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Biomedical subjects

K J Williams

Publications and source records attributed to K J Williams.

124 records · Page 7Linked to original sources
PubMed1981

The relative amounts of the collagen chains alpha 1(I), alpha 2 and alpha 1(III) in the skin of 31 patients with osteogenesis imperfecta.

1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent alpha 1(III) and alpha 1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the alpha 1(I) to alpha 2 chains of type I collagen has also been measured. 2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio alpha 1(III)/alpha 1(I) was significantly increased (P less than 0.001) and the ratio alpha 1(I)/alpha 2 significantly decreased (P less than 0.005) compared with age-matched control subjects. 3. In three infants with lethal (type II) osteogenesis imperfecta the ratio alpha 1(III)/alpha 1(I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients. 4. The ratio of alpha 1(I)/alpha 2 and of alpha 1(III)/alpha 2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio alpha 1(III)/alpha 1(I) was increased. 5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied. 6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the alpha 1(I) chain rather than of the alpha 2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.

Adolescent↗
PubMed1981

Cytogenetic features of human neuroblastomas and cell lines.

We reviewed the banded karyotypes of 24 human neuroblastomas and cell lines to identify any consistent chromosomal abnormalities. Six of the 10 primary tumors and one of the 14 cell lines were studied at this institution. Of the 24 neuroblastomas karyotyped, 20 were near-diploid, one was near-triploid, and 3 were near-tetraploid. One primary tumor had a diploid karyotype without numerical or structural rearrangements. The 20 cases with a karyotype in the diploid range were statistically analyzed for gain or loss of while chromosomes and for structural abnormalities of each chromosome arm. The short arm of chromosome 1 was preferentially involved in structural rearrangements, occurring in 14 cases (p less than 0.01). In 11 of these cases, the abnormality of chromosome 1 included deletion of bands 1p32 leads to 1pter, rendering the cells monosomic for this genetic material. Of the remaining three cases, one involved a reciprocal translocation of chromosomes 1p and 12q, another had insertion of genetic material at band 1p13, and the third had an extra dark band at 1p36. No other numerical or structural abnormalities occurred with sufficient frequency to reach statistical significance (p greater than 0.20). Six of the primary tumors or cell lines in the diploid range had double minute chromatin bodies, four cell lines had homogeneously staining regions, and two cell lines had either double minute chromatin bodies or homogeneously staining regions in subpopulations of cells. Hence, partial monosomy for the short arm of chromosome 1 was the most consistent cytogenetic abnormality in the human neuroblastomas studied.

Cell Line↗
PubMed1979

Clonal characteristics of experimentally induced "atherosclerotic" lesions in the hybrid hare.

The female hybrid hare (Lepus timidus x Lepus europaeus) is heterozygous for electrophoretically separable, X-linked isoenzymes of glucose-6-phosphate dehydrogenase. The isoenzymes of this animal have been used as cellular markers in the study of the clonal origins of experimentally induced atherosclerotic lesions. Aortic lesions produced in the hybrid hare by feeding cholesterol and injuring the aortic wall with a catheter have been shown to have polyclonal characteristics and in this way are fundamentally different from atherosclerotic fibrous plaques in man.

Animals↗
PubMedDate not supplied

The effect of a self-care minimal intervention for colds and flu on the use of medical services.

OBJECTIVE: To determine the impact of mailed distribution of a brief self-care pamphlet on upper respiratory infection (URI)-related-medical care utilization. DESIGN: Randomized controlled clinical trial with randomization by physician panel. SETTING: Health maintenance organization. PATIENTS: 20,127 patients assigned to the panels of 22 primary care physicians randomly divided into an experimental group (n = 12,353) and a control group (n = 7,774), each consisting of 11 physician panels. INTERVENTION: A mailed four-page self-care pamphlet for URI care. MEASUREMENTS AND MAIN RESULTS: The medical records and survey data of a random sample of 790 persons were studied during a baseline period and an intervention period. URI visit rates decreased 14% more in the experimental group versus the control group (p = 0.878). Appropriateness of URI visits during the intervention period in the experimental group (80%) was comparable to that in the control group (76%). URI drug prescriptions during the intervention period for all 20,127 patients showed no significant difference. CONCLUSIONS: A simple mailed self-care pamphlet has little effect on medical care utilization for URI care.

Adult↗
PubMedDate not supplied

Nomegestrol acetate and vascular reactivity: nonhuman primate experiments.

Prevention of coronary artery disease has been recognized as a major benefit of estrogen replacement therapy (ERT) in postmenopausal women. However, endometrial hyperplasia induced by unopposed ERT has raised important safety concerns. Progesterone or synthetic progestins have been used in combined hormone replacement therapy (HRT) to prevent endometrial cancer risk. Therefore, a major concern has been to ensure that the vascular beneficial effects of estrogens are not opposed when combined with progestins. Nomegestrol acetate (NOMAC) is an orally active progestin widely prescribed for HRT. Its vascular effects were evaluated in two models of coronary vascular reactivity in primates: 1) the paradoxical vasoconstriction to acetylcholine (Ach) coronary infusion after 5 months of mildly atherogenic diet in ovariectomized (OVX) Cynomolgus monkeys and 2) the pharmacologically evoked coronary vasospasm in the OVX Rhesus monkey. In the first model, after 3 months of continuous oral administration in the diet at 0.1 mg/kg/day, E2 prevented the paradoxical response to Ach, alone as well as combined with 0.25 mg/kg/day NOMAC, whereas NOMAC counteracted the endometrial stimulation. In the second model, after one artificial cycle consisting of 28 days of E2 subcutaneous (s.c.) implant and of daily oral gavage with 1 mg/kg/day of NOMAC for the last 14 days, no vasospasm (0 of 11 tested animals) occurred when the complete challenge protocol, including serotonin and the thromboxane agonist U46619, was administered to OVX Rhesus monkeys. In the balanced crossover design, identical artificial cycles with medroxyprogesterone acetate (MPA) at the same dose resulted in 7 vasospasms in 12 animals. In parallel, effective progestative activity was demonstrated by a secretory pattern in endometrial sections obtained at the end of the cycle. In these two nonhuman primate cardiovascular models, NOMAC did not have the negating effects observed with MPA.

Acetylcholine↗
PubMedDate not supplied

Myofibroblast involvement in glycosaminoglycan synthesis and lipid retention during coronary repair.

Myofibroblasts of adventitial origin have been linked to neointimal formation and remodeling after coronary injury. Accordingly, the goal of this study was to examine whether myofibroblasts contribute to focal accumulation of glycosaminoglycans (GAGs) and lipids during coronary repair. GAG synthesis was assessed by ex vivo labeling of balloon-injured porcine coronary arteries with (14)C-glucosamine. The synthesis of total GAGs transiently increased at 8 days in the normolipemic model (a 2.2-fold increase over baseline, p < 0.05). The majority of newly synthesized GAGs were sensitive to chondroitin ABC lyase (chondroitin/dermatan sulfate GAGs). Versican was localized to myofibroblast-rich regions in the adventitia and neointima [positive for alpha-smooth muscle (SM) actin, negative for h-caldesmon and SM myosin heavy chain]. In contrast, the adjacent SM-rich media showed no increase in versican expression. The association between injury-induced GAG accumulation and lipid retention was examined at 2 weeks after coronary injury in the hyperlipemic model. Lipid (Oil Red O) accumulated in the neointima and adventitia, but not in the adjacent media. Coronary repair under hyperlipemic conditions was associated with macrophage infiltration (19 +/- 5 vs. 3 +/- 2% of neointimal cells in normolipemic animals, p < 0.001) and increased neointimal formation (1.8 +/- 0.5 vs. 1.0 +/- 0.3 mm(2) in normolipemic animals, p < 0.01). In conclusion, this study demonstrated a transient increase in GAG synthesis following coronary injury. Chondroitin sulfate proteoglycans (e.g., versican) were rapidly synthesized by activated adventitial and neointimal cells which could contribute to early lipid retention in injured vessels.

Animals↗
PubMedDate not supplied

Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages.

Intralipid is widely used for intravenous alimentation and contains triglyceride-emulsion particles and phospholipid liposomes. After infusion, triglyceride-emulsion particles resemble chylomicron remnants and thus may be atherogenic. On the other hand, intravenous infusion of phospholipid liposomes produces regression of experimental atherosclerosis and abolishes the ability of hypercholesterolemic rabbit plasma to cholesterol-load cultured macrophage foam cells. To determine the net effect of intralipid infusion on cellular cholesterol balance, J-774 macrophages were incubated for 18 hours with human serum obtained before, during, and after a 6-hour infusion of 10% Intralipid. Compared to serum-free medium, pre-infusion serum increased cellular unesterified cholesterol by 76% and cholesteryl ester by 78%. In contrast, serum obtained after the 6-hour infusion reduced cellular unesterified cholesterol by 23% and cholesteryl ester by 15%. Serum obtained 18 hours after the end of the infusion still showed impaired cholesterol-loading ability. Mouse peritoneal macrophages incubated with these serum samples behaved similarly. Compared to pre-infusion serum, postinfusion serum inhibited cellular uptake of 125I-low density lipoprotein and 125I-very low density lipoprotein by 50% and 80%, respectively, and also enhanced the efflux of cellular cholesterol by 46%. We conclude that the ability of human serum to cause cholesterol accumulation in cultured macrophages is abolished by an infusion of Intralipid. This effect is mediated by a reduction in cholesterol uptake by the cells and by an increase in cell cholesterol efflux. If similar events occur in the arterial wall, Intralipid infusion might inhibit foam cell formation in vivo.

Animals↗