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M J Edwards

Publications and source records attributed to M J Edwards.

At least 55 records · Page 3Linked to original sources
PubMed2001

Accuracy of sentinel lymph node biopsy for patients with T2 and T3 breast cancers.

Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.

Breast Neoplasms↗
PubMed2000

Two influenza A virus-specific Fabs neutralize by inhibiting virus attachment to target cells, while neutralization by their IgGs is complex and occurs simultaneously through fusion inhibition and attachment inhibition.

Mabs H36 (IgG2a) and H37 (IgG3) recognize epitopes in antigenic sites Sb and Ca2, respectively, in the HA1 subunit of influenza virus A/PR/8/34 (H1N1). Their neutralization was complex. Our aim here was to investigate the mechanism of neutralization by the IgGs and their Fabs. In MDCK and BHK cells, both IgGs neutralized primarily by inhibiting virus-cell fusion, although at higher IgG concentrations virus attachment to target cells was also inhibited. In contrast, the Fabs neutralized entirely by inhibiting virus attachment, although a higher concentration of Fab than IgG was required to bring this about. Both H36 and H37 exerted a concentration-dependent spectrum of neutralization activity, with virus-cell fusion inhibition and virus-cell attachment inhibition being the predominant mechanisms at low- and high-antibody concentration, respectively, and both mechanisms occurring simultaneously at intermediate concentrations. However, it may be that attachment inhibition was a secondary event, occurring to virus that had already been neutralized through inhibition of its fusion activity. Neutralization by H36 and H37 Fabs was a simple process. Both inhibited virus attachment but required much higher (>100-fold) molar concentrations for activity than did IgG. The functional affinities of the IgGs were high (0.4-0.6 nM) and differences between these and the affinity of their Fabs (H36, nil; H37, 23-fold) were not sufficient to explain the differences observed in neutralization. Similar neutralization data were obtained in two different cell lines. The dose-response curve for neutralization by H36 F(ab')(2) resembled that for IgG, although eightfold more F(ab')(2) was required for 50% neutralization. Overall, neutralization mechanisms of H36 and H37 antibodies were similar, and thus independent of antigenic site, antibody isotype, and target cell.

Animals↗
PubMed2000

Herrmann multiple synostosis syndrome with neurological complications caused by spinal canal stenosis.

A young man was found to have multiple synostosis syndrome type I after presenting with a neck injury causing a cervical spinal cord contusion. Neurological symptoms and signs suggested spinal cord compression. Magnetic resonance (MR) and computerized tomography (CT) imaging of the spine showed spinal canal stenosis with cord compression at C3-C6, a deformed spinal canal flattened in the anteroposterior dimension, vertebral fusions and deformed lateral processes of the vertebrae. He had a long broad nose with hypoplasia of the alae nasi, conductive hearing loss requiring hearing aids, muscular build, stiff spine, prominent acromia, pectus excavatum, ischial prominences, short fifth fingers, fusion at the proximal interphalangeal joints of the fifth fingers with indistinct overlying creases, and toe syndactyly. Spinal cord stenosis is a serious complication of multiple synostosis syndrome, that should be kept in mind in considering the risk of neck or back injury associated with certain sports or other activities. In both the multiple synostosis syndrome and the less severe proximal symphalangism deafness syndrome, mutations have been detected in the human homologue of the noggin gene on chromosome 17q21-q22.

Abnormalities, Multiple↗
PubMed2000

Robust gut-specific gene expression in transgenic Aedes aegypti mosquitoes.

Genetic modification of the vectorial capacity of mosquito vectors of human disease requires promoters capable of driving gene expression with appropriate tissue and stage specificity. We report on the characterization in transgenic Aedes aegypti of two mosquito gut-specific promoters. A 1.4-kb DNA fragment adjacent to the 5' end of the coding region of the Ae. aegypti carboxypeptidase (AeCP) gene and a corresponding 3.4-kb DNA fragment at the 5' end of the Anopheles gambiae carboxypeptidase (AgCP) gene were linked to a firefly luciferase reporter gene and introduced into the Ae. aegypti germ line by using Hermes and mariner (Mos1) transposons. Six independent transgenic lines were obtained with the AeCP construct and one with the AgCP construct. Luciferase mRNA and protein were abundantly expressed in the guts of transgenic mosquitoes in four of the six AeCP lines and in the AgCP line. Expression of the reporter gene was gut-specific and reached peak levels at about 24 h post-blood ingestion. The AeCP and AgCP promoters can be used to drive the expression of genes that hinder parasite development in the mosquito gut.

Aedes↗
PubMed2000

Esophageal dysmotility in brothers with an FG-like syndrome.

We present 4 brothers with developmental delay, minor anomalies, and symptoms due to gastrointestinal dysmotility. There was some resemblance with FG syndrome, although none of the brothers had sufficient findings to make this diagnosis. The index case presented with at age 1 month with screaming episodes, mild gastro-esophageal reflux (GER), and severe constipation. Esophageal manometry studies were consistent with the diagnosis of "nutcracker esophagus." Symptomatic and manometric improvement followed treatment with oral calcium channel blockers. Two older and less severely affected brothers had similar manometric findings but did not require treatment. A fourth brother with symptoms in infancy now has normal esophageal manometry findings. These boys in all likelihood have an X-linked syndrome with manifestations of FG syndrome, in which treatment with calcium channel blockers, produces clinical and manometric improvement. The FG syndrome is an X-linked syndrome of multiple congenital anomalies/mental retardation with facultative manifestations of gastrointestinal dysmotility, including gastro-esophageal reflux, severe feeding difficulties, and constipation. Esophageal dysmotility, in particular "nutcracker esophagus," should be suspected in infants with the FG syndrome and screaming attacks.

Abnormalities, Multiple↗
PubMed2000

Basosquamous carcinoma: analysis of prognostic factors influencing recurrence.

BACKGROUND: Basosquamous carcinoma is a rare malignancy, with features of both basal cell carcinoma and squamous cell carcinoma. Some authors believe that basosquamous carcinoma merely is a variant of basal cell carcinoma, whereas others have suggested that basosquamous carcinoma may behave more aggressively. To the authors' knowledge the largest published series to date, comprised of 35 cases, was reported >20 years ago. The authors reviewed their recent experience with basosquamous carcinoma to identify prognostic factors influencing recurrence. METHODS: The medical records of all patients with the diagnosis of basosquamous carcinoma treated at the University of Louisville-affiliated hospitals between 1985-1988 were reviewed by a senior pathologist. Prognostic factors were analyzed using Cox regression analysis and the log rank test. RESULTS: Thirty-one cases of basosquamous carcinoma were identified in 28 patients. The median age at diagnosis was 68 years (range, 10-94 years). The median follow-up was 60 months (range, 12-312 months). Seventy-five percent of cases were located on the face, neck, and scalp. One patient had regional lymph node metastasis synchronous with the primary tumor. Patterns of recurrence were: local recurrence only (five patients), local recurrence plus regional lymph nodes (three patients), and pulmonary plus regional lymph nodes (one patient). One patient died of pulmonary metastasis. Significant factors predictive of recurrence (P<0.01) were male gender, positive surgical resection margin, lymphatic invasion, and perineural invasion. Although tumor size was not a statistically significant factor overall (P = 0.076), the 3 patients with lymph node metastases had large tumors (measuring 2 cm, 5 cm, and 5 cm, respectively). CONCLUSIONS: Basosquamous carcinoma is an aggressive epithelial neoplasm with a propensity for local recurrence and potential for distant metastatic spread. This behavior differs substantially from basal cell carcinoma. Complete resection with negative surgical margins is essential. Long term follow-up for the detection of local recurrence and distant metastatic spread is recommended.

Adolescent↗
PubMed2000

Vascular problems of the pelvis.

Vascular tumors of the pelvis are a rare, diverse group of neoplasms. These benign or malignant tumors can arise from the endothelium, smooth muscle cells, or pericytes of the arterial venous or lymphatic walls. They are rarely diagnosed by physical examination but more commonly seen with imaging studies such as computed tomography, magnetic resonance imaging, or angiography. Benign and malignant tumors can be differentiated pathologically by the two major anatomic characteristics of vascular channel formation and the regularity of endothelial cell proliferation. This review will focus on the clinical presentation, diagnosis, treatment, outcomes, and surgical approaches to benign and malignant vascular tumors of the pelvis.

Angiography↗
PubMed2000

Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory role of STAT6.

OBJECTIVE AND DESIGN: The ability of interleukin-4 (IL-4) to modulate activation of the transcription factors, NF-kappaB and STAT6, reduce proinflammatory cytokine expression and protect against liver injury induced by ischemia/reperfusion was assessed. MATERIALS AND SUBJECTS: C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by 1 or 8 h of reperfusion with or without intravenous administration of 1 microg (0.5 microg just prior to ischemia, 0.5 microg at reperfusion) recombinant murine IL-4. Liver expression of TNFalpha mRNA was determined by RT-PCR. Activation of NF-kappaB and STAT6 in liver nuclear extracts was assessed by mobility shift assay. RESULTS: Hepatic ischemia/reperfusion increased hepatic expression of tumor necrosis factor-alpha (TNFalpha), induced significant neutrophil accumulation and liver injury. Treatment with IL-4 greatly suppressed liver TNFalpha mRNA expression, neutrophil accumulation and liver injury. IL-4 had no effect on liver NF-kappaB activation, but greatly increased the activation of STAT6. CONCLUSIONS: The data suggest that STAT6 activation by IL-4 may be responsible for the protective effects of this cytokine.

Animals↗
PubMed2000

Regulation of liver inflammatory injury by signal transducer and activator of transcription-6.

Liver injury induced by hepatic ischemia/reperfusion is characterized by activation of the transcription factor NF-kappaB, increased production of tumor necrosis factor-alpha (TNFalpha), liver neutrophil accumulation, and hepatocellular damage. Exogenous administration of interleukin-4 (IL-4) or IL-13 was recently shown to regulate this inflammatory injury in association with activation of signal transducer and activator of transcription-6 (STAT6). The objective of the present study was to determine whether STAT6 was required for the regulation of liver inflammation by IL-4 and IL-13. Wild-type and STAT6 knockout mice underwent 90 minutes of hepatic ischemia followed by 8 hours of reperfusion. Hepatic ischemia/reperfusion in wild-type and STAT6 knockout mice significantly increased (P < 0.05) NF-kappaB activation, serum levels of TNFalpha, liver accumulation of neutrophils [measured by myeloperoxidase (MPO) content], and hepatocellular damage [measured by serum alanine aminotransferase (ALT)] compared to sham controls. In wild-type mice, activation of STAT6 was not observed after ischemia/reperfusion. Administration of 1 microg of IL-4 or IL-13 at reperfusion reduced serum TNFalpha, liver neutrophil accumulation, and hepatocellular injury in wild-type mice. Treatment with IL-4 or IL-13 had no effect on liver NF-kappaB activation but significantly increased activation of STAT6. In STAT6 knockout mice, neither IL-4 nor IL-13 had any effect on TNFalpha, MPO, or ALT values, the regulatory effects of these cytokines being completely abolished. The data suggest that activation of STAT6 may regulate liver inflammatory injury.

Animals↗
PubMed2000

State-of-the-art lymph node staging for breast cancer in the year 2000.

Axillary staging for breast cancer is vitally important for determining appropriate adjuvant hormone and chemotherapy. In the absence of distant metastases, axillary lymph node status remains the most accurate predictor of clinical outcome. Sentinel lymph node biopsy is a minimally invasive approach with enhanced accuracy and less morbidity than conventional axillary dissection. The stage is now set for the sentinel lymphadenectomy staging to move from state-of-the-art care to the standard care in coming years.

Axilla↗
PubMed2000

Credentialing issues with sentinel lymph node staging for breast cancer.

Sentinel lymphadenectomy (SL) is a minimally invasive approach for staging patients with breast cancer. SL, when performed in lieu of axillary dissection, is associated with less morbidity and is potentially more cost effective and more accurate than the historical axillary dissection in the detection of regional nodal metastases. The credentialing and privileging of SL, as with any surgical procedure, is by the policies of the local hospital or institution. The suggested credentialing criteria for local hospitals has been an area of controversy. Herein the authors outline the credentialing controversy and suggest criteria for the implementation of sentinel lymph node staging for breast cancer.

Breast↗
PubMed2000

The details of successful sentinel lymph node staging for breast cancer.

Sentinel lymphadenectomy is an effective and accurate tool for staging breast cancer. In recent years the details of a successful program have become better defined. The authors outline practical considerations for the performance of successful sentinel lymph node staging from a multidisciplinary perspective.

Breast Neoplasms↗
PubMed2000

Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and renders liver susceptible to hepatic ischemia/reperfusion.

BACKGROUND/AIMS: Obstructive jaundice is associated with increased surgical morbidity and mortality. While parenchymal injury has been defined in obstructive jaundice, the pathogenesis of hepatic sinusoidal endothelial cell injury in obstructive jaundice is unclear. The aims of this study were to investigate hepatic sinusoidal endothelial cell injury in obstructive jaundice by determining serum hyaluronic acid levels, purine nucleoside phosphorylase/alanine aminotransferase ratios, and hyaluronic acid elimination rate, and also to determine whether hepatic parenchymal cell injury in obstructive jaundice is induced more than in normal liver after hepatic ischemia/reperfusion. METHODS: Male Wistar rats underwent ligation and division of the common bile duct (obstructive jaundice group) or sham operation (Sham group). Serum hyaluronic acid levels and purine nucleoside phosphorylase/alanine aminotransferase ratios in both groups were examined at intervals up to 21 days after surgery. Hepatic blood flow, permeability, neutrophil accumulation, and hyaluronic acid elimination rates in both groups were measured 14 days after surgery. Changes in serum hyaluronic acid and alanine aminotransferase concentrations were determined after 15 min of hepatic ischemia followed by reperfusion. RESULTS: Serum hyaluronic acid levels remained elevated after bile duct ligation. Hepatic sinusoidal endothelial cell swelling was observed by electron microscopy, and hepatic permeability was increased 14 days after bile duct ligation in association with neutrophil accumulation. Hepatic blood flow in obstructive jaundice remained unchanged, but hyaluronic acid elimination capacity was less than that in the Sham group. After hepatic reperfusion, the disappearance rate of serum hyaluronic acid in obstructive jaundice was lower, and serum alanine aminotransferase levels were higher than those in the Sham group. CONCLUSIONS: Our findings suggest that obstructive jaundice impairs sinusoidal endothelial cells and that sinusoidal endothelial cell damage in association with sinusoidal deterioration during obstructive jaundice renders liver susceptible to ischemia/reperfusion relative to normal liver.

Animals↗
PubMed2000

The journey of the malaria parasite in the mosquito: hopes for the new century.

In this review, Anil Ghosh, Marten Edwards and Marcelo Jacobs-Lorena follow the journey of the Plasmodium parasite in the mosquito vector. At each developmental step, they highlight some of the major unanswered questions currently challenging cell and molecular biologists. A more thorough understanding of Plasmodium-mosquito interactions might lead to the development of mosquitoes unable to support parasite development.

Animals↗
PubMed2000

Characterization of a carboxypeptidase A gene from the mosquito, Aedes aegypti.

A gut-specific carboxypeptidase A gene (AeCPA) from the mosquito, Aedes aegypti, was cloned and characterized. The gene has an open reading frame that predicts a protein of 427 amino acids, 61% of which are identical to an Anopheles gambiae carboxypeptidase A sequence. AeCPA messenger RNA (mRNA) was not detected during larval and pupal development. In situ hybridization experiments indicated that AeCPA mRNA is expressed by posterior midgut epithelial cells. In sharp contrast to An. gambiae carboxypeptidase A gene expression, AeCPA mRNA accumulates to high levels only late ( approximately 16-24 h) after ingestion of a blood meal. The temporal profile of AeCPA gene induction is similar to that of Ae. aegypti late trypsin, suggesting the existence of common regulatory elements.

Aedes↗
PubMed2000

A gut-specific serine protease from the malaria vector Aanopheles gambiae is downregulated after blood ingestion.

A chymotrypsin-like serine protease gene (AgChyL) was cloned from the mosquito Anopheles gambiae by a polymerase chain reaction (PCR)-based subtractive cDNA cloning strategy. AgChyL messenger RNA (mRNA) is abundant in the adult female gut prior to, and for 8 h following, a blood meal. During the peak of digestion, from 12 to 24 h following a blood meal, AgChyL mRNA abundance decreased to barely detectable levels. AgChyL mRNA was abundant again by 48 h following a blood meal. Recombinant pro-AgChyL was expressed in Escherichia coli. The pro-enzyme can be activated by trypsin. Activated AgChyL cleaves the synthetic chymotrypsin substrate succinyl-L-Ala-Ala-Pro-Phe-nitroanilide, but not two other synthetic chymotrypsin substrates or synthetic trypsin and elastase substrates. The potential role of AgChyL in the coordination of An. gambiae digestion is discussed.

Amino Acid Sequence↗
PubMed2000

Protein phosphatase type 1-dependent dephosphorylation of the retinoblastoma tumor suppressor protein in ultraviolet-irradiated human skin and keratinocytes.

This study provides evidence for the involvement of a type 1 protein serine/threonine phosphatase in the ultraviolet radiation-induced dephosphorylation of retinoblastoma tumor suppressor protein in human skin and cultured keratinocytes. The retinoblastoma gene product was localized to the nuclei and nucleoli of keratinocytes, and to the nuclei of basal and spinous layer cells of normal human epidermis. Western blot analysis of the retinoblastoma tumor suppressor protein antigen from keratinocytes and skin established the presence of the hypophosphorylated and hyperphosphorylated forms of retinoblastoma tumor suppressor protein. The exposure of keratinocytes and human skin to 200 J per cm2 of ultraviolet radiation, resulted in a rapid depletion in hyperphosphorylated retinoblastoma tumor suppressor protein, and the accumulation of growth inhibitory hypophosphorylated retinoblastoma tumor suppressor protein(105). In unirradiated and ultraviolet-irradiated keratinocytes retinoblastoma tumor suppressor protein was localized to the spindles of M-phase cells. In contrast, the exposure of keratinocytes to ultraviolet in the presence of 5 mM okadaic acid, resulted in an inhibition of retinoblastoma tumor suppressor protein translocation to the mitotic spindles of M-phase keratinocytes. In addition, the ultraviolet radiation-induced depletion in hyperphosphorylated retinoblastoma tumor suppressor protein, and accumulation of hypophosphorylated retinoblastoma tumor suppressor protein(105) was inhibited by 5 mM okadaic acid. Okadaic acid (0.5 nM), however, did not affect the ultraviolet radiation-induced dephosphorylation and depletion of hyperphosphorylation of the retinoblastoma tumor suppressor protein. Western blot analysis of ultraviolet-irradiated keratinocytes demonstrated that the hypophosphorylated growth inhibitory 105 kDa form of retinoblastoma tumor suppressor protein coimmunoprecipitated with the 38 kDa catalytic subunit of a type 1 protein serine/threonine phosphatase.

Blotting, Western↗