Biomedical subjects

Jennifer Schwartz

Publications and source records attributed to Jennifer Schwartz.

4 recordsLinked to original sources

PubMed2006

Structure of phosphorylated enzyme I, the phosphoenolpyruvate:sugar phosphotransferase system sugar translocation signal protein.

Bacterial transport of many sugars, coupled to their phosphorylation, is carried out by the phosphoenolpyruvate (PEP):sugar phosphotransferase system and involves five phosphoryl group transfer reactions. Sugar translocation initiates with the Mg(2+)-dependent phosphorylation of enzyme I (EI) by PEP. Crystals of Escherichia coli EI were obtained by mixing the protein with Mg(2+) and PEP, followed by oxalate, an EI inhibitor. The crystal structure reveals a dimeric protein where each subunit comprises three domains: a domain that binds the partner PEP:sugar phosphotransferase system protein, HPr; a domain that carries the phosphorylated histidine residue, His-189; and a PEP-binding domain. The PEP-binding site is occupied by Mg(2+) and oxalate, and the phosphorylated His-189 is in-line for phosphotransfer to/from the ligand. Thus, the structure represents an enzyme intermediate just after phosphotransfer from PEP and before a conformational transition that brings His-189 approximately P in proximity to the phosphoryl group acceptor, His-15 of HPr. A model of this conformational transition is proposed whereby swiveling around an alpha-helical linker disengages the His domain from the PEP-binding domain. Assuming that HPr binds to the HPr-binding domain as observed by NMR spectroscopy of an EI fragment, a rotation around two linker segments orients the His domain relative to the HPr-binding domain so that His-189 approximately P and His-15 are appropriately stationed for an in-line phosphotransfer reaction.

Binding Sites↗

PubMed2004

EGF gene polymorphism and the risk of incident primary melanoma.

Overexpression of the epidermal growth factor (EGF) pathway has been implicated in melanoma pathogenesis, and a recent case-control study identified a single nucleotide polymorphism (G to A) in the EGF gene where the G allele was associated with increased EGF expression and an increased risk of melanoma. To further evaluate this association, we conducted a case-control analysis from the Genes, Environment, and Melanoma study at the University of Michigan site using two different study designs. Incident cases of histopathologically confirmed first primary melanoma that were diagnosed between January 1, 2000 and December 31, 2000 from the University of Michigan Melanoma Clinic (n = 330) were compared with the following two different sources of nonmelanoma controls: spouse/friend controls (n = 84) and healthy volunteer controls from a case-control study of psoriasis (n = 148). Using a second analytic design, comparisons between multiple primary melanoma cases (n = 62) and single primary melanoma cases (n = 330) were also evaluated to estimate odds ratios (ORs). Genotyping for the single nucleotide substitution (G to A) at position 61 in the 5' untranslated region of the EGF gene was performed from genomic DNA, and epidemiological risk factors were assessed through a telephone interview. When EGF genotypes were compared between incident primary melanoma cases and the nonmelanoma controls, the risk associated with the homozygous G/G genotype was not statistically significantly associated with an increased risk for incident primary melanoma compared with the homozygous A/A genotype [OR, 1.09; 95% confidence interval (CI); 0.65-1.85]. No strong associations with EGF G/G genotype were observed in comparisons of multiple primary and single primary melanoma cases (OR, 0.66; 95% CI; 0.25-1.73). Case subjects with tumors >/=3.5 mm compared with those <3.5 mm were not significantly associated with the G/G genotype (OR, 0.54; 95% CI; 0.12-2.35). Our data do not support a significant association between melanoma and the EGF 61*G allele or the homozygous G/G genotype. The EGF polymorphism is not a reproducible risk factor for melanoma or thick melanoma in our data. The two analytic approaches used in the study provide evidence against a strong association between EGF 61*G and melanoma and demonstrate the potential utility of case-case designs for evaluating the role of single nucleotide polymorphisms and cancer. Additional independent studies will be required to elucidate relationships between genetic variation in the EGF gene and risk of melanoma.

Alleles↗

PubMed2003

Reliability of sentinel lymph node mapping with biopsy for head and neck cutaneous melanoma.

OBJECTIVES: To determine (1) the reliability of sentinel lymph node mapping with biopsy (SLNB) in head and neck cutaneous melanoma to accurately stage nodal basins and (2) the safety of SLNB in both the neck and parotid regions. DESIGN: Retrospective cohort study with a median follow-up of 25 months. All patients had a minimum follow-up of 1 year. SETTING: Academic medical center. PATIENTS: Eighty evaluable patients diagnosed as having head and neck cutaneous melanoma and staged using SLNB. INTERVENTIONS: Sentinel lymph nodes were identified using preoperative lymphoscintigraphy and a combination of intraoperative gamma probe and isosulfan blue dye. Patients with a SLN positive for melanoma underwent therapeutic lymphadenectomy followed by an evaluation for adjuvant therapies. Patients with a negative SLNB result were followed up clinically. MAIN OUTCOME MEASURES: Percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), and procedure complications. RESULTS: The mean Breslow depth was 2.35 mm. A SLN was identified in 77 (96.3%) of cases, with an average of 2.18 nodes per patient. Of the sentinel nodes identified, 74% were from the neck region. The remaining 26% were from the parotid basin. No facial nerve complications occurred. Of the patients, 14 (18%) were SLN positive for metastatic melanoma. The regional failure rate in the setting of a negative SLNB result was 4.5%. CONCLUSIONS: Sentinel lymph node mapping with biopsy is a reliable technique to diagnose regional spread from head and neck cutaneous melanoma. This procedure can be performed in both neck and parotid nodal basins with safety and accuracy similar to non-head and neck sites.

Adolescent↗

PubMedDate not supplied

Current melanoma staging.

American Joint Committee on Cancer (AJCC), TNM staging, represents the cornerstone of management for cutaneous melanoma. This staging system groups patients with similar prognoses and has important implications in optimizing management and treatment and conducting better clinical trials. T describes the extent of the primary tumor, N the extent of regional lymph node metastases, and M the extent of distant metastases. The AJCC staging system for cutaneous melanoma underwent significant revision in 2002. The revised, current AJCC staging system and the TNM classification are detailed in this review.

Humans↗