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Biomedical subjects

J K Williams

Publications and source records attributed to J K Williams.

At least 19 recordsLinked to original sources

Human cardiac and skeletal muscle spectrins: differential expression and localization.

We describe multiple human cardiac and skeletal muscle spectrin isoforms. Cardiac muscle expresses five erythroid alpha,beta spectrin-reactive isoforms with estimated MR's of 280, 274, 270, 255, and 246 kD, respectively. At least one nonerythroid alpha-spectrin of MR 284 kD is expressed in heart. While skeletal muscle shares the 280, 270, and 246 kD erythroid spectrins, it expresses an immunologically distinct 284 kD nonerythroid alpha-spectrin isoform. The 255 kD erythroid beta-spectrin isoform is specific for cardiac tissue. By immunocytochemistry, both erythroid beta- and nonerythroid alpha-spectrins are localized to costameres, the plasma membrane, and the neuromuscular junctional region.

Adult

Intrapleural bupivacaine in the control of postthoracotomy pain.

A randomized, double-blind trial was conducted to determine the effectiveness of intrapleural bupivacaine hydrochloride in the management of pain after thoracotomy. Thirty-three men and 7 women with a mean age of 62 years (range, 21 to 76 years) undergoing elective posterolateral thoracotomy were randomly allocated preoperatively to either a study group receiving 20 mL of 0.25% bupivacaine or a control group receiving 20 mL of 0.9% saline solution through a pleural catheter every 4 hours. Patients received supplementary doses of intramuscular papaveretum as required. Assessment of pain, somnolence, and breathing capacity was performed after the intrapleural injections at 4, 24, 48, and 72 hours postoperatively. Pain assessment, as measured by a linear analog scale, was lower in the bupivacaine group at all times, reaching significance at 4, 24, and 72 hours (p less than 0.05). The forced vital capacity and forced expiratory volume in 1 second at 6 weeks postoperatively remained significantly lower than preoperatively (p less than 0.05). The fall in forced vital capacity from this postoperative level was significantly less in the bupivacaine group at 4, 24, and 48 hours, and the fall in forced expiratory volume in 1 second was significantly less at 4 and 48 hours in the treated group. When used in conjunction with doses of parenteral narcotic, intrapleural bupivacaine gives better pain control with less respiratory depression than intermittent doses of narcotic alone.

Adult

An in vitro study on the effect of UVA radiation on human gingival fibroblasts.

The recent availability of a 99.9% UVA source has made possible studies that show that low energy wavelengths, previously considered innocuous, significantly affected wound healing in hairless guinea pigs. Decreased wound tensile strength and a slower rate of wound contraction in irradiated animals were among the changes noted. Because of their advocated role in the wound healing process, fibroblasts were chosen to study the effects of pure UVA exposure at a cellular level. 3H-thymidine uptake levels were measured in 8 groups of fibroblast cultures (12 samples/group). The cultures were exposed to varying concentrations of pure UVA. Previously incorporated 14C-thymidine levels were used to compensate for differences in cell numbers between samples. At a fluence of 3.65 x 10(-3) watts/cm2, a significant decrease in 3H-thymidine incorporation (compared to controls) was seen for all exposure periods and there was a dose-dependent decrease only in 3H-thymidine uptake for cells exposed to 1-4 min of UVA. Using post-exposure incubations of 2-16 h, a time-dependent recovery of 3H-thymidine uptake was also demonstrated, from 40% of control at 4 h, to 75% at 8 h, and 99% at 16 h. The near-complete recovery at 16 h was seen in exposures up to 2.73 joules/cm2 (12 min), whereas higher concentrations showed only partial recovery. These studies demonstrated the deleterious, though reversible, effects of UVA on fibroblasts and suggest a possible pathophysiologic process for UVA's effect on wound healing in this animal model.

Cells, Cultured

Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries.

OBJECTIVES: This experiment sought to determine the effect of short-term administration of estrogen on endothelium-dependent dilation in the coronary arteries of 13 surgically postmenopausal female cynomolgus monkeys. BACKGROUND: Long-term estrogen replacement therapy prevents impaired endothelium-dependent dilation of atherosclerotic coronary arteries in postmenopausal female monkeys. However, it remains unclear whether this action of estrogen is due to long-term effects on plasma lipids and atherogenesis or to direct short-term effects on the endothelium. METHODS: The monkeys consumed an atherogenic diet for 18 months after bilateral ovariectomy. Vascular responses were measured just before euthanasia and necropsy. Dextrose in water (control), acetylcholine, 10(-6)M, and nitroglycerin were infused for 2.5 min each both before and 20 min after intravenous injection of 54 ng ethinyl estradiol. RESULTS: Quantitative coronary angiography revealed that the arteries constricted (-17 +/- 3%) in response to intracoronary infusion of acetylcholine before estrogen treatment but dilated (+5 +/- 3%) 20 min after intravenous injection of ethinyl estradiol (p less than 0.05). Coronary arteries dilated in response to nitroglycerin both before and after administration of estrogen (p greater than 0.05). Vascular responses of coronary arteries, both before and after administration of estrogen, were not associated with variation in plasma lipid concentrations, blood pressure, heart rate or plaque size. CONCLUSIONS: Estrogen affects endothelium-dependent coronary dilation within 20 min of administration and may have rapid direct effects on the vascular endothelium.

Acetylcholine

Comparison of visual-spatial performance strategy training in children with Turner syndrome and learning disabilities.

This study examined the effects of a verbal mediation strategy on three groups of subjects who had visual-spatial deficits. Thirteen females with Turner syndrome, 13 females with nonverbal learning disabilities, and 14 males with nonverbal learning disabilities, who ranged in age from 7 to 14 years, were taught via a cognitive behavioral modification approach to verbally mediate a spatial matching task. Pretest and posttest performance differences on parallel forms of a visual-spatial orientation task were examined. All three groups showed significant improvement in visual-spatial task performance after the training. There were no significant differences in the degree of improvement among the three groups. The results suggest that children with Turner syndrome may benefit from problem-solving strategy training in a manner similar to children with nonverbal learning disabilities.

Adolescent

School-aged children with Turner's syndrome.

Turner's syndrome (TS) is an abnormality of the X chromosome associated with cognitive and psychosocial adjustment problems as well as congenital anomalies. Children with TS are at risk for problems in academic achievement and psychosocial development. Recognition of these risks allows nurses to provide nursing interventions including anticipatory guidance, facilitation of parental interactions with the school, and interventions for management of problems in psychosocial development.

Adolescent

Fluoro-Gold's toxicity makes it inferior to True Blue for long-term studies of dorsal root ganglion neurons and motoneurons.

We studied the long-term effects of two retrogradely transported fluorescent dyes on survival of dorsal root ganglion neurons (DRGNs) and motoneurons (MNs). In adult female rats, we labeled DRGNs and MNs by soaking the cut sciatic nerve in Fluoro-Gold or True Blue. With True Blue, we found no difference in the number of labeled MNs or DRGNs in rats surviving 4 days or 20 weeks after nerve soak. With Fluoro-Gold, labeled DRGNs and MNs were decreased at 20 weeks compared with 4 days. Since there was no offsetting increase in unlabeled DRGNs at 20 weeks, Fluoro-Gold caused cell death.

Animals

Effects of oestrogens and progestogens on coronary atherosclerosis and osteoporosis of monkeys.

We have used the cynomolgus macaque as a model for the study of the effects of endogenous and exogenous sex steroid hormones on atherosclerosis and osteoporosis. As in human beings, premenopausal female cynomolgus macaques develop much less extensive coronary artery atherosclerosis than their male counterparts. Furthermore, surgical menopause results in a more atherogenic plasma lipoprotein pattern and an approximate doubling of atherosclerosis extent. Frequent pregnancy, a hyperoestrogenic state, results in an approximate 50% reduction in atherosclerosis extent. Physiological replacement with 17 beta-oestradiol alone or in combination with progesterone prevents the increase in coronary artery atherosclerosis extent associated with ovariectomy. This effect is independent of plasma lipoprotein concentrations and appears to be accounted for, at least in part, by an inhibitory effect of oestrogen replacement therapy on the uptake and degradation of LDL by the artery wall. Also, as in human beings, treatment with certain types of combination oral contraceptives results in marked decreases in plasma HDL-C concentration. Nonetheless, coronary artery atherosclerosis extent is reduced in monkeys by oral contraceptive treatment, and this effect is most pronounced among animals at highest risk due to theoretically adverse plasma lipoprotein profiles. It appears that, as with oestrogen replacement therapy, this effect can be accounted for, at least in part, by an inhibition of the uptake and degradation of low density lipoprotein by the artery wall. The monkey also appears to be a good model for studies of postmenopausal bone loss. As in women, surgical menopause results in significant diminution of bone mineral density and bone mineral content. Also, serum biomarkers of bone turnover (total alkaline phosphatase, acid phosphatase, tartrate-resistant acid phosphatase and osteocalcin) are increased in surgically postmenopausal monkeys, indicating increased bone turnover resulting from the surgical menopause. These increases in bone loss and indices of bone turnover were prevented by physiological oestrogen replacement therapy. Cynomolgus monkeys seem to be exceptionally useful models for studies of the effects of sex steroid hormones on atherosclerosis and osteoporosis, two major public health problems in postmenopausal women.

Animals

Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis.

BACKGROUND: Healthy arteries exhibit endothelium-dependent dilation in response to both local acetylcholine and increased blood flow. In humans, clinically overt coronary artery disease is characterized by loss of dilation to both acetylcholine and blood flow. The temporal relation, however, between functional abnormalities of the endothelium and the development of atherosclerosis has not been established. METHODS AND RESULTS: We examined endothelial vasodilator function in vivo at an early stage of the development of atherosclerosis. Two groups of seven Macaca fascicularis monkeys were studied; one group was fed a high cholesterol diet (0.73-1.0 mg cholesterol per calorie) for 11 months. Cholesterol feeding was associated with increased plasma cholesterol levels and with intimal thickening of the iliac arteries but with no reduction in luminal diameter. Endothelium-dependent vasomotor responses of the iliac arteries were then examined in vivo by quantitative contrast angiography. Acetylcholine produced significant dilation in the controls but paradoxical constriction in the group with early atherosclerosis (+9.0 +/- 3.2% versus -5.3 +/- 5.4%, p less than 0.05). In response to a twofold increase in blood flow achieved by administering adenosine distal to the arterial segment under examination, the controls again dilated, whereas the atherosclerotic group failed to dilate (+ 11.6 +/- 2.1% versus + 0.5 +/- 2.4%, p less than 0.05). Both groups, however, were able to dilate, and dilated equally, to the nonendothelium-dependent agent nitroglycerin (+ 13.7 +/- 4.8% versus + 19.1 +/- 4.3%, NS). CONCLUSIONS: Endothelium-dependent vasodilation in response to both acetylcholine and increased blood flow may be lost early in the course of developing atherosclerosis before the appearance of stenosing and occlusive disease.

Acetylcholine

Psychosocial factors impair vascular responses of coronary arteries.

BACKGROUND: Four sets of monkeys were used to examine the effect of chronic psychosocial disruption and diet on dilator responses of coronary arteries. METHODS AND RESULTS: One set consisted of monkeys consuming monkey chow and living in a stable social setting (nonatherosclerotic controls, n = 6). Three sets consumed an atherogenic diet for 14 months followed by one of three treatments for the next 16 months: 1) a high-cholesterol diet and housed in unstable social groups (n = 9); 2) a low-cholesterol diet and housed in unstable (n = 8); or 3) stable groups (n = 10). Quantitative coronary angiography revealed that intracoronary infusion of acetylcholine resulted in a change of diameter (versus infusion of 5% dextrose in water) of +4 +/- 1% in control monkeys and -11 +/- 4% in unstable monkeys consuming a high-cholesterol diet (p less than 0.05). In monkeys consuming the cholesterol-lowering diet, the change in artery diameter was +2 +/- 4% in stable and -10 +/- 4% in unstable social conditions (p less than 0.05) despite a similar plaque size (0.4 +/- 0.2 and 0.5 +/- 0.1 mm2) and total plasma cholesterol concentrations (179 +/- 9 and 172 +/- 6 mg/dl), respectively. The arterial response to nitroglycerin was similar among all groups of monkeys. CONCLUSIONS: We conclude that chronic social disruption is associated with relative arterial constriction in response to acetylcholine in atherosclerotic monkeys consuming a cholesterol-lowering diet.

Animals

Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis.

Diet-induced coronary artery atherosclerosis develops in rhesus monkeys (Macaca mulatta). The goal of this study was to establish the rhesus monkey as an animal model of coronary heart disease (CHD). From a colony of 160 rhesus monkeys fed an atherogenic diet, we identified 14 monkeys with electrocardiographic and echocardiographic evidence of CHD. When compared with 14 rhesus monkeys matched for age, gender, and dietary history with normal electrocardiograms and echocardiograms, monkeys with CHD had higher arterial blood pressures (mean +/- SEM, 92 +/- 4 mm Hg vs 75 +/- 5 mm Hg, respectively), lower high-density lipoprotein cholesterol concentrations (mean +/- SEM, 1.70 +/- 0.25 mmol/L vs 2.32 +/- 0.28 mmol/L [66 +/- 10 mg/dL vs 90 +/- 11 mg/dl]), and lower A-l apolipoprotein concentrations (mean +/- SEM, 200 +/- 17 mg/dL vs 252 +/- 15 mg/dL). Monkeys with CHD tended to have higher total plasma cholesterol concentrations (mean +/- SEM, 11.6 +/- 1.55 mmol/L vs 9.36 +/- 0.93 mmol/L [450 +/- 60 mg/dL vs 362 +/- 36 mg/dL]) and higher low-density lipoprotein cholesterol concentrations (mean +/- SEM, 8.71 +/- 1.75 mmol/L vs 6.12 +/- 0.90 mmol/L [337 +/- 68 mg/dL vs 237 +/- 35 mg/dl]) than monkeys with normal electrocardiograms and echocardiograms. We conclude that rhesus monkeys, like human beings, develop CHD as a complication of coronary artery atherosclerosis. Furthermore, risk factors for CHD in rhesus monkeys and human beings are similar.

Animals

Synthesis of IL-1 alpha and IL-1 beta by arterial cells in atherosclerosis.

Interleukin-1 (IL-1) has been implicated as a regulatory protein in the development and clinical sequelae of atherosclerosis. To determine which cells in the atherosclerotic plaque synthesize IL-1 in situ, the authors evaluated histologic sections of iliac arteries from cynomolgus monkeys using probes for IL-1 alpha and beta. A polyclonal antibody to IL-1 alpha and beta was used to determine if proteins were concomitantly produced. The predominant cells expressing IL-1 alpha and beta mRNA were foam cells in the intima. Adherent leukocytes and vascular smooth muscle cells (VSMCs) expressed mRNA for IL-1 alpha. Microvascular endothelium expressed mRNA for both IL-1 alpha and beta. IL-1 proteins were located frequently in cells expressing IL-1 mRNA. These results indicate that endothelium and VSMCs, in conjunction with macrophages, serve as localized sources of IL-1 protein synthesis. These findings suggest that vascular cells may contribute directly to the pathogenesis of atherosclerotic vascular disease by actively secreting potent biologic mediators that modify vascular and immune cell function.

Animals

Oral contraceptives and reproductive system cancer. Benefits and risks.

Large epidemiologic studies conducted to date in the United States and abroad have not demonstrated any statistically significant increase in the overall incidence of breast cancer among women who used oral contraceptives (OCs). The cumulative risk of breast cancer among women less than 60 years of age is clearly not related to OC use, although the incidence of breast cancer in certain subgroups of premenopausal women who used OCs may be increased and warrants monitoring. Evidence of a latency period in the development of breast cancer among OC users is not convincing. Studies to date have indicated that the risk of invasive cervical cancer appears to be unaffected by OC use. The data on cervical intraepithelial neoplasia are inconclusive and fraught with confounding variables. There is unequivocal evidence that OC use reduces the incidence of other reproductive system cancers, notably ovarian and endometrial.

Breast Neoplasms

Use of the labor-delivery-recovery room in an urban tertiary care hospital.

Single-room maternity care is an attractive delivery system to obstetricians and consumers. We reviewed the first 15 months' experience in a committed labor-delivery-recovery room unit where all patients were admitted for single-room care regardless of risk. The rate of transfer to a traditional delivery room for vaginal delivery was 3.8%.

Delivery Rooms

Retrograde transport of fluoro-gold in corticospinal and rubrospinal neurons 10 and 20 weeks after T-9 spinal cord transection.

Retrograde labeling with horseradish peroxidase is greatly diminished in corticospinal and rubrospinal neurons axotomized by complete T-9 spinal cord transection. We found, 10 or 20 weeks after a complete T-9 cord transection, that the number of corticospinal and rubrospinal neurons retrogradely labeled after Fluoro-Gold insertion into a new transection at T-1 did not differ from that of controls. While transection alters uptake, transport, and/or intracellular metabolism of some transportable substances, it does not affect the ability of the neurons to be retrogradely labeled with Fluoro-Gold.

Animals

Thrombin activity induced by balloon angioplasty of the coronary artery in Macaca fascicularis (cynomolgus monkey).

In this paper we address the question of whether balloon angioplasty induces thrombin action. In the studies reported here we measured fibrinopeptide A levels in a group of atherosclerotic monkeys undergoing coronary angioplasty. A blood collection catheter was introduced into the inferior vena cava through a femoral vein, and the angioplasty catheter introduced via the femoral artery. Heparin was administered immediately after insertion of the arterial catheter. Serial blood samples were collected for 20 min before angioplasty and for 10 min after angioplasty. Baseline levels of FpA were high, presumably in response to the trauma of introducing the catheters. After heparin administration the FpA concentration declined with a half-time of 1.1 min. In response to balloon inflation there was a clear increase in the concentration of FpA, despite the presence of a therapeutic concentration of heparin. The magnitude of the FpA rise was markedly different between animals, but was evident in the aggregate data after subtraction of background levels of FpA. By integration of the plasma FpA concentration curve, the amount of fibrinogen converted to fibrin in response to angioplasty was calculated to be approximately 0.4 mg/animal. We conclude that angioplasty induces significant activation of the coagulation system.

Angioplasty, Balloon, Coronary