EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngeal carcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop.

Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.

Laparoscopic Witzel gastrostomy--a reappraised technique.

BACKGROUND: Laparoscopic gastrostomy is the best alternative for long-term enteral feeding when percutaneous endoscopic gastrostomy is not possible. The aim of the present study was to determine the feasibility, complications, adequacy of feeding support, and tolerability of laparoscopic Witzel gastrostomy (LWG) in head and neck cancer patients. The initial results and the results of extended follow-up were evaluated. METHODS: A consecutive series of 48 patients with stenotic head and neck or esophageal cancer were referred for laparoscopic gastrostomy. The patients consisted of 42 men and 6 women aged 36 to 82 years (mean, 54 years). After laparoscopic placement of a Foley catheter of 16 F into the stomach, a seromuscular tunnel 4 cm in length is created, embedding the catheter by interrupted sutures. Three stay sutures for gastropexy are fixed and tied on the abdominal skin at the end of the procedure. The mean duration of the procedure was 62.4 +/- 11 min (52-124 min). RESULTS: Laparoscopic Witzel gastrostomy could be performed successfully in all patients with aerodigestive cancer. None of the laparoscopic gastrostomy tube placement procedures was converted to an open surgery, and none of the 48 patients in this series died as a result of the laparoscopic procedure. All LWG complications (11%) were minor, consisting of superficial wound infections, balloon rupture, and chronic granulation. No major complications were encountered. The mean usage time of gastrostomy was 6.3 +/- 5.3 months. CONCLUSIONS: Current techniques of LWG could be an alternative to percutaneous endoscopic gastrostomy (PEG) for long-term enteral access, because it has proved to be safe and reproducible with relatively few complications.

Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance.

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.

ABO/secretor genetic complex is associated with the susceptibility of childhood asthma in Taiwan.

BACKGROUND: Histo-blood groups, ABO, Lewis (Le) and secretor (Se) were found to be associated with lower lung function and wheezing in coal miners as well as in asthmatic children in some studies but not others, possibly reflecting the genetic heterogeneity among different ethnicities and local environmental exposure. OBJECTIVE: The present study was conducted to determine the association between ABO, Lewis and secretor genetic complex with susceptibility of childhood asthma in Taiwan. METHODS: We randomly selected 136 asthmatic children and 161 age-matched controls from a childhood asthma survey conducted in primary schools. ABO and Lewis blood groups were determined by red blood cell agglutination methods. Analysis of Se genotype was performed by PCR with sequence-specific primers. RESULTS: There was a higher prevalence rate in secretor subjects (Se/Se) (odds ratio (OR)=1.7, confidence interval (CI)=1.022-2.938) in asthma as compared with controls. The combined effect of these three blood systems revealed that blood group O/secretor phenotype (Se/Se) (OR=2.7, CI=1.126-6.033), and blood group O/Le(a-b-) (OR=3.6, CI=1.080-11.963, P<0.03) individuals were significantly associated with asthma. The Lewis Le(a-b-) recessive genotype (OR=3.3, CI=1.267-8.482), or the joint blood group O/Le(a-b-) phenotype (OR=5.2, CI=1.259-21.429, P<0.02), was significantly associated with high serum IgE (>500 IU), respectively. There was no association of these three blood systems with the sensitivity of dust mite, Dermatophagoide pteronyssinus, in our study population. CONCLUSIONS: We concluded that blood group O/secretors (Se/Se) and O/Le(a-b-) were associated with childhood asthma, and may act as one of the predominant factors for environmental triggers of allergy for asthmatic children in Taiwan.

Neurotrophin-3 prevents mitochondrial dysfunction in sensory neurons of streptozotocin-diabetic rats.

Sensory neurons from streptozotocin (STZ)-diabetic rats exhibit depolarization of mitochondria and the related induction of reactive oxygen species has been proposed to contribute to the etiology of sensory polyneuropathy in diabetes. There is deficient neurotrophin-3 (NT-3)-dependent neurotrophic support of sensory neurons in diabetes and treatment of STZ-diabetic rats with NT-3 prevents neuropathological alterations in peripheral nerve. Therefore, we hypothesized that loss of NT-3 may contribute to mitochondrial dysfunction in sensory neurons in diabetic sensory neuropathy. The specific aim of this study was to determine whether treatment of STZ-diabetic rats with systemic NT-3 could prevent depolarization of the mitochondrial inner membrane potential (Deltapsi(m)). In vitro studies with cultured DRG neurons from control rats revealed that treatment with 50 ng/ml NT-3 for 6 h enhanced the Deltapsi(m), e.g., a higher polarized membrane potential, compared to untreated neurons (P < 0.05). Studies on DRG sensory neurons from control vs. STZ-diabetic rats demonstrated that NT-3 therapy prevented the diabetes-induced depolarization of Deltapsi(m) (P < 0.05) in parallel with normalization of diabetes-dependent deficits in sensory nerve conduction velocity. Furthermore, alterations in mitochondrial function in vitro and in vivo correlated with the level of activation/expression of Akt in DRG neurons.

Modified devascularization surgery for isolated gastric varices assessed by endoscopic ultrasonography.

BACKGROUND: This study aimed to assess the role of endoscopic ultrasonography (EUS) in the surgical management of isolated gastric varices (IGV), and to report the authors' experience in the treatment of IGV with modified devascularization surgery. METHODS: In this study, 26 cirrhotic patients with IGV were treated with devascularization surgery for variceal hemorrhage. Preoperatively, percutaneous transhepatic portography (PTP) and EUS were used to determine the mode of therapy for IGV. Fundectomy was performed for 14 patients with fundic IGV, whereas 12 patients with cardiac IGV underwent proximal gastrectomy. RESULTS: A significantly higher proportion of patients with cardiac varices showed grade 3 IGV on preoperative EUS than those who had fundic varices (p < 0.05). No major complications were observed during or after the operation, and only one patient died of prolonged shock and massive transfusion. Postoperatively, gastric varices had been eradicated completely in 25 of 26 patients, as determined by EUS study. During a mean follow-up period of 50 months, two patients had recurrent varices without bleeding, as demonstrated by EUS. The overall 5-year survival rate for the fundic IGV group was 67.9%, whereas that for the cardiac IGV group was 64.3% (p > 0.05). CONCLUSIONS: This study showed that devascularization surgery is highly effective for the prevention of recurrent bleeding from IGV and provides an alternative treatment method. Preoperatively, EUS is very helpful in detailed devascularization of patients with specific IGV, and may be used also for postoperative follow-up evaluation.

Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3.

AIMS/HYPOTHESIS: In diabetic sensory polyneuropathy the earliest and most severe pathophysiology occurs in neurones with the longest axons. The aim of this study was to characterise a diabetes-induced neurodegenerative marker that was selective for sensory neurones with the longest axons. We studied alterations in calcium homeostasis since this occurs in other neurodegenerative diseases. METHODS: Sensory neurones were cultured from control and streptozotocin-diabetic rats, treated with or without human recombinant neurotrophin-3 (hrNT-3), and neurones from L4-L6 dorsal root ganglia (DRG) which exhibit the longest axons in vivo were compared with those from C5-L3 DRG. Fluorescent video-imaging was used to measure cytoplasmic calcium dynamics. RESULTS: Streptozotocin diabetes of 8 to 14 weeks, induced an increase in resting internal Ca(2+) concentration ([Ca(2+)](i)), from 67 +/- 7 nmol/l in small neurones and 79 +/- 9 nmol/l in big neurones obtained from control animals to 214 +/- 19 nmol/l in small neurones and 273 +/- 30 nmol/l in big neurones after 14 weeks of diabetes ( p < 0.05) in L4-L6 DRG cultures. Neurones from C5-L3 ganglia and non-neuronal cells were not affected. Treatment of 14-week streptozotocin-diabetic rats with subcutaneous injection of 5 mg/kg NT-3 normalised the increase in resting [Ca(2+)](i). The amplitudes induced by depolarisation, caffeine and ATP [Ca(2+)](i) responses were reduced in small ( < 30 microm diameter) but not big ( > 35 microm diameter) neurones of L4-L6 DRG from streptozotocin-diabetic animals; the C5-L3 DRG were not similarly affected and the changes in the L4-L6 DRG were corrected by NT-3 treatment. CONCLUSIONS/INTERPRETATION: Altered calcium homeostasis could be an early molecular marker linked to the onset of diabetic sensory neuropathy. This neurodegenerative index can be corrected by NT-3 therapy and should encourage further work aimed at understanding the mechanistic basis of these observations.

Video-assisted endoscopic lumbar discectomy.

BACKGROUND: The optimal management of symptomatic lumbar disc herniations (LDH) remains controversial. This study examines the feasibility and safety of a video-assisted endoscopic intracanalicular technique for managing symptomatic LDH. METHODS: From September 1999 to June 2000, we used the current technique, the Vertebroscope System, on 11 patients (six men, five women), aged from 18 to 61 years (mean, 45), who had suffered symptomatic LDH. The disc levels involved were at L4-L5 (n = 8), and L5-S1 (n = 3). The Vertebroscope, which has a 30 degrees viewing angle and a working channel 1.7 cm in diameter, was used for the minimally invasive endoscopic procedures. The mean follow-up period was 12 months (range, 6-15). RESULTS: The operating time ranged from 60 to 335 min (mean, 136.5), and the estimated blood loss during operation was minimal to 200 ml. The mean length of the paramedian skin incisions was 2 cm. No drainage tube was used postoperatively. The mean hospital stay was 3 days (range, 2-5), with five patients discharged on the 1st postoperative day. Complications included one superficial wound infection, one conversion to an open procedure when muscle herniation into the working channel created a technical difficulty in approaching the ligamatum flavum, and one minor tear of the nerve root sleeve that did not require further surgery. In the first five patients studied herein, the mean operating time was significantly longer than that for the later five patients (201 vs 72 min, p < 0.001). CONCLUSIONS: The advantages of the current endoscopic disectomy technique include its minimally invasive character, with less paraspinal muscle trauma, direct address to the lesion site that resembles the open technique, and enhanced operative field visualization with a paramedian skin incision of just 2 cm. Practice is needed to perfect such an endoscopic approach for lumbar disc excision, so the operating time decreased significantly as the surgeons became more familiar with this endoscopic technique. It has proved to be safe and effective for treating patients with symptomatic LDH.

Inflammatory pseudotumor of the spleen--a case report.

A 36-year-old woman had suffered from epigastric fullness for half a year. A splenic mass was found by ultrasonography. She was treated with splenectomy. Inflammatory pseudotumor of the spleen was diagnosed pathologically. This benign tumor in the spleen is extremely rare. To our knowledge, only 67 cases had been reported in the literature. Recognition of this rare entity is important because it may mimic splenic malignancy clinically and radiographically.

Overexpression of the c-met protooncogene in human gastric carcinoma--correlation to clinical features.

Overexpression of hepatocyte growth factor receptor (c-met) has been detected in many human tumors. To investigate the possible involvement of c-met in human gastric carcinogenesis, we examined c-met expression in 45 patients with gastric carcinoma using Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical staining. The c-met mRNA expression was increased twofold and sevenfold in gastric carcinoma tissues compared to the adjacent normal tissues by Northern blot analysis and RT-PCR, respectively. In the immunohistochemical study, c-met protein was detected in 32 of 45 (71.1%) patients, with marked overexpression in gastric carcinoma compared with matched normal gastric tissues. The c-met-positive immunoreactivities were more frequently encountered in serosa-exposed and serosa-infiltrating gastric cancer (p = 0.003). In addition, tumor stage was another statistically significant parameter that was observed between the two groups (p = 0.02). Multivariate analyses revealed that the tumor stage (p = 0.014) and c-met overexpression (p = 0.031) were independently correlated with survival. These data suggest that overexpression of c-met may play a part in gastric carcinogenesis and may represent a prognostic factor for gastric cancer.

A novel transcription factor inhibitor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen-exposed rat.

1. We examined the effect of SP100030, a novel inhibitor of activator protein-1 (AP-1) and nuclear factor (NF)-kappa B transcription factors, in a rat model of asthma. 2. Sensitized Brown-Norway rats were treated with SP100030 (20 mg kg(-1) day(-1) for 3 days) intraperitoneally prior to allergen challenge. Allergen exposure of sensitized rats induced bronchial hyperresponsiveness (BHR), accumulation of inflammatory cells in bronchoalveolar lavage (BAL) fluid, and also an increase in eosinophils and CD2(+), CD4(+) and CD8(+) T-cells in the airways together with mRNA expression for IL-2, IL-4, IL-5, IL-10, and IFN-gamma. 3. Pre-treatment with SP100030 inhibited BAL lymphocyte influx (P<0.03), specifically reduced CD8(+) T-cell infiltration in the airway submucosa (P<0.03), and mRNA expression for IL-2, IL-5, and IL-10 (P<0.05). Neutrophil, eosinophil, and CD4(+) T-cells accumulation in the airways and BHR were not affected by SP100030. 4. Our results indicate that suppression of IL-2 and IL-5 mRNA expression may not necessarily lead to suppression of BHR. The expression of IL-5 mRNA may contribute to the airway accumulation of eosinophils, but does not correlate with the extent of eosinophilia. 5. The joint AP-1 and NF-kappa B inhibitor, SP100030, selectively inhibits CD8(+) T-cells, and mRNA expression of both Th1 and Th2 cytokines in vivo, but does not inhibit allergen-induced airway eosinophilia and BHR.

[Quantitative detection of HER-2 oncogene amplification in primary hepatocellular carcinoma using dual FISH technique and its clinical significance].

To investigate the frequency of HER-2 oncogene amplification in primary hepatocellular carcinoma (HCCs) and its relationships with clinicopathological parameters and prognosis, 42 surgical samples from patients with primary HCCs were detected for their HER-2 oncogene amplification by dual FISH technique, and then the correlations between HER-2 amplification and clinicopathological characteristics and prognosis were analyzed statistically. HER-2 oncogene amplification was detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%) cases with high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2 amplification was associated significantly with postoperative survival time of HCC patients examined (P = 0.046) and the presence of HER-2 gene amplification showed a trend toward a correlation with tumor size (P = 0.085), but wasn't relative to sex, age, AFP level, HBV infection, postoperative relapse and clinical staging of HCC patients tested (P > 0.05). On the other hand, gain of the HER-2 oncogene copy was examined in 31 of 42(73.8%) primary HCCs, consisting of 9 (21.4%) cases with HER-2 amplification and 22(52.4%) ones with aneusomy 17/polysomy 17. There weren't significant relationships between gain of HER-2 oncogene copy and, HCC patient's sex, tumor size, clinical staging, postoperative relapse and survival time (P > 0.05), but gain of HER-2 oncogene copy correlated significantly to patients' age, AFP level and HBV infection (P < 0.05). The study indicated that there were a lower frequency of HER-2 oncogene amplification and a higher frequency of aneusomy 17/polysomy 17 in primary HCCs and that HER-2 oncogene amplification activation might be involved in the development and progression of a subset of HCCs, and seemed to be a valuably independent prognosis factor predicting postoperative poorer survival for patients with HCC.

Heme oxygenase-2 interaction with metalloporphyrins: function of heme regulatory motifs.

Heme oxygenase-2 (HO-2) degrades heme [Fe-protoporphyrin IX (Fe-PP)] to CO and bilirubin. The enzyme is a hemoprotein and interacts with nitric oxide. HO-2 has two copies of heme regulatory motif (HRM) with a conserved core of Cys264-Pro265 and Cys281-Pro282. We examined interaction of HO-2 HRMs with Fe-PP, Zn-protoporphyrin IX (Zn-PP; HO-2 inhibitor), and protoporphyrin IX (PP IX). Spectral analyses, using 1:4 or 1:1 molar ratio of the heme to 10-residue peptides, corresponding to HRM containing HO-2 sequences, revealed specific interactions as indicated by a shift in the absorption spectrum of heme. Five residue peptides qualitatively produced similar results. Substitution of cysteine with alanine in either peptide eliminated interactions, and substitution of proline with alanine reduced the peptides' affinity for heme. Neither Zn-PP nor PP IX absorption spectrum was affected by HRM peptides. The circular dichroism spectra confirmed heme-HRM peptides interactions. An astounding 4,000-6,000-fold higher concentrations of KCN were required at pH 7.5 to displace HRM peptides from heme. Data suggest (a) each HRM can contribute to HO-2-heme interaction, (b) heme iron interacts with cysteine thiol, (c) charged residues upstream of Cys264-Pro265 result in its high-affinity heme binding, and (d) inhibition of HO-2 activity by synthetic metalloporphyrins does not involve HRMs. We suggest that heme bound to HRMs may serve as a binding site/reservoir for gaseous signal molecules.

The diagnostic value of galactography in patients with nipple discharge.

To evaluate preoperative galactographic findings in the differentiation between the benign and malignant lesions in patients presenting spontaneous nipple discharge without mass. Of the 215 patients who have undergone the galactography, 181 cases with abnormal galactography had surgery performed. All galactrograms were reviewed and galactographic findings were correlated to the pathological results to determine diagnostic differentiation. Of the 181 cases we operated on, 112 cases were macroscopically bloody, with 30 cases having cancers (26.8%). Fifty-four cases with serous discharge had seven cancer cases (13.0%). No cancer cases with other color discharge were found. Of the 37 cancer cases, 11 cases had lesions located in the main mammary ducts (lactiferous duct and the segmental duct) (29.7%) and 26 cases had lesions in the peripheral ducts (the subsegmental duct and its branches) (70.3%) (P<.05). Of 113 cases with benign proliferative ductal lesions, 88 cases were located in the main mammary duct (77.9%) and 25 cases in the peripheral mammary duct (22.1%) (P<.05). Otherwise, 29 cancer cases (82.9%) had ductal obstructions and 28 cancer cases (75.7%) had irregular intraductal defects that appeared in the galactograms, which is different from the 113 benign proliferative ductal lesion cases that had 88 cases (71.7%) with ductal dilatation and 90 cases (79.6%) with lobular or smooth intraductal defects (P<.05). These results showed that the cancer cases had a higher rate of locating in the peripheral duct, irregular intraductal duct defects, and ductal obstruction, and a lower rate associated with ductal dilatation or torsion. The galactographic findings were evaluated using the tumor location, types of intraductal defects, ductal obstruction, and dilatation. Preoperative diagnostic galactography is useful in differentiating between the benign or malignant lesions in patients with spontaneous nipple discharge.

Expression of HER-2/NEU oncoprotein in familial and non-familial breast cancer.

The HER-2/neu proto-oncogene amplification or oncoprotein overexpression is an important prognostic factor and a predictive factor for resistance to endocrine therapy and adjuvant chemotherapy in breast cancers. Moreover, it is an entry criterion in the assessment of patients for whom Herceptin (Trastuzumab) treatment is considered. The overexpression rate of HER-2/neu oncoprotein has been identified in 10% to 40% of human breast cancers. In Taiwan, a higher grade of pathobiologic characteristics of familial breast cancer was also noted than that found in the non-familial group. It is worthwhile to evaluate whether the overexpression is more frequent in familial breast cancers. Fifty-six familial and 111 non-familial breast cancers were studied between 1990 and 1999 to assess both the overexpression of HER-2/neu oncoprotein immunohistochemically and the correlation with the histological type, grade and stage of breast carcinoma. The overexpression rate is higher in the familial breast cancer group (50.0%) when compared with non-familial breast cancer group (36.9%), which did not prove to be statistically significant (P = 0.1068). However, when the infiltrating ductal carcinomas of both groups are compared, it is statistically significant (52.3% vs. 33.7%, P = 0.0429). Overexpression correlated with node status and histological grade of infiltrating ductal carcinomas in non-familial and overall breast cancers. It also correlated with nuclear pleomorphism and mitotic counts, but not tubule formation or tumor size. All 3 cases of Paget's disease revealed overexpression, whereas all 12 cases of mucinous and one case of metaplastic carcinoma and one case of medullary carcinoma were negative. The overexpression rate was higher both in familial and non-familial intraductal carcinomas (57.1% vs. 73.3%, P = 0.4716). No statistical difference was identified between the 2 subsets. A case of infiltrating ductal carcinoma combined with intraductal carcinoma revealed heterogeneous staining in the component of ductal carcinoma in situ, while the invasive component did not. This suggests that overexpression decreases within individual tumors as they evolve from in situ to invasive lesioins. The HER-2/neu may imply a different role in intraductal carcinoma, Paget's disease and invasive duct carcinoma. Although the overexpression rate of HER-2/neu oncoprotein of familial breast cancer was not significantly higher than that of the non-familial group, it is appropriate to evaluate the rate of HER-2/neu overexpression according to the histological type of breast cancers from familial breast cancer and non-familial breast cancer. The prognoses will be needed for future evaluation.

Minimal access surgery in managing anterior lumbar disorders.

Traditional anterior lumbar surgery usually requires a long and sometimes painful skin incision. The current study evaluated the feasibility and safety of minimal access surgery for anterior lumbar disorders, emphasizing indications, operative technique, and the minimum 2-year followup results. From May 1996 to December 1997, the authors used this technique on 25 patients whose indications for surgery included syndromes of failed back surgery, selected cases of lumbar disc herniations, tuberculous or pyogenic spondylitis, selected spondylolisthesis, and vertebral tumors. In 23 of 25 patients, the site of interest was approached through a left flank incision, regardless of the laterality of the lesion. The mean length of the main incision was 5 cm. There were no injuries to great vessels or any neurologic deterioration after the procedures. Solid interbody fusion could be identified radiographically between 3 and 6 months after surgery. At a mean followup of 39.6 months, nine patients had excellent clinical outcomes, 11 patients had good outcomes, two patients had fair outcomes, and one patient had a poor outcome. The authors think such minimal access surgery is simple, effective, and safe for anterior lumbar disorders. The merits of the current technique include no need for endoscopic, microscopic, or complex surgical instruments, a lower amount of radiation exposure during surgery, and a shortened learning curve because the approach is similar to the anterior open lumbar technique, although the skin incision is only 5 cm in length.

Mutations of p53 gene in gastric carcinoma in Taiwan.

BACKGROUND: p53 gene mutation and p53 protein accumulation is the most common event in human cancers. The present study was conducted to investigate the occurrence of p53 mutations in patients with gastric carcinoma in Taiwan. MATERIALS AND METHODS: Tumor samples from 36 patients with primary gastric carcinoma undergoing radical gastrectomy were evaluated. The mutational status of the p53 (exons 5 to 8) was screened by polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. These results were compared with p53 protein expression as assessed by immunohistochemical staining. RESULTS: Of all 36 gastric carcinomas, mutations of the p53 gene were found in 7 cases (19.4%). These results from direct sequencing indicated that mutations consisted of five missence mutations, one silent mutation and one mutation within the splice donor site of intron 5. Mutations were found at codon 145 in exon 5 (1 case), intron 5 (1 case), codon 248 in exon 7 (1 case), codon 251 in exon 7 (2 cases), codon 285 in exon 8 (1 case) and codon 287 in exon 8 (1 case). The mutation hot spot at codon 251 in gastric cancer has not been observed previously. Over-expression of p53 oncoprotein was observed in 10 patients (27.8%) immunohistochemically. CONCLUSIONS: p53 gene mutation might contribute to the pathogenesis of human gastric carcinoma. However, the suggestion awaits further investigation for confirmation.

Dexamethasone inhibits luteinizing hormone-induced synthesis of steroidogenic acute regulatory protein in cultured rat preovulatory follicles.

The effect of dexamethasone on LH-induced synthesis of steroidogenic acute regulatory (StAR) protein was studied in a serum-free culture of preovulatory follicles. StAR protein is a steroidogenic tissue-specific, hormone-induced, rapidly synthesized protein previously shown to be involved in the acute regulation of steroidogenesis, probably by promoting the transfer of cholesterol to the inner mitochondrial membrane and the cytochrome P450 side-chain cleavage (P450(scc)) enzyme. Treatment of preovulatory follicles dissected from ovaries of cyclic adult rats on the morning of proestrus with LH for 24 h resulted in a dose-dependent increase in the level of StAR protein that reached a maximum at 10 ng LH/ml. This increase was associated with an increase in progesterone production. Treatment of the follicles with increasing concentrations (1-1000 ng/ml) of dexamethasone suppressed LH (10 ng/ml)-induced StAR protein levels and progesterone production in a dose-dependent manner. The amount of P450(scc) was not affected by this dexamethasone treatment, indicating that the loss of steroidogenic capacity was not a result of inhibition of P450(scc). Dexamethasone also decreased StAR protein levels and progesterone production induced by the adenylate cyclase activator forskolin (10(-5) M) or a cAMP analogue 8-Br-cAMP (0.5 mM). The effects of dexamethasone on 8-Br-cAMP-induced StAR protein levels and progesterone production were blocked by cotreatment of the follicles with glucocorticoid receptor antagonist RU-486. These results demonstrate that dexamethasone inhibits the LH-induced StAR protein levels and that the effects of dexamethasone are mediated by the glucocorticoid receptor.