest that the prevalence of intracranial aneurysms is about 13% in ADPKD, and that MRA is useful in screening for occult intracranial aneurysms in patients with ADPKD.

Adult↗
PubMed1998

[Lymphocyte chemotactic factor in tuberculous pleural effusion].

To evaluate whether lymphocyte chemotactic factor is involved in the accumulation of lymphocytes in tuberculous pleurisy, we measured lymphocyte chemotactic activity in tuberculous pleural effusions, and compared with that in malignant pleural effusions and transudate. The lymphocyte chemotactic activity was measured in vitro with chemotactic chamber. The cells suspended in the culture medium was added to the upper well and the effusions, normal human serum (NHS), or culture medium were placed below nitrocellulose filter. The lymphocyte migration was quantified by counting the number of cells migrating beyond a distance of 70 microns from top of the filter in 5 selected fields. The chemotactic activity of the effusions was expressed as a percentage of the control migration in the culture medium. When we used the freshly isolated peripheral blood lymphocytes as responding cells, the chemotactic activity was 176.0 +/- 41.3% in tuberculous effusions, 115.1 +/- 53.8% in malignant effusions, 87.1 +/- 16.1% in transudate, and 113.3 +/- 24.2% in NHS, respectively. The activity of tuberculous effusions was significantly higher than that of transudate and NHS. When we used PHA-activated lymphocytes, the activity was 284.4 +/- 159.3% in tuberculous effusions, 123.1 +/- 77.6% in malignant effusions, 75.8 +/- 10.3% in transudate, and 52.6 +/- 10.1% in NHS, respectively. The activity of tuberculous effusions was significantly higher than that of malignant effusions, transudate and NHS. The chemotactic activity of tuberculous effusions to PHA-activated lymphocytes was significantly higher than that to freshly isolated lymphocytes. The activity was specific for T lymphocytes, and showed both chemotaxis and chemokinesis by checkerboard analysis. Gel filtration performed with Sephacryl S-200 revealed that the chemotactic activities in a tuberculous fluid had three peaks located in the regions between blue dextran and immunoglobulin G, near to human albumin and cytochrome c marker. The most potent activity was found at the region near human albumin. Lymphocyte chemotactic factor in tuberculous effusion may stimulate the migration of T lymphocytes, especially the activated T lymphocytes to the pleural spaces.

Chemokines, C↗
PubMed1998

[A clinicopathological study of recurrent IgA nephropathy following renal transplantation].

The present study was conducted to examine the clinicopathological features of recurrent IgA nephropathy (IgAN) following renal transplantation. Serial renal biopsies were performed regularly at 0-hour, 1-hour and 2-hours, and 39 episode biopsies were carried out when patients had increased serum creatinine levels and proteinuria. In 49 renal allograft recipients with IgAN, 12 patients were proved to be recurrent IgAN (24.5%). There was a significantly increased five- and ten-year risk of graft loss in the renal allograft recipients with biopsy-proved recurrent IgAN. Graft survival in 49 renal allograft recipients with IgAN was worse (68.8% at 5 years and 40.4% at 10 years) than that in 997 whole transplants (80.7% at 5 years, and 67.7% at 10 years). We found significant differences in the prevalence of HLA-DR4 (66.7%) and BW35 (25%) in the renal allograft recipients with recurrent IgAN when compared with normal healthy subjects. The renal allograft recipients with recurrent IgAN had a high incidence of proteinuria (8/12), hypertension (9/12) and renal dysfunction of less than 50 ml/min (7/12). Mean hemodialysis duration before renal transplantation in recurrent IgAN transplants was 12.5 months, which was shorter than in those without recurrent IgAN. Histopathological studies revealed that renal lesions due to IgAN frequently appeared in the renal allograft recipients with recurrent IgAN. Taken together, these findings suggest that donor-recipient matching may be carefully reconsidered, and recurrent IgAN after renal transplantation must be treated with effective immunosuppressive therapy.

Adult↗
PubMed1998

[The coexistence of pulmonary tuberculosis and thymoma a case report].

A 33-year-old male was admitted with complaints of cough, dysphagia, and swelling of face and upper extremities. Chest X-ray and CT scan revealed a large mediastinal mass and infiltrates in the right upper lobe. Percutaneous biopsy proved the mediastinal tumor as thymoma with cellular atypia. After irradiation, the tumor was surgically removed. Caseous epitheloid granulomas were found in the dissected mediastinal lymph nodes. AFB (Acid fast bacillus) stain of the patient's gastric fluid was positive for Mycobacterium. The coexistence of these two diseases was incidental, however, this case suggested that clinicians should perform careful evaluation of lung parenchyma as well as mediastinum on chest X-ray to identify occult diseases including pulmonary tuberculosis in patients with mediastinal mass lesion.

Adult↗
PubMed1997

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction.

BACKGROUND: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. METHODS: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotides and energy charge levels. The values were compared with those in the sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography--mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. RESULTS: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissues linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and each adenine nucleotide level did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. CONCLUSIONS: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in both the BDO and FD lobes of the liver.

Adenine Nucleotides↗
PubMed1997

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction.

BACKGROUND: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. METHODS: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotide and energy charge levels. The values were compared with those in sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography-mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. RESULTS: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissue linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and adenine nucleotide levels did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. CONCLUSIONS: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in either BDO or FD lobes of the liver.

Adenine Nucleotides↗
PubMed1997

Cholestyramine loading test to assess hepatic reserve for bile acid synthesis in patients with chronic liver diseases.

BACKGROUND & AIMS: Serum 7alpha-hydroxycholesterol level reflects hepatic bile acid synthesis in humans. The aim of this study was to examine the maximal bile acid synthesis in patients with chronic liver diseases. METHODS: Cholestyramine (12 g/day) was administered for 3 days to patients with compensated liver cirrhosis (n = 7), patients with chronic hepatitis (n = 10), and control subjects (n = 9), and serum total 7alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry. RESULTS: A preliminary study showed that cholestyramine increased the serum value to the maximum by the third day. Before cholestyramine treatment, there were no significant differences in serum 7alpha-hydroxycholesterol levels among the groups. Three days of cholestyramine treatment increased the serum levels 5.71 +/- 2.90-fold in the controls, 3.25 +/- 0.85-fold in patients with chronic hepatitis, and 1.70 +/- 0.78-fold in cirrhotic patients. Cirrhotic patients had significantly lower serum 7alpha-hydroxycholesterol levels after the treatment compared with other groups. Serum 7alpha-hydroxycholesterol levels stimulated by cholestyramine significantly correlated with serum albumin levels and indocyanine green retention rate. CONCLUSIONS: Three days of cholestyramine loading increased the bile acid synthesis to its maximal level. The cholestyramine test showed that patients with chronic hepatitis had enough hepatic reserve for bile acid synthesis; however, patients with compensated liver cirrhosis had significantly decreased capacity.

Aged↗
PubMed1997

Clinical assessment of the significance of platelet-derived growth factor in patients with immunoglobulin A nephropathy.

To examine the role of platelet-derived growth factor (PDGF) in the pathogenesis of IgA nephropathy (IgAN), we investigated the expression of PDGF and the PDGF receptor in glomeruli with immunohistochemistry, the plasma levels of PDGF with ELISA, and the expression of PDGF in peripheral blood monocytes (PBMCs) with reverse transcription polymerase chain reaction (RT-PCR). We also assessed the effect of corticosteroid therapy on the plasma levels of the PDGF B-chain. At the time of kidney biopsy, the expression of the PDGF B-chain and the PDGF beta receptor in the glomeruli was upregulated in patients with IgAN. In addition, the plasma concentration of the PDGF B-chain was significantly higher in patients with IgAN than in normal subjects. Moreover, mRNA expression of PDGF beta-chain in PBMCs was up-regulated in patients with IgAN when compared with other patients with glomerulonephritis. We divided the patients into two groups according to the grade of urinary protein excretion (U[p]) after corticosteroid therapy. In patients in group 1 in whom U(p) was decreased by more than 50% or 1 gm/day after corticosteroid therapy, the expression of the PDGF B-chain and the PDGF beta receptor in the glomeruli was up-regulated. Finally, corticosteroid therapy decreased the plasma levels of PDGF B-chain in patients in group 1. Up-regulation of the PDGF B-chain and beta receptor in the glomeruli, elevated plasma levels of PDGF B-chain, and increased expression of PDGF mRNA in PBMCs could be associated with the pathogenesis of IgAN. The plasma concentration of PDGF B-chain may be a useful marker for patients with IgAN who would be responsive to corticosteroid therapy.

Adolescent↗
PubMed1997

Periodontal parameters of osseointegrated dental implants. A 4-year controlled follow-up study.

The aim of this study was to evaluate the periodontal parameters of osseointegrated dental implants. The condition of the peri-implant mucosa was assessed using periodontal parameters, i.e., of plaque index, bleeding on probing, probing pocket depth, probing attachment level and Periotest scores as well as a radiographic parameter, over a 4-year follow-up period. 32 non-submerged ITI dental implants, all placed in the mandible, were studied in 12 patients who had good oral hygiene. All patients were regularly recalled at 6-month intervals. The overall implant success rate was 100%. None of the implants showed any signs of inflammation, radiographic bone loss or any detectable mobility during the follow-up period. Methods similar to those used to evaluate the natural dentition were effectively employed to assess the clinical status of the dental implants. The diagnostic value of these parameters could not, however, be determined from this study due to the absence of any peri-implant tissue complications. The results indicated that some periodontal parameters of healthy peri-implant mucosa might be slightly different from healthy periodontal tissue.

Alveolar Process↗
PubMed1997

Systemic autoimmune nephritogenic components induce CSF-1 and TNF-alpha in MRL kidneys.

MRL-Faslpr mice are an appealing strain to understand the importance of cytokines in the pathogenesis of autoimmune renal destruction, since injury is rapid and predictable. Colony stimulating factor 1 (CSF-1) and tumor necrosis factor alpha (TNF-alpha) are detected in the kidney and circulation prior to renal injury and continue to increase with progressive renal damage in MRL-Faslpr, Fas deficient mice, but not the congenic Fas intact MRL-(++) strain. Delivery of CSF-1, but not TNF-alpha, into the kidney via gene transfer incites local renal injury. By comparison, dual gene transfer of CSF-1 and TNF-alpha incites autoimmune renal injury that is far more severe than CSF-1 alone. The purpose of this study was to establish whether CSF-1 and TNF-alpha incites autoimmune renal injury that is far more severe than CSF-1 alone. The purpose of this study was to establish whether CSF-1 and TNF-alpha expression in the kidney of MRL-Faslpr mice induced by a circulating stimulant resulted from a primary defect in the kidney. Therefore, we transplanted (Tx) a MRL-(++) kidney without CSF-1, TNF-alpha and renal injury into an MRL-Faslpr recipient after removing nephritic kidney expressing CSF-1 and TNF-alpha. The Tx kidneys were examined after 2, 4, 5, 6, and 12 weeks. CSF-1 and TNF-alpha were rapidly induced in the MRL-(++) Tx kidney. CSF-1 and TNF-alpha were evident by two weeks and continually increased for 12 weeks post-transplantation. Within several weeks, the rapid expansion of M phi and T cells and induction of glomerulonephritis and interstitial nephritis in the MRL-(++) Tx kidney was similar to the age-matched native MRL-Faslpr kidney. In conclusion, we have constructed an experimental transplantation system that can explore whether cytokine expression in the kidney induced by a circulating stimulant is a result of a primary defect in the kidney. Using this approach, we established that the MRL-Faslpr kidney is not defective, but rather a circulating stimulant in the MRL-Faslpr mouse can induce CSF-1, TNF-alpha and renal injury in a normal MRL-(++) kidney. Thus, we exclude an intrinsic defect in the MRL-Faslpr kidney as the pathogenic mechanism responsible for tissue damage. We suggest purging the circulation of molecules that induce CSF-1 and TNF-alpha as a therapeutic strategy for autoimmune renal injury.

Animals↗
PubMed1997

Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus.

The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg/kg for vancomycin; and >200, >200, and 15.9 mg/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P < 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem.

Animals↗
PubMed1997

A new type of illegitimate recombination is dependent on restriction and homologous interaction.

Illegitimate (nonhomologous) recombination requires little or no sequence homology between recombining DNAs and has been regarded as being a process distinct from homologous recombination, which requires a long stretch of homology between recombining DNAs. Under special conditions in Escherichia coli, we have found a new type of illegitimate recombination that requires an interaction between homologous DNA sequences. It was detected when a plasmid that carried 2-kb-long inverted repeats was subjected to type II restriction in vitro and type I (EcoKI) restriction in vivo within a delta rac recBC recG ruvC strain. Removal of one of the repeats or its replacement with heterologous DNA resulted in a reduction in the level of recombination. The recombining sites themselves shared, at most, a few base pairs of homology. Many of the recombination events joined a site in one of the repeats with a site in another repeat. In two of the products, one of the recombining sites was at the end of one of the repeats. Removal of one of the EcoKI sites resulted in decreased recombination. We discuss the possibility that some structure made by homologous interaction between the long repeats is used by the EcoKI restriction enzyme to promote illegitimate recombination. The possible roles and consequences of this type of homologous interaction are discussed.

Base Sequence↗
PubMed1997

Urokinase-type plasminogen activator in carcinomatous pleural fluid.

Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant cells during proliferation and migration, and is associated with tumour cell invasion and metastasis. This study was undertaken to evaluate whether u-PA is significantly increased in carcinomatous pleural fluids compared to those due to other aetiologies, and to identify the cells in the pleural space that are involved in its accumulation. Using an enzyme-linked immunosorbent assay, we quantified u-PA in the pleural fluid specimens of 40 patients with carcinomatous pleuritis, 18 with tuberculosis, 18 with parapneumonic pleuritis and 11 with congestive heart failure (CHF). The level of u-PA was elevated in carcinomatous pleural fluid compared with the level in transudative pleural fluid from patients with CHF (p<0.0001). The levels of u-PA were not statistically different between patients with cancer and tuberculosis, or between patients with cancer and pneumonia. The levels of u-PA in patients who did not respond to chemical pleurodesis were significantly higher than those who had complete response (p=0.0001). In immunocytochemical and immunoblotting studies, cancer cells in pleural fluids as well as mesothelial cells contained u-PA. u-PA was detected in the culture supernatants of viable pleural cells in the majority of patients with carcinomatous pleuritis. Our results suggest that local release of urokinase-type plasminogen activator by viable cells, including cancer cells and mesothelial cells, may affect the levels of urokinase-type plasminogen activator in pleural fluids.

Adenocarcinoma↗