[Clinical study on application of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions].

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.

[Performance of limiting-antigen avidity enzyme immunoassay and pooling PCR in detection of recent HIV-1 infection among men who have sex with men in Yunnan province].

Objective: To assess and compare the performance of limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) and pooling PCR in the surveillance for recent infection rates of HIV-1 in men who have sex with men (MSM). Methods: Blood samples were collected from MSM selected through snowball sampling method in sentinel surveillance in 13 prefectures of Yunnan province from 2016 to 2017. The samples were tested for HIV-1 antibody. The confirmed positive samples were tested by LAg-Avidity EIA. The negative samples were tested by pooling PCR. The recent infection rates of HIV-1 were estimated by the algorithm based on LAg-Avidity EIA and pooling PCR respectively. The two results were compared. Results: During 2016-2017, a total of 5 363 blood samples were collected from MSM, in which 407 samples were HIV-1 positive (including 177 positive tested previously) and 4 956 samples were HIV-1 negative. A total of 211 samples(91.7%) were tested by LAg-Avidity EIA, 69 were confirmed to be recent infections. A total of 4 469 samples were tested by pooling PCR, 8 were confirmed to be acute infections. The recent infection rates of HIV-1 from 2016 to 2017 estimated by LAg-Avidity EIA were 3.36% and 4.84%, and the recent infection rates estimated by pooling PCR were 3.27% and 3.02% respectively. The differences in recent infection rates of HIV-1 estimated by the two algorithms were not significant. Conclusions: The recent infection rates of HIV-1 estimated by LAg-Avidity EIA and pooling PCR in sentinel surveillance in MSM in Yunnan had good consistency from 2016 to 2017. Using the two methods might have a better stability in continuous surveillance for recent infection rates of HIV-1.

Research on sleeve gastrectomy for the treatment of rats with type 2 diabetes mellitus and the regulation of ghrelin and intestinal lesions.

OBJECTIVE: To explore the effect of sleeve gastrectomy on type 2 diabetes mellitus (T2DM) in regulating ghrelin and intestinal lesions. MATERIALS AND METHODS: Specific pathogen free (SPF) Wistar rats were injected with streptozotocin (STZ) after giving a high-sugar and high-fat diet, to establish a T2DM rat model. The rats were randomly divided into a sleeve gastric excision group, a non-surgical group and a fake surgical group, with 10 rats in each group. The weight, blood glucose, glucose tolerance and ghrelin hormone of rats were compared. The feces of rats in each group at the 8th week after surgery were collected, to extract the total bacterial deoxyribonucleic acid (DNA). The bacterial 16S universal primer was used to expand the 16SrRNA V46 conserved region. The total Polymerase Chain Reaction (PCR) products were sequenced by PE101-bp to classify the gene and genera. RESULTS: The weight of the rats after sleeve gastrectomy significantly decreased (p <0.05). The area under the blood glucose curve and the area under the insulin curve were significantly smaller than those in the non-surgical group and the fake surgical group (p <0.05). Compared with the sleeve gastric excision group, the abundance of Phylum Firmicutes was higher, that of Bacteroidetes was lower. Compared with the sleeve gastric excision group, there were more genera in the fake surgical group and the non-surgical group. The genera with higher abundance in the three groups were Lactobacillus and Bacteroidetes. Compared with the sleeve gastric excision group, the fake surgical group and the non-surgical group had higher abundance of Phylum Firmicutes (p <0.05) and lower abundance of Bacteroidetes (p <0.05). CONCLUSIONS: To sum up, sleeve gastrectomy can reduce the weight of rats in T2DM rat model, lower blood glucose levels of rats in the model and improve insulin resistance levels. The related mechanism may be related to the upregulation of ghrelin and intestinal flora.

Resection of the irradiated esophagus: the impact of lymph node yield on survival.

There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal (<9) or extensive (≥9) lymph node yield. Demographic, operative, and postoperative outcomes were compared between the groups. Kaplan-Meier analysis with the log rank test was used to compare survival between the yield groups. Cox proportional hazards model was used to determine the association between lymph node yield and survival. In total, 886 cases were included: 349 (39%) belonging to the minimal node group and 537 (61%) to the extensive group. Unadjusted 5-year survival was similar between the minimal and extensive groups, respectively (37.3% vs. 38.8%; P > 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66-0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

LncRNA DQ786243 expression as a biomarker for assessing prognosis in patients with gastric cancer.

OBJECTIVE: Recent studies have revealed that long noncoding RNA DQ786243 (DQ786243) plays an important role in the development of gastric cancer (GC) and colorectal cancer. However, the expression and function of DQ786243 in GC patients remain largely unknown. The purpose of our study was to investigate the clinical significance of DQ786243 expression in GC. PATIENTS AND METHODS: qRT-PCR was used to examine DQ786243 expression in 172 paired GC samples and matched adjacent normal tissues. Besides, the relationship between DQ786243 expression and clinicopathologic characteristics was analyzed. Overall survival (OS) and progression-free survival (PFS) curves of patients in subgroups were constructed by the Kaplan-Meier method. Multivariate regression analyses were performed to analyze independent factors affecting prognosis. RESULTS: We found a significant up-regulation of DQ786243 in GC tissues compared to normal tissues (p < 0.01). High DQ786243 expression was closely associated with invasion depth (p = 0.006), TNM stage (p = 0.009) and lymphatic metastasis (p = 0.017). Moreover, Kaplan-Meier analysis showed that patients with DQ786243 high expression tumors had worse OS (p = 0.0012) and PFS (p = 0.0002) compared to patients with DQ786243 low expression tumors. Finally, multivariate analysis showed that DQ786243 was a significant and independent prognostic predictor for both OS (p = 0.002) and PFS (p = 0.001) of GC patients. CONCLUSIONS: Our data suggest, for the first time, that the evaluation of the DQ786243 expression in GC tissues is a useful tool for predicting prognosis of GC.

[The prevalence of ideal cardiovascular health metrics in Southeast Chinese middle-aged men].

Objective: To observe the prevalence and distribution of ideal cardiovascular health metrics in middle-aged men living in Su-Xi-Chang region and explore the relationship between health behavior and health factors. Methods: A total of 27 824 middle-aged men, who took part in health examination in the Center for Healthcare Management, Taihu Rehabilitation Hospital of Jiangsu Province from January 2014 to June 2015, were enrolled in this cross-sectional study. The ideal cardiovascular health metrics were defined by the American Heart Association criteria with minor modification in that the amount of vegetable intake was replaced by salt intake. The prevalence and distribution of ideal cardiovascular health metrics as well as the association between ideal cardiovascular health metrics and health factors were analyzed in this cohort. Results: The body mass index in the whole cohort was (25.1±3.0) kg/m2, waist circumference was (87.3±8.42) cm; the percent of subjects with all seven ideal cardiovascular health metrics was only 0.5% (n=133). The highest proportion of ideal metric was total cholesterol (68.5%, n=19 056), followed by fasting glucose (66.9%, n=18 616), body mass index (50.2%, n=13 963), physical exercise (45.6%, n=12 697), smoking (40.3%, n=11 216), blood pressure (22.5%, n=6 257) and salt intake (15.6%, n=4 351). The proportion of ideal cardiovascular health metrics reduced gradually and the proportion of poor cardiovascular health metrics status increased gradually with aging(χ2=106.746, P=0.000). The total cholesterol level of non-smokers was significantly lower than that of smokers(F=8.571, P=0.000); total cholesterol, blood pressure and fasting glucose levels increased in proportion with increasing body mass index(all P<0.01); total cholesterol and fasting blood glucose of subjects with regular active physical exercise were significantly lower than those with inactive physical exercise(all P<0.01); total cholesterol and blood pressure of subjects with high salt intake were significantly higher than those with low salt intake(all P<0.01). Conclusions: The proportion of subjects with ideal cardiovascular health metrics is very low in middle-aged men living in Su-Xi-Chang region, and the downtrend with poor cardiovascular health metrics increases with aging. Overweight or obese, smoking, high salt diet and poor control of blood pressure are the major cardiovascular risk factors in this cohort.

Quantitative analysis of gains and catch-up saccades of video-head-impulse testing by age in normal subjects.

OBJECTIVES: To evaluate video-head-impulse test (vHIT) results in normal subjects, to determine the normative values of vHIT for the vestibulo-ocular reflex (VOR) and to characterise the catch-up saccades (CSs). DESIGN: Prospective cohort study. SETTING: Tertiary care academic referral centre. PARTICIPANTS: Fifty healthy subjects with no history of vestibular impairment, ten each in their 20's, 30's, 40's, 50's and 60's, underwent vHITs in the lateral semicircular canal plane. MAIN OUTCOME MEASURES: vHIT gains and the incidence and amplitudes of covert and overt CSs. RESULTS: The mean vHIT gain was 1.02 ± 0.07, and the mean gain asymmetry was 2.39 ± 1.96%, with no significant differences among age groups. CSs were observed during 22.6% of the trials and in 49% of the ears. The incidence of CSs was not associated with age. The mean velocity of CSs was 55.5 ± 16.9°/s, and its mean interaural difference was 11.8 ± 10.7°/s. CONCLUSIONS: vHIT gains were consistently equal to 1.0 in all age groups (20's to 60's), suggesting that abnormal criteria for vHIT gain (e.g. 0.8) and gain asymmetry (e.g. 8%) can be used, regardless of age. CSs were observed in about half of normal ears, suggesting that VOR is a hypometric system. The amplitudes and interaural difference of CSs were also similar in all age groups, suggesting that abnormal criteria for CS amplitude (e.g. 100°/s) and interaural difference (e.g. 40°/s) can be used, regardless of age.

α-SMA-Cre-mediated excision of PDK1 reveals an essential role of PDK1 in regulating morphology of cardiomyocyte and tumor progression in tissue microenvironment.

The phosphoinositide-3 kinase (PI3K) - phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade plays a critical role in cardiovascular development and tumor genesis. But the role of PDK1 in the microenvironment of heart and tumor remains unknown. To clarify the effects of PDK1 on tissue microenvironment in vivo, here, we created α-SMA-Cre-mediated excision of PDK1 mice. And the mice were injected subcutaneously with Lewis lung carcinoma (LLC) cells. We found PDK1-deficient mice had post-natal praecox dilated cardiomyopathy, decelerated tumor growth and severe tumor metastasis. Histopathological analysis revealed abnormality of vascular microenvironment in heart and primary tumor. In conclusion, PDK1 plays a pivotal role in regulating cardiac function and tumor metastasis by interfering with microenvironment.

The combined role of serotonin and interleukin-6 as biomarker for autism.

Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction and repetitive behaviors. Diagnosis of autism is currently phenotype based with no reliable laboratory test available to assist clinicians. It has been shown that dysfunction of serotonin (5-HT) and interleukin-6 (IL-6) are involved in autism. The goal of this study was to evaluate the combined role of 5-HT and IL-6 as potential biomarkers for autism. The whole blood concentration of 5-HT and plasma concentration of IL-6 of individuals with autism were significantly elevated compared with the control group, and the concentration of 5-HT and IL-6 had positive correlations with the severity of autism. The results of receiver operating characteristic (ROC) analysis indicated that the combination of 5-HT and IL-6 produced the best sensitivity and specificity for diagnosis of autism. Therefore, the present study has revealed a simple clinical method with great potential for assisting the diagnosis of autism.

MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients.

OBJECTIVES: Methylthioadenosine phosphorylase (MTAP), a ubiquitously expressed protein, plays important roles in purine biosynthesis. Locating near to each other on chromosome 9p21-22, codeletion of the MTAP and p16(Ink4A) genes have been reported in non-small cell lung cancer (NSCLC). The aim of this study is to determine the respective prognostic value of MTAP and p16 by considering their correlation in NSCLC patients. MATERIALS AND METHODS: We analyzed MTAP and p16 protein expression by immunohistochemical staining on 99 NSCLC tissue microarray samples. The association between MTAP and p16 expression levels and prognosis were analyzed using the Kaplan-Meier method and Cox proportional hazards model for prognosis. RESULTS: Patients with a low MTAP expression level had poor overall survival (P = 0.010) and disease-free survival (P = 0.002). Low p16 expression indicated a trend toward poor overall survival (P = 0.138) and disease-free survival (P = 0.199). There was a significant positive correlation between MTAP and p16 expression levels (Spearman's ρ = 0.402, P < 0.001). By multivariate analyses, the MTAP expression level retained its independent prognostic power and p16 expression loss of the correlation with prognosis. Concordant loss of MTAP and p16 expression was observed in 24 out of 99 patients (24.2%). Patients with concordant loss of MTAP and p16 expression had the worst prognosis compared to patients with high expression of both markers. CONCLUSION: MTAP expression is an independent prognostic factor and has greater prognostic significance than p16 expression in NSCLC. Concordant loss of MTAP and p16 expression indicates poor outcomes in lung cancer patients.

Endoplasmic reticulum ribosome-binding protein 1 (RRBP1) overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78.

Lung cancer is the leading cause of cancer deaths and is the most occurring malignancy worldwide. Unraveling the molecular mechanisms involved in lung tumorigenesis will greatly improve therapy. During early tumorigenesis, rapid proliferating tumor cells require increased activity of endoplasmic reticulum (ER) for protein synthesis, folding and secretion, thereby are subjected to ER stress. Ribosome-binding protein 1 (RRBP1) was originally identified as a ribosome-binding protein located on the rough ER and associated with unfolding protein response (UPR). In this report, we investigated the role of RRBP1 in lung cancer. RRBP1 was highly expressed in lung cancer tissue, as compared with adjacent normal tissues as assessed by immunohistochemistry (IHC) using lung cancer tissue array (n=87). Knockdown of RRBP1 by short-hairpin RNAs caused ER stress and significantly reduced cell viability and tumorigenicity. This effect was associated with a significant reduction in the expression of glucose-regulated protein 78 (GRP78). UPR regulator GRP78, an anti-apoptotic protein that is widely upregulated in cancer, has a critical role in chemotherapy resistance in some cancers. According to our results, cells with a higher level of RRBP1 were more resistant to ER stress. Ectopic expression of RRBP1 alleviated apoptosis that was induced by the ER-stress agent tunicamycin, 2-deoxy-D-glucose (2DG) or doxorubicin via enhancing GRP78 protein expression. A strong correlation was observed between the expression of RRBP1 and GRP78 in tumor biopsies using the database GSE10072. Our results also indicated that RRBP1 may involve in the regulation of mRNA stability of UPR components including ATF6 and GRP78. Taken together, RRBP1 could alleviate ER stress and help cancer cell survive. RRBP1 is critical for tumor cell survival, which may make it a useful target in lung cancer treatment and a candidate for the development of new targeted therapeutics.

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer.

We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser(473) and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal.

The epithelial to mesenchymal transition (EMT) is a highly conserved cellular programme that has an important role in normal embryogenesis and in cancer invasion and metastasis. We report here that Twist2, a tissue-specific basic helix-loop-helix transcription factor, is overexpressed in human breast cancers and lymph node metastases. In mammary epithelial cells and breast cancer cells, ectopic overexpression of Twist2 results in morphological transformation, downregulation of epithelial markers and upregulation of mesenchymal markers. Moreover, Twist2 enhances the cell migration and colony-forming abilities of mammary epithelial cells and breast cancer cells in vitro and promotes tumour growth in vivo. Ectopic expression of Twist2 in mammary epithelial cells and breast cancer cells increases the size and number of their CD44(high)/CD24(low) stem-like cell sub-populations, promotes the expression of stem cell markers and enhances the self-renewal capabilities of stem-like cells. In addition, exogenous expression of Twist2 leads to constitutive activation of STAT3 (signal transducer and activator of transcription 3) and downregulation of E-cadherin. Thus, the overexpression of Twist2 may contribute to breast cancer progression by activating the EMT programme and enhancing the self-renewal of cancer stem-like cells.

Clinical features, antimicrobial susceptibilities, and outcomes of Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) bacteremia at a medical center in Taiwan, 1999-2006.

A total of 118 patients with Elizabethkingia meningoseptica bacteremia at a medical center in Taiwan from 1999 to 2006 were studied. Minimum inhibitory concentrations (MICs) of 99 preserved isolates were determined. The incidence (per 100,000 admissions) of E. meningoseptica bacteremia increased from 7.5 in 1996 to 35.6 in 2006 (p = 0.006). Among them, 84% presented with fever, 86% had nosocomial infections, and 60% had acquired the infection in intensive care units (ICUs). The most common underlying diseases were malignancy (36%) and diabetes mellitus (25%). Seventy-eight percent of patients had primary bacteremia, followed by pneumonia (9%), soft tissue infection, and catheter-related bacteremia (6%). Forty-five patients (38%) had polymicrobial bacteremia. Overall, the 14-day mortality was 23.4%. Multivariate analysis revealed E. meningoseptica bacteremia acquired in an ICU (p = 0.048, odds ratio [OR] 4.23) and presence of effective antibiotic treatment after the availability of culture results (p = 0.049, OR 0.31) were independent predictors of 14-day mortality. The 14-day mortality was higher among patients receiving carbapenems (p = 0.046) than fluoroquinolones or other antimicrobial agents. More than 80% of the isolates tested were susceptible to trimethoprim-sulfamethoxzole, moxifloxacin, and levofloxacin. The MIC(50) and MIC(90) of the isolates to tigecycline and doxycycline were both 4 µg/mL and 8 µg/ml, respectively.

Autoinhibition of IL-15 expression in KC cells is ERK1/2 and PI3K dependent.

Interleukin (IL)-15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL-15 on expression of IL-15, IL-6 and TNF-alpha in KC are unknown. We have investigated the effects of IL-15 on the expression of the three genes in primary culture of KC by the real-time PCR, Western blot and ELISA. We observed that exogenous IL-15 suppressed the endogenous expression of IL-15, decreased the expression of IL-6 at mRNA and protein levels in KC. The inhibition was blocked by anti-IL-15 monoclonal antibody and by inactive IL-15, I50D mutant IL-15. In contrast, IL-15 increased TNF-alpha transcription in these cells. Mechanistic studies demonstrated that the auto-regulation of IL-15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto-inhibitory mechanism controlling cellular IL-15 levels.

The impact of age on the demographic, clinical, radiographic characteristics and treatment outcomes of pulmonary tuberculosis patients in Taiwan.

BACKGROUND: The characteristics of pulmonary tuberculosis (TB) in the elderly are different from young patients. This leads to delay in diagnosis and higher mortality from TB in the aged population. The aim of this study was to investigate the impact of age on the demographic, clinical, radiographic characteristics, and treatment outcomes of pulmonary TB patients in Taiwan. MATERIALS AND METHODS: We performed a retrospective analysis of the medical charts and chest radiographs of 83 elderly (> or =60 years old) and 74 young (< 60 years old) culture-proven pulmonary TB patients from 1 August 2003 to 31 July 2006. RESULTS: Elderly patients showed lower frequencies of infectious TB contact history, alcoholism, cavity, and positive acid-fast bacilli sputum smears. In contrast, the elderly population had higher frequencies of chronic obstructive lung disease, heart failure, stroke, dyspnea, lower lung field involvement, pleural effusion and mortality. There were no differences between these two groups regarding sex, initial body weight, previous TB disease, hospital admission, diabetes mellitus, end-stage renal disease, neoplasm, liver cirrhosis, upper lung field involvement, cure, and treatment completion. Furthermore, age of 60 and older, lower initial body weight less than 50 kg, coexisting medical diseases, and extensive radiographic disease were factors independently associated with unfavorable outcomes. CONCLUSIONS: Elderly patients with pulmonary TB are more likely to present with negative sputum smears, cavity-negative lesions, lower lung field involvement and pleural effusion on chest radiographs. The prognosis is poor for the elderly pulmonary TB patients with lower body weight, coexisting medical diseases, and extensive radiographic disease.

Isocupressic acid blocks progesterone production from bovine luteal cells.

The needles of ponderosa pine (Pinus ponderosa Laws.) were reported to induce abortions when fed to late-term pregnant beef cows in North America. An in vivo study of pregnant cows suggested that isocupressic acid (IA) was the main abortifacient isolated from needles and bark of the pine. However, the mechanism of abortifacient activity of IA is not clear yet. In a pregnant cow, the corpus luteum of the ovary helps the maintenance of pregnancy by its progesterone production. This study involved the IA extracted from the root of the Taiwan cypress (Juniperus formosana) and used a frozen-thawed bovine luteal cell culture system to investigate the action of IA on progesterone production. Thawed bovine luteal cells (1 x 10(5) cells/ml/well) in M199 medium were cultured in 24-well culture plates at 37 degrees C in a 5% CO2 incubator. Ten ml of tested drugs, IA at 1 to 1000 ng/ml and/or ovine luteinizing hormone (oLH) at 1 to 100 ng/microl or 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) with 0.1-10 mM, were added into each well. After 4 hours of incubation, the media were harvested and assayed for progesterone by an enzyme immunoassay. Progesterone production from cells was the indicator used to evaluate the action of IA. All tested doses of IA significantly inhibited progesterone production in both basal and oLH stimulating conditions. Also those dosages inhibited cyclic adenosine-3',5'- monophosphate (cAMP) stimulation, suggesting a post-cAMP mechanism is involved in the IA action. We concluded that IA can induce pregnant cows to abort partly through blocking luteal function and may be identified as a new abortifacient chemical.