Evolution of cooperativity in hemoglobins: what can invertebrate hemoglobins tell us?

While vertebrate hemoglobins typically are tetrameric and show highly regulated and cooperative ligand binding, little is known of the evolution of these properties. We are studying the structural and functional properties of the hemoglobins from Caudina arenicola, an echinoderm. The echinoderms are in the lineage most closely related to the vertebrates to express hemoglobin. C. arenicola has three sets of red cells, in the water vascular system, the coelomic cavity, and in an intestinal vein. Each of these expresses a distinct array of globins. The hemoglobins are cooperative and exhibit unusual ligand-linked associative properties, being dimeric when oxygenated and forming tetramers and higher aggregates on deoxygenation. The major coelomic hemoglobins have been subjected to a detailed examination by a combination of ligand binding analyses and protein and DNA sequencing, as well as X-ray crystallography. Two typical globin introns were identified, along with a unique intron that bisects an N-terminal extension of the globin from the remainder of the gene. X-ray crystallographic analysis shows that the subunit interfaces of C. arenicola hemoglobins differ radically from those of vertebrate hemoglobins and indeed from some other invertebrate hemoglobins, but closely resemble the packing arrangements found in a clam hemoglobin (Scapharca). However, the residues implicated in cooperativity in these two types of hemoglobins differ substantially.     

Texas Medication Algorithm Project: definitions, rationale, and methods to develop medication algorithms

BACKGROUND: The Texas Medication Algorithm Project (TMAP), a public-academic collaborative effort, is a 3-phase project to develop, implement, and evaluate medication treatment algorithms for public sector patients with schizophrenia, major depressive disorders, or bipolar disorders. DISCUSSION: This paper, the first in a series describing the activities of the TMAP, focuses on the various definitions and reasons why guidelines have gained popularity. Also discussed are their strengths, the limitations of the various methods used to develop them, and potential barriers to their implementation.     

Effects of ketorolac on bone repair: A radiographic study in modeled demineralized bone matrix grafted rabbits

The treatment of instability of the multiply reoperated knee is a complex problem. The causes for failure are numerous and include repeated trauma, insufficient fixation and non-anatomic placement of the graft, inadequate replacement material, isolated anterior cruciate ligament (ACL) reconstruction in complex knee instability or the use of a ligament prosthesis. With every surgical procedure, however, the anatomical and technical conditions become worse. Problems like degenerative changes, joint stiffness and gait abnormalities occur and often become a more focal point than the instability itself. The purpose of this paper is to present the problems and the dilemma of instability of the multiply reoperated knee and the possible solutions. Between 1976 and 1996, a total of 1752 ACL reconstructions were carried out in Munich and Hannover. Of these, 228 (13%) were revision, mostly of failed ACL reconstructions performed elsewhere. Since 1989, we have chosen the severest cases from this group (more than three operations on the same knee) for this study. Seventeen patients were investigated who had undergone up to 25 operations. The mean number of operations was 7. All primary operations were performed in other hospitals. In 10 cases only the ACL reconstruction was performed as a final procedure, mostly in combination with other procedures like medial meniscus replacement, extra-articular stabilization or arthrolysis. In the other cases operations such as osteotomies, arthrodesis or amputation were necessary. The results present the main dilemma in instability of the multiply reoperated knee since they were not successful in all patients. Finally, 15 patients report still having instability, pain or swelling in isolation or in combination. Nine patients were satisfied with their subjective results. Even after the socalled definitive procedures, certain complications arose. The main goal in the treatment of instability of the multiply reoperated knee is to avoid a series of operations, hospitalization and history of illness. General revision surgery for the entire complaint is not the aim of the treatment. The specific problem of the patient should be extracted from the complex situation, and this should be solved with the most limited procedure possible only.     

The exposed ocular surface and its relationship to spontaneous eyeblink rate in elderly caucasians

1. Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodelling and the localization of atherosclerotic plaque. Uraemia is a proatherogenic process and is expected to be associated with impaired vascular reactivity.2. To study this, 12 male Wistar rats were rendered uraemic by five-sixths nephrectomy and 12 control rats were sham operated simultaneously. After 8 weeks a tail-cuff systolic blood pressure was recorded, blood samples were taken and the animals killed. Isolated femoral arteries were dissected and mounted on a pressure myograph and myogenic tone was assessed over a range of intravascular pressures from 40 to 160 mmHg. Histologically the arteries were comparatively examined for gross morphology, calcification and deposition of collagen.3.Biochemically the serum urea and creatinine were greater in the uraemic compared with the control rats (urea: 23.5+/-6 mmol/l and 6.8+/-01 mmol/l respectively, P not significant; creatinine: 130.7+/-13 mmol/l and 70.3+/-5 mmol/l respectively, P<0.01) but systolic blood pressure was the same in both groups (control, 97+/-1 mmHg; uraemic, 98+/-2 mmHg), compatible with mild uraemia.4. Myogenic tone was significantly greater in uraemic vessels (7.3+/-1.8% versus 2.3+/-0. 4% in control, P=0.01). The actual vessel lumen diameter was also smaller in pressurized uraemic vessels compared with control vessels (471+/-30 microm versus 604+/-33 microm, P<0.01) after equilibration in physiological salt solution. However, when incubated in calcium-free physiological salt solution, the passive internal diameter was similar in uraemic vessels (538+/-25 microm compared with 595+/-31 microm in control). Histologically, there were no differences between the two groups.5. We conclude that some aspects of vascular reactivity are altered in mild experimental uraemia as shown by a reduced internal lumen diameter and increased myogenic tone. Furthermore, these changes are apparent in the absence of hypertension and precede structural changes.     

Heart rate and prostate cancer mortality: results of a prospective analysis

Recent studies suggest that local levels of sympathetic nervous activity influence the growth of prostatic tissue. In several epidemiological studies, resting heart rate, an indicator of overall sympathetic activity, was positively associated with all noncardiovascular and cancer death among men. However, no previous analyses have focused on the specific relationship of heart rate to prostate cancer mortality. We studied 22,380 men enrolled in the Chicago Heart Association cohort from 1967-1973, who had heart rate (HR) determined by electrocardiogram. Mean length of follow-up (for mortality) was 19.2 years. We computed age-adjusted rates for prostate cancer death by variable of interest and fitted proportional hazards models to estimate relative risks (RRs) adjusted for potential confounders. In a model controlling for age, body mass index, blood pressure, serum cholesterol, smoking, postload plasma glucose, and years of education, the RR for a 10 beat/min higher HR was 1.26 (95% confidence interval = 1.04-1.51). Age-adjusted RRs across higher quintiles for HR were 1.00, 1.55, 1.85, 2.18, and 2.69 (P trend = 0.006). Survival curves indicated that the elevated risk was not confined to the early years of follow-up. Because little is known about factors that determine risk of prostate cancer death, these results could prove important even if due to an unmeasured etiological factor other than heart rate itself. The results are consistent with the hypothesis that local neurotrophic factors associated with sympathetic activity influence the progression of prostate cancer     

How sexually permissive are Singaporeans?

This paper presents data on two surveys done in 1989 and 1992 that indicated the attitudes of Singaporeans to sexuality. Both surveys revealed that Singaporeans have sexually conservative attitudes and those who have a lower education, are single, above the age of 40, are Malays/Muslims hold more conservative views.     

Superconducting magnets for the CBA project

The superconducting magnets that were designed and tested for the BNL colliding beam accelerator are described, including dipoles, quadrupoles and trim coils. The dipoles had an effective length of 436 cm, a good field aperture of 8.8 cm diameter, and were designed for an operating field of 5.28 T in a temperature range between 2.6 K and 3.8 K (provided by supercritical helium). The quadrupoles had the same aperture, an effective length of 138.5 cm, and were designed to operate in series with the dipoles, with a gradient of 70.8 T/m. The dipoles incorporated internal sextupole, octupole, and decapole trim coil windings; the quadrupole trim coils consisted of dipole, quadrupole, and dodecapole windings. The design, construction, and performance (training, field quality, quench protection characteristics) of prototype magnets are discussed in considerable detail.