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Biomedical subjects

C Tate

Publications and source records attributed to C Tate.

At least 19 recordsLinked to original sources

Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation.

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.

Administration, Oral↗

Murine CD4+ T lymphocyte subsets and host defense against Pneumocystis carinii.

The recruitment of specific subsets of CD4(+) T lymphocytes to the lungs in response to Pneumocystis carinii was investigated. For mice inoculated with P. carinii, an ELISPOT assay was used to calculate the numbers of lymph node and lung tissue CD4(+) cells that secreted interferon (IFN)-gamma (Th1 cytokine) and interleukin (IL)-4 (Th2 cytokine) after concanavalin A stimulation. An ELISA was used to assay culture supernatants for cytokine concentrations. Precursor frequency of both IFN-gamma- and IL-4-secreting cells was increased in lymph nodes at 1 week, whereas increases in Th1 and Th2 cells in lung tissue were delayed 3 weeks before declining. The frequency of IL-4-secreting cells always was greater than the frequency of IFN-gamma secreting cells. These results demonstrate an early T lymphocyte response in draining lymph nodes, followed by later recruitment of Th1 and Th2 lymphocytes into lung tissue. The overall CD4(+) T cell response to P. carinii involves both Th1 and Th2 subsets, but the response is Th2 dominant in both lymph node and lung tissue.

Animals↗

Physical performance of elite New Zealand Olympic class sailors.

OBJECTIVE: The purpose of this study was to compare the physical performance of elite New Zealand and other nations olympic class sailors and to undertake an initial examination of the relation between physical and sailing performance. EXPERIMENTAL DESIGN: A comparative study. SETTING: Healthy elite national level olympic class sailors were examined. PARTICIPANTS: Thirty-one elite New Zealand Olympic sailing squad team members and 108 Olympic team sailors from ten other nations. INTERVENTIONS: The data for the two groups of subjects was compared using unpaired "t"-tests. A qualitative analysis was used to examine the relation between physical and sailing performance. MEASURES: Measurements included age, body mass, muscular strength endurance (as assessed by the maximum number of push-ups, pull-ups and sit-ups that could be performed) and serobic power (as assessed by the time taken to cover 2500 m and the distance completed in 12 minutes in a maximal effort rowing ergometer test). Sailing performance was assessed by national coach ranking of each New Zealand sailor. RESULTS: On average the New Zealanders were younger and lighter than the sailors from the other nations. They tended to have greater shoulder/arm strength endurance as reflected in their performance for push-ups and pull-ups, but a lesser ability in their sit-up performance. They also tended to be aerobically fitter. There were clear and logical differences between body mass and both class of vessel and the position of the sailor i.c. crew or helmsman. Lighter sailors sailed lighter craft whilst heavier sailors sailed the heavier craft. Crew members were generally heavier than helmsmen. Age appeared to be related to sailing performance. CONCLUSIONS: Elite New Zealand Olympic class sailors tend to be younger, lighter, stronger and aerobically fitter than elite sailors from other nations. Age appeared to be related to on-water sailing performance.

Adolescent↗

Direct-space methods in phase extension and phase refinement. VI. PERP (phase extension and refinement program).

Several techniques for extending and refining phases for macromolecular structures have been incorporated into a program package PERP. In addition to previously employed techniques such as solvent flattening and histogram matching, PERP includes a new way of applying the Sayre equation [Refaat, Tate & Woolfson (1995). Acta Cryst. D51, 1036-1040], low-density elimination [Shiono & Woolfson (1992). Acta Cryst. A48, 451-456] and two double-histogram methods [Refaat, Tate & Woolfson (1996). Acta Cryst. D52, 252-256]. PERP is an easy-to-use package controlled by keywords and provided with default parameters that usually give near-optimum results. Examples are given of refinement, and also extension and refinement, for six known protein structures with a variety of characteristics. In each case PERP gives a very satisfactory outcome as measured by improvements in the mean-phase-error and conventional map-correlation coefficient. The main conclusion is that the several methods used in sequence give more effective extension and refinement than using any single method alone.

Journal Article↗

Direct-space methods in phase extension and phase refinement. IV. The double-histogram method.

In the conventional histogram-matching technique for phase extension and refinement for proteins a simple one-to-one transformation is made in the protein region to modify calculated density so that it will have some target histogram in addition to solvent flattening. This work describes an investigation where the density modification takes into account not only the current calculated density at a grid point but also some characteristic of the environment of the grid point within some distance R. This characteristic can be one of the local maximum density, the local minimum density or the local variance of density. The grid points are divided into ten groups, each containing the same number of grid points, for ten different ranges of value of the local characteristic. The ten groups are modified to give different histograms, each corresponding to that obtained under the same circumstances from a structure similar to the one under investigation. This process is referred to as the double-histogram matching method. Other processes which have been investigated are the weighting of structure factors when calculating maps with estimated phases and also the use of a factor to dampen the change of density and so control the refinement process. Two protein structures were used in numerical trials, RNApl [Bezborodova, Ermekbaeva, Shlyapnikov, Polyakov & Bezborodov (1988). Biokhimiya, 53, 965-973] and 2-Zn insulin [Baker, Blundell, Cutfield, Cutfield, Dodson, Dodson, Hodgkin, Hubbard, lsaacs, Reynolds, Sakabe, Sakabe & Vijayan (1988). Philos. Trans. R. Soc. London Ser. B, 319, 456--469]. Comparison of the proposed procedures with the normal histogram-matching technique without structure-factor weighting or damping gives mean phase errors reduced by up to 10 degrees with map correlation coefficients improved by as much as 0.14. Compared to the normal histogram used with weighting of structure factors and damping, the improvement due to the use of the double-histogram method is usually of order 4 degrees in mean phase error and an increase of 0.06-0.08 in the map correlation coefficient. It is concluded that the most reliable results are found with the local-maximum condition and with R in the range 0.5-0.6 A.

Journal Article↗

Hepatic Veno-Occlusive Disease: A Role for Tissue Plasminogen Activator?

There are five published case reports of bone marrow transplantation (BMT) patients with hepatic veno-occlusive disease (VOD) who were treated with recombinant tissue plasminogen activator (rt-PA) and low-dose heparin. Two of the five patients had an initial response to rt-PA. One had complete resolution of clinical signs and symptoms. Bleeding occurred in three of the five. In a prospective, uncontrolled pilot study of seven allogeneic BMT patients, rt-PA was administered intravenously for two consecutive days, followed by low-dose heparin therapy. Five of the seven patients had a reduction in total bilirubin, and three of the five resolved their signs and symptoms of VOD. Adverse effects observed were limited to localized bleeding.

Journal Article↗

Canine cardiac sarcoplasmic reticulum is not altered with endurance exercise training.

To investigate the effect of exercise training on calcium movements by isolated cardiac sarcoplasmic reticulum (SR), mongrel dogs either remained sedentary (S) or were exercise-trained (E) via running for a period of 8-10 wk. The trained state was confirmed by the increase in skeletal muscle citrate synthase activity and decreases in submaximal exercise heart rates in the E group but not in the S dogs. The properties of isolated cardiac SR were identical between the groups. The variables tested included ATP-dependent calcium transport and calcium-stimulated ATPase activity. Importantly, there was no difference in spontaneous calcium release which occurred after peak ATP-dependent calcium accumulation was reached. Calcium release from passively loaded vesicles induced by calcium and ionophore also did not differ in the SR isolated from the E dogs. The change in the affinity of the SR Ca ATPase for calcium after the addition of the polyanion, heparin, was similar in both groups, indicating that the regulation of calcium-stimulated ATPase activity by the SR protein, phospholamban, is not modified by exercise training. We conclude that exercise training of 8-10 wk duration does not alter the calcium handling properties of cardiac SR isolated from mongrel dogs.

Animals↗

Endogenous opioids do not mediate HCl-induced myocardial dysfunction.

We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 +/- 0.01 to 6.97 +/- 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance.

Acidosis↗

Testicular torsion does not cause autoimmunization in man.

Forty-seven patients have been reviewed 2-10 years after torsion of the testicle. Thirty-six (77 per cent) were found to have abnormalities of exocrine or endocrine gonadal function. None showed evidence of testicular autoimmunization using standard assays of sperm agglutination and immobilization by serum or seminal plasma, and the serum mixed agglutination reaction (MAR) test. In addition, 11 cases of acute torsion were followed at intervals for 3-6 months after surgery, but no evidence was observed of the transient development of sperm antibodies. Our findings confirm poor gonadal function after torsion, but do not support the recent suggestion that it is caused by autoimmunization.

Adolescent↗

Spontaneous calcium release from sarcoplasmic reticulum. A re-examination.

A recent study by Blayney and co-workers (Blayney, L., Thomas, H., Muir, J. and Henderson, A. (1977) Biochim. Biophys. Acta 470, 128--133) purported to demonstrate that apparent spontaneous calcium release in sarcoplasmic reticulum is an artifact of the uptake of murexide dye. This report demonstrates that spontaneous calcium release (1) takes place despite equilibration of murexide sarcoplasmic reticulum to a stable baseline; (2) may be reversed by addition of ATP or oxalate after release has begun. The identical phenomenon can be demonstrated utilizing the indicator arsenazo III or Millipore filtration methods. The results suggest that equilibration of the murexide with sarcoplasmic reticulum vesicles must occur prior to ATP addition in order to achieve a stable baseline but that spontaneous calcium release is not an artifact.

Adenosine Triphosphate↗

Age at menarche and selected menstrual characteristics in athletes at different competitive levels and in different sports.

Ages at menarche in 110 non-athletes, 59 high school atjletes, 53 college athletes, and 18 olympic volleyball candidates were determined through interview. The athletes attained menarche significantly later than the non-athletes (p less than .001), and the olympic athletes attained menarche significantly later than the high school and college athletes (p less than .001). The high school and college athletes did not differ significantly in the mean age at menarche. When menarche in college athletes was analyzed by specific sports, the small samples of participants in golf (n = 4), volleyball (n = 7), swimming (n = 7), basketball (n = 16), and gymnastics and track (n = 6) did not differ significantly from each other in the mean age at menarche. The olympic volleyball aspirants attained menarche significantly later than all sport-specific groups (p less than .05 to p less than .001) except the gymnastics-track and tennis (n = 13) athletes. Smaller samples of non-athletes (n = 27) and college athletes (n = 21 from volleyball and basketball), plus the olympic athletes were also interviewed regarding selected menstrual characteristics. Although the athletes reported a greater incidence of dysmenorrhea and menstrual irregularity, none of the chi square values comparing the three groups was significant.

Adolescent↗