Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 271 records · Page 15Linked to original sources

PubMed1997

Human T-cell leukemia virus type I Tax transactivates the promoter of human prointerleukin-1beta gene through association with two transcription factors, nuclear factor-interleukin-6 and Spi-1.

The human T-cell leukemia virus type I (HTLV-I), which infects a wide variety of mammalian cells including monocytes and macrophages, encodes a transactivating protein designated as Tax. We now report that Tax induces the human prointerleukin-1beta (IL1B) gene promoter in monocytic cells. In our transient transfection assays using human THP-1 monocytic cells, a chloramphenicol acetyltransferase (CAT) construct containing the IL1B promoter sequence between positions -131 and +12 showed an approximately 90-fold increase in activity following cotransfection of a Tax expression vector. Moreover, Tax synergized with lipopolysaccharide (LPS) to induce the IL1B promoter activity. Analyses of specific nucleotide substitutions further indicated that the Tax-induced transcriptional activation requires two transcription factor binding motifs within the IL1B promoter; one is a binding site for nuclear factor (NF)-IL6 (CCAAT/enhancer binding protein beta, C/EBP beta), which belongs to the basic region-leucine zipper (bZIP) family and the other for Spi-1 (PU.1), which is an Ets family protein found principally in monocytes, macrophages, and B lymphocytes. In electrophoretic mobility shift assays (EMSA) using in vivo THP-1 nuclear extracts, Tax expression in THP-1 monocytic cells significantly increased binding of the two factors to their target IL1B promoter sequences. However, in contrast to NF-IL6 and Spi-1, DNA binding activity of Oct-1, an ubiquitously expressed octamer-binding protein was not affected by Tax. Additional EMSA using in vitro translated proteins also showed that recombinant Tax enhances DNA binding of both of recombinant NF-IL6 and Spi-1 proteins. These data were supported by our glutathione S-transferase (GST)-pull-down data, which indicated that Tax physically interacts with the two proteins. Based on the results obtained from the present study, we conclude that the IL1B promoter is a Tax-responsive sequence as a result of ability of Tax to induce binding of NF-IL6 and Spi-1 to the IL1B promoter sequence through protein-protein interaction.

Binding Sites↗

PubMed1997

Enzymatic treatment to eliminate the extracellular ATP for improving the detectability of bacterial intracellular ATP.

A novel and effective treatment of biological samples with a combination of adenosine phosphate deaminase and apyrase was developed for reducing extracellular ATP, which has been a major problem encountered in improving the sensitivity of assays for intracellular ATP by the firefly luciferin-luciferase (L-L) method. Under the enzymatic reaction conditions, ATP and the related adenosine derivatives were converted to IMP, which are not active to the L-L system. In the model system (3.2 x 10(-8) M ATP in 1% yeast extract solution) the treatment with adenosine phosphate deaminase resulted in the reduction of ATP to 1.3 x 10(-11) M, and the concomitant use of apyrase lowered the concentration to 3.3 x 10(-13) M. The treatment (0.05 U/ml of adenosine phosphate deaminase and apyrase) was applied to the detection of bacteria in broth by the L-L method, affording the detection of 42 colony-forming unit (CFU)/ml of Escherichia coli and 10 CFU/ml of Staphylococcus aureus in the broth.

Adenosine Deaminase↗

PubMed1997

A Combination Therapy with Mitomycin C, Etoposide, Doxifluridine and Medroxyprogesterone Acetate as Second Line Therapy for Advanced Breast Cancer Refractory to Combination Chemotherapy of Cyclo-phoshamide, Doxorubicin and 5-Fluorouracil.

Thirty-two patients with advanced breast cancer refractory to combination chemotherapy with cyclophosphamide (CPA), doxorubicin (ADR) and 5-fluorouracil (5-EU) (CAF) were treated with the combination of mitomycin C, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy. Observed responses included 6 patients (18.7%) with complete response (CR) and 7 (21.9%) with partial response (PR). Two (50%) out of 4 patients who had bone pain due to bone metastasis noted pain relief. CR or PR were obtained in 4 out of 12 patients who had not responded to the previous CAF therapy. While grade III myelosuppression was observed in 3 patients, other adverse effects were minimal. It is suggested that this combination therapy may be recommended for advanced breast cancer patients as a second therapy.

Journal Article↗

PubMed1997

Novel genes encoding 2-aminophenol 1,6-dioxygenase from Pseudomonas species AP-3 growing on 2-aminophenol and catalytic properties of the purified enzyme.

2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-aminophenol. The product from 2-aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (alpha-subunit) and 40 kDa (beta-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of alpha2beta2. The genes coding for the alpha- and beta-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA and amnB corresponded to the NH2-terminal amino acid sequences of the alpha-subunit (AmnA) and beta-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coli W and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.

Amino Acid Sequence↗

PubMed1997

Inhaled nitric oxide attenuates reperfusion injury in non-heartbeating-donor lung transplantation. Paris-Sud University Lung Transplantation Group.

BACKGROUND: Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation. METHODS: The effect of inhaled NO on PMNs was studied by measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9 each). In the NO group, cadavers and recipients were ventilated with oxygen and 30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN adherence to tumor necrosis factor-alpha- and calcium ionophore-stimulated PAECs was measured before and after reperfusion, and lung PMN sequestration was determined after death. RESULTS: NO-treated animals exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05). CONCLUSIONS: Inhaled NO attenuates I-R injury after NHBD lung transplantation. This is likely due to the prevention of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue injury.

Administration, Inhalation↗

PubMed1997

Chemonucleolysis with human stromelysin-1.

STUDY DESIGN: Immunohistologic analysis was performed on surgically removed samples of herniated nucleus pulposus to examine the expression of stromelysin-1. We performed in vitro and in vivo experiments to determine whether recombinant human (rh) stromelysin-1 is capable of degrading nucleus pulposus. OBJECTIVE: To analyze the production of stromelysin-1 in various types of herniated nucleus pulposus, and to examine the effects of this recombinant protein on nucleus pulposus tissues. SUMMARY OF BACKGROUND DATA: The authors previously demonstrated a progressive decrease in herniated nucleus pulposus size in some of the transligamentous and sequestration types of herniated nucleus pulposus using magnetic resonance imaging. An increased production of stromelysin-1, a cartilage proteoglycan degrading enzyme, in herniated nucleus pulposus was reported recently. The authors speculated that if stromelysin-1 is involved in the degradation of herniated nucleus pulposus, stromelysin-1 itself may be used as a chemonucleolytic agent. METHODS: Immunohistologic analysis using streptoavidin-biotin method was performed on 20 herniated nucleus pulposus samples to investigate the expression of stromelysin-1. Five herniated nucleus pulposus samples were incubated in a tissue culture medium in the presence or absence of rh stromelysin-1. After 24 hours of incubation, their weight changes were measured, and the loss of proteoglycan was assessed by Safranin O staining. Rat nucleus pulposus tissues were obtained from coccygeal intervertebral discs, and autologous subcutaneous transplantation was performed. Rh stromelysin-1 was injected into the grafted materials, and the reduction in size was followed by two-dimensional measurements from the skin surface, using engineer's calipers. RESULTS: Immunohistologic analysis demonstrated the production of stromelysin-1 in the granulation tissues of herniated nucleus pulposus. When stromelysin-1 was injected into the murine nucleus pulposus tissues, they reduced in size more rapidly than the control group. In addition, human herniated nucleus pulposus materials obtained at surgery showed significant weight loss when treated with stromelysin-1 in an organ culture system. Safranin O staining revealed extensive depletion of proteoglycan in these herniated nucleus pulposus samples. CONCLUSIONS: Stromelysin-1 is a possible key enzyme in herniated nucleus pulposus resorption, and stromelysin-1 may be a good candidate for use in chemonucleolysis. Administration of human stromelysin-1 may physiologically facilitate the resorption process of herniated nucleus pulposus, increase the healing rate and decrease complications after chemonucleolysis.

Adult↗

PubMed1997

Delineation of regions important for heteromeric association of hepatitis C virus E1 and E2.

Hepatitis C virus (HCV) is the major causative agent of blood-borne non-A non-B hepatitis. The persistence of HCV infection is believed to reflect escape from the host immunosurveillance system by mutations in hypervariable region 1 (HVR1) of the envelope protein 2 (E2). Two envelope proteins of HCV, E1 and E2, have been reported to form a heteromeric complex but the exact organization of the viral envelope proteins remains uncertain. We examined the interaction of E1 and E2 by far- Western blotting using the bacterial recombinant proteins and also by pull-down assay using mammalian expressed proteins. The major E1-interacting site of E2 was mapped within the N-terminal part of E2 (NCD1) (aa 415 to 500 of the polyprotein). Both HVR1 and HVR2, located at the N-terminal part of E2, were dispensable for the interaction. Although several discontinuous regions within NCD1 seemed to contribute to the strong binding to E1, the highly conserved amino acid sequences flanking HVR2 had the most significant effect. The amino acid residues "WHY" from 489 to 491 of E2 played an especially crucial role since the constructs with the internal deletion or substitution of the residues showed severely impaired E1-binding. The N-terminal part of E1 is important for the E2-binding as determined by far-Western blotting using the mammalian- and bacterial-expressed E2 proteins as probes. The mammalian-expressed, glycosylated forms of the E1 and E2 proteins exhibited E1-E2 binding activities similar to those of the bacterial-expressed, nonglycosylated forms in pull-down assays, suggesting that glycosylation is not prerequisite for the heteromeric complex formation of E1 and E2.

Amino Acid Sequence↗

PubMed1997

Kinetic evaluation of beta-neoendorphin hydrolysis by the somatic and testicular isozymes of human angiotensin-converting enzyme.

Angiotensin-converting enzyme (ACE) has both somatic and testicular isozymes, the former possessing two catalytically active domains, amino-terminal and carboxyl-terminal, while the latter has only the carboxyl-terminal one. We compared hydrolysis processes of the nonapeptide beta-neoendorphin by the two isozymes of human ACE. Both isozymes hydrolyzed the peptide to Tyr1-Gly2-Gly3 by the sequential removal of carboxyl-terminal dipeptides in three consecutive steps. The rate constant values for the second step, conversion of beta-neoendorphin1-7 to Leu-enkephalin, by the somatic isozyme in the presence of 10 or 200 mM NaCl were 4-fold higher than those for the first step, conversion of beta-neoendorphin1-9 to beta-neoendorphin1-7. The k(cat) values of the somatic isozyme for beta-neoendorphin1-7 were 2-fold higher than those for beta-neoendorphin1-9, indicating that beta-neoendorphin1-7 is more rapidly hydrolyzed than beta-neoendorphin1-9. The rate constant value for the second step at 10 mM NaCl was 5-fold higher than that for the testicular isozyme. Similar extent of difference was also observed in k(cat) values for beta-neoendorphin1-7 between the two isozymes. These results suggest that the amino-terminal domain of the somatic isozyme mainly contributes to the conversion of beta-neoendorphin1-7 to Leu-enkephalin at a low NaCl concentration. Optimal chloride concentrations for the individual steps of beta-neoendorphin1-9 hydrolysis differed between the two isozymes.

Humans↗

PubMed1997

Distinct phenotype of leukemic T cells with various tissue tropisms.

There is an emerging concept, the validity of which remains to be proven, that preferential expression of selective adhesion molecules on particular T cell subsets may result in tissue-specific migration. L-selectin, cutaneous lymphocyte-associated Ag (CLA), and integrin alpha4beta7 are proposed to be involved in selective migration of T cell subsets into peripheral lymph nodes, skin, and gastrointestinal mucosa, respectively. Adult T cell leukemia (ATL) is associated with lymphoid infiltration of tissues and secondary lymphoid organs. To clarify the role of these putative homing molecules in vivo, we assessed their expression on circulating ATL cells from patients with lymph node, skin, and gut involvement. L-selectin expression was significantly higher on peripheral ATL cells in patients with lymphadenopathy than in patients without it. CLA was highly expressed on peripheral ATL cells compared with normal T cells: its expression was also significantly higher on peripheral ATL cells from patients with skin involvement compared with cells from patients without it. beta7 was particularly highly expressed on peripheral ATL cells from patients with gastrointestinal involvement. In summary, the differential expression of beta7 and beta1 on peripheral ATL cells correlates with the presence of gastrointestinal involvement. Similarly, the presence of skin involvement is associated with the expression of CLA(high)beta7low on peripheral ATL cells. These results, which are consistent with the molecules CLA and alpha4beta7 mediating preferential T cell migration to the skin and gastrointestinal mucosa, respectively, may allow for a refinement of the classification of lymphoid neoplasms on the basis of differential expression of homing molecules.

Adult↗

PubMed1997

Serum Soluble Interleukin-2 Receptor Levels in Patients with Breast Cancer.

Preoperative levels of serum soluble interleukin-2 receptor (1L-2R) were examined in 37 patients with breast cancer. We investigated the correlations of serum soluble IL-2R levels with various factors such as stage grouping, lymph node metastasis, distant metastasis, tumor size, histophthological type, estrogen receptor (ER), progesterone receptor (PgR) and CA 15-3. Serum soluble 1L-2R levels were measured with an enzyme-linked immunosorbent assay. Levels of serum soluble 1L-2R in the patients with stage III and IV breast cancer were significantly higher than those in the normal controls, and patients with stage I and II breast cancer. Preoperative levels of serum soluble IL-2R in patients with T3 and T4 were also significantly higher than those in patients with T1 and T2. Serum levels of IL-2R in patients with distant metastasis were also significantly higher than those in patients without distant metastasis. Moreover, serum levels of soluble IL-2R in patients with higher CA 15-3 were significantly higher than those in patients with normal CA 15-3 levels. We conclude that preoperative serum soluble IL-2R levels in patients with breast cancer may be a valuable parameter, especially in evaluating whether they have distant metastasis or not.

Journal Article↗

PubMed1997

Hepatitis B virus X protein is a transcriptional modulator that communicates with transcription factor IIB and the RNA polymerase II subunit 5.

Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through a wide variety of cis-elements. However, the mechanism is still obscure. Our finding that HBx directly interacts with RNA polymerase II subunit 5 (RPB5), a common subunit of RNA polymerases, implies that HBx directly modulates the function of RNA polymerase (Cheong, J. H., Yi, M., Lin, Y., and Murakami, S. (1995) EMBO J. 14, 142-150). In this context, we examined the possibility that HBx and RPB5 interact with other general transcription factors. HBx and RPB5 specifically bound to transcription factor IIB (TFIIB) in vitro, both of which were detected by either far-Western blotting or the glutathione S-transferase-resin pull-down assay. Delineation of the binding regions of these three proteins revealed that HBx, RPB5, and TFIIB each has two binding regions for the other two proteins. Co-immunoprecipitation using HepG2 cell lysates that express HBx demonstrated trimeric interaction in vivo. Some HBx substitution mutants, which had severely impaired transacting activity, exhibited reduced binding affinity with either TFIIB or RPB5 in a mutually exclusive manner, suggesting that HBx transactivation requires the interactions of both RPB5 and TFIIB. These results indicated that HBx is a novel virus modulator that facilitates transcriptional initiation by stabilizing the association between RNA polymerase and TFIIB through communication with RPB5 and TFIIB.

Gene Expression Regulation, Viral↗

PubMed1997

Classification of catechol 1,2-dioxygenase family: sequence analysis of a gene for the catechol 1,2-dioxygenase showing high specificity for methylcatechols from Gram+ aniline-assimilating Rhodococcus erythropolis AN-13.

Gram+ aniline-assimilating Rhodococcus erythropolis AN-13 (AN-13) produces catechol 1,2-dioxygenase (C12O) showing high enzymatic activities for 3- and 4-methylcatechols [Aoki et al. (1984) Agric. Biol. Chem. 48, 2087-2095]. A 3.0 kb Sau3AI fragment carrying a gene encoding C12O(catA) was cloned by selection of transformants showing C12O activity from a gene library of AN-13. Furthermore, we specified a 1.6 kb SalI fragment containing catA from the Sau3AI fragment by subcloning. Sequence analysis revealed that the 1.6 kb SalI fragment carried a 855 bp open reading frame (ORF) encoding the entire AN-13 catA, preceded by a potential ribosome binding site (RBS). From comparison of the deduced amino acid (aa) sequence of C12O from AN-13 with other C12O reported previously, it was found that the AN-13 enzyme shares 56.0% aa sequence identity with C12o from Arthrobacter sp. mA3 (mA3) [Eck and Belter (1991) Gene 123, 87-92] compared with less than 36.4% aa sequence identities with others. In conclusion, we classified all C12O including the AN-13 enzyme into three subfamilies on the basis of similarity of aa sequences, numbers of aa residues, and substrate specificity.

Amino Acid Sequence↗

PubMed1997

Human hepatitis B virus enhancer 1 is responsive to human interleukin-6.

Serum levels of interleukin-6 (IL-6) are elevated in acute and chronic hepatitis B patients. The effect of IL-6 and its transcription factor of NF-IL6 (a nuclear factor for IL-6) on hepatitis B virus (HBV) enhancer 1 (Enh1), which controls HBV X expression, were investigated in HepG2 cells. Twenty ng/ml of IL-6 increased 4-fold the enhancer activity of Enh1 according to the CAT assay. The IL-6 stimulation was abolished by introducing a mutation either in an AP-1-related site or a C-stretch sequence in the Enh1 sequence, demonstrating that the cis-elements are necessary for the IL-6 response. Co-transfection of NF-IL6 expression plasmid similarly increased the enhancer activity of Enh1 through both binding sites. Further, a specific complex formation of the Enh1 was detected using HepG2 nuclear lysates by electromobility shift assays, and the complex formation was increased in the lysates of cells treated with IL-6 and NF-IL6-transfection. In competition assays, one half of the complex formed was found to remain in the presence of 500-times excess competitor DNA fragment harboring NF-IL2 binding site, suggesting indirect binding of NF-IL6 to the Enh1 sequence. These results indicate that IL-6 increased the enhancer activity of HBV Enh1 through signal transduction pathways, indirectly involving NF-IL6, and may control HBV X expression and viral replication in HBV infected liver.

Base Sequence↗

PubMed1997

Treatment of Ramsay Hunt syndrome with acyclovir-prednisone: significance of early diagnosis and treatment.

Although the antiviral agent acyclovir is currently used for the treatment of Ramsay Hunt syndrome, its effects on facial nerve and hearing recovery remain controversial. We retrospectively analyzed the effects of acyclovir-prednisone treatment in 80 Ramsay Hunt patients. Of 28 patients for whom treatment was begun within 3 days of the onset of facial paralysis, the recovery from paralysis was complete in 21 (75%). By comparison, of 23 patients for whom treatment was begun more than 7 days after onset, recovery from facial paralysis was complete in only 7 (30%). A significant difference in facial nerve recovery was found between these groups. Early administration of acyclovir-prednisone was proved to reduce nerve degeneration by nerve excitability testing. Hearing recovery also tended to be better in patients with early treatment. There was no significant difference in facial nerve outcome between intravenous and oral acyclovir treatment.

Acyclovir↗

PubMed1997

Sequential dynamics of monocyte chemotactic protein-1 expression in herniated nucleus pulposus resorption.

We previously demonstrated that the granulation tissues of herniated nucleus pulposus are composed of a marked infiltration of macrophages that strongly express monocyte chemotactic protein-1. Monocyte chemotactic protein-1 is a chemotactic cytokine that contributes to the activation and recruitment of macrophages. Relatively little is known about its role in the resorption process of herniated nucleus pulposus. To clarify the sequential dynamics of expression of monocyte chemotactic protein-1 in the granulation tissues of herniated nucleus pulposus, we introduced a rat autologous transplantation model of nuclear materials onto its lumbar dura mater and performed immunohistological analysis and competitive polymerase chain reaction assay using the grafted samples. Immunohistological analysis demonstrated that the majority of infiltrating mononuclear cells expressed monocyte chemotactic protein-1. Monocyte chemotactic protein-1 mRNA was expressed in the first 3 weeks after the procedure and was significantly and maximally upregulated at 1 week. To determine whether human recombinant monocyte chemotactic protein-1 facilitates the resorption process of herniated nucleus pulposus, we introduced another model of autologous transplantation, wherein the nuclear materials were grafted to the abdominal subcutaneous tissues and recombinant monocyte chemotactic protein-1 was subsequently applied to these materials. When monocyte chemotactic protein-1 was injected into the murine nucleus pulposus tissues, they reduced in size more rapidly than in the control group. These findings suggest that monocyte chemotactic protein-1 plays an important role in the recruitment of macrophages in the early phase of the resorption process of herniated nucleus pulposus and that its application may physiologically facilitate the resorption process of the nucleus pulposus.

Animals↗

PubMed1997

Expression of PCNA and p53 in esophageal dysplasia and esophageal carcinoma.

We examined the immunohistochemical expression of proliferating-cell nuclear antigen (PCNA) and p53 proteins in dysplasia and intramucosal carcinoma of the esophagus. Immunohistochemistry was performed with monoclonal antibodies directed against PCNA and p53. We used surgically resected specimens from 29 patients who had a total of 55 lesions of severe dysplasia (n = 16), intraepithelial carcinoma (n = 21), and mucosal carcinoma (n = 18). The mean PCNA index with immunoreactivity for p53 was 48.9 +/- 6.5 in areas of severe dysplasia (n = 7), 58.2 +/- 7.3 in areas of intraepithelial carcinoma (n = 10), and 71.4 +/- 9.3 in the invasive areas of mucosal carcinoma (n = 10). The mean PCNA index without immunoreactivity for p53 was 41.2 +/- 5.5 in areas of severe dysplasia (n = 9), 48.0 +/- 7.4 in areas of intraepithelial carcinoma (n = 11), and 63.7 +/- 9.1 in invasive areas of mucosal carcinoma (n = 8). The PCNA indices of the areas of severe dysplasia with immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma with immunoreactivity for p53. Similarly, the PCNA indices of severe dysplasia without immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma without immunoreactivity for p53. These results thus suggest that severe dysplasia has a lower proliferative potential than carcinoma and may therefore represent a precancerous lesion.

Adult↗

PubMed1997

Treatment of bronchial stricture due to endobronchial tuberculosis.

Between 1974 and 1995 we encountered 19 cases of bronchial stricture or obliteration caused by endobronchial tuberculous lesions. In 11 the involvements were located at the right bronchus (including involvements of segmental and middle lobe bronchi) and in 8 at the left bronchus. On bronchoscopic biopsy of the stenosed bronchus, 7 patients showed histopathologic findings of tuberculous bronchitis, but 12 patients showed nonspecific inflammatory granular tissue. Five patients were kept under conservative observation because of mild subjective symptoms or refusal to undergo operation. Two patients underwent stent procedures but had poor outcomes. Twelve patients underwent operation. As the bronchial lesions in four of them were confined to the lobar or segmental bronchus, lobectomy was performed. One patient with a history of infantile tuberculosis had developed complete obliteration of the left main bronchus and cystic bronchiectasis in the entire lung parenchyma; pneumonectomy was essential. Seven patients who had strictures involving the main bronchus underwent bronchoplastic surgery with right (n = 4) or left (n = 3) upper sleeve lobectomy. None of the patients treated surgically showed any postoperative complication or recurrence of the tuberculosis. These surgical results for endobronchial tuberculosis indicate the need for early detection and operation. Bronchoscopy and computed tomography are the methods of choice for accurate diagnosis of bronchial involvement and assessment of the surgical indications. It is emphasized that bronchoplastic surgery is the best treatment for bronchial stricture involving bilateral main bronchi.

Adult↗

PubMed1997

ACAT inhibitor HL-004 accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats (SHRSP): stimulation of bile acid production by HL-004.

The effect of the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor HL-004 on bile acid production was studied during the regression phase of pre-established hypercholesterolemia in stroke-prone spontaneously hypertensive rats (SHRSP). These rats were fed a hypercholesterolemic diet containing 5% cholesterol, 2% cholic acid, and 20% suet for 30 days to induce hypercholesterolemia. The regression phase was started by switching the diet to normal chow, followed by another 30 days of the diet. The decrease in serum cholesterol level was accelerated by treatment with 0.09% HL-004. At the end of regression, hepatic ACAT activity was significantly lower in the HL-004 treated animals, an event concomitant with the significant decrease in cholesteryl ester content in the liver. In contrast hepatic cholesterol 7 alpha-hydroxylase activity was maintained at a higher level in the HL-004 treated animals. HL-004 increased the secretion of bile acid and biliary lipids in bile duct-cannulated SHRSP. In HepG2:cells, HL-004 at 1-30 microM dose-dependently stimulated bile acid synthesis from [3H]cholesterol. When cholesterol 7 alpha-hydroxylase activity of the liver was compared ex vivo in the presence and in the absence of exogenous cholesterol, it was suggested that the higher 7 alpha-hydroxylase activity of the HL-004 group could be attributed not only to expansion of the endogenous cholesterol pool, which may be the result of hepatic ACAT inhibition by HL-004 but to the direct effect of HL-004 on bile acid production. Thus, HL-004 accelerates the regression of hypercholesterolemia, an event which may be related to the stimulation of bile acid production in the liver.

Acetanilides↗