Can a mast cell subtype (MC(T)) play a role in the progression of endometrial cancer through angiogenesis?
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Disease Progression↗
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A new Real-Time-RT-PCR for quantitation of human endogenous retroviruses type K (HERV-K) RNA load in plasma samples: increased HERV-K RNA titers in HIV-1 patients with HAART non-suppressive regimens.
Viral components of the human endogenous retroviruses type K (HERV-K) have been largely detected in plasma from HIV-1 infected individuals. A Sybr Green Real-Time RT-PCR approach was optimized for detection and quantitation of HERV-K RNA titers in plasma samples using the iCycler technology. The method detected 1000 HERV-K RNA copies/mL of plasma sample. The Intra- and Inter-assay performance revealed a coefficient of variations that ranged from 0.2 to 2.46%, demonstrating accuracy and reproducibility. We quantified the HERV-K RNA load in 20 HIV-1 patients receiving highly active antiretroviral therapy (HAART). We found increased HERV-K RNA titers in patients with non-suppressive HAART (patients who may develop drug-resistance and/or received suboptimal therapeutic doses), compared to suppressive regimens (p < 0.001). HERV-K RNA was not detected in HCV-1 positive or seronegative controls. Sequencing of Real-Time RT-PCR products revealed particular HERV-K subtypes activated in the HIV-1 infection. The application of this assay could expand the understanding of the role of HERV-K in the HIV-1 infection and others pathological conditions.
Analysis of Variance↗
Multiple roles of protein kinases in the modulation of gamma-aminobutyric acid(A) receptor function and cell surface expression.
gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that mediate the majority of fast synaptic inhibition in the brain and that are also important drug targets for benzodiazepines, barbiturates, and neurosteriods. These receptors are pentameric hetero-oligomers that can be assembled from 7 subunit classes with multiple members: alpha(1-6), beta(1-3), gamma(1-3), delta, epsilon, theta, and pi. Most receptor subtypes in the brain, however, are believed to be composed of alpha-, beta-, and gamma-subunits. Modifications of GABA(A) receptor function are continually implicated in a range of pathologies, including epilepsy, anxiety, insomnia, and substance abuse. Moreover, changes in the efficacy of synaptic inhibition mediated by GABA(A) receptors are believed to be play central roles in certain forms of synaptic plasticity, including rebound potentiation in the cerebellum, and hippocampal long-term potentiation. Given the critical role that GABA(A) receptors play as mediators of synaptic transmission, it is of fundamental importance to understand the endogenous mechanisms used by neurones to control the function of these receptors. This review will focus on the dynamic regulation of GABA(A) receptor phosphorylation state and channel function as mechanisms involved in determining the efficacy of synaptic inhibition. In addition, the possible role of GABA(A) receptor phosphorylation in controlling receptor internalization and recycling will also be explored.
Allosteric Regulation↗
An analysis of features of pathogenesis in two animal models of Ebola virus infection.
Virus reproduction and the time course of changes in liver and kidney functions and in the blood clotting system were studied in the visceral organs of green monkeys and baboons infected with Ebola virus (subtype Zaire). It was shown that monocytes and macrophages were the first cells to be infected with the virus, followed by hepatocytes, adrenocorticocytes, fibroblasts, and endotheliocytes. The early and late pathologic changes in the monkey organs are described. Biochemical data on changes in blood clotting and liver and kidney functions in the course of the infection are presented. The responses of blood clotting and vascular permeability were species specific: Fibrin deposited in blood vessels in green monkeys, while hemorrhages developed in baboons. The results show that species-specific features of monkeys must be taken into account when choosing an experimental model for studying Ebola virus infection.
Animals↗
Association of Epstein-Barr virus genome with mixed cellularity and cellular phase nodular sclerosis Hodgkin's disease subtypes.
Association of Epstein-Barr virus (EBV) genome with Hodgkin's disease (HD) histological subtypes was investigated using the polymerase chain reaction (PCR). A highly significant association of EBV genome with the mixed cellularity (MC) subtype (10 positive out of 15 cases; 66%) was observed, suggesting a possible etiopathogenetic role of EBV in the induction of this subset. By contrast, a markedly lower frequency of association with EBV genome was found in nodular sclerosis (NS) (12 positive out of 46 cases; 26%) and in nodular lymphocytic predominance (NLP) (0 positive out of 5 cases) HD subtypes. In addition, in the NS series, the presence of EBV genome was mainly restricted to the 'cellular phase' NS subset. This finding strengthens the possibility, suggested by clinico-pathological features and survival rates, that 'cellular phase NS' is a disease more akin to MC than to typical NS HD.
Genome, Viral↗
Grade of stromal invasion in small adenocarcinoma of the lung: histopathological minimal invasion and prognosis.
The pathologic features of invasion such as stromal disruption and pleural/vascular involvement have been shown to be of prognostic value in adenocarcinoma. However, the relationship between the degree of invasion, histologic subtype of adenocarcinoma, and prognosis remains unclear. We retrospectively studied 380 peripheral adenocarcinomas of < or = 2.0 cm in diameter with regard to histology and clinical profiles. Their degree of invasive growth was classified into four grades as follows according to the structural deformity and its location in the adenocarcinoma lesion: Grade 0 had a pure bronchioloalveolar growth pattern and no evidence of stromal invasion. Grade 1 had stromal invasion in the area of bronchioloalveolar growth. Grade 2 had stromal invasion localized on the periphery of a fibrotic focus. Grade 3 had stromal invasion into the center of a fibrotic focus. The clinicopathological data were obtained from medical records. The distribution of the histologic grade of invasion was as follows: grade 0 in 85 tumors (22%), grade 1 in 37 (10%), grade 2 in 46 (12%), and grade 3 in 212 (56%). This histologic grade of invasion was closely related to other indicators of tumor spread. Vascular/lymphatic permeation was seen in none of grade 0, in 1 lesion each of grade 1 and grade 2, and 144 (68%) of grade 3. Lymph node metastasis was seen in 57 (27%) lesions of grade 3 but not in grades 0, 1, or 2. The 5-year disease-free survival rates were 100%, 100%, 100%, and 59.6% for tumors with grade 0, grade 1, grade 2, and grade 3 invasion, respectively. Tumors with grade 1 and grade 2 invasion, like tumors with grade 0 invasion (bronchioloalveolar carcinoma), showed an excellent prognosis. Therefore, tumors with grade 1 and grade 2 invasion could be considered "minimally invasive" or "early" adenocarcinomas.
Adenocarcinoma↗
Postoperative wound infection: a controlled study of the increased duration of hospital stay and direct cost of hospitalization.
The increased hospital stay and direct cost of hospitalization that resulted from a postoperative wound infection (presence of pus at the incision site) after each of 6 common operations were evaluated. With the aid of the hospital computer, matched controls were obtained with respect to patient age, sex, exact operation performed, clinical service performing operation, pathologic finding, and underlying disease process which might alter the patient's predisposition toward infection. Several of the operations (appendectomy. cholecystectomy, total abdominal hysterectomy, and coronary artery bypass graft) were subtyped in order to obtain equivalence between controls and infected patients. In general, an infection doubles the postoperative stay and significantly increases the hospital expense.
Adolescent↗
Hodgkin's disease in HIV-infected individuals.
The clinical and pathologic characteristics of Hodgkin's disease as they are diagnosed in patients with HIV infection differ from those of the general population. In fact, a higher frequency of unfavorable histologic subtypes, advanced stage, and poor therapeutic outcome have been reported in the HIV setting. Complete response rate after chemotherapy ranges from approximately 45% to 70%, although the disease-free survival is very short, and the median overall survival is only 18 months. The survival of these patients may be improved by the optimal combination of antineoplastic and antiretroviral treatment with the support of hematologic growth factors. However, new strategies of therapeutic intervention must be explored.
HIV Infections↗
The detection and significance of minimal residual disease in acute and chronic leukemia.
Minimal residual disease (MRD) can be detected in many patients with leukemia who have achieved complete remission as defined by conventional pathology examination. The detection of MRD, be it by flow cytometry or by polymerase chain reaction assays, has now been found to be associated with subsequent relapses in most leukemia subtypes, either following chemotherapy or following hematopoietic stem cell transplantation. These assays are now increasingly used in clinical trial design to optimize therapy and provide a novel way to assess treatment efficacy.
Flow Cytometry↗
Lung adenocarcinoma with a micropapillary pattern: a clinicopathological study of 25 cases.
Lung adenocarcinoma with a micropapillary pattern has recently been described, but its biological behavior is as yet uncertain. In this article we present a clinicopathological study of lung adenocarcinoma with micropapillary morphology. We selected 25 patients with lung adenocarcinoma with micropapillary morphology from the 2001-2004 pathology files (age range 54 to 81 years; mean 64.5 years). Micropapillary carcinoma is predominantly located at the periphery of the tumor nodule or mass and occurs irrespective of the subtype of the adenocarcinoma. A micropapillary component was seen against a mucinous background in three cases and microcalcifications resembling psammoma bodies were seen in one case. Four cases showed intensive invasive growth such as micropapillary adenocarcinoma of the breast and 21 showed alveolar type morphology with piling-up of the neoplastic cells with or without stromal invasion. Seven of twenty-three (30.4%) showed lymph node metastases at time of operation. Twelve of twenty-five (48%) showed pleural invasion. Regarding clinical outcome, 14 patients were alive without disease, 5 were alive with disease, and 5 died of the lung adenocarcinoma. No significant relationship was found between the extent of the micropapillary component and prognosis. However, the carcinoma seen in the five patients who died showed breast type histology with intensive invasive growth in three cases and alveolar type histology with intensive stromal invasion in two. Lung micropapillary carcinoma of breast type may behave more aggressively than the alveolar type.
Adenocarcinoma↗
Possible role of endothelin in endothelial regulation of vascular tone.
In vascular beds, a potent vasoconstrictor of endothelin-1 (ET-1) is produced by endothelial cells and released preferentially to the basal side of endothelial cells. It acts on endothelial cells and on the underlying smooth muscle cells, as a modulator of vascular tone, in an autocrine and paracine manner. ET-1 induces release of relaxing factors (nitric oxide and prostacycline) from endothelial cells. Whether relaxation or constriction is predominantly elicited by endogenous ET-1 may depend on the concentration of ET-1 in vascular beds, the density and mode of distribution of ET receptor subtypes on the endothelial and smooth muscle cells, the turnover of the receptors, and the existing conditions of each vascular beds. When ET-1 is overproduced by endothelial cells at pathological conditions, endogenous ET-1 acts as a vasoconstrictor. However, ET-1 may act as a vasodilator at physiologically low concentrations, depending on the existing condition.
Amino Acid Sequence↗
Preceding infections, immune factors, and outcome in Guillain-Barré syndrome.
OBJECTIVE: To test the hypothesis that different preceding infections influence the neurophysiologic classification and clinical features of Guillain-Barré syndrome (GBS). METHODS: We tested pretreatment sera, 7 +/- 3 (mean +/- SD) days from onset, from 229 patients with GBS in a multicenter trial of plasma exchange and immunoglobulin, for serological markers of infection, adhesion molecules, and cytokine receptors, and compared these with neurophysiologic and clinical features. RESULTS: Recent infection by Campylobacter jejuni was found in 53 patients (23%), cytomegalovirus in 19 (8%), and Epstein-Barr virus in four (2%). Patients with C. jejuni infection were more likely than others to have neurophysiologic criteria of axonal neuropathy or inexcitable nerves, antiganglioside GM(1) antibodies, pure motor GBS, lower CSF protein, and worse outcome. Patients with cytomegalovirus infection were younger and more likely than others to have raised serum concentrations of molecules important in T lymphocyte activation and migration, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte selectin, and soluble interleukin-2 receptor (sIL-2R). Concentrations of sICAM-1 and soluble tumor necrosis factor receptor were higher in patients with inexcitable nerves than those with demyelinating neurophysiology. Logistic regression analysis showed death or inability to walk unaided at 48 weeks were associated with diarrhea, inexcitable nerves, severe arm weakness, age over 50, raised sIL-2R concentration and absence of immunoglobulin (Ig) M antiganglioside GM(1) antibodies. CONCLUSIONS: Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features. A single infectious agent caused more than one type of pathology in GBS, implying interaction with additional host factors. Most patients had no identified infection.
Antibodies↗
[Reproduction physiology and prostanoids].
Prostanoids, which consist of prostaglandins (PGs) and thromboxane, are produced from arachidonic acid by cyclooxygenases (COXs) as a rate-limiting step, and they exert various biological actions. Classically, prostanoids are suspected to be closely related to female reproductive processes such as ovulation, luteolysis and uterine contraction, as well as pathological processes such as fever generation and pain modulation. Recently the cDNA cloning of a series of prostaglandin-synthesizing enzymes and receptors enabled us to clarify which isoform or subtype is involved in each reproductive process by generating individual gene-deficient mice. In late pregnancy, PGF2 alpha synthesized by COX-1 is essential for induction of parturition via luteolysis. Furthermore, impaired induction of COX-2 in the myometrium of PGF2 alpha receptor-deficient mice is accompanied with loss of parturition, suggesting that COX-2 is presumably responsible for producing uterotonic PGs. In early pregnancy, PGE2 synthesized by COX-2 induces the expansion of cumulus cells through EP2 receptor and contributes to ovulation and fertilization. These results may be useful in not only developing novel drugs in the reproductive area but also understanding and overcoming harmful reproductive side effects of classical and novel drugs in non-reproductive areas.
Animals↗
[Endogenous prostaglandins and angiogenesis].
Angiogenesis is a process involved in several physiological events including embryonic development, female reproductive cycle placentation and wound repair. It also plays a part in various pathological conditions such as tumor growth, diabetic retinopathy and rheumatoid arthritis. Angiogenesis is a very complex multistep process involving a variety of biologically active substances, among which are the prostaglandins (PGs), which can induce several growth factors and proliferation of endothelial cells in vitro and in vivo. Angiogenesis is reportedly enhanced by prostaglandins (PGs). We investigated whether or not COX-2 mediated angiogenesis in chronic and proliferate granuloma. In rat sponge implants, angiogenesis was gradually developed over a 14-day experimental period as granuloma formed. In sponge granuloma, mRNA of COX-1 was constitutively expressed, whereas that of COX-2 was increased with neovascularization in parallel with the increased expression of vascular endothelial growth factor (VEGF). bFGF-stimulated angiogenesis was inhibited by indomethacin or a selective COX-2 inhibitor, NS-398. These results suggested that endogenous PGs generated through COX-2 may enhance the neovascularization in sponge granuloma by increased expression of VEGF and that a COX-2 inhibitor would facilitate the management of conditions involving angiogenesis.
Animals↗
Pharmacological properties of the potent epileptogenic amino acid dysiherbaine, a novel glutamate receptor agonist isolated from the marine sponge Dysidea herbacea.
Dysiherbaine (DH) is a marine sponge-derived amino acid that causes seizures upon injection into mice. In this report we investigate the behavioral effects and characterize the pharmacological activity of DH. DH induced convulsive behaviors in mice with ED(50) values of 13 pmol/mouse, i.c.v. and 0.97 mg/kg, i.p. In rat brain synaptic membranes DH displaced binding of [3H]kainic acid (KA) and [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) with K(i) values of 26 and 153 nM, respectively; in contrast, DH did not displace the N-methyl-D-aspartic acid (NMDA) receptor ligand [3H]CGS-19755. DH displaced [3H]KA from recombinant GluR5 and GluR6 kainate receptor subunits expressed in HEK293 cells with K(i) values of 0.74 and 1.2 nM, respectively. In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, DH evoked inward currents from both AMPA and KA receptors with EC(50) values of 9.7 microM and 210 nM, respectively. AMPA receptor currents were blocked by GYKI 53655, whereas KA receptor currents were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Surprisingly, in calcium imaging experiments we found that DH also activated recombinant mGluR5 receptors but did not activate mGluR1 receptors. DH did not activate glutamate transporters or gamma-aminobutyric acid A (GABA(A)) receptors. These results indicate that DH is a potent non-NMDA-type agonist with very high affinity for KA receptors, as well as a subtype-selective mGluR agonist. DH possesses the most potent epileptogenic activity among the amino acids yet identified. This novel excitatory amino acid may prove useful for evaluating the physiological and pathological roles of non-NMDA receptors, especially KA receptors, in the central nervous system.
ATP-Binding Cassette Transporters↗
New insights into mammographic correlations in breast pathology.
Meticulous correlation of mammographic and pathologic findings is essential to improve detection and understanding of the many processes that affect the breast. A review of recent radiologic papers dealing with several breast cancer variants as well as two benign lesions, the radial scar and the breast hamartoma, is presented. Important papers from the pathologic, oncologic, and radiologic literature are reviewed. These papers described the evolving concepts of proliferative breast disease as risk markers, as well as insights into prognostic differences among the histologic subtypes of ductal carcinoma in situ.
Biopsy↗
[Mitotic conditions in different variants of lymphogranulomatosis].
The features of mitotic regimen of lymphogranuloma were established in examinations of 50 involved lymph nodes in patients with lymphogranulomatosis: increased mitotic activity and the number of pathological mitoses from lymphoid prevalence to lymphoid exhaust. In all the types of metaphase was the predominant stage of mitosis. Significant differences were found in the mitotic regimen and various subtypes of nodular sclerosis.
Adolescent↗
The prognostic significance of cervico-vaginal cytology in endometrial cancer.
In patients with endometrial cancer, preoperative identification of certain poor prognostic factors is helpful in planning therapy. To determine the place of cervico-vaginal cytology in this respect, we have studied the relationship between cervico-vaginal cytology and the well-known prognostic factors of endometrial cancer such as grade, myometrial invasion, peritoneal cytology, stage and histological subtype. A hundred and sixty two patients, all of whom underwent surgical therapy in our clinic, were included in this study in order to correlate the cytological results with the pathological findings. Cervico-vaginal cytology was negative in 88 patients (54%), suspicious in 26 patients (16%) and malignant in 48 patients (30%). Twenty four per cent of cases with adenocarcinoma and adenoachantoma, and fifty two per cent of patients with adenosquamous carcinoma, papillary adenocarcinoma and clear cell carcinoma had positive cervicovaginal cytology (p < 0.001). Seventy four per cent of patients with negative cervico-vaginal cytology had grade I tumor, while 5% of patients with negative cytology had grade III tumor. On the other hand, only 9% of patients with positive cervico-vaginal cytology had grade I tumor, while 55% had grade III tumor (p < 0.001). 8% of patients with inner 1/2 myometrial invasion had positive cytology, whereas 51% of patients with 1/2 outer myometrial invasion had malignant cells in their smear (p < 0.001). As for the staging of the endometrial cancer according to FIGO, 19% of patients with Stage I disease had positive cervico-vaginal cytology while 60% of patients in Stage II and 66% of patients in Stage III-IV had positive cytology (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗