Is a proton relay involved in the mechanism of 3-oxo-delta 5-steroid isomerase?

Previous reports of a UV spectral shift upon binding of the competitive inhibitor 19-nortestosterone (1) to 3-oxo-delta 5-steroid isomerase (KSI), coupled with UV resonance Raman results, have led to the conclusion that the enone moiety is polarized to a degree similar to that produced by complete protonation and that a proton relay may be involved in the enzymatic mechanism (Austin et al., 1992). These conclusions were partly based upon interpretations of the corresponding UV spectra of 1 in aqueous acid solutions.

Time limitation and the role of research in the worldwide attempt to eradicate malaria.

The U.S. Congress established an intense, time-limited, worldwide malaria eradication program in 1958 and assigned operational responsibility to the U.

Health care for all: long-term care, the missing piece. A roundtable discussion: Part 3.

Long-term care has been described as the "missing piece" in many healthcare reform proposals. Yet the cost of nursing home care often exceeds that of acute care, especially for the elderly with Alzheimer's disease. In this final installment of a three-part roundtable discussion, panelists discuss the options for providing long-term care, such as social insurance, a single-payer system, play or pay, or private insurance models.

Delayed dissemination of Lyme disease spirochetes from the site of deposition in the skin of mice.

To determine whether the agent of Lyme disease disseminates in vertebrate hosts directly after deposition by an infecting tick, a 6-mm disk of skin was excised from the sites where nymphal Ixodes dammini ticks infected by Lyme disease spirochetes, Borrelia burgdorferi, had fed. Infection in each mouse was tested by examining xenodiagnostic ticks that had engorged on these mice 4 weeks later and by serologic testing. Generalized infection was aborted when the site of inoculation was excised within 2 days after the infecting tick detached but not after 2 weeks.

Health care for all: comparing proposals for reform. A roundtable discussion: Part 2.

Part 1 of this roundtable discussion [Geriatrics 1992; 47(Sept):34-48] examined the flaws in our current healthcare system and factors that are interfering with our nation's ability to achieve reforms. This month, the panelists discuss the benefits and drawbacks of the major healthcare reform proposals, including managed care, single-payer systems, and so-called "play or pay." The practical aspects of any redistribution of healthcare resources are considered as each panelist outlines a favored approach.

Macrosomia in postdates pregnancies: the accuracy of routine ultrasonographic screening.

Objective: The purpose of this study was to assess the efficacy of routine ultrasonographic assessment of fetal weight in predicting fetal macrosomia in postdates pregnancies.

Study Design: A total of 519 pregnancies of > or = 41 weeks' duration were subjected to ultrasonographic estimation of fetal weight within 1 week of delivery. Estimated fetal weights were compared with birth weights.

Babesiosis: an underdiagnosed disease of children.

Babesiosis is a malaria-like illness caused by the intraerythrocytic parasite Babesia microti and is transmitted by the same tick that transmits Borrelia burgdorferi, the causative agent of Lyme disease. Babesiosis is well recognized in adult residents of southern New England and New York but has been described in only five children. To determine whether children are infected with B microti less often than are adults, a prospective serosurvey was carried out on Block Island, RI, where babesiosis is endemic.

Calcium release after acid pretreatment of fluoridated and nonfluoridated enamel.

Spectrophotometric analysis of calcium released by the acid-etching procedure was used to evaluate the effect of topical fluoride on the acid resistivity of enamel. The influence of superficial enamel surface reduction (chamfering) on the efficacy of the etching procedure was investigated.

Nature of the intermediate in the 3-oxo-delta 5-steroid isomerase reaction.

The role of Tyr-14 of 3-oxo-delta 5-steroid isomerase (KSI) was probed by analysis of the spectra of 3-amino-1,3,5(10)-estratrien-17 beta-ol (4) and equilenin (5) bound to the active site of KSI. The ultraviolet spectrum of 4 bound to KSI is identical to that for 4 in neutral solution. This observation indicates that Tyr-14 does not protonate the amine group of 4 at the active site.

Consumers vs. other interests.

We have to choose to protect the interests of the insurance and health-care industries or the interests of everyone else.

Human major HSP70 protein complements the localization and functional defects of cytoplasmic mutant SV40 T antigen in Swiss 3T3 mouse fibroblast cells.

The CT3 cytoplasmic localization mutant of SV40 T antigen is neither properly transported to the nucleus nor is it functional in rodent cells. Human precrisis cells are able to complement this mutation, as they are fully transformed by CT3 with wild-type efficiency. The human-specific factors responsible for this species-specific difference in response to CT3 were localized to human chromosome 6 by synteny in a panel of six somatic cell hybrids.

Energetics of 3-oxo-delta 5-steroid isomerase: source of the catalytic power of the enzyme.

Knowledge of the partitioning of the putative dienol intermediate (2) by steroid isomerase (KSI) (Hawkinson et al. 1991), in conjunction with various steady-state kinetic parameters, allows elucidation of the detailed free energy profile for the KSI-catalyzed conversion of 5-androstene-3,17-dione (1) to 4-androstene-3,17-dione (3). This free energy profile shows four kinetically significant energy barriers (substrate binding, the two chemical steps, and dissociation of product) that must be traversed upon conversion of 1 to 3.

Rectal infusion and aspiration of material through the guts of ixodid ticks (Acari: Ixodidae).

A technique for inoculating and removing substances via the anus of vector ticks was devised to define features of vector competence precisely. Calibrated inocula (greater than 5 nanoliter) containing aqueous dye and polystyrene beads as well as infectious agents were infused into the rectal sacs of ticks using glass microcapillary pipettes placed within the expanded anal orifice. The guts of preadult and adult ticks, Ixodes dammini Spielman, Clifford, Piesman & Corwin, Dermacentor variabilis (Say), Hyalomma impeltatum Schulze & Schlottke, and Amblyomma americanum (L.

Governmental regulations concerning infection control in dentistry.

This review discusses how governmental regulations concerning infection control affect dental practice procedures. Recently, changes have been made in state and federal legislation regarding these matters. These changes have forced dentists to evaluate seriously the risks involved in providing patient care.

The effect of lightness contrast on the colored Müller-Lyer illusion.

Two subjects estimated the length of the central line in red and blue Müller-Lyer figures that were viewed both foveally and parafoveally. The illusion figures were defined by either lightness and hue differences between figure and ground or by a hue difference alone. For both subjects, the figures defined solely by hue produced larger illusions.

Kinetic competence of an externally generated dienol intermediate with steroid isomerase.

The putative intermediate dienol (2) in the steroid isomerase (KSI) catalyzed conversion of 5-androstene-3,17-dione (1) to 4-androstene-3,17-dione (3) has been independently generated and tested as a substrate for KSI. At pH 7, dienol 2 is converted by KSI to a mixture of 1 (46%) and 3 (54%). The apparent second-order rate constant for reaction of 2 with KSI to produce 3 (kappa cat/Km = 2.