Incidence and risk factors for perineal hernia after robotic abdominoperineal resection: a single-center, retrospective cohort study.

BACKGROUND: Perineal hernia (PH) is a late complication of abdominoperineal resection (APR) that may compromise a patient's quality of life. The frequency and risk factors for PH after robotic APR adopting recent rectal cancer treatment strategies remain unclear. METHODS: Patients who underwent robotic APR for rectal cancer between December 2011 and June 2022 were retrospectively examined. From July 2020, pelvic reinforcement procedures, such as robotic closure of the pelvic peritoneum and levator ani muscles, were performed as prophylactic procedures for PH whenever feasible. PH was diagnosed in patients with or without symptoms using computed tomography 1 year after surgery. We examined the frequency of PH, compared characteristics between patients with PH (PH+) and without PH (PH-), and identified risk factors for PH. RESULTS: We evaluated 142 patients, including 53 PH+ (37.3%) and 89 PH- (62.6%). PH+ had a significantly higher rate of preoperative chemoradiotherapy (26.4% versus 10.1%, p = 0.017) and a significantly lower rate of undergoing pelvic reinforcement procedures (1.9% versus 14.0%, p = 0.017). PH+ had a lower rate of lateral lymph node dissection (47.2% versus 61.8%, p = 0.115) and a shorter operative time (340 min versus 394 min, p = 0.110). According to multivariate analysis, the independent risk factors for PH were preoperative chemoradiotherapy, not undergoing lateral lymph node dissection, and not undergoing a pelvic reinforcement procedure. CONCLUSIONS: PH after robotic APR for rectal cancer is not a rare complication under the recent treatment strategies for rectal cancer, and performing prophylactic procedures for PH should be considered.

Efficacy of laparoscopic surgery for loop colostomy: a propensity-score-matched analysis.

PURPOSE: Colostomy is a common procedure for fecal diversion, but the optimal colostomy approach is unclear in terms of surgical outcomes and stoma-related complications. The purpose of this study was to examine the efficacy and feasibility of laparoscopic loop colostomy. METHODS: This retrospective cohort study included patients who underwent loop colostomy at Shizuoka Cancer Center in Japan between April 2010 and March 2022. Patients were divided into two groups based on surgical approach: the laparoscopic (LAP) and open (OPEN) groups. Surgical outcomes and the incidences of stoma-related complications such as stomal prolapse (SP), parastomal hernia (PSH), and skin disorders (SD) were compared with and without propensity score matching. RESULTS: Of the 388 eligible patients, 180 (46%) were in the LAP group and 208 (54%) were in the OPEN group. The male-to-female ratio was 5.5:4.5 in the Lap group and was 5.3:4.7 in the OPEN group, respectively. The median age was 68 years (range, 31-88 years) in the LAP group and 65 years (range, 23-93 years) in the OPEN group, respectively. The LAP group, compared with the OPEN group, had a shorter operative time and lower incidences of surgical site infection (3.9% versus 16.3%, respectively; p < 0.01) and SD (11.7% versus 24.5%, respectively; p < 0.01). There was no significant difference between the LAP and OPEN groups in the incidence of SP (17.3% versus 17.3%, respectively) or PSH (8.9% versus 6.7%, respectively). After propensity score matching, the incidences of surgical site infection and SD were significantly lower in the LAP group than in the OPEN group, while there were no significant differences in the operative time or the incidences of SP and PSH. CONCLUSION: Our results suggest that laparoscopic surgery could be beneficial and feasible in loop colostomy.

Health care transition for cerebral palsy with intellectual disabilities: A systematic review.

OBJECTIVE: Today, most individuals with cerebral palsy are adults who need a paediatric-to-adult health care transition. However, many remain in paediatric care for treatment of adult-onset health issues. Therefore, a systematic review based on the 'Triple Aim' framework was performed to determine the status of paediatric-to-adult health care transition for people with cerebral palsy. A comprehensive evaluation of transitional care was proposed for using this framework. It consists of 'experience of care', meaning satisfaction with the care, 'population health', meaning the well-being of patients, and 'cost', meaning cost-effectiveness. METHOD: Electronic database (PubMed) searches were performed. The inclusion criteria were original articles published between 1990 and 2020. The search terms used in this study were ('cerebral palsy' AND 'transition to adult health care') OR ('cerebral palsy' AND 'transition'). The study type had to be epidemiological, case report, case-control, and cross-sectional, but not qualitative. The outcomes of the studies were categorised into 'care experience', 'population health', and 'cost', according to the Triple Aim framework. RESULTS: Thirteen articles met the abovementioned inclusion criteria. Few studies have examined the effect of the intervention of transition for young adults with cerebral palsy. Participants in some studies had no intellectual disability. Young adults were dissatisfied with the 'care experience', 'population health', and 'cost' and had unmet health needs and inadequate social participation. INTERPRETATION: Further transition intervention studies with a comprehensive assessment and proactive involvement of individuals are warranted. The presence of an intellectual disability should be considered.

Detailed Arterial Anatomy and Its Anastomoses of the Sphenoid Ridge and Olfactory Groove Meningiomas with Special Reference to the Recurrent Branches from the Ophthalmic Artery.

BACKGROUND AND PURPOSE: Detailed arterial anatomy of the sphenoid ridge and olfactory groove meningiomas is complicated due to the fine angioarchitecture and anastomoses between each feeder. Herein, we present details of the arterial anatomy and the relationships of feeders in these lesions. MATERIALS AND METHODS: This study included 20 patients admitted to our department between April 2015 and March 2020. Conditions of subjects consisted of 16 sphenoid ridge meningiomas and 4 olfactory groove meningiomas. We mainly analyzed arterial anatomy using 3D rotational angiography and slab MIP images of these lesions. We also analyzed the anastomoses of each feeder. RESULTS: We found that 19 (95%), 15 (75%), and 15 (75%) lesions had feeders from the ophthalmic, internal carotid, and external carotid arteries, respectively. As feeders from the ophthalmic artery, recurrent meningeal arteries were involved in 18 lesions (90%). Fifteen lesions (75%) had anastomoses between each feeder. CONCLUSIONS: Most of the meningiomas in the sphenoid ridge and olfactory groove had feeders from the ophthalmic and internal carotid arteries. There were various anastomoses between each feeder. This is the first report to demonstrate the detailed arterial anatomy and frequency of recurrent branches from the ophthalmic artery and their anastomoses using detailed imaging techniques.

Which is more important in the management of splenic flexure colon cancer: strict central lymph node dissection or adequate bowel resection margin?

BACKGROUND: What qualifies as optimal lymph node (LN) dissection in the surgical management of splenic flexure colon cancer (SFCC) still remains controversial because few studies have evaluated the distribution of LN metastasis of SFCC. The aim of this study was to clarify detailed distribution of LN metastasis and long-term outcomes of SFCC. METHODS: This retrospective study enrolled patients who had curative colectomy for primary transverse or descending colon cancer of pathological stage I, II, or III at a single high-volume cancer center between April 2002 and December 2018. The 538 eligible patients were divided into three groups: patients with SFCC (SFCC group, n = 168), patients with proximal transverse colon cancer (PTCC group, n = 290), and patients with distal descending colon cancer (DDCC group, n = 80). LNs were classified into horizontal (pericolic) and vertical (intermediate and main) nodes. Intermediate and main LN station numbers were defined according to the Japanese Society for Cancer of the Colon and Rectum classification. Distributions of LN metastasis and long-term outcomes were compared. RESULTS: In the SFCC group, the mean age was 67.3 ± 10.5 years and 110 patients (65.5%) were male. The proportion of patients with LN metastasis in the intermediate or main region was significantly lower in the SFCC group (8%) than in the PTCC (37%) (p < 0.01) or DDCC group (29%) (p < 0.01) in pathological stage III patients. In the SFCC group, the incidence of pericolic LN metastasis on the oral side of tumor (43%) was significantly higher than in the PTCC group (21%) (p < 0.01) and was similar to that in the DDCC group (42%) (p = 0.51), while in the SFCC group, the incidence of pericolic LN metastasis on the anal side of tumor (17%) was lower than in the PTCC group (31%) and was also similar to that in the DDCC group (21%). There were no significant differences in disease-specific survival rates among all groups. CONCLUSIONS: LN metastasis occurred mainly in the pericolic region, especially on the oral side of the tumor in SFCC. It may, therefore, be important to have an adequate bowel resection margin, especially on the oral side, for SFCC.

Robotic-assisted multivisceral resection for rectal cancer: short-term outcomes at a single center.

BACKGROUND: The safety and feasibility of robotic-assisted multivisceral resection for locally advanced rectal cancer remain unclear. The aim of this study was to assess the short-term outcomes of this procedure at our institution. METHODS: From December 2011 to December 2016, patients who underwent robotic-assisted multivisceral resection for rectal cancer were investigated. Patient demographics, treatment characteristics, perioperative outcomes, and pathological results were evaluated retrospectively. RESULTS: There were 31 patients; 17 men (54.8%) and 14 women (45.2%), with a median age of 65 years (range 40-82 years). Twenty-one patients (67.7%) had a cT4 tumor, 9 patients (29.0%) had a pT4b tumor, and all patients except one (96.8%) underwent complete resection of the primary tumor with negative resection margins. Eleven patients (35.5%) received neoadjuvant chemoradiation. The most commonly resected organ was the vaginal wall (n = 12, 38.7%), followed by the prostate (n = 10, 32.3%). Lateral lymph node dissection was performed in 20 patients (64.5%). The median operative time was 394 min (range 189-549 min), and the median blood loss was 41 mL (range 0-502 mL). None of the patients received intraoperative blood transfusions or required conversion to open. Overall, postoperative complications occurred in 11 patients (35.5%). The most frequent complication was urinary retention (n = 5, 16.1%), and none of the patients developed serious complications classified as Clavien-Dindo grades III-V. CONCLUSIONS: Robotic-assisted multivisceral resection for rectal cancer is safe and technically feasible.

Directional Migration of MDA-MB-231 Cells Under O2/pH Gradients.

We hypothesized that cancer cells actively migrate toward intratumor microvessels, guided by tissue gradients of metabolic substrates (such as O2) and/or metabolites (such as CO2/H+). To test this hypothesis, we developed an in vitro model in which cellular energy metabolism establishes gradients of O2/nutrient/metabolite in monolayer cells cultured in a conventional culture dish. When gradients of O2 ranging from 3% to ~0% were produced, MDA-MB-231 cells located at 300, 500 and 1500 µm downstream in the gradient demonstrated significant directional migrations (Rayleigh z test). We also found a similar directionality in cell migration at the same location even when the initial O2 level in the O2 gradient was raised from 3% to 21%. Interestingly, such directionalities were no longer demonstrated when the cell density was lowered from 1.8 × 106 to 0.9 × 106 cells/ml. In the former, the magnitude of the extracellular pH gradient in regions 300 and 500 µm downstream in the gradient was significantly larger. Thus, the direction of cell migrations appeared to depend on the gradient of extracellular pH rather than on O2.

Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX.

BACKGROUND: The establishment of a precise and rapid method to detect metastatic lymph nodes (LNs) is essential to perform less invasive surgery with reduced gastrectomy along with reduced lymph node dissection. We herein describe a novel imaging strategy to detect 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence in excised LNs specifically with reduced effects of tissue autofluorescence based on photo-oxidation of PpIX. We applied the method in a clinical setting, and evaluated its feasibility. METHODS: To reduce the unfavorable effect of autofluorescence, we focused on photo-oxidation of PpIX: Following light irradiation, PpIX changes into another substance, photo-protoporphyrin, via an oxidative process, which has a different spectral peak, at 675 nm, whereas PpIX has its spectral peak at 635 nm. Based on the unique spectral alteration, fluorescence spectral imaging before and after light irradiation and subsequent originally-developed image processing was performed. Following in vitro study, we applied this method to a total of 662 excised LNs obtained from 30 gastric cancer patients administered 5-ALA preoperatively. RESULTS: Specific visualization of PpIX was achieved in in vitro study. The method allowed highly sensitive detection of metastatic LNs, with sensitivity of 91.9% and specificity of 90.8% in the in vivo clinical trial. Receiver operating characteristic analysis indicated high diagnostic accuracy, with the area under the curve of 0.926. CONCLUSIONS: We established a highly sensitive and specific 5-ALA-induced fluorescence imaging method applicable in clinical settings. The novel method has a potential to become a useful tool for intraoperative rapid diagnosis of LN metastasis.

RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan.

In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan--a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.

Evaluation of Rotational Vertebral Artery Occlusion Using Ultrasound Facilitates the Detection of Arterial Dissection in the Atlas Loop.

PURPOSE: Head rotation can cause occlusion of the vertebral artery most commonly at the atlas loop, and repetitive compression from head turning induces vertebral artery dissection (VAD). Although ultrasound examinations are useful in diagnosis, dissected lesions unaccompanied by hemodynamic changes can be overlooked. Because the narrowed, dissected vessel in the atlas loop may cause rotational occlusion, we confirmed whether adding submaximal head rotation to a cervical ultrasound examination would facilitate the detection of VAD in the atlas loop. METHODS: We investigated 7 patients who developed infarction in the posterior circulation and were clinically suspected of VAD. Using a 7.5-MHz linear probe, we recorded the waveform of the vertebral artery at the C4-C6 level and diagnosed rotational vertebral artery occlusion (RVAO) when head rotation induced the disappearance of end-diastolic flow. RESULTS: All 3 patients with VAD in the atlas loop demonstrated RVAO of the dissected vertebral arteries in the acute stroke phase. RVAO was not observed in the dissected vertebral arteries excepting the atlas loop, nor in the nondissected vertebral arteries of any patients. CONCLUSION: For posterior circulation stroke patients, adding submaximal head rotation to the cervical ultrasound examination facilitated the detection of VAD in the atlas loop.

Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests.

SUMMARY The prevalence of Helicobacter pylori infection in Indonesia is controversial. We examined the H. pylori infection rate in 78 patients in a hospital in Surabaya using five different tests, including culture, histology, immunohistochemistry, rapid urease test, and urine antibody test. Furthermore, we analysed virulence factors in H. pylori strains from Indonesia. The H. pylori infection rate was only 11.5% in all patients studied, and 2.3% of Javanese patients and 18.0% of Chinese patients were infected (P = 0.01). Although severe gastritis was not observed, activity and inflammation were significantly higher in patients positive for H. pylori than in patients negative for H. pylori. Among genotypes identified from five isolated strains, cagA was found in four; two were vacA s1m1. All cagA-positive strains were oipA 'on' and iceA1 positive. We confirmed both a low H. pylori infection rate and a low prevalence of precancerous lesions in dyspeptic patients in a Surabaya hospital, which may contribute to the low incidence of gastric cancer in Indonesia.

A novel method for transcranial Doppler microembolic signal monitoring at the vertebrobasilar junction in vertebral artery dissection patients.

BACKGROUND: Vertebral artery dissection (VAD) is one of the most important etiologies in young stroke patients. VAD causes ischemic stroke by embolism and transcranial Doppler (TCD) monitoring can detect microemboli originating from the dissection point as high intensity transient signals (HITS). We developed a simple but novel method of TCD monitoring at the vertebrobasilar junction in VAD patients. METHODS: We placed a Welder TCD headband upside down on the patient's head and rotated it by 90°. Then we fixed a pulsed-wave 2-MHz TCD probe to the headband and put it on the suboccipital paramedian area of the patient. With a patient in the lateral decubitus position, the vertebrobasilar junction was identified at a depth of approximately 80 mm. RESULTS: We examined 11 patients with VAD and detected HITS in 2 patients (18%). In 1 patient HITS disappeared after heparinization, and in the other patient HITS disappeared after treatment with aspirin. All of 9 HITS-negative patients and 1 of 2 HITS-positive patients experienced no ischemic recurrence during hospitalization. CONCLUSION: We successfully detected HITS at the vertebrobasilar junction in VAD patients, which may lead not only to an appropriate choice of antithrombotic drugs but also to individual evaluation of early risk of ischemic recurrence.

Clinical relevance of cagPAI intactness in Helicobacter pylori isolates from Vietnam.

The purpose of this paper is to investigate the relationship between clinical outcome and the intactness of cagPAI in Helicobacter pylori strains from Vietnam. The presence or absence of 30 cagPAI genes was investigated by polymerase chain reaction (PCR) and dot-blotting. H. pylori-induced interleukin-8 secretion and hummingbird phenotype, and H. pylori adhesion to gastric epithelial cells were examined. The serum concentration of pepsinogen 1, pepsinogen 2, and gastrin was also measured in all patients. cagPAI was present in all 103 Vietnamese H. pylori isolates, of which 91 had intact cagPAI and 12 contained only a part of cagPAI. Infection with the partial cagPAI strains was less likely to be associated with peptic ulcer and chronic gastric mucosal inflammation than infection with strains possessing intact cagPAI. The partial cagPAI strains lacked almost all ability to induce interleukin-8 secretion and the hummingbird phenotype in gastric cells. Their adhesion to epithelial cells was significantly decreased in comparison with intact cagPAI strains. Moreover, for the first time, we found an association between cagPAI status and the serum concentration of pepsinogens 1 and 2 in infected patients. H. pylori strains with internal deletion within cagPAI are less virulent and, thus, less likely to be associated with severe clinical outcomes.

Helicobacter pylori typing as a tool for tracking human migration.

Helicobacter pylori strains from different geographic areas exhibit clear phylogeographical differentiation; therefore, the genotypes of H. pylori strains can serve as markers for the migration of human populations. Currently, the genotypes of two virulence factors of H. pylori, cagA and vacA, and multilocus sequence typing (MLST) are widely used markers for genomic diversity within H. pylori populations. There are two types of cagA: the East Asian type and the Western type. In addition, the right end of the cag pathogenicity island is divided into five subtypes and there are distinct mosaic structures at the signal region and the middle region of vacA. Using combinations of the cagA, cag right end junction, and vacA genotypes, five major groups (East Asia type, South/Central Asia type, Iberian/Africa type and Europe type) have been defined according to geographical associations. MLST has revealed seven modern population types and six ancestral population types of H. pylori, and is a useful tool for mapping human migration patterns. Serial studies of large numbers of H. pylori strains, including strains isolated from aboriginal populations, show that MLST analysis provides more detailed information on human migration than does the analysis of human genetics. H. pylori infection is rapidly declining as a result of improvements in personal hygiene and quality of life. The molecular epidemiology of H. pylori infection has much to tell us and should be studied before it disappears entirely.

The association of vacA genotypes and Helicobacter pylori-related gastroduodenal diseases in the Middle East.

The variations in the three regions of the Helicobacter pylori vacA gene, the signal (s1 and s2), intermediate (i1 and i2) and middle regions (m1 and m2), are known to cause the differences in vacuolating activities. However, it was unclear whether these vacA genotypes are associated with the development of gastric cancer and peptic ulcer in the Middle East. The aim was to identify the prevalence of vacA genotypes in the Middle East and the association with gastroduodenal diseases. We investigated the relationship of vacA genotypes to H. pylori-related disease development by meta-analysis using previous reports of 1,646 patients from the Middle East. The frequency of the vacA s1, m1 and i1 genotypes in the Middle Eastern strains was 71.5% (1,007/1,409), 32.8% (427/1,300) and 40.7% (59/145), respectively. Importantly, the frequency of vacA s- and m-region genotypes significantly differed between the north and south parts of the Middle East countries (P < 0.001). The vacA genotypes significantly increased the risk of gastric cancer (odds ratio [OR]: 4.02, 95% confidence interval [CI]: 1.98-8.14 for the s1 genotype; 2.50, 1.62-3.85 for m1; 5.27, 1.97-14.1 for s1m1; 15.03, 4.69-48.17 for i1) and peptic ulcers (OR: 3.07, 95% CI: 2.08-4.52 for s1; 1.81, 1.36-2.42 for m1). The cagA-positive genotype frequently coincided with the s1, m1 and i1 genotypes. The vacA s- and m-region genotypes may be useful risk factors for gastrointestinal diseases in the Middle East, similar to European and American countries. Further studies will be required to evaluate the effects of the i-region genotype.

The association of vacA genotype and Helicobacter pylori-related disease in Latin American and African populations.

In the populations of Western countries, particular genotypes of the vacuolating cytotoxin gene, vacA (vacA s, signal region variants; vacA m, middle region variants) of Helicobacter pylori are believed to be risk factors for the development of peptic ulcers and gastric cancer. However, it was unclear whether these vacA gene variants are associated with the development of gastrointestinal diseases in developing nations. The relationship between vacA genotypes and H. pylori-related disease development in Latin American and African populations was investigated using meta-analysis of 2612 patients from Latin America (2285 strains) and 520 patients from Africa (434 strains). The frequencies of vacA s and m genotypes differed between strains from Latin America (77.2% for s1 and 68.1% for m1) and Africa (83.9% for s1 and 56.7% for m1). Latin American strains with s1 and m1 genotypes increased the risk of gastric cancer (OR 4.17, 95% CI 2.49-6.98 for s1, and 3.59, 2.27-5.68 for m1) and peptic ulcers (e.g. 1.73, 1.37-2.20 for s1). African strains with the s1 or m1 genotypes also increased the risk of peptic ulcers (8.69, 1.16-64.75 for s1) and gastric cancer (10.18, 2.36-43.84 for m1). The cagA-positive genotype frequently coincided with s1 and m1 genotypes in both populations. Overall, the vacA s and m genotypes were related to gastric cancer and peptic ulcer development and might be useful markers of risk factors for gastrointestinal disease, especially in Latin America. Further studies will be required to evaluate the effects of vacA genotypes in African populations because of the small sample number currently available.

Determination of Helicobacter pylori virulence by analysis of the cag pathogenicity island isolated from Iranian patients.

BACKGROUND: The cag pathogenicity island (PAI), which can be divided into two parts, cagI and cagII, is the most well-known virulence factor of Helicobacter pylori. AIMS: We investigated the association between genetic variations within the cag PAI (cagA and cagE in the cagI and cagT in the cagII) and clinical outcomes in Iranian patients. SUBJECTS: A total of 231 patients including 182 patients with gastritis, 41 with peptic ulcer and 8 with gastric cancer. METHODS: The presence of the cagA, cagE and cagT genes were measured by polymerase chain reaction and the results were compared with clinical outcomes and gastric histology. RESULTS: The cagA, cagE and cagT genes were found in 154 (66.7%), 90 (39.0%) and 70 (30.3%) of clinical isolates. At least 144 (62.3%) strains possessed partially deleted cag PAI (e.g., 69 [29.9%] strains were cagA-positive, but cagE and cagT-negative). CONCLUSION: The single genes as well as the combination of genes in the cag PAI appeared not to be useful markers to predict H. pylori-related diseases in Iranian patients. The genomic sequences of the cag PAI in Iranian strains might be considerably different from those in other geographic locations.

Neuroprotection by propargylamines in Parkinson's disease: intracellular mechanism underlying the anti-apoptotic function and search for clinical markers.

In Parkinson's and other neurodegenerative diseases, a therapeutic strategy has been proposed to halt progressive cell death. Propargylamine derivatives, rasagiline and (-)deprenyl (selegiline), have been confirmed to protect neurons against cell death induced by various insults in cellular and animal models of neurodegenerative disorders. In this paper, the mechanism and the markers of the neuroprotection are reviewed. Propargylamines prevent the mitochondrial permeabilization, membrane potential decline, cytochrome c release, caspase activation and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase. At the same time, rasagiline induces anti-apoptotic pro-survival proteins, Bcl-2 and glial cell-line derived neurotrophic factor, which is mediated by activated ERK-NF-kappaB signal pathway. DNA array studies indicate that rasagiline increases the expression of the genes coding mitochondrial energy synthesis, inhibitors of apoptosis, transcription factors, kinases and ubiquitin-proteasome system, sequentially in a time-dependent way. Products of cell survival-related gene induced by propargylamines may be applied as markers of neuroprotection in clinical samples.

Helicobacter pylori outer membrane proteins and gastroduodenal disease.

BACKGROUND AND AIMS: A number of Helicobacter pylori outer membrane proteins (OMPs) undergo phase variations. This study examined the relation between OMP phase variations and clinical outcome. METHODS: Expression of H pylori BabA, BabB, SabA, and OipA proteins was determined by immunoblot. Multiple regression analysis was performed to determine the relation among OMP expression, clinical outcome, and mucosal histology. RESULTS: H pylori were cultured from 200 patients (80 with gastritis, 80 with duodenal ulcer (DU), and 40 with gastric cancer). The most reliable results were obtained using cultures from single colonies of low passage number. Stability of expression with passage varied with OipA > BabA > BabB > SabA. OipA positive status was significantly associated with the presence of DU and gastric cancer, high H pylori density, and severe neutrophil infiltration. SabA positive status was associated with gastric cancer, intestinal metaplasia, and corpus atrophy, and negatively associated with DU and neutrophil infiltration. The Sydney system underestimated the prevalence of intestinal metaplasia/atrophy compared with systems using proximal and distal corpus biopsies. SabA expression dramatically decreased following exposure of H pylori to pH 5.0 for two hours. CONCLUSIONS: SabA expression frequently switched on or off, suggesting that SabA expression can rapidly respond to changing conditions in the stomach or in different regions of the stomach. SabA positive status was inversely related to the ability of the stomach to secrete acid, suggesting that its expression may be regulated by changes in acid secretion and/or in antigens expressed by the atrophic mucosa.

Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection.

In neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, apoptosis is a common type of cell death, and mitochondria emerge as the major organelle to initiate death cascade. Monoamine oxidase (MAO) in the mitochondrial outer membrane produces hydrogen peroxide by oxidation of monoamine substrates, and induces oxidative stress resulting in neuronal degeneration. On the other hand, a series of inhibitors of type B MAO (MAO-B) protect neurons from cell death. These results suggest that MAO may be involved in the cell death process initiated in mitochondria. However, the direct involvement of MAO in the apoptotic signaling has been scarcely reported. In this paper, we present our recent results on the role of MAO in activating and regulating cell death processing in mitochondria. Type A MAO (MAO-A) was found to bind an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, and induce apoptosis in dopaminergic SH-SY5Y cells containing only MAO-A. To examine the intervention of MAO-B in apoptotic process, human MAO-B cDNA was transfected to SH-SY5Y cells, but the sensitivity to N-methyl(R)salsolinol was not affected, even though the activity and protein of MAO-B were expressed markedly. MAO-B oxidized dopamine with production of hydrogen peroxide, whereas in control cells expressing only MAO-A, dopamine autoxidation produced superoxide and dopamine-quinone, and induced mitochondrial permeability transition and apoptosis. Rasagiline and other MAO-B inhibitors prevent the activation of apoptotic cascade and induce prosurvival genes, such as bcl-2 and glial cell line-derived neurotrophic factor, in MAO-A-containing cells. These results demonstrate a novel function of MAO-A in the induction and regulation of apoptosis. Future studies will clarify more detailed mechanism behind regulation of mitochondrial death signaling by MAO-A, and bring out new strategies to cure or ameliorate the decline of neurons in neurodegenerative disorders.