Drug resistance mutations among virological failure HIV-1 infected patients in Malaysia

The determination of HIV drug resistance mutations (DRMs) towards antiretroviral (ARV) drugs among HIV-1 treated patients with virological failure is crucial for further management of the patient. This study aimed to assess the most common genomic mutation and to analyse subtypes among the HIV-1 patients with viral load level > 1,000 copies/mL. A total of 101 virological failure HIV-1 patients from four different regions of Peninsular Malaysia with a viral load measurement facility were included in the study. Majority of patients (89.1%) have at least 1 mutation associated with clinical resistance to either protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs). Major resistance mutations among the patients towards NRTIs and NNRTIs were 70.3% and 18.8%, respectively. The most common mutation for NRTIs was M184V while K103N mutation was detected in the majority of patients who were treated with NNRTIs. The most commonly observed mutations for major PI and minor PI seen among the study population were V82A/T and L10V, respectively. In HIV-1 subtype analysis, CRF33_01B was the most predominant HIV-1 subtype in this study group. The vast detection of DRMs in this study emphasized the importance of genotypic resistance test in the management of HIV patients as DRMs can alter patient’s susceptibility towards ARV drugs. Further study on larger number of samples is essential for the development of a database on HIV-1 DRMs among patients that experience virological failure in Malaysia.

El cabello, fuente de información del estado de salud / The hair, source of health information

El cabello y especialmente el localizado en la cabeza provee importante información sobre posibles exposiciones ambientales y/o laborales a diferentes elementos. El pelo puede ser considerado como un producto excretor, y su estudio reflejaría el metabolismo de minerales en el cuerpo. Nuestro propósito en el presente estudio es conocer si datos existentes dan información poblacional sobre la presencia de elementos tóxicos o no a través del análisis del cabello humano. RESULTADOS: Fue analizada la información proveniente de 241 muestras de cabello, de los cuales 163 (67,6%) corresponden al sexo femenino y 78 (32,4%) al masculino. Fueron analizados 22 elementos esenciales y 17 elementos de tóxicos. Entre los elementos esenciales presentaron resultados elevados Calcio (Ca), Magnesio (Mg), Manganeso (Mn), Molibdeno (Mo), Vanadio (V), Estroncio (Sr) y Circonio (Zr); entre los elementos tóxicos tuvieron valores elevados Aluminio (Al), Arsénico (As), Bario (Ba), Bismuto (Bi), Cadmio (Cd), Níquel (Ni), Plomo (Pb), Mercurio (Mg), Plata (Ag), Estaño (Sn). CONCLUSIÓN. Nuestro estudio muestra a nivel poblacional, no individual, puntos de alerta por la carencia o exceso de algunos elementos analizados debiéndose continuar con estudios locales interdisciplinarios en los cuales exista información sobre enfermedades, hábitos alimentarios, hábitos tóxicos, actividad laboral y exposición ambiental a los diferentes elementos. (AU)

Hair, especially localized in the head, provides important information on possible environmental and/or labor exposures to different elements. Hair can be considered as an excretory product, and its study would reflect the metabolism of minerals in the body. Our purpose in this study was to determine whether existing population data provide information on the presence of toxic and non-toxic elements by analizing human hair. RESULTS: We analyzed information from 241 hair samples, of which 163 (67.6%) are from females and 78 (32.4%) are from males. There were analyzed 22 essential elements and 17 toxic elements. Among the essential elements that had elevated results there were: Calcium (CA), magnesium (Mg), manganese (Mn), molybdenum (Mo), vanadium (V), strontium (Sr) and zirconium (Zr); among the toxic elements, those with higher values were: Aluminum (Al), arsenic (As), barium (BA), bismuth (Bi), Cadmium (Cd), Nickel (Ni), lead (Pb), Mercury (Mg), silver (Ag), tin (Sn). CONCLUSION. Our study shows at population level, not individual, warning points due to the lack or excess of some elements analyzed. It is reccommended to continue the research with local interdisciplinary studies which include information on diseases, eating habits, toxic habits, work activity and environmental exposure to different elements. (AU)

Prevalence of depression and associated factors among elderly Sudanese: a household survey in Khartoum State

We assessed depression among 300 elderly Sudanese [age 60+ years]. We conducted a cross-sectional household survey in 3 localities in Khartoum State. A 2-stage stratified sampling was carried out to select the localities and then the areas using simple random sampling; then systematic random sampling was used to select households. The prevalence of depression was 47.5%. Depression was significantly associated with age [P = 0.002], level of education [P = 0.015], occupation [P < 0.001], the problems of everyday living [P = 0.026], and social problems [P < 0.001]. After controlling for confounders using multiple logistic regression, we found that depression was 4 times greater among the elderly retired compared to the elderly working, 3 times greater among the elderly with social problems and those who were suffering from urine incontinence and 2 times greater among the elderly with living problems

Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K.

We have shown previously that the AKT2 pathway is essential for cell survival and important in malignant transformation. In this study, we demonstrate elevated kinase levels of AKT2 and phosphatidylinositol-3-OH kinase (PI3K) in 32 of 80 primary breast carcinomas. The majority of the cases with the activation are estrogen receptor alpha (ERalpha) positive, which prompted us to examine whether AKT2 regulates ERalpha activity. We found that constitutively activated AKT2 or AKT2 activated by epidermal growth factor or insulin-like growth factor-1 promotes the transcriptional activity of ERalpha. This effect occurred in the absence or presence of estrogen. Activated AKT2 phosphorylates ERalpha in vitro and in vivo, but it does not phosphorylate a mutant ERalpha in which ser-167 was replaced by Ala. The PI3K inhibitor, wortmannin, abolishes both the phosphorylation and transcriptional activity of ERalpha induced by AKT2. However, AKT2-induced ERalpha activity was not inhibited by tamoxifen but was completely abolished by ICI 164,384, implicating that AKT2-activated ERalpha contributes to tamoxifen resistance. Moreover, we found that ERalpha binds to the p85alpha regulatory subunit of PI3K in the absence or presence of estradiol in epithelial cells and subsequently activates PI3K/AKT2, suggesting ERalpha regulation of PI3K/AKT2 through a nontranscriptional and ligand-independent mechanism. These data indicate that regulation between the ERalpha and PI3K/AKT2 pathway (ERalpha-PI3K/AKT2-ERalpha) may play an important role in pathogenesis of human breast cancer and could contribute to ligand-independent breast cancer cell growth.

A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells.

Pancreatic cancer is an extremely aggressive neoplasm whose incidence equals its death rate. Despite intensive analysis, the genetic changes that mediate pancreatic cancer development and effective therapies for diminishing the morbidity associated with this disease remain unresolved. Through subtraction hybridization, we have identified a gene associated with induction of irreversible growth arrest, cancer reversion, and terminal differentiation in human melanoma cells, melanoma differentiation associated gene-7 (mda-7). Ectopic expression of mda-7 when using a recombinant adenovirus, Ad.mda-7, results in growth suppression and apoptosis in a broad spectrum of human cancers with diverse genetic defects, without exerting deleterious effects in normal human epithelial or fibroblast cells. Despite the apparently ubiquitous antitumor effects of mda-7, pancreatic carcinoma cells are remarkably refractory to Ad.mda-7 induced growth suppression and apoptosis. In contrast, the combination of Ad.mda-7 with antisense phosphorothioate oligonucleotides, which target the K-ras oncogene (a gene that is mutated in 85 to 95% of pancreatic carcinomas), induces a dramatic suppression in growth and a decrease in cell viability by induction of apoptosis. In mutant K-ras pancreatic carcinoma cells, programmed cell death correlates with expression and an increase, respectively, in MDA-7 and BAX proteins and increases in the ratio of BAX to BCL-2 proteins. Moreover, transfection of mutant K-ras pancreatic carcinoma cells with an antisense K-ras expression vector and infection with Ad.mda-7 inhibits colony formation in vitro and tumorigenesis in vivo in nude mice. These intriguing observations demonstrate that a combinatorial approach, consisting of a cancer-specific apoptosis-inducing gene and an oncogene inactivation strategy, may provide the foundation for developing an effective therapy for pancreatic cancer.

Potent dibasic GPIIb/IIIa antagonists with reduced prolongation of bleeding time: synthesis and pharmacological evaluation of 2-oxopiperazine derivatives.

A series of 2-oxopiperazine derivatives, possessing basic moieties at the 3- and the 4-positions, were synthesized and evaluated for their abilities to inhibit platelet aggregation and for their effects on bleeding time. Among the compounds, 2-[(3S)-4-[2-[(4-guanidinobenzoyl)amino]acetyl]-3-[3-[(4-guanidinobenzoyl)amino]propyl]-2-oxopiperazinyl]acetic acid (12c) showed a potent inhibitory effect on platelet aggregation and good dissociation between the efficacy and the bleeding side effect. Intravenous infusion of compound 12c at 1.6 microg/mL/min completely prevented arterial thrombus formation induced by endothelial injury in guinea pigs. The dose of 12c that prolonged the bleeding time to three times the control value was 5.8 microg/mL/min. These results suggest that compound 12c might be useful in the clinical treatment of thrombotic diseases, and we selected 12c (TAK-024) as a candidate for the clinical trials.

Application of ab initio molecular dynamics for a priori elucidation of the mechanism in unimolecular decomposition: the case of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO).

We have tested a new and general approach for the theoretical study of unimolecular decomposition. By combining the power of the ab initio molecular dynamics (MD) and ab initio molecular orbital (MO) methods, our approach requires no prior experimental knowledge or intuitive assumptions about the decomposition. Instead, the reaction channels are first sampled theoretically by simulating a molecule at high temperature in a number of trajectories, using the density functional theory (DFT) based ab initio MD method with a planewave basis set and pseudopotentials. Each type of these channels is then further examined by well-established ab initio MO method to locate the energy barrier and transition structure and to verify the ab initio MD results. The power of such an approach is demonstrated in a case study for the complicated unimolecular thermal decomposition of NTO (5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one), with several interesting new features uncovered. The C-NO2 homolysis is indeed the dominant channel at high temperature, while the departing NO2 could capture a H atom from the NTO ring to form HONO, by either a concerted bond breaking mechanism or by a bimolecular reaction between the NO2 group and the triazol ring. At lower temperature, the dissociation channels initiated by hydrogen migrations should be activated first. The channel with hydrogen migration followed by ring opening and then by HONO loss has an energy barrier of 38.0 kcal/mol at the rate-determining step, being the lowest among all the investigated dissociation paths and much lower than previously thought. The energy barrier for nitro-nitrite rearrangement is lower than that for the C-NO2 homolysis but makes only a minor contribution due to the entropy factor. And the NTO ring could rupture in the two C-N bonds connected to the carbonyl carbon, and the energy barriers for such processes are only 2-4 kcal/mol higher than that for the C-NO2 homolysis.

Angiogenin activates human umbilical artery smooth muscle cells.

Angiogenin stimulates proliferation of human umbilical artery smooth muscle cells. This activity of angiogenin depends on the cell density and requires nuclear translocation of the ligand as well as activation of SAPK/JNK MAP kinase. Angiogenin binds to a 170-kDa putative receptor on the cell surface and induces phosphorylation of SAPK/JNK. It also undergoes nuclear translocation in a time and concentration dependent manner. Neomycin inhibits nuclear translocation of angiogenin and abolishes angiogenin-induced cell proliferation but does not inhibit SAPK/JNK phosphorylation. The data demonstrate that smooth muscle cells are targets for angiogenin and that both SAPK/JNK phosphorylation and nuclear translocation of the ligand are required for angiogenin to activate smooth muscle cells.

PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins.

We have identified a new mammalian protein arginine N-methyltransferase, PRMT5, formerly designated Janus kinase-binding protein 1, that can catalyze the formation of omega-N(G)-monomethylarginine and symmetric omega-N(G),N(G')-dimethylarginine in a variety of proteins. A hemagglutinin peptide-tagged PRMT5 complex purified from human HeLa cells catalyzes the S-adenosyl-l-[methyl-(3)H]methionine-dependent in vitro methylation of myelin basic protein. When the radiolabeled myelin basic protein was acid-hydrolyzed to free amino acids, and the products were separated by high-resolution cation exchange chromatography, we were able to detect two tritiated species. One species co-migrated with a omega-N(G)-monomethylarginine standard, and the other co-chromatographed with a symmetric omega-N(G),N(G')-dimethylarginine standard. Upon base treatment, this second species formed methylamine, a breakdown product characteristic of symmetric omega-N(G),N(G')-dimethylarginine. Further analysis of these two species by thin layer chromatography confirmed their identification as omega-N(G)-monomethylarginine and symmetric omega-N(G),N(G')-dimethylarginine. The hemagglutinin-PRMT5 complex was also able to monomethylate and symmetrically dimethylate bovine histone H2A and a glutathione S-transferase-fibrillarin (amino acids 1-148) fusion protein (glutathione S-transferase-GAR). A mutation introduced into the S-adenosyl-l-methionine-binding motif I of a myc-tagged PRMT5 construct in COS-1 cells led to a near complete loss of observed enzymatic activity. PRMT5 is the first example of a catalytic chain for a type II protein arginine N-methyltransferase that can result in the formation of symmetric dimethylarginine residues as observed previously in myelin basic protein, Sm small nuclear ribonucleoproteins, and other polypeptides.

[Isolation of pathogenic bacteria in pasteurized type C milk sold in Recife City, Pernambuco, Brazil]. / Pesquisa de bactérias patogênicas em leite pasteurizado tipo C comercializado na cidade do Recife, Pernambuco, Brasil.

In order to improve information about the microbiological quality of the milk commercially available in the city of Recife, 250 samples of pasteurized type-C milk and 50 samples of raw milk were analyzed for Yersinia enterocolitica and Listeria monocytogenes and verify the possible occurrence of Yersinia enterocolitica and Listeria monocytogenes. These bacteria can develop in refrigeration temperatures and are responsible for food-born diseases. Neither Y. enterocolitica nor L. monocytogenes were found in the samples analyzed. However, the presence of Y. intermedia and Y. frederiksenii was detected, these environmental species behave as opportunist pathogens. Through the methodology used for Listeria isolation, one isolate of Salmonella Montevideo was obtained from a sample of pasteurized milk and another isolated from one sample of raw milk. Besides these, several other bacteria species were found. It is likely that the large microbiota present in the samples and the procedures employed to destroy it could have hindered the isolation of Y. enterocolitica and L. monocytogenes.

Identification of putative downstream genes of Oct-4 by suppression-subtractive hybridization.

As a step toward understanding how toti/pluripotence is maintained by Oct-4, we have first constructed a cell model with differentially expressed Oct-4 in embryonic stem cells, and then used suppression-subtractive hybridization (SSH) method to identify the downstream genes of Oct-4. Among the 384 clones we screened, 40 clones were detected as differentially expressed genes with colony hybridization, and 13 clones were confirmed as the putative downstream genes of Oct-4 by Northern blot analysis. Sequencing showed 12 different genes, 8 known genes (Oct-4, Rex-1, Sox-2, Creatine kinase B, Makorin 1, Importin beta, Histone H2A.Z, Ribosomal protein S7) and 4 new genes. Except Oct-4 and Rex-1, the other genes have not been reported to be regulated by Oct-4. These results showed that SSH provides a very efficient means to identify the downstream genes of transcription factor. Some known genes identified may provide new insight of the function of Oct-4 in stem cells.

Structure and dynamics of the alpha-lactalbumin molten globule: fluorescence studies using proteins containing a single tryptophan residue.

The fluorescence properties of three variants of alpha-lactalbumin (alpha-LA) containing a single tryptophan residue were investigated under native, molten globule, and unfolded conditions. These proteins have levels of secondary structure and stability similar to those of the wild type. The fluorescence signal in the native state is dominated by that of W104, with the signal of W60 and W118 significantly quenched by the disulfide bonds in their vicinity. In the molten globule state, the magnitude of the fluorescence signal of W60 and W118 increases, due to the loss of rigid, specific side chain packing. In contrast, the magnitude of the signal of W104 decreases in the molten globule state, perhaps due to the protonation of H107 or quenching by D102 or K108. The solvent accessibilities of individual tryptophan residues were investigated by their fluorescence emission maximum and by acrylamide quenching studies. In the native state, the order of solvent accessibility is as follows: W118 > W60 > W104. This order changes to W60 > W104 > W118 in the molten globule state. Remarkably, the solvent accessibility of W118 in the alpha-LA molten globule is lower than that in the native state. The dynamic properties of the three tryptophan residues were examined by time-resolved fluorescence anisotropy decay studies. The overall rotation of the molecule can be observed in both the native and molten globule states. In the molten globule state, there is an increase in the extent of local backbone fluctuations with respect to the native state. However, the fluctuation is not sufficient to result in complete motional averaging. The three tryptophan residues in the native and molten globule states have different degrees of motional freedom, reflecting the folding pattern and dynamic heterogeneity of these states. Taken together, these studies provide new insight into the structure and dynamics of the alpha-LA molten globule, which serves as a prototype for partially folded proteins.

Multivariate prognostic analysis of stage I(E) primary non-Hodgkin's lymphomas of the nasal cavity.

From January 1968 to December 1997, a total of 71 patients with stage I(E) (Ann Arbor staging system, 1971) primary non-Hodgkin's lymphomas of the nasal cavity received treatment in the Cancer Center of Sun Yat-Sen University of Medical Sciences. Thirty-seven lesions were limited to the nasal cavity (limited I(E)), whereas the other 34 were extended to the structure out of the nasal cavity (extended I(E)). Forty-four patients were treated with radiochemotherapy and 27 with radiotherapy alone. Kaplan-Meier methods were used in the survival analysis. Multivariate analysis was carried out using the Cox proportional hazard model. The 5- and 10-year survival rates were 71.85% and 59.67% for the patients with a complete response to irradiation, and both were 13.89% for the patients with residue lesions (p = 0.0004). The 5- and 10-year survival rates were 69.81% and 56.72% for limited I(E), and 40.65% and 35.57% for extended I(E) (p = 0.0047). The prognosis was better for those younger than 44 years (p = 0.0003). The 10-year survival rates for radiotherapy alone and combined radiochemotherapy are 52% and 75% for limited I(E) versus 37.58% and 45% for extended I(E) (p = 0.0644). B symptoms did not significantly affect clinical outcome (p = 0.729). Multivariate analysis showed that complete response of local lesion after radiotherapy, invasion of the primary tumor to adjacent structures, and patients' age were independent prognostic factors. Our study showed that radiotherapy is the main treatment method for the primary non-Hodgkin's lymphomas of the nasal cavity; the addition of chemotherapy may improve long-term survival. The local tumor response to radiotherapy, whether the extranasal structures were invaded, and patients' age were independent prognostic factors.

Blot overlays with 32P-labeled fusion proteins.

Proteins labeled with 32P can be used as sensitive "prime" in blot overlays to detect binding proteins or domains. Small G-protein Ras can bind GTP with extremely high affinity (Kd approximately 10(-11)-10(-12) M) in the presence of Mg2+. We have taken advantage of this property of Ras to develop a vector that expresses proteins of interest such as glutathione S-transferase (GST)/Ras fusion proteins for noncovalent labeling with [gamma-32P]GTP. The labeling efficiency of this method is >60% and involves a single short incubation step. We have previously identified several binding proteins for the second SH3 domain of the adaptor Nck using this method. Here we illustrate the overlay method using the GST/Ras system and compare results with the SH3 domain labeled by phosphorylation with [gamma-32P]ATP. Both methods are similarly specific and sensitive; however, we show that signals are dependent primarily on GST-mediated probe dimerization. These dimeric probes allow a more stable probe-target complex similar to immunoglobulin interactions, thus significantly improving the sensitivity of the technique.

Kinetic equation with exact charge conservation.

A kinetic master equation for multiplicity distributions is formulated for charged particles which are created or destroyed only in pairs due to the conservation of their Abelian charge. It allows one to study time evolution of the multiplicity distributions in a relativistic many-body system with arbitrary average particle multiplicities. It is shown to reproduce the equilibrium results for both canonical (rare particles) and grand canonical (abundant particles) systems. For canonical systems, the equilibrium multiplicity is much lower and the relaxation time is much shorter than the naive extrapolation from grand canonical results. Implications for chemical equilibration in heavy-ion collisions are also discussed.

Effects of matrix proteins on the expression of matrix metalloproteinase-2, -9, and -14 and tissue inhibitors of metalloproteinases in human cytotrophoblast cells during the first trimester.

The activity of matrix metalloproteinases (MMPs) specifies the ability of the trophoblast cell to degrade extracellular matrix (ECM) substrates. Usually the process of normal human placentation involves a coordinated interaction between the fetal-derived trophoblast cells and their microenvironment in the uterus. In this study, the effects of ECM proteins on the expression of MMP-2, -9, and -14 (membrane-type MMP-1); and the production of tissue inhibitors of metalloproteinase (TIMP) types -1, -2, and -3 have been investigated. Cytotrophoblast cells at 9 or 10 wk of gestation were cultured on various ECM coated dishes under serum-free conditions. Gelatin zymography analysis showed that cells grown on fibronectin (FN), laminin (LN), and vitronectin (VN) secreted more MMP-9 (about 1.5- to 3-fold more) than cells cultured on collagen I (Col I), whereas the secretion of MMP-9 by cells cultured on collagen IV (Col IV) was only half that by the cells on Col I. Northern Blot analysis gave the same results as zymography, indicating that expression of the MMP-9 gene in cytotrophoblast cells can be affected by matrix proteins. There was no significant difference in the expression of MMP-2 either at protein or mRNA levels among the cells cultured on the different matrix substrates. The expression of MMP-14 was regulated in a manner similar to that of MMP-2. Using ELISA, we detected higher levels of TIMP-1 in the culture medium of cells grown on VN, LN, and FN compared with that grown on Col I. But the expression of TIMP-3 mRNA was remarkably inhibited by VN, and ECM proteins had no effect on TIMP-1 and TIMP-2 mRNA expression. It was also observed that cultured cytotrophoblast cells expressed the corresponding receptors for the tested matrix proteins, such as integrins alpha(1), alpha(5), alpha(6), beta(1), and beta(4). Furthermore, the adhesiveness of cytotrophoblast cells on Col I, Col IV, FN, and LN was increased by 62%, 45%, 21%, and 22%, respectively, when compared with adhesiveness on VN. Isolated cytotrophoblast cells remained stationary when cultured on dishes coated with Col I and Col IV, but they assumed a more motile morphology and aggregated into a network when cultured on LN and VN. These data indicate that human trophoblast cells interact with their microenvironment to control their behavior and function.

Altered expression of nuclear non-histone protein (p44/46) in different stages of B-chronic lymphocytic leukemia.

Our previous data have shown some differences in electrophoretic characteristics of proteins from cellular fractions (nuclear, mitochondrial, microsomal and cytosolic) isolated from peripheral blood mononuclear cells of B-cell chronic lymphocytic leukemia (B-CLL), acute lymphoblastic leukemia (ALL) patients and healthy donors. The main differences were found in electrophoretic patterns of nuclear proteins from normal and leukemia cells, especially in the nuclear mass regions of 36-52, 58-85, and 120-180 kDa. Electrophoretically-specific nuclear non-histone protein in the molecular mass zone 44/46 kDa of cells obtained from the peripheral blood of a B-CLL patient was used to produce rabbit polyclonal antiserum. SDS-polyacrylamide gel electrophoresis as well as immunological techniques (Western blot and immunocytochemistry) indicate that the nuclear protein with a molecular mass of 44/46 kDa is specifically expressed in mononuclear cells from B-CLL patients. The expression of this particular nuclear protein seems to correlate with the progression of the leukemia.

Frequency of portal and systemic bacteremia in acute appendicitis.

BACKGROUND: Acute appendicitis is the most common condition requiring an emergency abdominal operation in childhood. In the present study, we analyzed the frequency of portal and systemic bacteremia in 42 patients with acute appendicitis and determined the microbial agents responsible for an acute appendicitis and for portal and systemic bacteremia. METHODS: Appendectomies were performed on 50 young patients (5-18 years of age), as well as clinical and bacteriological tests. Six independent samples from each patient isolated from the peripheral vein, superior mesenteric vein, appendix and peritoneum were obtained prior to surgery, during surgery and after surgery for biochemical, immunologic and bacteriologic examination. RESULTS: Pathohistology confirmed the diagnosis of appendicitis in 42 patients, while in the other eight patients there were no obvious pathologic findings, so they served as a control group. Of 50 patients with a clinical appearance of acute appendicitis, in 19 patients (38%) we detected portal bacteremia in the mesenteric vein, while in only three cases (6%) did we find systemic bacteremia detected from the peripheral vein. Furthermore, bacteriologic analysis revealed that Bacteroides spp. and Escherichia coli were the predominant species isolated. CONCLUSIONS: The results presented in this paper suggests that portal bacteremia did not influence peripheral blood reactions. Furthermore, in the present study we have found a positive correlation between the smear and bacteremia of the superior mesenteric vein, but not with the bacteremia of systemic blood.

The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates proliferation in a cell-type-specific fashion.

The neurofibromatosis 2 (NF2) tumor suppressor belongs to the Protein 4.1 family of molecules that link the actin cytoskeleton to cell surface glycoproteins. We have previously demonstrated that the NF2 protein, merlin, can suppress cell growth in vitro and in vivo as well as impair actin cytoskeleton-associated processes, such as cell spreading, attachment, and motility. Recently, we determined that expression of a second Protein 4.1 tumor suppressor, DAL-1, was lost in 60% of sporadic meningiomas, but not schwannomas. In this report, we demonstrate that DAL-1 suppresses cell proliferation in meningioma, but not schwannoma cells. Similar to merlin, DAL-1 interacts with other ERM proteins and betaII-spectrin, but not the merlin interactor protein, SCHIP-1. In addition, we report the identification of the full-length DAL-1 tumor suppressor, termed KIAA0987. Collectively, these results suggest that the two Protein 4.1 meningioma tumor suppressors, merlin and DAL-1, may be functionally distinct proteins with different mechanisms of action.