Severe immersion pulmonary edema in a novice elderly scuba diver after heavy alcohol intake.

BACKGROUND: There are no reports of immersion pulmonary edema induced by excessive alcohol intake. We describe the case of a novice scuba diver who developed apnea due to immersion pulmonary edema during scuba diving after heavy alcohol intake. CASE PRESENTATION: A 71-year-old hypertensive man, without regular antihypertensive therapy, performed diving after excessive alcohol intake (total amount, approximately 253 g) until the night before. When swimming at a depth of 12 m, the patient experienced chest discomfort and ascended immediately but became unconscious. Respiratory arrest was confirmed, and he spat pink foamy sputum. On hospital admission, hypoxemia was confirmed, and chest radiography revealed butterfly-shaped shadows. Therefore, mechanical ventilation was initiated. The next day, his blood oxygenation level improved, and the radiographic shadows disappeared. He was discharged on day 7 of hospitalization without sequelae. CONCLUSION: A scuba diver with untreated hypertension might develop immersion pulmonary edema during diving after heavy alcohol intake.

Cerebrospinal vascular diseases misdiagnosed as decompression illness: the importance of considering other neurological diagnoses.

The diagnosis of decompression illness (DCI), which is based on a history of decompression and clinical findings, can sometimes be confounded with other vascular events of the central nervous system. The authors report three cases of divers who were urgently transported to a hyperbaric facility for hyperbaric oxygen treatment of DCI which at admission turned out to be something else. The first case, a 45-year-old experienced diver with unconsciousness, was clinically diagnosed as having experienced subarachnoid hemorrhage, which was confirmed by CT scan. The second case, a 49-year-old fisherman with a hemiparesis which occurred during diving, was diagnosed as cerebral stroke, resulting in putaminal hemorrhage. The third case, a 54-year-old fisherman with sensory numbness, ataxic gait and urinary retention following sudden post-dive onset of upper back pain, was diagnosed as spinal epidural hematoma; he also showed blood collection in the spinal canal. Neurological insults following scuba diving can present clinically with confusing features of cerebral and/or spinal DCI. We emphasize the importance of considering cerebral and/or spinal vascular diseases as unusual causes of neurological deficits after or during diving.

Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells.

Currently 5-fluorouracil (5-FU) plays a central role in the chemotherapeutic regimens for colorectal cancers and thus it is important to understand the mechanisms that determine 5-FU sensitivity. The expression profiles of human colon cancer cell line DLD-1, its 5-FU-resistant subclone DLD-1/FU and a further 21 types of colon cancer cell lines were compared to identify the novel genes defining the sensitivity to 5-FU and to estimate which population of genes is responsible for 5-FU sensitivity. In the hierarchical clustering, DLD-1 and DLD-1/FU were most closely clustered despite over 100 times difference in their 50% inhibitory concentration of 5-FU. In DLD-1/FU, the population of genes differentially expressed compared to DLD-1 was limited to 3.3%, although it ranged from 4.8% to 24.0% in the other 21 cell lines, thus indicating that the difference of 5-FU sensitivity was defined by a limited number of genes. Next, the role of the cellular inhibitor of apoptosis 2 (cIAP2) gene, which was up-regulated in DLD-1/FU, was investigated for 5-FU resistance using RNA interference. The down-regulation of cIAP2 efficiently enhanced 5-FU sensitivity, the activation of caspase 3/7 and apoptosis under exposure to 5-FU. The immunohistochemistry of cIAP2 in cancer and corresponding normal tissues from colorectal cancer patients in stage III revealed that cIAP2 was more frequently expressed in cancer tissues than in normal tissues, and cIAP2-positive patients had a trend toward early recurrence after fluorouracil-based chemotherapy. Although the association between drug sensitivity and the IAP family in colorectal cancer has not yet been discussed, cIAP2 may therefore play an important role as a target therapy in colorectal cancer.

Orthotopic implantation mouse model and cDNA microarray analysis indicates several genes potentially involved in lymph node metastasis of colorectal cancer.

In colorectal cancer (CRC) patients, metastasis to the regional lymph node (LN) is an important first step in the dissemination of cancers. To identify the genes possibly involved in LN metastasis of CRC, we analyzed LN metastases in an orthotopic implantation mouse model with 22 CRC cell lines using Matrigel, an extracellular matrix protein derived from mice sarcoma, and combined the data with gene expression profiles of cDNA microarray of those cell lines. With this implantation analysis, the incidence of LN metastasis was 60% in 228 orthotopically implanted mice and varied from 100% to 0% among the cell lines. KM12c and Clone A showed LN metastasis in all orthotopically implanted mice, but DLD-1, HCT-8, and SW948 did not show LN metastases at all. In contrast, the incidence of liver and lung metastasis in 22 CRC cell lines was 13% and 1%, respectively. Combining those data with cDNA microarray in vitro, we isolated 636 genes that were differentially expressed depending on the incidence of LN metastasis. Among those genes, the expression level of ring finger protein 125 (RNF125), previously known as an E3 ubiquitin ligase in T cell activation, was significantly different between primary tumors in Stage III CRC patients with LN metastasis and Stage II patients without LN metastasis. In conclusion, the orthotopic implantation mice model with Matrigel was useful, and we isolated candidate genes such as RNF125 that possibly play an important role in LN metastasis of CRC cells.

Mutations in the lrpE gene of Ralstonia solanacearum affects Hrp pili production and virulence.

The Ralstonia solanacearum hrpB-regulated gene lrpE (hpx5/brg24) encodes a PopC-like leucine-rich repeat (LRR) protein that carries 11 tandem LRR in the central region. Defects in the lrpE gene slightly reduced the virulence of R. solanacearum on host plants and changed the bacterial morphology leading to the formation of large aggregates in a minimal medium. The aggregation in the deltalrpE background required the presence of a functional Hrp type III secretion system. In wild-type R. solanacearum, Hrp pili disappeared from the bacterial surface at the end of the exponential growth phase, when the pili form into long bundles. However, even in the late growth phase, bundled Hrp pili were still observed on the cell surface of the deltalrpE mutant. Such bundles were entangled and anchored the mutant cells in the aggregates. In contrast to PopC, LrpE accumulated in bacterial cells and did not translocate into plant cells as an effector protein. The expression levels of hrp genes increased three- to fivefold in the deltalrpE background compared with those in the wild type. We propose that LrpE may negatively regulate the production of Hrp pili on the cell surface of R. solanacearum to disperse bacterial cells from aggregates. In turn, dispersal may contribute to the movement of the pathogen in the plant vascular system and, as a consequence, the pathogenicity of R. solanacearum.

Network-based de-noising improves prediction from microarray data.

BACKGROUND: Prediction of human cell response to anti-cancer drugs (compounds) from microarray data is a challenging problem, due to the noise properties of microarrays as well as the high variance of living cell responses to drugs. Hence there is a strong need for more practical and robust methods than standard methods for real-value prediction. RESULTS: We devised an extended version of the off-subspace noise-reduction (de-noising) method to incorporate heterogeneous network data such as sequence similarity or protein-protein interactions into a single framework. Using that method, we first de-noise the gene expression data for training and test data and also the drug-response data for training data. Then we predict the unknown responses of each drug from the de-noised input data. For ascertaining whether de-noising improves prediction or not, we carry out 12-fold cross-validation for assessment of the prediction performance. We use the Pearson's correlation coefficient between the true and predicted response values as the prediction performance. De-noising improves the prediction performance for 65% of drugs. Furthermore, we found that this noise reduction method is robust and effective even when a large amount of artificial noise is added to the input data. CONCLUSION: We found that our extended off-subspace noise-reduction method combining heterogeneous biological data is successful and quite useful to improve prediction of human cell cancer drug responses from microarray data.

Isolation of Ralstonia solanacearum hrpB constitutive mutants and secretion analysis of hrpB-regulated gene products that share homology with known type III effectors and enzymes.

The Hrp type III secretion system (TTSS) is essential for the pathogenicity of the Gram-negative plant pathogen Ralstonia solanacearum. To examine the secretion of type III effector proteins via the Hrp TTSS, a screen was done of mutants constitutively expressing the hrpB gene, which encodes an AraC-type transcriptional activator for the hrp regulon. A mutant was isolated that in an hrp-inducing medium expresses several hrpB-regulated genes 4.9-83-fold higher than the wild-type. R. solanacearum Hrp-secreted outer proteins PopA and PopC were secreted at high levels into the culture supernatants of the hrpB constitutive (hrpB(c)) mutant. Using hrpB(c) mutants, the extracellular secretion of several hrpB-regulated (hpx) gene products that share homology with known type III effectors and enzymes was examined. Hpx23, Hpx24 and Hpx25, which are similar in sequence to Pseudomonas syringae pv. tomato effector proteins HopPtoA1, HolPtoR and HopPtoD1, are also secreted via the Hrp TTSS in R. solanacearum. The secretion of two hpx gene products that share homology with known enzymes, glyoxalase I (Hpx19) and Nudix hydrolase (Hpx26), was also examined. Hpx19 is accumulated inside the cell, but interestingly, Hpx26 is secreted outside the cell as an Hrp-secreted outer protein, suggesting that Hpx19 functions intracellularly but Hpx26 is a novel effector protein of R. solanacearum.

Genetic screening of Hrp type III-related pathogenicity genes controlled by the HrpB transcriptional activator in Ralstonia solanacearum.

As in many other Gram-negative phytopathogenic bacteria, the Hrp type III secretion system is essential for the pathogenicity of Ralstonia solanacearum on host plants. The expression of most of the type III effector genes previously isolated from R. solanacearum is co-regulated with those of hrp genes by an AraC-type transcriptional activator, HrpB. In order to isolate type III-related pathogenicity genes, we screened hrpB-regulated genes in R. solanacearum. Using a transposon-based system, we isolated 30 novel hpx (hrpB-dependent expression) genes outside the hrp gene cluster. Most of the hpx genes contain a PIP (plant-inducible promoter) box-like motif in their putative promoter regions. Seven hpx genes encoded homologues of known type III effectors and type III-related proteins found in other animal and plant pathogens. Four encoded known enzymes, namely, glyoxalase I, Nudix hydrolase, spermidine synthase and transposase. Interestingly, six hpx genes encoded two types of leucine-rich repeat (LRR) protein. Products of the remaining genes did not show any significant homology to known proteins. We also identified two novel hrpB-regulated genes, hpaZ and hpaB, downstream of hrpY in the hrp cluster. The hpaB gene of R. solanacearum, but not hpaZ, was required for both the pathogenicity and ability to induce hypersensitive reaction on plants. We show that a hpaB null mutant still produces Hrp pili on the cell surface although it shows a typical Hrp-defective phenotype on plants.

[High concentration of E-cadherin in portal drainage vein of colorectal cancer patients may predict metachronous liver metastasis].

AIMS: Liver metastasis is the most common recurrence after curative surgery for colorectal cancer. Adjuvant chemotherapy such as hepatic arterial infusion or intensive systemic infusion may protect against metastatic tumor formation in the liver, but conversely have some adverse effects on patients. Therefore, the patients with a high risk of liver metastasis after curative resection should be selected for the chemotherapy. Portal blood samples of tumor drainage vein were obtained during operation from 148 colorectal cancer patients (Dukes' A: 41, B: 41, C: 33, D: 33) in our institutes from August 1998 to June 2001. Serum E-cadherin concentration (ng/ml) was estimated using an ELISA kit according to the manufacturer's instructions (Takara Shuzo Co.). After at least 6 months follow-up, each patient's status regarding recurrence was re-examined, as were the sites of any recurrences. Serum E-cadherin concentration in each Dukes' stage at the primary operation was as follows: A: 1,664.0, B: 1,974.6, C: 2,270.8, D: 3,123.1. In these follow-up periods, 21 patients developed metastatic tumor (liver: 13, extrahepatic: 8) and 95 did not. The average E-cadherin concentration in each group was as follows: liver: 3,585.6, extrahepatic: 2,261.8, no metastasis: 1,848.4 (p < 0.01 as shown in Figure 4). If the cut-off point is set at 3,000 ng/ml, liver metastasis can be predicted with sensitivity of 62.1%, specificity of 90.3%, and positive predictive value of 64.3%. High levels (> 3,000 ng/ml) of serum E-cadherin in portal blood may predict metachronous liver metastasis after curative surgery.