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At least 577 records · Page 32Linked to original sources

Is systematic scalene node biopsy in pretreatment evaluation of locally advanced cervical carcinoma necessary? Systematic dissection and histopathology of left scalene node biopsies in patients with locally advanced cervical carcinoma.

OBJECTIVE: Cervical carcinomas mainly spread via lymphatics, stepwise from pelvic to aortic and scalenic lymph nodes. Metastatic nodes are the major prognostic factor in this disease. When scalenic nodes are involved, cervical cancer is considered to be disseminated. Since there is a major discrepancy in reported percentages of metastatic scalene nodes in the literature (0 to 50%), we proceeded to systematic pretreatment scalene node biopsy and then evaluated the validity of this procedure. METHODS: From January 1998 to May 2003, 72 patients with locally advanced cervical carcinoma and no suspicious paraaortic or scalenic nodes (respectively on magnetic resonance imaging and clinically) had a systematic surgical pretreatment lymph node evaluation (retroperitoneal laparoscopic infrarenal paraaortic lymph node dissection and left scalenic lymph node biopsy). Scalene biopsy was examined using hematoxylin/eosin stain and immunohistochemistry (KL1 antibodies). RESULTS: Among the 72 patients, 20 were stage IB2, 4 were IIA, 14 were IIB, 4 were IIIA, 27 were IIIB, 1 was IVA and 2 had a recurrent cervical carcinoma. Fourteen women had histologically confirmed paraaortic metastases (11 macroscopic, 3 microscopic). No metastatic involvement of the scalene nodes was detected. Fifteen patients developed a recurrence within 12 months (3 to 19 months). None of the patients developed scalenic recurrence. CONCLUSION: Left scalene node biopsy does not appear to be mandatory in routine pretherapeutic lymph node evaluation of patients with advanced cervical carcinoma and no clinical suspicious nodes. It may be useful to prove disseminated disease in patients with suspicious clinical nodes or hot spots on PET-scan, if fine needle biopsy is unconclusive.

Adenocarcinoma↗

Systemic preoperative chemotherapy with cisplatin, methotrexate and vinblastine for locally advanced bladder cancer: local tumor response and early followup results.

A total of 44 patients with infiltrating, locally advanced bladder cancer (stages T 3a-b, T 4a-b and N+/N0) were treated with the systemic chemotherapy regimen of cisplatin, methotrexate and vinblastine (CMV) in the neoadjuvant setting, of whom 39 were evaluable for response. After planned radical cystectomy and 2 to 3 cycles of chemotherapy no tumor was found on the pathological specimen of 4 patients (10%), the tumor was downstaged in 19 (49%) and no change was observed in 16 (41%). Toxicity included leukopenia in 29 patients (66%), 1 of whom died of granulocytopenic sepsis, nausea and vomiting in 39 (89%) and mild to moderate mucositis in 18 (41%). Median followup is 12 months with a range of 6 to 39 months. Of 32 patients followed for longer than 6 months 6 (19%) experienced progression or recurrence of disease. We conclude that preoperative CMV chemotherapy is effective in inducing downstaging of the tumor, although systemic toxicity limits its use to cautiously selected patients.

Adult↗

Neoadjuvant chemotherapy for locally advanced transitional cell carcinoma of the bladder: do local findings suggest a potential for salvage of the bladder?

Sixteen patients with locally advanced transitional cell carcinoma of the bladder were given two to four cycles of combination chemotherapy with methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), and cisplatin (M-VAC) in an effort to reduce tumor size and enhance the potential for surgical resection. All patients had initial clinical staging (based on cystoscopy and cystoscopic biopsy, urine cytology, computed tomographic scanning, and excretory urography). Before each cycle, all patients had repeat clinical staging tests. Ten patients underwent postchemotherapy bilateral pelvic lymphadenectomy and radical cystoprostatectomy, and their bladders were examined histopathologically by step-sectioning techniques. One patient underwent abdominal exploration, bilateral pelvic lymphadenectomy, and ipsilateral partial cystectomy. Five patients had repeat clinical staging only without removal of their bladders. Of the 16 patients, 5 (31%) had residual invasive tumor and no tumor response. Three patients (19%) had a partial response, two of whom had only carcinoma in situ (one with prostatic duct involvement) and one of whom had stage pT1, NO, MO disease. Five patients (31%) had normal findings on computed tomographic scans, cystoscopy, biopsy, and urine cytology and thus had complete responses. In addition, 3 of 11 patients who underwent pathologic staging had no residual tumor on clinical and surgical staging and were complete responders. The overall (partial + complete) response rate was 69%, and the overall complete remission rate (pathologic + clinical staging) was 50%. These results suggest that the concept of possible salvage of the bladder with the current treatment program might be premature and must be applied selectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A human short-chain dehydrogenase/reductase gene: structure, chromosomal localization, tissue expression and subcellular localization of its product.

We have previously described the cloning of Hep27, a short-chain dehydrogenase/reductase, which is synthesized in human hepatoblastoma HepG2 cells following growth arrest induced by butyrate treatment. The present report describes the cloning, the structure and the physical and cytogenetic mapping of the gene coding for Hep27. We also show that Hep27 is synthesized in a limited number of human normal tissues and that it is localized in the nuclei and cytoplasm of HepG2 cells.

Alcohol Dehydrogenase↗

Superficial gastric carcinoma developed on localized hypertrophic lymphocytic gastritis: a variant of localized Ménétrier's disease?

Ménétrier's disease is a rare premalignant condition that usually involves the entire stomach. Only few cases of localized disease have been reported, rarely with cancer. Lymphocytic gastritis is a newly described entity that may share a common pathogenesis with Ménétrier's disease. The authors report the case of a 62 year old woman with known liver cirrhosis in whom endoscopic examination of the stomach showed an antral tumor. Examination of the surgical specimen showed a superficial gastric adenocarcinoma developed on an hypertrophic gastropathy with both Ménétrier's disease and lymphocytic gastritis features. This observation strengthens the hypothesis of a common mechanism between Ménétrier's disease and lymphocytic gastritis, which may be part of the same disease spectrum. This disease could also correspond to the "hypertrophic lymphocytic gastritis" recently described.

Adenocarcinoma↗

[Comparative study of the effects of a local antibiotic and a local antiseptic in emergency hand surgery].

An open randomised comparative study was conducted in patients presenting with a hand injury requiring a surgical operation, in order to compare the efficacy of topical application of rifamycin SV with that of iodinated polyvidone dermal solution, in terms of the quality and rate of healing evaluated by the clinician, 268 patients were included in the study and 223 of them participated in the analysis of the results. Analysis of the results demonstrated the following conclusions: signs of infection developed in 8 patients in the rifamycin SV group (7%) and in 20 patients in the iodinated polyvidone group (18.5%). This difference was significant (p = 0.011) in favour of rifamycin SV. The rate of healing was considered to be rapid in 10% of patients in the rifamycin SV group and in 4% of patients in the iodinated polyvidone group. It was considered to be slow in 14% of the subjects in the rifamycin SV group and in 21% of those in the iodinated polyvidone group. This difference was also significant in favour of the rifamycin SV group (p = 0.038). In terms of local tolerance, 32 patients equally distributed between the two treatment groups developed signs of cutaneous intolerance.

Administration, Topical↗

Cloning and cellular localization of the canine progesterone receptor: co-localization with growth hormone in the mammary gland.

The mammary gland has been found to express the gene encoding growth hormone (GH) in several species. Within the mammary gland, it may act as an autocrine/paracrine growth factor for cyclic epithelial changes, and may be a determinant in mammary carcinogenesis. In the dog, progestins enhance mammary GH expression. To elucidate the mechanism of progestin-induced mammary GH expression, the canine progesterone receptor (PR) is characterized and the cellular localization of the PR in normal and tumorous mammary tissues is examined. Sequence analysis of the canine PR revealed two in-frame ATG codons, encoding a putative PR-B protein of 939 amino acids and a putative PR-A protein of 765 amino acids. Western blot analysis indicated that both isoforms occur in uterus and mammary gland issues. Immunohistochemical analysis of the PR revealed that the PR was differentially expressed in mammary tissue, with many PR-positive epithelial cells in the proliferation phase of the glandular tissue and a low number of PR-positive cells in differentiated mammary tissue. Stromal and myoepithelial cells had no specific PR staining. Mammary tumours had a variety of staining patterns, including no staining, normal nuclear staining, marked heterogeneous immunoreactivity and perinuclear staining of tumorous epithelial cells and cytoplasmic-staining of spindle cells. Double staining showed that all GH-producing cells were positive for PR, whereas not all PR containing cells stained for GH. It is concluded that the activated PR may transactivate GH expression in the mammary gland within the same cell and functions as a pre-requisite transcription factor. However, during malignant transformation this regulation may be lost.

Amino Acid Sequence↗

Management of high-risk localized prostate cancer: the integration of local and systemic therapy approaches.

Using a combination of PSA, Gleason score, and clinical stage, it is possible to identify a group of patients with prostate cancer who have a high risk of relapse following initial treatment (e.g., radiotherapy or radical prostatectomy). For these patients, multi-modal therapy may result in improved outcomes. We reviewed published literature to identify methods to identify high-risk patients as well as options for adjuvant or neoadjuvant therapy to reduce risk of disease recurrence. At the present time, the most promising adjuvant therapy is hormonal therapy following radiotherapy for locally advanced disease (T3-T4, or N1). In phase III trials in these patients, survival is improved. For all other applications, including adjuvant and neoadjuvant hormonal therapy, chemotherapy, or radiotherapy, the benefits are unclear. Perhaps most promising at this time, and the subject of a current phase III trial, is the utility of adjuvant chemotherapy in high-risk patients. It will be through the conduct of phase III trials that the benefits of multi-modal therapy will be evaluated. Patients with high-risk prostate cancer undergoing radiotherapy or surgery should be offered participation in these clinical trials.

Adenocarcinoma↗

Spike cluster analysis in neocortical localization related epilepsy yields clinically significant equivalent source localization results in magnetoencephalogram (MEG).

OBJECTIVE: In magnetoencephalogram (MEG) recordings of patients with epilepsy several types of sharp transients with different spatiotemporal distributions are commonly present. Our objective was to develop a computer based method to identify and classify groups of epileptiform spikes, as well as other transients, in order to improve the characterization of irritative areas in the brain of epileptic patients. METHODS: MEG data centered on selected spikes were stored in signal matrices of C channels by T time samples. The matrices were normalized and euclidean distances between spike representations in vector space R(CxT) were input to a Ward's hierarchical clustering algorithm. RESULTS: The method was applied to MEG data from 4 patients with localization-related epilepsy. For each patient, distinct spike subpopulations were found with clearly different topographical field maps. Inverse computations to selected spike subaverages yielded source solutions in agreement with seizure classification and location of structural lesions, if present, on magnetic resonance images. CONCLUSIONS: With the proposed method a reliable categorization of epileptiform spikes is obtained, that can be applied in an automatic way. Computation of subaverages of similar spikes enhances the signal-to-noise ratio of spike field maps and allows for more accurate reconstruction of sources generating the epileptiform discharges.

Adult↗

ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals.

ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones. Upon ER stress, ATF6 translocates from the ER to the Golgi where it is processed to its active form. We have found that the ER chaperone BiP/GRP78 binds ATF6 and dissociates in response to ER stress. Loss of BiP binding correlates with the translocation of ATF6 to the Golgi, which was slowed in cells overexpressing BiP. Two Golgi localization signals (GLSs) were identified in ATF6. Removal of BiP binding sites from ATF6, while retaining a GLS, resulted in its constitutive translocation to the Golgi. These results suggest that BiP retains ATF6 in the ER by inhibiting its GLSs and that dissociation of BiP during ER stress allows ATF6 to be transported to the Golgi.

3T3 Cells↗

Local knowledge and attitudes about onchocerciasis in Oji-River local government area of Enugu State, Nigeria.

A total of 556 individuals in Agbalenyi Community of Oji-River local government area of Enugu State, Nigeria were studied using questionnaires, focus group discussions and key informant interviews to determine the socio-cultural factors affecting the transmission of onchocerciasis. The result revealed a low level of knowledge about the cause, prevention and complications of onchocerciasis. Respondents have developed a cultural system around the disease due to long exposure. The majority are aware of the disease which they recognize once their body starts itching or musculoskeletal pain develops but only 64.4, 34.0, 1.4 and 3.6%, respectively attributed chronic itching, nodules, bad vision and leopard skin to blackfly bite. Other perceived causes mentioned include ageing, the type of food eaten, farm work and 'bad blood'. Only 0.8% knew diagnosis could be made through skin snips. Neither Oji-River nor any of the river systems were associated with any of the complications of onchocerciasis. Significant differences in most socio-demographic characteristics were associated with differences in the level of knowledge about the disease.

Adolescent↗

Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.

Animals↗

Localization of the histidine kinase PilS to the poles of Pseudomonas aeruginosa and identification of a localization domain.

Transcription of the type IV pilus subunit gene of Pseudomonas aeruginosa is controlled by a two-component signal transduction system. PilS, the histidine kinase, is membrane bound and PilR, its cognate response regulator, is cytoplasmic. The signal that activates PilS is unknown. PilS has three domains: (i) The N-terminus, predicted to form six transmembrane (TM) helices; (ii) a central linker domain; and (iii) the C-terminal transmitter domain containing all the conserved residues of sensor kinases. A translational fusion of the gfp gene (green fluorescent protein) to the 3' end of pilS was used to determine the position of PilS in the bacterial cell. Epifluorescence microscopy revealed that PilS is retained to the poles of P. aeruginosa but is distributed evenly about the membrane of Escherichia coli. Deletions of the PilS-GFP fusion revealed that the TM domain was sufficient and necessary to bring GFP to the membrane of P. aeruginosa and E. coli but was not sufficient to confine GFP to the poles. Retention to the poles of P. aeruginosa required both the TM and linker domains. Replacement of the PilS TM domain with an E. coli membrane protein, MalG, still allowed polar localization. Therefore, the PilS TM domain positions the linker domain close to the membrane allowing it to interact with the putative polar anchor which is specific to P. aeruginosa.

Bacterial Proteins↗

PKD2 interacts and co-localizes with mDia1 to mitotic spindles of dividing cells: role of mDia1 IN PKD2 localization to mitotic spindles.

Mutations in pkd2 result in the type 2 form of autosomal dominant polycystic kidney disease, which accounts for approximately 15% of all cases of the disease. PKD2, the protein product of pkd2, belongs to the transient receptor potential superfamily of cation channels, and it can function as a mechanosensitive channel in the primary cilium of kidney cells, an intracellular Ca(2+) release channel in the endoplasmic reticulum, and/or a nonselective cation channel in the plasma membrane. We have identified mDia1/Drf1 (mammalian Diaphanous or Diaphanous-related formin 1 protein) as a PKD2-interacting protein by yeast two-hybrid screen. mDia1 is a member of the RhoA GTPase-binding formin homology protein family that participates in cytoskeletal organization, cytokinesis, and signal transduction. We show that mDia1 and PKD2 interact in native and in transfected cells, and binding is mediated by the cytoplasmic C terminus of PKD2 binding to the mDia1 N terminus. The interaction is more prevalent in dividing cells in which endogenous PKD2 and mDia1 co-localize to the mitotic spindles. RNA interference experiments reveal that endogenous mDia1 knockdown in HeLa cells results in the loss of PKD2 from mitotic spindles and alters intracellular Ca(2+) release. Our results suggest that mDia1 facilitates the movement of PKD2 to a centralized position during cell division and has a positive effect on intracellular Ca(2+) release during mitosis. This may be important to ensure equal segregation of PKD2 to the daughter cell to maintain a necessary level of channel activity. Alternatively, PKD2 channel activity may be important in the cell division process or in cell fate decisions after division.

Animals↗

Subcellular localization of sterol carrier protein-2 in rat hepatocytes: its primary localization to peroxisomes.

Sterol carrier protein-2 (SCP-2) is a nonenzymatic protein of 13.5 kD which has been shown in in vitro experiments to be required for several stages in cholesterol utilization and biosynthesis. The subcellular localization of SCP-2 has not been definitively established. Using affinity-purified rabbit polyclonal antibodies against electrophoretically pure SCP-2 from rat liver, we demonstrate by immunoelectron microscopic labeling of ultrathin frozen sections of rat liver that the largest concentration of SCP-2 is inside peroxisomes. In addition the immunolabeling indicates that there are significant concentrations of SCP-2 inside mitochondria, and associated with the endoplasmic reticulum and the cytosol, but not inside the Golgi apparatus, lysosomes, or the nucleus. These results were confirmed by immunoblotting experiments with proteins from purified subcellular fractions of the rat liver cells carried out with the anti-SCP-2 antibodies. The large concentration of SCP-2 inside peroxisomes strongly supports the proposal that peroxisomes are critical sites of cholesterol utilization and biosynthesis. The presence of SCP-2 inside peroxisomes and mitochondria raises questions about the mechanisms involved in the differential targeting of SCP-2 to these organelles.

Animals↗

Mapping of local cerebral functional activity by measurement of local cerebral glucose utilization with [14C]deoxyglucose.

A method has been developed to measure the rates of glucose utilization in the individual structural and functional components of the central nervous system. It can be applied to conscious as well as anaesthetized animals. The method is based on the use of [14C]deoxyglucose as a tracer for glucose consumption. [14C]Deoxyglucose-6-phosphate accumulates in the tissue in a mathematically definable relationship to the rate of the tissue's glucose utilization. The [14C]deoxyglucose-6-phosphate concentrations in the various tissues of the nervous system are measured by a quantitative autoradiographic technique. The autoradiographs themselves are pictorial representations of the relative rates of glucose consumption in these tissues. Application of this method to rats and monkeys in various states of altered function demonstrates a clear and close relationship between the local levels of functional activity and energy metabolism. The method appears to be useful for mapping functional neural pathways on the basis of evoked metabolic responses (Plum, Gjedde and Samson, 1976).

Animals↗

Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex.

SNAT1 mediates glutamine (Gln) influx into neurons and is believed to replenish the transmitters pools of glutamate (Glu) and gamma-aminobutyric acid (GABA). We investigated its distribution and cellular localization in the cerebral cortex and neighboring regions of rats and humans using light and electron microscopic immunocytochemical methods with specific antibodies. In the first somatic sensory cortex of rats and in areas 9, 10, 21 and 46 of the human cortex, numerous SNAT1-positive (+) cells were present in the cortical parenchyma and in the white matter; >95% of SNAT1+ cells were neurons, but some were astrocytes. Most SNAT1+ cells were pyramidal neurons, but numerous non-pyramidal neurons were also observed: SNAT1/GABA double-labeling studies showed that SNAT1 is expressed in all GABA+ neurons. SNAT1/synaptophysin studies showed that <0.1% of all synaptophysin+ puncta coexpressed SNAT1. SNAT1 immunoreactivity (ir) was also in leptomeninges, ependymal cells and choroid plexus. Electron microscopic studies showed that neuronal SNAT1 ir was almost exclusively observed in perikarya and dendritic profiles. SNAT1 ir was also in distal astrocytic processes, including end feet profiles, and in leptomeninges. These findings suggest that the major function of SNAT1 is not to replenish the transmitter pools of Glu and GABA.

Amino Acid Transport System X-AG↗

cDNA cloning of nuclear localization signal binding protein NBP60, a rat homologue of lamin B receptor, and identification of binding sites of human lamin B receptor for nuclear localization signals and chromatin.

We previously purified and characterized a nuclear localization signal (NLS) binding protein, NBP60, in rat liver nuclear envelopes. In this study, we cloned and sequenced the cDNA of rat NBP60, and predicted an amino acid sequence comprising 620 amino acids. The sequence revealed that NBP60 is a rat homologue of lamin B receptor (LBR), and is 79 and 63% identical in amino acids to human and chicken LBR, respectively. Using three fusion proteins containing different parts of the amino-terminal domain of human LBR, it was shown that the stretch comprising amino acids 1 to 89, which contains a Ser-Arg rich region (RS region), binds to nucleoplasmin and that the binding was inhibited by a common NLS-peptide. These results suggested that the amino-terminal domain of LBR contains an NLS-binding site. Furthermore, it was shown that the stretch comprising amino acids 1 to 53, which does not contain the RS region or the predicted DNA-binding site, binds to Xenopus laevis sperm chromatin.

Amino Acid Sequence↗