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Biomedical subjects

S Kohno

Publications and source records attributed to S Kohno.

At least 253 records · Page 14Linked to original sources

Activation of lymphocytes and increased interleukin-5 levels in bronchoalveolar lavage fluid in acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is a recently described illness and the number of case reports has increased during the last few years. However, the role of interleukin (IL)-5 and activated lymphocytes in the pathogenesis or activity of AEP is still not clear. The clinical features, lymphocyte surface analysis and IL-5 concentrations in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) of a young female patient with AEP are described before and at 2 weeks, 4 weeks and 6 months after a 3-day course of i.v. methylprednisolone. Serum and BALF concentrations of IL-5 before treatment were 5,200 and 8,400 pg x mL(-1), respectively. Activated CD4 lymphocytes bearing CD25 and human leukocyte antigen (HLA)-DR in BALF were higher than in PB. Treatment caused a rapid fall in these cells and levels of IL-5 in BALF returned to normal levels in parallel with clinical improvement. There was no evidence of recurrence after cessation of steroid therapy. In contrast, eosinophilia in BALF persisted for 4 weeks after steroid therapy in spite of normalization of the chest radiograph and arterial blood gases. The number of CD8+CD11b- (suppressor/cytotoxic) T-cells subsequently increased while the number of CD8+CD11b+ cells decreased. These results suggest that activated CD4 cells and interleukin-5 elevation contribute to the development of acute eosinophilic pneumonia rather than persistent eosinophilia in the lung and that a short course of steroid therapy may effectively control acute eosinophilic pneumonia.

Acute Disease↗

Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis.

Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.

Adult↗

Elevated levels of beta-chemokines in bronchoalveolar lavage fluid (BALF) of individuals infected with human T lymphotropic virus type-1 (HTLV-1).

Pulmonary complications are known to develop in HTLV-1 carriers, including T lymphocytic alveolitis, and increased IL-2 receptor alpha (CD25)-bearing T cells have been found in BALF. Several chemokines may contribute to accumulation of T lymphocytes in the lungs of HTLV-1 carriers. Here, we compared the distribution of T lymphocyte subsets and beta-chemokines, such as macrophage inflammatory peptide-1alpha (MIP-1alpha), regulated on activation normal T expressed and secreted (RANTES), and macrophage chemoattractant protein-1 (MCP-1), in BALF and peripheral blood between HTLV-1 carriers and non-infected healthy normal subjects. Flow cytometric analysis with MoAbs to cell surface antigens was used to identify T lymphocyte subsets in BALF samples from HTLV-1 carriers (n = 13) and non-infected healthy controls (n = 10). The levels of different beta-chemokines were estimated by ELISA. High percentages of CD3+ cells, CD3 expressing HLA-DR antigen and CD3+CD25+ cells were detected in BALF of HTLV-1 carriers compared with non-infected controls. The concentration of MIP-1alpha in BALF of patients was significantly higher than in non-infected healthy controls and correlated well with the percentage of CD3+CD25+ cells. The level of RANTES in BALF was also significantly high in HTLV-1 carriers, but did not correlate with the percentage of CD3+CD25+ cells. On the other hand, the level of MCP-1 in BALF of HTLV-1 carriers was not different from that of controls. Our results suggest a possible interaction between activated T cells bearing CD25 and beta-chemokines, especially MIP-1alpha, which may contribute to the pulmonary involvement in HTLV-1 carriers.

Adult↗

A close relationship between Helicobacter pylori infection and gastric xanthoma.

BACKGROUND: Although the pathogenesis of gastric xanthoma (GX) remains unclear, an association of GX with atrophic gastritis has been reported. Helicobacter pylori is closely related to atrophic gastritis. The aim of this study was to investigate the relationship among GX, H. pylori, and atrophic gastritis. METHODS: Sixty-seven patients with GX were assessed for H. pylori infection by serum anti-H. pylori IgG antibody, in addition to the rapid urease test, culture, and histologic examination using biopsy specimens of the antrum and corpus. The findings were compared with 67 age- and sex-matched control subjects without GX. The distribution of atrophic gastritis was assessed endoscopically. The severity of atrophic gastritis was determined endoscopically and histologically. Serum pepsinogen (PG) levels were also measured. Immunohistochemical staining of GX samples for H. pylori antigen was performed. H. pylori clinical isolates from patients with GX and controls were assessed for cagA by means of polymerase chain reaction. RESULTS: The prevalence of H. pylori was significantly higher in patients with GX than in controls (94% and 72%, respectively). A significantly more extensive atrophic gastritis was present in patients with GX, as determined endoscopically and histologically, than in controls. Serum PG-I levels and the PG-I/PG-II ratio were significantly lower in the GX group than in the control group. H. pylori antigens were frequently identified in the cytoplasm of xanthoma cells in H. pylori-positive specimens of GX (54 of 63 specimens, 86%), whereas no immunoreactivity for H. pylori antigens was detected in H. pylori-negative specimens of GX. There was no significant difference in the positive rate of cagA between the two groups. CONCLUSIONS: Our results identified a close relationship among H. pylori infection, GX, and atrophic gastritis. A proportion of GXs may be provoked by H. pylori infection.

Aged↗

Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.

In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.

Cisplatin↗

Relationship between genetic alteration of the rpsL gene and streptomycin susceptibility of Mycobacterium tuberculosis in Japan.

We have investigated the effect of genetic alterations in the rpsL gene on the MICs of streptomycin for Mycobacterium tuberculosis strains. Direct DNA sequencing showed a point mutation in 23/121 strains; in 18 strains the mutation was associated with an amino acid change. The MICs of streptomycin in 22 out of 23 point-mutated strains were > or = 256 mg/L. Restriction fragment length polymorphism (RFLP) analysis showed mutations at codon 43 in all 18 strains with point mutations in the same codon. Our results suggest that both RFLP and base sequencing analysis of the rpsL gene are useful for the rapid prediction of highly streptomycin-resistant strains of M. tuberculosis.

Deoxyribonucleases, Type II Site-Specific↗

Rhodamine 6G efflux for the detection of CDR1-overexpressing azole-resistant Candida albicans strains.

We investigated the drug efflux mechanism in azole-resistant strains of Candida albicans using rhodamine 6G (R6G). No significant differences in R6G uptake were observed between azole-sensitive B2630 (9.02 +/- 0.02 nmol/10(8) cells) and azole-resistant B67081 (8.86 +/- 0.03 nmol/10(8) cells) strains incubated in glucose-free phosphate buffered saline. A significantly higher R6G efflux (2.0 +/- 0.21 nmol/10(8) cells) was noted in the azole-resistant strain (B67081) when glucose was added, compared with that in the sensitive strain B2630 (0.23 < or = 0.14 nmol/10(8) cells). A fluconazole-resistant strain C40 that expressed the benomyl resistance gene (CaMDR) also showed a low R6G efflux (0.16 +/- 0.06 nmol/10(8) cells) as did the sensitive strains. Accumulation of R6G in growing C. albicans cells was inversely correlated with the level of CDR1 mRNA expression. Our data also suggest that measurement of intracellular accumulation of R6G is a useful method for identification of azole-resistant strains due to CDR1-expressed drug efflux pump.

Antifungal Agents↗

In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.

Animals↗

Simultaneous assessment of right ventricular function and hypertrophy by Tc-99m MIBI.

PURPOSE: Tc-99m MIBI allows the simultaneous performance of cardiac blood pool scintigraphy and myocardial SPECT. The authors performed studies to determine whether right ventricular function and hypertrophy can be evaluated simultaneously using Tc-99m MIBI in patients with right heart disease. METHODS: Using right heart catheterization, several parameters of pulmonary circulation were measured, including right ventricular ejection fraction, in 23 patients with chronic pulmonary disease and pulmonary vascular disease. Within 1 week, right heart blood pool scintigraphy was performed using the first-pass method using Tc-99m MIBI. The right ventricular ejection fraction calculated from right heart blood pool scintigraphy was compared with that measured using right heart catheterization. Myocardial SPECT was performed 1 hour after right heart blood pool scintigraphy. On the short axis images, which allowed optimal visualization of the right ventricle, the right and left ventricular free walls were established as regions of interest. Myocardial wall counts were determined. The right ventricular uptake: left ventricular uptake ratio was calculated to study the relation of that ratio to mean pulmonary artery pressure and total pulmonary resistance. RESULTS: A significant correlation was observed between the right ventricular ejection fraction calculated on right heart catheterization and that calculated on right heart blood pool scintigraphy. The right ventricular uptake:left ventricular uptake ratio correlated positively with pulmonary artery pressure and total pulmonary resistance. CONCLUSION: These results suggest that Tc-99m MIBI allows simultaneous noninvasive evaluation of cardiac function and structure, which previously was considered impossible in patients with right heart disease.

Female↗

Development of hepatocellular carcinoma in a patient with chronic hepatitis C after 6 years of a sustained and complete response to IFN-alpha.

The authors report a rare case of hepatocellular carcinoma (HCC) that developed 6 years after a sustained and complete response to interferon (IFN) therapy for chronic hepatitis C. A 61-year-old Japanese man presented with a mass in the liver that was diagnosed as HCC. Six years earlier he was treated with IFN-alpha and responded successfully to therapy, with sustained normalization of serum aminotransferases and eradication of serum hepatitis C virus (HCV)-ribonucleic acid (RNA). HCV-RNA was also not detected in the resected tumorous and nontumorous liver tissues. The findings suggest that all patients with chronic HCV infection should be followed closely for as long as possible for the potential development of HCC even after a complete and sustained response to IFN treatment.

Carcinoma, Hepatocellular↗

Low prevalence of Helicobacter pylori in individuals with HTLV-I infection.

BACKGROUND: The prevalence of Helicobacter pylori in HIV-positive individuals is significantly lower than in HIV-negative controls. However, its prevalence in individuals infected with human T-cell leukaemia virus type I (HTLV-I), another important member of the human retrovirus family, has not been previously investigated. OBJECTIVE: To establish the prevalence of H. pylori in HTLV-I-positive individuals in the Nagasaki Prefecture, which is an area endemic for HTLV-I. METHODS: We examined sera from 146 HTLV-I-positive individuals with a mean age of 56.7 years, consisting of 45 adult T-cell leukaemia (ATL) patients, 13 HTLV-I-associated myelopathy (HAM) patients and 88 healthy carriers. Serum samples of 292 age- and sex-matched HTLV-I-negative controls were also examined. Serum anti-H. pylori immunoglobulin (Ig) G antibody was examined using an enzyme-linked immunosorbent assay kit. Twenty-eight HTLV-I-positive patients were examined endoscopically, assessed for H. pylori by culture, histology and CLO test using gastric biopsy specimens, and gastritis in these patients was also graded histologically. RESULTS: The seroprevalence of H. pylori was 48% in HTLV-I-positive individuals versus 64% in HTLV-I-negative controls (P < 0.01). In the three HTLV-I-positive groups, ATL patients and carriers had significantly lower seroprevalence of H. pylori than the HTLV-I-negative controls (P < 0.05). Assessment of H. pylori using gastric biopsy specimens also showed a significantly lower prevalence of H. pylori infection in HTLV-I-positive patients than controls (46% versus 70%, P < 0.05). Histological examination showed a significantly higher degree of activity, inflammation and glandular atrophy in the antrum and corpus in H. pylori-positive patients compared to H. pylori-negative patients. H. pylori-positive patients with HTLV-I infection had a more severe degree of glandular atrophy in the corpus than H. pylori-positive controls without HTLV-I infection. CONCLUSION: We have found a reduced prevalence of H. pylori in HTLV-I-positive individuals. Whatever the explanation, infection with HTLV-I does not predispose to the risk of H. pylori infection.

Adult↗

Autoimmune cholangitis and primary biliary cirrhosis--an autoimmune enigma.

AIMS/BACKGROUND: Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected antimitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases PBC and 16 cases of AIH from selected Japanese patients. METHODS: The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared. RESULTS: By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex. CONCLUSION: Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.

Adult↗

[A case of a sudden death from Vibrio vulnificus septicemia in a patient with liver cirrhosis].

A 46-year-old male patient with alcoholic cirrhosis of the liver was carried to our out-patient clinic as he had developed shock while under routine follow-up, and died on the way to the hospital. He had been admitted several times since the diagnosis eight years ago, and was finally discharged from the hospital six weeks ago with improved physical condition and laboratory findings. A vesicle and bulla formation with phlegmon on the skin of right leg and sole of foot was noticed. Vibrio vulnificus was detected from the purulent discharge of the skin on culture. We conclude that the patient developed V. vulnificus-septicemia which resulted in sudden death. Since V. vulnificus infection may frequently take a fulminant course in patients with liver cirrhosis, adequate measures should be taken for early diagnosis and treatment to prevent the fatal outcome.

Bacteremia↗

[A case of pulmonary cryptococcosis with lung cancer in a pulmonary lobe].

A 63-year old female was admitted because of an abnormal shadow on chest X-ray film. Chest CT showed a nodular shadow in the right S6 and a patchy shadow in the right S10. Right lower lobectomy was performed under a diagnosis of lung cancer made by TBLB in the right S6. Pathological examination of the resected lung revealed papillary adenocarcinoma in the right S6 and numerous cryptococci in the right S10. No cryptococcal infection was found in the resected lymph nodes.

Adenocarcinoma, Papillary↗

[The booster phenomenon in two-step tuberculin testing of employees in a community hospital].

A study was made to clarify to what degree the booster phenomenon was present when the employees in a community hospital in Japan received two-step tuberculin testing (PPD). Of the seventy-five employees, most of all BCG-vaccinated subjects, twenty-three showed strongly positive of more than 30 mm of induration at the first test (PPD/T1), and the remaining fifty-two subjects received a second (PPD/T2) after 2 weeks. The second PPD showed a marked increase in reactivity, sixteen subjects newly became strongly positive and six of eight who were initially PPD negative (< 10 mm) were converted positive, and the mean reaction size changed from 14.7 +/- 5.6 mm (PPD/T1) to 31.5 +/- 15.5 mm (PPD/T2). The degree of boosting, measured by the change in millimeters induration size between PPD/T1 and PPD/T2 (PPD/T2-PPD/T1), was correlated with neither the size of PPD/T1 nor the age of the study participants, and was not associated with the difference of the position in the hospital. Thus, we could not explain the factor why such a marked boosting was observed in this study. However, these results indicated that the two-step tuberculin testing is an essential means of distinguishing new tuberculous infection from booster phenomenon. We agree with the current recommendation for routine two-step testing of new employees in the hospital.

Adult↗

Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988-991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 microg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 +/- 132 versus 995 +/- 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% +/- 22.1%) and high at neutrophilia with rhG-CSF therapy (73. 0% +/- 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r2 = 0.91; P < 0.0001) and neutrophil count (r2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.

Adjuvants, Immunologic↗

In vitro and in vivo activities of NS-718, a new lipid nanosphere incorporating amphotericin B, against Aspergillus fumigatus.

We evaluated the in vitro and in vivo potencies of a new lipid nanosphere that incorporates amphotericin B (AmB), NS-718, against Aspergillus fumigatus. The in vitro activity of NS-718 (the MIC at which 90% of strains are inhibited [MIC90], 0.25 microgram/ml) against 18 isolates of A. fumigatus was similar to that of deoxycholate AmB (D-AmB; Fungizone; MIC90, 0.25 microgram/ml), but NS-718 was more potent than liposomal AmB (L-AmB; AmBi-some; MIC90, 1.0 microgram/ml). The in vivo efficacy of NS-718 in a rat model of invasive pulmonary aspergillosis was compared with those of D-AmB and L-AmB. A low dose (1 mg/kg of body weight) of L-AmB was ineffective (survival rate, 0%), although equivalent doses of D-AmB and NS-718 were more effective (survival rate, 17%). However, a higher dose of NS-718 (3 mg/kg) was more effective (survival rate, 100%) than equivalent doses of D-AmB and L-AmB (survival rate, 0%). To explain these differences, pharmacokinetic studies showed higher concentrations of AmB in the plasma of rats treated with NS-718 than in the plasma of those treated with D-AmB. Our results suggest that NS-718, a new preparation of AmB, is a promising antifungal agent with activity against pulmonary aspergillosis.

Amphotericin B↗

Comparison between PCR and detection of antigen in sera for diagnosis of pulmonary aspergillosis.

We evaluated the usefulness of PCR and antigen detection for the diagnosis of pulmonary aspergillosis. Forty-four serum samples from patients with pulmonary aspergillosis (33 with pulmonary aspergilloma, 4 with allergic bronchopulmonary aspergillosis, 4 with invasive pulmonary aspergillosis, and 3 with aspergillus pyothorax) were used in this study. PCR detection of Aspergillus DNA in serum samples was successful in 39 patients. Galactomannan antigen was detected by sandwich enzyme-linked immunosorbent assay in 25 patients and by latex agglutination test in 13 patients. Detection of Aspergillus DNA in serum samples by nested PCR had the highest sensitivity of the three methods tested for the diagnosis of pulmonary aspergillosis.

Antigens, Fungal↗