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Biomedical subjects

D Booth

Publications and source records attributed to D Booth.

At least 37 records · Page 2Linked to original sources
PubMed1997

Myoblast-mediated gene transfer to the joint.

Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression. In this study, data were investigated regarding the use of muscle cells as an alternative gene-delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra-articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post-mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post-mitotic myofibers in the knee joint raises the possibility of long-term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene-delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.

Adenoviridae↗
PubMed1997

Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.

The gastrointestinal tract, with its rapid cell replacement, is sensitive to cytotoxic damage and can be a site of dose-limiting toxicity in cancer therapy. Here, we have investigated the use of one growth modulator to manipulate the cell cycle status of gastrointestinal stem cells before cytotoxic exposure to minimize damage to this normal tissue. Transforming growth factor beta-3 (TGF-beta3), a known inhibitor of cell cycle progression through G1, was used to alter intestinal crypt stem cell sensitivity before 12-16 Gy of gamma irradiation, which was used as a model cytotoxic agent. Using a crypt microcolony assay as a measure of functional competence of gastrointestinal stem cells, it was shown that the administration of TGF-beta3 over a 24-h period before irradiation increased the number of surviving crypts by four- to six-fold. To test whether changes in crypt survival are reflected in the well-being of the animal, survival time analyses were performed. After 14.5 Gy of radiation, only 35% of the animals survived within a period of about 12 days, while prior treatment with TGF-beta3 provided significant protection against this early gastrointestinal animal death, with 95% of the treated animals surviving for greater than 30 days.

Animals↗
PubMed1996

A phase-I study of the safety, pharmacokinetics, and antiviral activity of combination didanosine and ribavirin in patients with HIV-1 disease. AIDS Clinical Trials Group 231 Protocol Team.

A phase-I study was conducted to examine the safety, pharmacokinetics, and activity of combination 2',3'-dideoxyinosine (ddI) and ribavirin against human immunodeficiency virus type 1 (HIV-1)-positive individuals with CD4+ cell counts of < or = 500/microliter. Nineteen patients were enrolled into the study in which ddI monotherapy (200 mg p.o.b.i.d.) was administered for the first 4 weeks, followed by the coadministration of ribavirin (600 mg p.o.q.d.) and ddI (200 mg p.o.b.i.d.) for 8 or 20 additional weeks. The combination regimen was safe and well tolerated. Three patients did not complete 12 weeks of the study because of adverse events or voluntary withdrawal. The pharmacokinetic studies performed at weeks 4, 6, and 12 on specimens collected from the 15 individuals who completed 12 weeks of therapy revealed no pharmacokinetic interaction between ddI and ribavirin. A significant decline from baseline in HIV-1 titer as measured by quantitative HIV-1 culture was detected both during the ddI-monotherapy phase (week 4, p < 0.001) and during the combination-therapy ddI + ribavirin phase (week 12, p < 0.001); the median drop observed was 0.90 log10 at week 4 and 0.92 log10 at week 12. While the addition of ribavirin did not result in further reductions in viremia in the following weeks on study treatment, 13 (81%) of the 16 patients had at least a -0.5 log10 change in viral titer at week 12. The median decline in plasma viral RNA was 0.68 log10 at week 4(p < 0.001) and 0.67 log10 at week 12 (p = 0.005). CD4+ cell counts increased above baseline significantly during the ddI-monotherapy phase of the study (p = 0.0038). The median increase was +26 cells/mm3 at week 4 and +11 cells/mm3 at week 12; for patients who remained on treatment through 24 weeks, the median CD4+ cell count increase was +10 cells/mm3. The L74V ddI resistance-conferring HIV-I reverse-transcriptase mutation emerged in 53% of the patients. Patients with non-syncytium-inducing HIV variants demonstrated greater responses to treatment with larger decreases in virus load and greater increases in CD4+ cell count. Our results reveal that the combination of ddI and ribavirin in HIV-positive patients is safe, well tolerated, without adverse pharmacologic interaction, and associated with significant and sustained declines in virus load over 12 weeks of therapy.

Adult↗
PubMed1996

Monoclonal antibodies against eosinophils in liver allograft rejection.

There has been recent interest in eosinophils as a histological diagnostic marker of liver allograft rejection. However, the reliability of counting eosinophils in sections stained with hematoxylin and eosin (H&E) has not been evaluated previously. We quantified eosinophils in 10 day-5 protocol liver biopsy specimens in 10 patients. The control groups were 5 patients with cytomegalovirus infection, 5 patients with obscure liver dysfunction, and 6 patients with HCV infection. Eosinophil count was assessed using H&E and by specific monoclonal antibody staining using (1) an anti-ECP antibody (EG2) and (2) a monoclonal antibody against human eosinophil major basic protein (MBP) (BMK-13). The average percentage of the total inflammatory infiltrate of eosinophils in portal tracts was 9% in the moderate to severe rejection group as compared with 0.25% in the mild rejection group (P < .001) and 0% in the control group (P < .001). The eosinophil count decreased markedly after successful treatment of rejection. The H&E staining correlated with MBP+ the (BMK-13 immunoreactive) cells but were more numerous with BMK-13. BMK-13 also stained significantly more cells when compared with EG2 (P < .01). This difference may be because EG2 staining only activated eosinophils, whereas BMK-13 is a pan-eosinophilic maker, regardless of activation. This study confirms that eosinophils are a specific feature of acute cellular rejection and are an aid to its diagnosis. BMK-13 is a useful pan-eosinophilic marker that is more efficient in obtaining eosinophil count when compared with H&E.

Antibodies, Monoclonal↗
PubMed1995

Oxygen availability and embryonic development in sand snail (Polinices sordidus) egg masses

The oxygen transport physiology of sand snail Polinices sordidus egg masses was investigated using oxygen microelectrodes and open-flow respirometry. P. sordidus eggs are laid in a jelly matrix that rapidly absorbs water and swells into a horseshoe-shaped sausage. The average diameter of these sausages is 37 mm. Eggs are enclosed in capsules that are distributed throughout the jelly matrix, but 65 % of the eggs are located within 3 mm of the outer surface. There is no circulatory or canal system within the matrix so all gas exchange between developing embryos and the environment must occur by diffusion through the jelly matrix. Oxygen tension in the outer layer remains moderately high (PO2>10 kPa) throughout incubation but decreases rapidly in more centrally located regions, so that by day 4 embryos in this region are exposed to extremely hypoxic conditions (PO2<1 kPa). This hypoxia limits oxygen consumption of embryos to low levels and appears to slow embryonic development or even to arrest it. From day 4 onwards, the central region gradually become less hypoxic because the hatching of peripherally located embryos causes the outer layers of the jelly matrix to disintegrate and thus reduces the diffusion distance for oxygen between the centrally located embryos and the surrounding sea water. As the oxygen tension rises, development accelerates and the embryos eventually hatch as viable veligers, apparently unharmed by their prolonged exposure to hypoxia.

Journal Article↗
PubMed1993

Local injury information, community participation and injury reduction.

Better injury prevention is now a national health priority in Australia. Applying the health promotion strategies of the Ottawa Charter to injury prevention forms the basis of the World Health Organization's worldwide Safe Communities program. Taking such a community-focused approach has led to quantifiable reductions in injuries in several overseas countries, particularly in Scandinavia where falls of up to 30 per cent in particular injuries have been reported over a three-year period. In the Illawarra area of New South Wales, data from local hospital emergency departments have been used as the basis for a 'community information' strategy, in an attempt to replicate this overseas experience in an Australian setting. Reductions of 17 per cent in attendances by children for injuries (P < 0.001) and a 14 per cent fall in accident-related hospital admissions of children (not statistically significant) have been observed over the course of the four-year intervention. Problems of community definition and external confounding influences outside the control of the project make it difficult to confirm a causal relationship. However, community information forms one important component in a comprehensive local injury-reduction strategy.

Accident Prevention↗
PubMed1991

Family medical leave. An employee benefit for working caregivers of elderly family members.

Future trends include a decrease in the number of adult children, an increase in the number of individuals over age 65, single parent families, working women, and individuals with no health care insurance. As more women with multiple roles and responsibilities enter and continue as part of the work force, employers recognize the need for support of family issues. Currently many employers lack initiative to make these needed changes. The occupational health nurses' role in relation to future policy for working caregivers includes assessment of how employment and caregiving impact work performance, job satisfaction, and health; and participation in defining public policy issues.

Aged↗
PubMed1990

The complete nucleotide sequence of enterovirus type 70: relationships with other members of the picornaviridae.

Enterovirus type 70 (EV70) is the causative agent of acute haemorrhagic conjunctivitis and may also give rise to a rare neurological complication closely resembling poliomyelitis. The complete nucleotide sequence of the genome of EV70 has been determined from cDNA cloned in Escherichia coli. The genome consists of a 5' non-coding region of 726 nucleotides (nt), a long open reading frame of 6582 nt and a 3' non-coding region of 82 nt prior to the poly(A) tract. Comparison of the nucleotide sequence and the predicted amino acid sequence of the polyprotein with those published for other enteroviruses reveals sufficiently high similarity to predict antigenic regions and polyprotein cleavage sites. The P1 region of EV70 is as similar to those of the entero- as to those of the rhinoviruses, whereas the P2 and P3 regions are more closely related to the coxsackie B and swine vesicular disease viruses than other entero- or rhinoviruses.

Amino Acid Sequence↗
PubMed1986

Relationship of contractile state to ejection performance in patients with chronic aortic valve disease.

To assess the relative contributions of afterload mismatch and impaired contractility to pump dysfunction in patients with chronic aortic valve disease, simultaneous left ventricular cineangiography and micromanometry were performed in 56 patients: 21 with severe aortic stenosis, 16 with severe aortic regurgitation, and 19 normal control subjects. Left ventricular mass was increased in patients with aortic stenosis and aortic regurgitation (172 +/- 52 and 224 +/- 63 g/m2, respectively, vs 89 +/- 16 for control subjects; p less than .05) as were end-diastolic volume (101 +/- 39 and 167 +/- 44 vs 77 +/- 16 ml/m2; p less than .05) and end-systolic volume (50 +/- 40 and 84 +/- 43 vs 24 +/- 7 ml/m2; p less than .05). Although ejection fraction was depressed in both abnormal groups (0.56 +/- 0.18 for patients with aortic stenosis and 0.53 +/- 0.13 for those with aortic regurgitation vs 0.69 +/- 0.05 for control subjects; p less than .05), the decrease in ejection fraction was disproportionate to the mild degree of afterload mismatch (end ejection stress 129 +/- 17 in patients with aortic stenosis and 154 +/- 58 in those with aortic regurgitation vs 117 +/- 46 kdyn/cm2 in control subjects; p = NS) with 10 of 21 patients with aortic stenosis and 12 of 16 patients with aortic regurgitation falling below the 95% prediction limit of the linear inverse relationship between ejection fraction and end-systolic stress for controls (EF = 0.78 - 0.00074 X ESS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Evaluation of left ventricular contractile pattern by intravenous digital subtraction ventriculography: comparison with cineangiography and assessment of interobserver variability.

The accuracy and reproducibility of measurements of left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and regional wall motion obtained by digital subtraction ventriculography (DSV) were compared with values of direct cineangiography in 40 patients, 21 of whom were ambulatory. DSV was performed with a 1-second, 30-ml contrast injection, which yielded real-time fluoroimages composed of 512 X 512 pixels at 30 frames/s. Single-plane right anterior oblique LV volumes were calculated by area-length methods for both DSV and cineangiography. Wall motion was assessed as percent area shortening for 12 equal myocardial segments, with results classified as abnormal if greater than 2 standard deviations below the mean of 20 normal values. DSV exhibited close correlation with angiography for EDV (r = 0.88), ESV (r = 0.92) and EF (r = 0.93). Intravenous DSV and direct cineangiography were concordant in classification of LV contractile pattern in 436 of 480 (91%) myocardial segments. Measurements of DSV obtained by 2 observers showed close correlations for EDV (r = 0.88), ESV (r = 0.95) and EF (r = 0.94), and wall motion classification was in agreement in 434 of 480 (90%) LV segments. Artifacts induced by respiratory motion, persistence of contrast in the right ventricle or left atrium, or low cardiac output may have contributed to the discrepancies observed. These data indicate that DSV is accurate in assessing LV volume and EF, correlates well with cineangiography and exhibits good interobserver reproducibility.

Analog-Digital Conversion↗
PubMed1983

Cholinergic inhibition of meal stimulated plasma neurotensin like immunoreactivity in man.

Meal stimulated plasma neurotensin like immunoreactivity (NTLI) was compared during saline or atropine infusion in six volunteers over six hours. Plasma gastrin and pancreatic polypeptide were also measured to compare the timing of their release to that of NTLI. Like plasma gastrin and PP, plasma NTLI rose rapidly following the meal, rising from 27 +/- 7 pmol/l to a peak of 45 +/- 8 pmol/l at 20 minutes (p less than 0.05). Also, like that of pancreatic polypeptide, the release of NTLI was biphasic. Sixty minutes after the meal, plasma NTLI had returned to basal values, followed by a rise to a prolonged peak of 64 +/- 10 pmol/l between 90-180 minutes (p less than 0.05) returning once more to basal values by 240 minutes. Following atropine, basal plasma NTLI fell from 22 +/- 4 pmol/l to 11 +/- 2 pmol/l (p less than 0.05), but rose to basal levels 30-60 minutes after the meal, where it remained unaltered for the remainder of the study. We conclude that both basal and meal stimulated plasma NTLI are inhibited by cholinergic blockade. Further, the similar temporal relationship between plasma NTLI and pancreatic polypeptide in the late phase of the meal response, suggests that a component of NTLI may mediate part of the intestinal phase of pancreatic polypeptide release.

Adolescent↗
PubMed1978

Enhancement of cardiac allografts in rats. Comparison of host responses to different treatment protocols.

Immunological responses to heterotopic (L X BN)F1 cardiac allografts placed in untreated L rats were compared with those grafts enhanced by different treatment regimens. Host pretreatment by antigen and antibody (Ag-Ab) 11 and 10 days before transplantation, respectively, was the most effective treatment regimen for prolongation of graft function; active or passive immunization alone increased survival only modestly. A late dose of antiserum administered to Ag-Ab-pretreated animals significantly shortened graft survival. Patterns of cellular responsiveness were measured serially by lymphocyte-mediated cytotoxicity; humoral immunity by Ab-lymphocyte-mediated cytotoxicity, capillary hemagglutination, and complement-dependent cytotoxicity. Allograft rejection in animals of all groups was heralded in vitro by increasing immunological activity. All cellular and humoral responses were depressed consistently in Ag-Ab-pretreated recipients. Cellular but not humoral responses were decreased in Ag-pretreated hosts, while humoral but not cellular responses were decreased in Ab-treated animals. The results suggest that the in vitro determinants of immunological activity used in this study generally followed clinical patterns of rejection or enhancement of cardiac allografts in the rat. Recipient pretreatment with Ag and Ab is more effective in graft prolongation than treatment with Ag or Ab alone, and in vitro data suggest an additive effect of these two regiments.

Animals↗