Rupture of a non sinus of Valsalva aneurysm during pregnancy: Case report and review of literatures.

Ruptured Sinus of Valsalva aneurysms during pregnancy is rare and presents a threat both to the mother and the fetus. We report a case of ruptured nonsinus of Valsalva aneurysms in a 26-year-old woman diagnosed at 32+4 weeks of gestation. A successful elective lower-segment cesarean section was conducted under general anesthesia. A successful surgical correction of the ruptured aneurysm under cardiopulmonary bypass (CPB) was performed with patch repair after 13 days. A multidisciplinary approach with respect to the pregnant patient's diagnosis, indications, and timing of surgery is necessary in ensuring the best possible outcomes for both the mother and the child.

Gland-sparing neck dissection: oncological and functional outcomes in oral cancer patients.

This study was performed to evaluate the subjective and objective functional outcomes of patients who had undergone submandibular gland-sparing neck dissection. All data were obtained from patients treated in a single hospital. Seventy-seven patients who had undergone complete submandibular gland sparing (CSGS) were included in the study. Cancer prognosis items were recorded. The subjective outcomes included patient self-evaluation of mouth dryness and the evaluation of the presence of saliva secretion following the application of digital pressure. Saliva scintigraphy served as the objective test. Self-reported xerostomia was compared between the CSGS patients and a control group of patients who had undergone unilateral submandibular gland removal (USGR; n = 74). In the CSGS group, local recurrence occurred in 3.8% of the 80 cancer sites, and neck recurrence occurred in 5.9% of neck dissection sites. Regarding the subjective measurements, 7.0% of the CSGS patients reported xerostomia and 91.9% demonstrated saliva secretion by digital pressure. Scintigraphy revealed actively secreting glands, with 42.9% of them showing normal gland function; none of the patients had severe xerostomia. The relative risk of dry mouth was significantly higher in the USGR patients than in the CSGS patients (P < 0.001). Submandibular gland sparing during neck dissection was found to result in satisfactory saliva secretion, with a relatively small risk of local or neck recurrence.

[Analysis of components of proteins from Echinococcus granulosus cyst fluid].

OBJECTIVE: To analyze the components of proteins from Echinococcus granulosus cyst fluid using the shotgun method, and to identify the active components with potential regulatory effects for immune dysregulation diseases. METHODS: The E. granulosus cyst fluid was collected aseptically from the hepatic cysts of patients with cystic echinococcosis, and characterized by liquid chromatography (LC) tandem mass spectrometry (MS/MS) following digestion with trypsin. The protein data were searched using the software MaxQuant version 1.6.1.0 and the cellular components, molecular functions, and biological processes of the identified proteins were analyzed using the Gene Ontology (GO) method. RESULTS: The E. granulosus cyst fluid separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) had a relative molecular mass of 25 to 70 kDa. LS-MS/MS analysis identified 37 proteins, including 32 known proteins and 5 unknown proteins. At least 4 proteins were preliminarily found to exhibit potential regulatory effects for immune dysregulation diseases, including antigen B, glutathione-S-transferase (GST), thioredoxin peroxidase (TPX) and malate dehydrogenase (MDH). GO enrichment analysis showed that the identified proteins had 149 molecular functions and were involved in 341 biological processes. CONCLUSIONS: E. granulosus cyst fluid has a variety of protein components, and four known proteins are preliminarily identified to be associated with immune dysregulation diseases.

Risk Factors for Maternal and Perinatal Complications during Pregnancy among Women with Tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease during pregnancy. Studies of risk factors are of great significance to maternal and fetal outcomes in patients with TOF. AIMS: To identify predictive risk factors for maternal and perinatal complications in women with TOF. SUBJECTS AND METHODS: 78 patients with TOF who delivered at Shanghai Obstetrical Cardiology Intensive Care Center between January 1993 and December 2017 were retrospective reviewed. A logistic regression model was used to identify risk factors for maternal and perinatal complications. RESULTS: There was no maternal death, five patients developed cardiac failure, sustained arrhythmias requiring treatments were recorded among 2 patients. Factors identified for maternal complications included previous cardiac events and oxygen saturation <90%. Oxygen saturation <90% was found to be independent predictor of maternal cardiac complications (RR = 21.455, 95%CI 2.186-210.572, P = 0.009). The perinatal survival rate was 87.18%, there were 52 term deliveries (66.67%). Perinatal poor outcomes include 9 therapeutic abortions (11.54%), 1 neonatal death (1.28%), 16 premature births (20.51%), 18 small for gestational age children (23.08%), 3 neonatal asphyxia (3.85%), and 3 neonatal cardiac malformations (3.85%). Factors identified for perinatal complications included without cardiac surgery, higher hemoglobin values, higher hematocrit values, oxygen saturation <90%, right ventricular hypertrophy, pulmonary stenosis, ventricular septal defect, and pulmonary hypertension. Oxygen saturation <90% was found to be independent predictor of perinatal complications (RR = 8.270, 95%CI 1.374-49.790, P = 0.021). CONCLUSIONS: Oxygen saturation <90% is associated with maternal and perinatal risks. Women with TOF whose oxygen saturation <90% are not recommended for pregnancy because of high maternal and perinatal complications.

Transoral vertical ramus osteotomy fixed with Kirschner pins.

Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle has the potential to sag, and because it needs lengthy maxillomandibular fixation. We have therefore introduced a simple method of fixation, and examined its effectiveness and complications. After the osteotomy, the proximal and distal segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in diameter are inserted percutaneously from the proximal to the distal segment while the condyle is positioned in the glenoid fossa. This is followed by a brief period of maxillomandibular fixation. We have reviewed the records of 95 patients who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two patients because excursion of the jaw was either too heavy or too early. The fixations were redone. All other fixations remained stable, including the 20 dual-jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal mouth opening at final follow-up was 44 (7) mm, and in only one patient was it less than 30mm. Numbness of the lip or chin developed in seven patients, five of whom had other anterior mandibular procedures. Four patients had discomfort on palpation of the site of the pins, and one required removal. The new method was effective, and resulted in few complications within its limitations.

Solid pseudopapillary neoplasm of pancreas in pregnancy treated with tumor enucleation: Case report and review of the literature.

Solid pseudopapillary neoplasm of pancreas (SPN) during pregnancy is rare and presents a threat both to the mother and the fetus. We report a case of SPN in a 26-year-old woman diagnosed at 21 weeks of gestation. Tumor enucleation was successfully performed by a general surgeon. A healthy female infant was delivered at 39 weeks and 5 days of gestation vaginally without complications. Our report provides an example that tumor enucleation of SPN during the second trimester could be successfully performed during pregnancy. A multidisciplinary approach with respect to the pregnant patient's diagnosis, indications, and timing of surgery is necessary in ensuring the best possible outcomes for both the mother and the child.

Investigation on the properties of borate bonding agents: Ti6Al4V-porcelain bonding, chemical durability and preliminary cytotoxicity.

The purpose of this study was to investigate the properties of the borate bonding agents (BBAS) including chemical durability, biocompatibility and bonding characteristics of porcelain to Ti6Al4V. The bond strength was performed by the three-point bending test. And the chemical durability and ion release of BBAS were tested by chemical soaking and inductively coupled plasma optical emission spectrometry (ICP-OES), respectively. Moreover, cytotoxicity was evaluated by cell viability assay and cell adhesion using human osteosarcoma cells (MG-63) and cell counter kit-8 (CCK-8) assay. To investigate the influences of composition and microstructure changes on all the properties mentioned above, the 11B and 27Al spectra and infrared spectra of BBAS were measured by solid-state nuclear magnetic resonance (SSNMR) and Fourier transform infrared spectroscopy (FTIR), respectively. Combined with all these properties of BBAS, the optimal addition proportion of Al2O3 into BBAS is 20 mol%. The relative contents of [BO3], [BO4], [AlO4], [AlO5] and [AlO6] have great influences on these properties of BBAS. BBAS, possessing excellent chemical durability, good biocompatibility and low ion release and being an effective way to improve the Ti6Al4V-porcelain bond strength, have significant clinical potentials in porcelain fused to metal restorations.

Effects of NGX6 expression on proliferation and invasion of nasopharyngeal carcinoma cells and survival of patients.

OBJECTIVE: To detect the expressions of nasopharyngeal carcinoma-associated gene 6 (NGX6) in nasopharyngeal carcinoma cells and tissues, and to investigate the effects of NGX6 on the proliferation and invasion of nasopharyngeal carcinoma cells and the survival of patients. PATIENTS AND METHODS: The human nasopharyngeal carcinoma cells (HONE1) and immortalized human nasopharyngeal epithelial cells (NP69) were selected and cultured. The mRNA and protein expression levels of NGX6 were detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The expression of NGX6 in HONE1 was up-regulated using the gene transfection technique. Moreover, the effects of NGX6 on the proliferation and invasion capacities of HONE1 were observed via methyl thiazolyl tetrazolium (MTT) assay and Transwell assay. 50 biopsy tissue specimens of nasopharyngeal carcinoma and 20 non-neoplastic nasopharyngeal biopsy tissue specimens were collected, and the immunohistochemical method was used to detect the protein expression of NGX6 in tumor tissues of patients with esophageal carcinoma. Finally, the follow-up data of patients were recorded, Kaplan-Meier method was used for survival analysis, and the difference in survival rates was detected using the Log-rank test. RESULTS: The results of qRT-PCR and Western blot showed that the mRNA and protein expressions of NGX6 in HONE1 were significantly lower than those in nasopharyngeal carcinoma cells (NP69). After the overexpression of NGX6, the protein expression of NGX6 in HONE1 was significantly increased, but the proliferation and invasion capacities of HONE1 were significantly decreased. Besides, the immunohistochemical results revealed that the expression of NGX6 in tumor tissues of patients with nasopharyngeal carcinoma was significantly lower than that in normal tissues; the survival analysis showed that the level of NGX6 was positively correlated with the survival and prognosis of patients with nasopharyngeal carcinoma. CONCLUSIONS: NGX6 is lowly expressed in nasopharyngeal carcinoma, and it can inhibit the proliferation and invasion of nasopharyngeal carcinoma cells, whose expression is positively correlated with the survival and prognosis of patients with nasopharyngeal carcinoma.

Knockdown of c-MET induced apoptosis in ABCB1-overexpressed multidrug-resistance cancer cell lines.

Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells. Moreover, leukemia cell lines overexpressing ABCB1 have also been shown to be more resistant to the tyrosine kinase inhibitor imatinib mesylate. These findings suggest that chemoresistant cancer cells may also develop a similar mechanism against chemotherapy agents. To circumvent clinical complications arising from drug resistance during cancer therapy, the present study was designed to investigate apoptosis induction in ABCB1-overexpressed cancer cells using c-MET-targeted RNA interference technology in vitro and in vivo. The results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner. In vivo reduction of tumor volume in mice harboring c-MET shRNA-knockdown MES-SA/Dx5 cells was clearly demonstrated. Our study demonstrated that downregulation of c-MET by shRNA-induced apoptosis in a multidrug resistance cell line.

Evaluation of wall correction factor of INER's air-kerma primary standard chamber and dose variation by source displacement for HDR ¹9²Ir brachytherapy.

The aim of the present study was to estimate the wall effect of the self-made spherical graphite-walled cavity chamber with the Monte Carlo method for establishing the air-kerma primary standard of high-dose-rate (HDR) ¹9²Ir brachytherapy sources at the Institute of Nuclear Energy Research (INER, Taiwan). The Monte Carlo method established in this paper was also employed to respectively simulate wall correction factors of the ¹9²Ir air-kerma standard chambers used at the National Institute of Standards and Technology (NIST, USA) and the National Physical Laboratory (NPL, UK) for comparisons and verification. The chamber wall correction calculation results will be incorporated into INER's HDR ¹9²Ir primary standard in the future. For the brachytherapy treatment in the esophagus or in the bronchi, the position of the isotope may have displacement in the cavity. Thus the delivered dose would differ from the prescribed dose in the treatment plan. We also tried assessing dose distribution due to the position displacement of HDR ¹9²Ir brachytherapy source in a phantom with a central cavity by the Monte Carlo method. The calculated results could offer a clinical reference for the brachytherapy within the human organs with cavity.

WWOX suppresses autophagy for inducing apoptosis in methotrexate-treated human squamous cell carcinoma.

Squamous cell carcinoma (SCC) cells refractory to initial chemotherapy frequently develop disease relapse and distant metastasis. We show here that tumor suppressor WW domain-containing oxidoreductase (WWOX) (also named FOR or WOX1) regulates the susceptibility of SCC to methotrexate (MTX) in vitro and cure of SCC in MTX therapy. MTX increased WWOX expression, accompanied by caspase activation and apoptosis, in MTX-sensitive SCC cell lines and tumor biopsies. Suppression by a dominant-negative or small interfering RNA targeting WWOX blocked MTX-mediated cell death in sensitive SCC-15 cells that highly expressed WWOX. In stark contrast, SCC-9 cells expressed minimum amount of WWOX protein and resisted MTX-induced apoptosis. Transiently overexpressed WWOX sensitized SCC-9 cells to apoptosis by MTX. MTX significantly downregulated autophagy-related Beclin-1, Atg12-Atg5 and LC3-II protein expression and autophagosome formation in the sensitive SCC-15, whereas autophagy remained robust in the resistant SCC-9. Mechanistically, WWOX physically interacted with mammalian target of rapamycin (mTOR), which potentiated MTX-increased phosphorylation of mTOR and its downstream substrate p70 S6 kinase, along with dramatic downregulation of the aforementioned proteins in autophagy, in SCC-15. When WWOX was knocked down in SCC-15, MTX-induced mTOR signaling and autophagy inhibition were blocked. Thus, WWOX renders SCC cells susceptible to MTX-induced apoptosis by dampening autophagy, and the failure in inducing WWOX expression leads to chemotherapeutic drug resistance.

Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive glioblastoma model.

Toca 511 (vocimagene amiretrorepvec), an amphotropic retroviral replicating vector (RRV), can successfully and safely deliver a functional, optimized cytosine deaminase (CD) gene to tumors in orthotopic glioma models. This agent, in conjunction with subsequent oral extended-release 5-fluorocytosine (5-FC) (Toca FC), is currently under investigation in patients with recurrent high-grade glioma . Temozolomide (TMZ) with radiation is the most frequently used first-line treatment for patients with glioblastoma, the most common and aggressive form of primary brain cancer in adults. However, subsets of patients with certain genetic alterations do not respond well to TMZ treatment and the overall median survival for patients who respond remains modest, suggesting that combinatorial approaches may be necessary to significantly improve outcomes. We show that in vitro TMZ delays but does not prevent RRV spread, nor interfere with Toca 511+5-FC-mediated cell killing in glioma tumor cells, and in vivo there is no significant hematologic effect from the combination of 5-FC and the clinically relevant dose of TMZ. A synergistic long-term survival advantage is observed in mice bearing an orthotopic TMZ-sensitive glioma after Toca 511 administration followed by coadministration of TMZ and 5-FC. These results provide support for the investigation of this novel combination treatment strategy in patients with newly diagnosed malignant glioma.

Gene expression profiling: identification of genes with altered expression in Ayu17-449 knockout mice.

Ayu17-449, a novel gene in mice, has been identified as a tumor-suppressor gene in myeloid malignancy; its product catalyzes the conversion of 5-methylcytosine of DNA to 5-hydroxymethylcytosine. However, in vivo, its functional target genes and biological function have remained unclear. Based on the assumption that alterations in the expression of the Ayu17-449 gene affect the expression of other related genes, we screened a microarray of altered gene expression in Ayu17-449(-/-) and Ayu17-449(+/+) mice. We identified 4049 genes with altered expression, including 1296 up-regulated (fold change ≥2) and 2753 down-regulated (fold change ≤0.5) genes in knockout mice compared with control mice. We then used qRT-PCR and RT-PCR to validate the chip data. Gene ontology and pathway analysis were performed on these altered genes. We found that these altered genes are functional genes in the complement and coagulation cascades, metabolism, biosynthesis, transcriptional regulation, proteolysis, and intracellular signaling pathways, such as the peroxisome proliferator-activated-receptor signaling pathway, the TNF-α-NF-κB pathway, the Notch signaling pathway, the MAPK signaling pathway, and the insulin signaling pathway. The results of our genome-wide comprehensive study could be helpful for comprehending the underlying functional mechanisms of the Ayu17-449 gene in mammals.

Expression of anti-neuroexcitation peptide III of scorpion Buthus martensii Karsch BmK ANEP III in plants.

Anti-neuroexcitation peptide III of Buthus martensii Karsch (BmK ANEP III) has better anti-epileptic and anticonvulsive effects in the test animal models. The present study is aimed at developing transgenic tomato and tobacco lines overproducing the ANEP III protein. Using the molecular cloning technique, the plant expression vector pBI-ANEP III was constructed successfully. The ANEP III expression cassette included a double CaMV 35S promoter with omega enhancers, the ANEP III gene with the Kozak sequence, the ER retention signal and the NOS terminator. Recombinant plasmids were transferred into Agrobacterium tumefaciens EHA105 by freeze-thaw transformation methods. By the Agrobacterium-mediated leaf disc transformation method, tobacco (Nicotiana tabacum) and tomato (Lycopersicum esculentum) lines were transformed. Transformants were screened and confirmed by PCR, RT-PCR and western blotting analysis. It was demonstrated that the ANEP III gene was successfully expressed in the genomic DNA of transgenic plants. The ANEP III protein was detected by immunofluorescence analysis, and the results confirmed the high amount of ANEP III protein, being 0.81 and 1.08% of total soluble proteins in transgenic tobacco and tomato. The study of plants with high expression levels of ANEP III has an important theoretical and practical significance and provides valuable information for establishing a new, economical and effective system for industrial protein production.

Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth.

AIM: The aim of this study was to determine the associations of telomere length to markers of obesity, insulin resistance and inflammation in Saudi children. METHODS: A total of 69 boys and 79 girls, aged 5-12 years, participated in this cross-sectional study. Anthropometrics were measured. Serum glucose and lipid profile were measured using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumour necrosis factor-alpha and active plasminogen activator inhibitor 1 were quantified using customized multiplex assay kits. C-reactive protein and angiotensin II were quantified using ELISA. Leucocyte telomere length was examined by quantitative real time PCR utilizing IQ cycler. RESULTS: Mean telomere length was significantly shorter in obese boys compared with their lean counterparts (p = 0.049), not in girls. It was not associated to insulin resistance, adipocytokines and markers of inflammation. In girls, the significant predictor of telomere length was waist circumference, explaining 24% of variance (p = 0.041) while in boys, systolic blood pressure explained 84% of the variance (p = 0.01). CONCLUSION: Childhood obesity in boys corresponds to shorter leucocyte telomere length which is not evident in girls. The association of leucocyte telomere length to blood pressure and waist circumference in children suggests clinical implications as to the contribution of these parameters in premature ageing.

Renovation of epithermal neutron beam for BNCT at THOR.

Heading for possible use for clinical trial, THOR (Tsing Hua Open-pool Reactor) at Taiwan was shutdown for renovation of a new epithermal neutron beam in January 2003. In November 2003, concrete cutting was finished for closer distance from core and larger treatment room. This article presents the design base that the construction of the new beam is based on. The filter/moderator design along the beam is Cd(0.1cm)+Al(10 cm)+FLUENTAL (16 cm)+Al(10 cm)+FLUENTAL(24 cm)+Void(18 cm)+Cd(0.1cm)+Bi(10 cm) with 6 cm Pb as reflector. Following the filter/moderator is an 88 cm long, 6 cm thick Bi-lined collimator with Li(2)CO(3)-PE at the end. The collimator is surrounded by Li(2)CO(3)-PE and Pb. The calculated beam parameters under 2 MW at the beam exit is phi(epi) = 3.4 x 10(9) n/cm(2)/s, Df/phi(epi) = 2.8 x 10(-11) cGy cm(2)/n, Dgamma/phi(epi) = 1.3 x 10(-11) cGy cm(2)/n, and J+/phi = 0.8. For a phantom placed 10 cm from beam exit, MCNP calculation shows that the advantage depth is 8.9 cm, and advantage ratio is 5.6 if boron concentration in tumor and normal tissue are assumed to be 65 and 18 ppm. The maximum dose rate for normal tissue is 50 cGy/min. The maximum therapeutic ratio is 6. The construction of the beam is scheduled to be finished by the end of April 2004.

Strain-dependent high-level expression of a transgene for manganese superoxide dismutase is associated with growth retardation and decreased fertility.

Manganese superoxide dismutase (MnSOD) is essential in protecting mitochondria against the damaging effects of superoxide radicals (O(2)(*-)), and increased expression of MnSOD protects cells and transgenic animals from various forms of oxidative stress. In addition, increased levels of MnSOD have been shown to slow down cell growth and induce differentiation. To study the effects of high MnSOD levels in vivo, we generated a series of transgenic mice using a mouse genomic sequence under control of the endogenous promoter. Four transgenic lines produced by pronuclear DNA injection exhibited up to 2-fold elevated MnSOD levels in brain and heart. However, using an embryonic stem cell approach, a line having 10-fold elevated MnSOD levels in the brain and 6- to 7-fold elevated levels in the heart and kidney was generated. Surprisingly, the genetic background of this transgenic line influenced the expression level of the transgene, with DBA/2 (D2) and C57BL/6 (B6) mice exhibiting low- and high-level transgene expression, respectively. This difference was the result of an increased transcription rate of the transgene. High-level MnSOD expression in B6 animals was associated with small size, male infertility, and decreased female fertility. These features are absent on the D2 background and indicate that high levels of MnSOD activity may interfere with normal growth and fertility.

Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial function and apoptosis.

Heart mitochondria from heterozygous (Sod2(-/+)) knockout mice have a 50% reduction in manganese superoxide dismutase (MnSOD) activity. The decrease in MnSOD activity was associated with increased mitochondrial oxidative damage as demonstrated by a decrease in the activities of iron sulfhydryl proteins sensitive to oxygen stress (aconitase and reduced nicotinamide adenine dinucleotide-oxidoreductase). Mitochondrial function was altered in the Sod2(-/+) mice, as shown by decreased respiration by complex I and an increase in the sensitivity of the permeability transition to induction by calcium and t-butylhydroperoxide. The increased induction of the permeability transition in heart mitochondria from Sod2(-/+.)mice was associated with increased release of cytochrome c and an increase in DNA fragmentation. Cardiomyocytes isolated from neonatal Sod2(-/+) and Sod2(-/-) mice were more sensitive to cell death than cardiomyocytes from Sod2(+/+) mice after t-butylhydroperoxide treatment, and this increased sensitivity was prevented by inhibiting the permeability transition with cyclosporin A. These experiments demonstrate that MnSOD may play an important role in the induction of the mitochondrial pathway of apoptosis in the heart, and this appears to occur primarily through the permeability transition.

Upregulation of inducible nitric oxide synthase and cytokine secretion in peripheral blood monocytes from pulmonary tuberculosis patients.

SETTING: Peripheral blood monocytes (PBM) are the main source of alveolar macrophages, which have an upregulation of inducible nitric oxide synthase (iNOS) in pulmonary tuberculosis (TB). TNF-alpha and IL-1 beta are thought to be involved in the immune response to mycobacterial infection. OBJECTIVE: To identify whether iNOS expression and cytokine release of PBM are upregulated and have a connection in TB infection. DESIGN: The expression of iNOS immunoreactivity on PBM from TB patients and normal subjects was measured by loading with anti-macrophage iNOS polyclonal primary antibody analyzed by flow cytometry. Expression of iNOS mRNA in PBM was detected by RT-PCR. The spontaneous generation of nitrite and cytokines (IL-1 beta and TNF-alpha) by cultured monocytes was also determined. RESULTS: Compared to normal subjects, iNOS immuno-reactivity, the capacity for spontaneous nitrite generation and the level of TNF-alpha or IL-1 beta secretion of PBM were significantly higher in TB patients. The amount of nitrite, TNF-alpha and IL-1 beta released from PBM of TB patients was inhibited by NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS. The level of iNOS immunoreactivity on PBM was highly correlated with nitrite generation both in all the subjects studied and in TB patients alone. Spontaneous TNF-alpha production showed a stronger correlation with nitrite production than with IL-1 beta. CONCLUSION: The NO and cytokine synthase activities of monocytes appear to be concomitantly upregulated in response to mycobacterial infection. The enhanced NO generation by monocytes in TB patients may play an autoregulatory role in amplifying the synthesis of pro-inflammatory cytokines.