Risk of colorectal neoplasia associated with the adenomatous polyposis coli E1317Q variant.

BACKGROUND: Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting. Using a case-control design, we investigated this relationship within a clinic-based cohort followed through the Integrated Cancer Prevention Center and the Tel-Aviv Sourasky Medical Center. MATERIALS AND METHODS: All study subjects were tested for the APC E1317Q variant at enrollment. Subjects underwent colonoscopic evaluation (+/-biopsy and/or polypectomy) and had cancer history and colorectal neoplasia risk factors assessed. The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated. RESULTS: The prevalence of the E1317Q variant was 1.4% in the entire study sample and 3.2% in Sephardic Jews. E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0-9.6]. When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8-9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8-5.3). After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0-10.8). CONCLUSIONS: The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed. Variant prevalence is elevated in Sephardic Jews.

Experimental testing of the role of cytoskeleton in the solution by neurons of problems facing the brain.

Investigation of the influence of cAMP on neuronal electric activity suggests that nerve cells can solve problems using an intraneuronal calculating medium based on the cytoskeleton. When a new problem is posed, this structure has to be disassembled and assembled by the neuronal molecular computer according to the program recorded in DNA. If DNA lacks an appropriate program, the cytoskeleton will not be assembled. In our experiments, fishes which were rotated simultaneously around two mutually perpendicular axes lost their swimming ability, and some dramatic changes were observed in the cytoskeleton of their Mauthner neurons. These changes disappeared after a long-term rest: the cytoskeleton was restored simultaneously with the ability for normal swimming.

Prospective assessment of microsatellite instability in gastrointestinal neoplasia in Ashkenazi and non-Ashkenazi Jews.

BACKGROUND: Microsatellite instability (MSI) is a useful marker of replication errors in neoplasia, resulting from mutations in the mismatch repair (MMR) genes. Nearly all hereditary non-polyposis colorectal cancer (HNPCC) and about 15% of sporadic colorectal cancers (CRC) exhibit high MSI (MSI-H). The use of the Amsterdam criteria for HNPCC diagnosis may fail to identify many HNPCC cases. Genetic screening of mutations in the MMR genes is laborious, time-consuming, expensive and limited by a low detection rate. Hence, MSI testing is a feasible and cost-effective method to select suspected HNPCC patients for genetic analysis. MSI has not been used routinely or prospectively in the assessment of newly diagnosed CRC. AIMS: To prospectively evaluate MSI status in a cohort of patients seen at the Gastrointestinal Oncology Unit of the Tel Aviv Medical Center. METHODS: Ninety-eight consecutive patients with colonic or gastric neoplasia were included. Samples from neoplastic and normal mucosa were obtained at the time of diagnostic endoscopy. MSI was determined based on five Bethesda markers using standard polymerase chain reaction procedures. RESULTS: The overall incidence of MSI was 20.4%. MSI-H was detected in 22.2% of CRC, 20% of colonic adenomas and 18.2% of gastric neoplasia. MSI-positive neoplasia tended to display multiple colonic sites, moderate-well differentiated tumors, and a higher rate of familial gastrointestinal neoplasia. CONCLUSIONS: MSI may be involved in the early stages of some colorectal tumorigenesis pathways since it may be detected in adenomas. MSI may serve as a cost-effective, reliable and important tool in the selection of HNPCC-suspected families for genetic testing. A small study population, referral bias or ethnic variation might explain the higher MSI rate. It is suggested that, similar to familial adenomatous polyposis, a state of attenuated HNPCC may exist. Hence, the clinical approach in positive patients, and their family members, should be conducted as for families with genetically proven HNPCC.

[Problems uniting biology, physics, and mathematics. Ideas in the new science]. / Problemy, ob''ediniaiushchie biologiiu, fiziku i matematiku. Idei novoi nauki.

The necessity of launching a new field of science that combines biology, physics, and mathematics for an adequate description of natural-science systems (khaimatika) is substantiated.

Papillary and follicular neoplasms of the thyroid gland. Differential immunohistochemical staining with high-molecular-weight keratin and involucrin.

The morphologic distinction between papillary and follicular neoplasms of the thyroid gland can be difficult, especially on small biopsy specimens or in fine-needle aspirations. To determine whether immunohistochemistry could help in achieving the correct diagnosis, we characterized the staining pattern for a series of papillary and follicular neoplasms of the thyroid gland. A pilot study was performed using a panel of antibodies, including high-molecular-weight keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20, AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK showed strong differential staining between follicular and papillary neoplasms. HMWK stained 91% of papillary carcinomas, including follicular variants, with a median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms with a median of 45% positive cells. HMWK stained only 20% of follicular neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed strong, although patchy, staining with HMWK and involucrin, whereas those follicular neoplasms that did have staining showed a weak, diffuse pattern of staining. We believe that HMWK, and involucrin to a lesser degree, could be useful in differentiating papillary from follicular neoplasms, especially for cytologic cell block material or for cases in which the architectural pattern is follicular.

Transmucosal fine-needle aspiration diagnosis of intraoral and intrapharyngeal lesions.

OBJECTIVES: The effectiveness of fine-needle aspiration biopsy (FNAB) for the diagnosis of neck, thyroid, and salivary gland masses is well documented. Very few reports explore the potential of an intraoral FNAB approach for the diagnosis of submucosal lesions. We describe our technique and present case examples of pertinent differential diagnostic entities. We recommend an expanded role for FNAB of the oral cavity and oropharynx. STUDY DESIGN: Retrospective review. METHODS: A uniform technique was employed for transmucosal FNAB of 76 patients with intraoral masses. In applicable cases, cytology results were compared with traditional biopsy methods and permanent histopathologic specimens for accuracy. RESULTS: Our experience demonstrates the high sensitivity (93%) and specificity (86%) of intraoral FNAB when compared with biopsy by conventional means. FNAB provides distinct advantages for the cytologic diagnosis of submucosal lesions, which may be difficult to reach and adequately sample through conventional biopsy. FNAB of the tonsil and tonsillar fossa provides a safe and effective means of diagnosing both lymphoma and squamous cell cancer. Transmucosal FNAB via the mouth led to rapid diagnosis of a number of benign and malignant lesions. Applying this uniform FNAB technique, we had no significant complications. CONCLUSION: We recommend transmucosal FNAB as an effective means for highly accurate diagnosis of submucosal lesions of the oral cavity and oropharynx. CLINICAL RELEVANCE: Traditional biopsy techniques in the oral cavity may require anesthesia and may have diagnostic difficulties, particularly for submucosal lesions. Transmucosal FNAB overcomes these shortcomings by providing a minimally invasive means to rapid diagnosis of intraoral lesions.

[Change in neuronal membrane permeability exposed to adenosine-3',5'-cyclophosphate]. / Izmeneie pronitsaemosti membrany neirona pod deistviem adenozin-3',5'-tsiklofosfata.

Ionic current induced by intracellular injection of cAMP was divided into constituent parts, and the dependence of these components on membrane potential and ionic composition of extracellular medium was demonstrated. The computation shows that practically all background neurone permeability for potassium ions is cAMP-dependent.

Activation of the grp78 and grp94 promoters by hepatitis C virus E2 envelope protein.

The hepatitis C virus E1 and E2 envelope proteins are targeted to the endoplasmic reticulum, but instead of being secreted, they are retained in a pre-Golgi compartment, at least partly in a misfolded state. Since secretory proteins which are retained in the endoplasmic reticulum frequently can activate the transcription of intraluminal chaperone proteins, we measured the effect of the E1 and E2 proteins on the promoters of two such chaperones, GRP78 (BiP) and GRP94. We found that E2 but not E1 protein activates these two promoters, as assayed by a reporter gene system. Furthermore, E2 but not E1 protein induces the synthesis of GRP78 from the endogenous cellular gene. We also found that E2 but not E1 protein expressed in mammalian cells is bound tightly to GRP78. This association may explain the ability of E2 protein to activate transcription, since GRP78 has been postulated to be a sensor of stress in the endoplasmic reticulum. Since overexpression of GRP78 has been shown to decrease the sensitivity of cells to killing by cytotoxic T lymphocytes and to increase tumorigenicity and resistance to antitumor drugs, this activity of E2 protein may be involved in the pathogenesis of hepatitis C virus-induced diseases.

[The etiological structure of the morbidity from influenza and other ARDs on the territory of Russia in the season of 1997-1998]. / Etiologicheskaia struktura zabolevaemosti grippom i drugimi ORZ na territorii Rossii, sezon 1997--1998 gg.

The antigenic properties of 51 strains of influenza virus A(H1N1), isolated in different cities of Russia during the epidemic of 1998, were studied. Most of these strains (49) proved to be similar to virus A/Bern/07/95 in the antigenic structure of hemagglutinin, but 2 strains isolated in Ulan-Ude were found to be closely related to new antigenic variants of this virus: A/Beijing/262/95 and A/Fukuoka/c7/98. The analysis of the antigenic structure of influenza-like diseases (ILD) in different cities of Russia revealed that adenoviruses causing up to 10.9-14.6% of all acute respiratory virus infections dominated at the pre- and post-epidemic periods. RS-viruses, parainfluenza viruses of types 2 and 3 circulated during the whole season (their proportion was 5.1-6.6%). The intensity of the circulation of influenza viruses A(H1N1) and A(H3N2) increased, starting from January, and continued till April 1998; its peak was observed in February-March in most of the cities of Russia (up to 37.5-41.6% according to the results of immunofluorescent diagnostics and 53-73% of ILD according to the results of the hemagglutination inhibition test). The occurrence of influenza B during this season was very low.

Foamy macrophages in acquired immunodeficiency syndrome cholangiopathy with Encephalitozoon intestinalis.

Acquired immunodeficiency syndrome (AIDS) cholangiopathy is a clinical syndrome characterized by right upper quadrant pain, low-grade fever, and bile duct dilatation or papillary stenosis. Cryptosporidia and cytomegalovirus have been most commonly reported as causes of AIDS cholangiopathy, but recently microsporidia have also been recognized as a causative agent. We here report an additional case of AIDS cholangiopathy with the microsporidian Encephalitozoon (Septata) intestinalis. Because this microsporidial species can disseminate throughout the body and is susceptible to treatment by albendazole, it is important to identify and separate this organism form other causes of AIDS cholangiopathy. A key histologic feature seen in this case, which has not been observed in AIDS cholangiopathy caused by other parasitic organisms, is the presence of numerous foamy macrophages in the lamina propria, which contain the microsporidial organisms, as seen by electron microscopy. The presence of these foamy macrophages may be an important histologic clue to the presence of infection by Encephalitozoon intestinalis.

Increased leukocyte adhesiveness/aggregation in patients with recurrent TIA.

OBJECTIVE: White blood cells might have a pathogenetic role in ischemic vascular conditions. Several studies have suggested that increased adhesiveness of these cells could contribute to such a damage. The present study was undertaken in order to examine the adhesive properties of leukocytes in the peripheral blood of patients with various degrees of ischemic neuro-vascular diseases. METHODS: The percentage of aggregated white blood cells was determined by using a direct slide test. RESULTS: The respective values of aggregated cells in 28 patients with major stroke, 11 with minor stroke, 17 with a single TIA, 11 with recurrent TIAs and 18 controls were 15.9 +/- 7.4%, 6.6 +/- 3.3%, 3.0 +/- 2.6%, 10.9 +/- 8.4% and 1.5 +/- 0.4%. The difference between patients with a single TIA and those with recurrent TIAs being significant at P < 0.05. CONCLUSION: Being a sensitive marker of inflammation, our test might reveal the presence of an underlying smoldering inflammation in patients with recurrent TIA. These results are in agreement with modern studies that show that inflammation is an important feature of atherosclerosis.

Cerebrospinal fluid leukocyte aggregation in meningitis.

OBJECTIVE: To evaluate whether the difference in aggregation of cerebrospinal fluid cells from patients with bacterial, viral, aseptic and partially treated meningitis can be used for diagnostic purposes. METHODS: Cerebrospinal fluid samples of 100 patients with meningitis (15 bacterial, 13 partially treated, 10 viral and 62 aseptic) were compared on the basis of the predefined leukocyte aggregation score (LAS). RESULTS: Mean LAS was 56% in the bacterial meningitis group (range, 15 to 90%), 5.8% in the partially treated meningitis group (range, 0 to 27%), 2% in the proven viral meningitis group (range, 0 to 5%) and 2% in the aseptic meningitis group (range, 0 to 15%). All patients with bacterial meningitis had a LAS of > 15%, whereas all those with viral or aseptic meningitis had a score of < 15%. Although most patients with partially treated meningitis had a low LAS, several had higher scores, which may indicate bacterial infection. There was no statistical correlation between number of cells, type of cells (mononuclear or polymorphonuclear) or cerebrospinal fluid protein and glucose concentration and degree of leukocyte aggregation for the different groups. CONCLUSION: Measurement of the LAS may contribute to the immediate differential diagnosis of bacterial or viral meningitis, especially in patients with very high pleocytosis, as sometimes seen in enteroviral meningitis. It may also serve as a guide for the likelihood of bacterial infection in cases of partially treated meningitis. Additional studies are needed to confirm these observations.

Increased adhesiveness of white blood cells in patients with unstable angina: additional evidence for an involvement of the immune-inflammatory system.

BACKGROUND: Data are being accumulated on the presence of inflammatory response in patients with acute coronary syndromes. HYPOTHESIS: The study was undertaken to confirm that the adhesive state of the peripheral blood leukocytes can provide information on an inflammatory process in patients with unstable angina pectoris. METHODS: The study included 21 patients with unstable angina, 32 patients with stable angina, and 13 patients with chest pain and no evidence of coronary artery disease. RESULTS: The percentage of aggregated leukocytes in patients with unstable angina (5.8 +/- 3.2%) was significantly (p < 0.02) increased compared with that of patients with no evidence of active coronary disease (3.2 +/- 2.6%). CONCLUSION: Additional evidence for an existing smoldering inflammatory process in unstable angina pectoris can be provided by testing the percentage of aggregated leukocytes in peripheral blood.

Increased leukocyte adhesiveness/aggregation in patients with inflammatory bowel disease during remission. Further evidence for subclinical inflammation.

PURPOSE: We have used a novel leukocyte adhesiveness/aggregation test (LAAT) to show that many patients with inflammatory bowel disease (IBD) in clinical remission have a subclinical low grade inflammation. METHODS: Included in the study are 500 controls, 96 patients with IBD in remission, and 106 patients in relapse. RESULTS: The percent of aggregated white blood cells detected in the peripheral blood was 5.9 +/- 3.9, 9.1 +/- 5.9, and 18.8 +/- 9.4, respectively. The difference between each group and any other was significant at P < 0.0001. Similar results were obtained when other acute phase reactants like the erythrocyte sedimentation rate, white blood cell count, differential count, and C-reactive protein level were examined. However, in a linear regression analysis, LAAT was the only significant (P < 0.0006) variable that could classify correctly each subject to the appropriate category of control and IBD in remission or relapse. CONCLUSIONS: Identification of patients with IBD in clinical remission who have ongoing inflammation may be of clinical-therapeutic relevance. The LAAT is a simple, rapid, and convenient test. The present study indicates that it is also very sensitive.

Cell molecular computers and biological information as the foundation of nature's laws.

It is proposed to unite the principles of new science mathematics, physics and biology for the description of living creatures. Such description is based on four principles: minimal price of action, optimum prediction, minimal irreversibility, and causality. In this new knowledge of nature not only the molecular biological experimental aspects have to be considered, but also the profound 'meaning' of molecular texts of DNA.

Increased leukocyte adhesiveness/aggregation is the single best biochemical indicator of disease activity in adolescent patients with inflammatory bowel disease.

We determined the relative utility of inflammatory markers in evaluating disease activity in adolescent patients with inflammatory bowel disease (IBD). Sixty-one adolescent patients and 50 age and sex matched volunteers who served as controls were evaluated prospectively. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBCC), and the leukocyte adhesiveness/aggregation (LAA) test were determined in each patient. There were 28 subjects in remission and 33 in relapse. Their percentage of aggregated white blood cells in the peripheral blood was 7 +/- 5 and 16 +/- 8, respectively, when compared with the control group (5 +/- 3) (p < 0.0001). Moreover, the LAA test was the only one which could effectively classify patients with IBD into their correct diagnostic categories of remission, mild-moderate, or moderate-severe disease activity. The LAA test is superior to other acute phase reactants used in daily practice to detect the presence of inflammation as well as for the assessment of its severity in adolescent patients with IBD. In addition, our findings may have biological relevance to the disease process and its potential manipulation by anti-adhesive agents.

Increase in leukocyte adhesiveness and aggregation with stress: a model of human congestive heart failure.

Stress has a significant influence on the function of the human organism. A simple, rapid, inexpensive, and reliable marker for stress would therefore be of great value. We have recently noted that stress increases the state of leukocyte adhesiveness and aggregation in the peripheral blood. We evaluated 64 patients who had various degrees of congestive heart failure, a condition known to induce a state of physiologic stress, to verify whether a relation exists between the intensity of the stress response and the magnitude of leukocyte adhesiveness. Included in the 64 were 53 patients without congestive heart failure, 23 with compensated failure, 22 with significant congestive heart failure, and 19 with florid pulmonary edema. The percentage of aggregated leukocytes in these four group was 6% +/- 4%, 6% +/- 4%, 10.5% +/- 5%, and 15% +/- 14%. Values for the third and fourth group differed in a statistically significant way. Thus, with further investigation into additional stress-inducing conditions, the state of leukocyte adhesion and aggregation may prove to be a reliable marker for the detection of stress and an inexpensive tool for quantifying its severity.

Increased leucocyte adhesiveness/aggregation is a most useful indicator of disease activity in patients with inflammatory bowel disease.

The aim of the study was to determine the comparative usefulness of inflammatory markers, in evaluating disease activity in patients with inflammatory bowel disease. Disease activity was assessed by the Mayo Clinic score for ulcerative colitis, and Harvey-Bradshaw score for Crohn's disease. Five hundred normal blood donors who had no underlying inflammatory condition served as controls. The erythrocyte sedimentation rate, platelet and white blood cell count, C reactive protein, and the leucocyte adhesiveness/aggregation test (LAAT) were determined in each patient. One hundred and twenty four patients with inflammatory bowel disease were tested while in remission and 128 in relapse. Their mean (SD) per cent of aggregated white blood cells in the peripheral blood was 8 (5) and 17 (10) respectively compared with controls 6 (4) (p < 0.0001). Moreover, the LAAT could effectively discriminate between various grades of disease activity, the values in patients with active disease being 13 (6)% in mild, 17 (10)% in moderate, and 26 (10)% in severe disease (p < 0.0001). Other acute phase reactants including the erythrocyte sedimentation rate, the white blood cell count, the platelet count, neutrophil count, as well as, the C reactive protein concentration did not differentiate as well between the various groups. Using logistic regression analysis to differentiate between inflammatory bowel disease patients in remission or relapse, the LAAT was the single best indicator. The addition of any other test did not contribute to the discrimination. Among the different laboratory variables tested only the LAAT significantly discriminated between the five different subgroups of controls, remission and mild, moderate or severe disease activity.

Molecular quantum computer of neuron.

Living cells are controlled by quantum regulators in which the price of action of elementary operations approaches Planck's constant. The description of such systems is based on four principles: (1) minimal price of action principle for control; (2) principle of optimality; (3) minimum irreversibility principle; and (4) the principle of causality.