Cost-effective treatment of women with advanced ovarian cancer by cytoreductive surgery and chemotherapy directed by an in vitro assay for drug resistance.

Purpose: Epithelial ovarian cancer is the fourth leading cause of cancer-related death in women. Five-year survival is about 25%, and new approaches to the treatment of this disease are dearly warranted. This study was designed to determine the feasibility of using an in vitro assay for drug resistance to guide treatment after cytoreductive surgery.

A job-satisfaction measure for internal medicine residency program directors.

Purpose: To develop a job-satisfaction measure that encompasses the multifaceted job of internal medicine residency program directors.

Method: Questions were devised to measure program directors satisfaction with various facets of their jobs. In 1996, the authors surveyed all non-military internal medicine program directors in the United States.

Crystallogenesis studies on yeast aspartyl-tRNA synthetase: use of phase diagram to improve crystal quality.

Aspartyl-tRNA synthetase (AspRS) extracted from yeast is heterogeneous owing to proteolysis of its positively charged N-terminus; its crystals are of poor quality. To overcome this drawback, a rational strategy was developed to grow crystals of sufficient quality for structure determination. The strategy is based on improvement of the protein homogeneity and optimization of crystallization, taking advantage of predictions from crystal-growth theories.

The unexpected result of an investigation of an outbreak of occupational lung disease.

The author describes the discovery of a cluster of cases of interstitial lung disease among employees of a textile manufacturing plant and the difficulties he and his university-hospital occupational medicine team encountered in attempting to identify the cause of the disease. At first accepted in a consultant capacity by the plant's management, the team met increasing resistance to its efforts as it uncovered evidence of a work-related cause of the disease and attempted ientists to communicate findings important to the health of the public, and the physician's overarching professional responsibility to his or her patients.

Attributes of excellent attending-physician role models.

Background: Although effective role models are important in medical education, little is known about the characteristics of physicians who serve as excellent clinical role models. We therefore conducted a case-control study to identify attributes that distinguish such physicians from their colleagues.

Methods: We asked members of the internal-medicine house staff at four teaching hospitals to name physicians whom they considered to be excellent role models.

Relation of low-severity violence to women's health.

Objective: To determine if women who experience low-severity violence differ in numbers of physical symptoms, psychological distress, or substance abuse from women who have never been abused and from women who experience high-severity violence.

Design: Cross-sectional, self-administered, anonymous survey.

Setting: Four community-based, primary care, internal medicine practices.

Thermus thermophilus: a link in evolution of the tRNA-dependent amino acid amidation pathways.

Thermus thermophilus possesses an aspartyl-tRNA synthetase (AspRS2) able to aspartylate efficiently tRNAAsp and tRNAAsn. Aspartate mischarged on tRNAAsn then is converted into asparagine by an omega amidase that differs structurally from all known asparagine synthetases. However, aspartate is not misincorporated into proteins because the binding capacity of aminoacylated tRNAAsn to elongation factor Tu is only conferred by conversion of aspartate into asparagine.

Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry.

Background: Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported previously.

Objective: To define the extent, clinicopathologic features, and potential causes of the apparent disease outbreak.

Activation of thiamin diphosphate in enzymes.

Activation of the coenzyme ThDP was studied by measuring the kinetics of deprotonation at the C2 carbon of thiamin diphosphate in the enzymes pyruvate decarboxylase, transketolase, pyruvate dehydrogenase complex, pyruvate oxidase, in site-specific mutant enzymes and in enzyme complexes containing coenzyme analogues by proton/deuterium exchange detected by 1H-NMR spectroscopy. The respective deprotonation rate constant is above the catalytic constant in all enzymes investigated. The fast deprotonation requires the presence of an activator in pyruvate decarboxylase from yeast, showing the allosteric regulation of this enzyme to be accomplished by an increase in the C2-H dissociation rate of the enzyme-bound thiamin diphosphate.

Glycyl-tRNA synthetase from Thermus thermophilus--wide structural divergence with other prokaryotic glycyl-tRNA synthetases and functional inter-relation with prokaryotic and eukaryotic glycylation systems.

The tRNA glycylation system is amongst the most complex aminoacylation systems since neither the oligomeric structure of the enzymes nor the discriminator base in tRNAs are conserved in the phylae. To understand better this structural diversity and its functional consequences, the prokaryotic glycylation system from Thermus thermophilus, an extreme thermophile, was investigated and its structural and functional inter-relations with those of other origins analyzed. Alignments of the protein sequence of the dimeric thermophilic glycyl-tRNA synthetase (Gly-tRNA synthetase) derived from its gene with sequences of other dimeric Gly-tRNA synthetases revealed an atypical character of motif 1 in all these class 2 synthetases.

Analysis of T-cell receptor gene rearrangement in lymph nodes of patients with mycosis fungoides. Prognostic implications.

Objective: To determine the prognostic value of analyzing lymph node (LN) DNA from patients with mycosis fungoides for the presence of a monoclonal T-cell population.

Design: Inception cohort study.

Setting: A tertiary care referral center in Seattle, Wash.

Heterogeneity of drug resistance in human breast and ovarian cancers.

Purpose: This study quantitates the extent of heterogeneity of drug resistance in breast and ovarian cancers. Identification of drug-specific resistance in tumors from multiple sites provides information necessary to understand the unique biology of a patient's disease.

Materials And Methods: Drug resistance to cisplatin, paclitaxel, and doxorubicin was measured in multiple synchronous or metachronous tumors using the extreme drug resistance (EDR) assay.

Structural and functional analyses of activating amino acid substitutions in the receiver domain of NtrC: evidence for an activating surface.

The bacterial enhancer-binding protein NtrC activates transcription when phosphorylated on aspartate 54 in its amino (N)-terminal regulatory domain or when altered by constitutively activating amino acid substitutions. The N-terminal domain of NtrC, which acts positively on the remainder of the protein, is homologous to a large family of signal transduction domains called receiver domains. Phosphorylation of an aspartate residue in a receiver domain modulates the function of a downstream target, but the accompanying structural changes are not clear.

Existence of two distinct aspartyl-tRNA synthetases in Thermus thermophilus. Structural and biochemical properties of the two enzymes.

Two aspartyl-tRNA synthetases (AspRSs) were isolated from Thermus thermophilus HB8. Both are alpha2 dimers but differ in the length of their polypeptide chains (AspRS1, 68 kDa; and AspRS2, 51 kDa). Both chains start with Met and are deprived of common sequences to a significant extent.

The repertoire of T cell antigen receptor beta-chain variable regions associated with psoriasis vulgaris.

We investigated whether the pattern of T-cell receptors expressed by T cells in inflamed psoriatic skin differed substantially from the pattern seen in T cells from the peripheral blood. A bias or restriction in the repertoire of T-cell receptors found in the lesional skin of different patients might imply that specific subsets of T cells were causally associated with initiating or maintaining the lesions. By using a polymerase chain reaction-based assay of T-cell receptor beta-chain variable region mRNA, we found that the patterns of beta-chain mRNAs displayed in 14 samples of lesional skin or six samples of noninvolved skin were not significantly less diverse than the patterns found in matched peripheral blood samples.

Clinical characteristics of women with a history of childhood abuse: unhealed wounds.

Objectives: To determine the prevalence of childhood physical or sexual abuse in women seen in primary care practices; to identify physical and psychologic problems associated with that abuse; and to compare the effects of childhood physical vs sexual abuse and childhood vs adult abuse.

Design: Cross-sectional, self-administered, anonymous survey.

Setting: Four community-based, primary care internal medicine practices.

The doctor's role in discussing advance preferences for end-of-life care: perceptions of physicians practicing in the VA.

Objectives: Although previous studies have shown physicians support advance directives, little is known about how they actually participate in decision-making. This study investigate (1) how much experience physicians have had discussing and following advance preferences and (2) how physicians perceive their role in the advance decision-making process.

Design: Mail survey conducted in 1993.

How thiamine diphosphate is activated in enzymes.

The controversial question of how thiamine diphosphate, the biologically active form of vitamin B1, is activated in different enzymes has been addressed. Activation of the coenzyme was studied by measuring thermodynamics and kinetics of deprotonation at the carbon in the 2-position (C2) of thiamine diphosphate in the enzymes pyruvate decarboxylase and transketolase by use of nuclear magnetic resonance spectroscopy, proton/deuterium exchange, coenzyme analogs, and site-specific mutant enzymes. Interaction of a glutamate with the nitrogen in the 1'-position in the pyrimidine ring activated the 4'-amino group to act as an efficient proton acceptor for the C2 proton.

Informatics applications in blood banking.

The dynamic nature of blood banking presents significant challenges in information acquisition, processing, and management. Blood banks have turned increasingly to computer technology for assistance with information handling. Novel applications of computer-based technology in blood banking and transfusion medicine have been developed and reported in the medical literature.

An enhanced-sensitivity branched-DNA assay for quantification of human immunodeficiency virus type 1 RNA in plasma.

The quantification of human immunodeficiency virus type 1 (HIV-1) RNA has facilitated clinical research and expedited the development of antiretroviral drugs. The branched-DNA (bDNA) assay provides a reliable method for the quantification of HIV-1 RNA in human plasma and is considered one of the most reproducible assays ready for use in clinical trials. A series of oligonucleotide probe design and solution changes have been developed to enhance the sensitivity of the bDNA assay while maintaining its performance characteristics.