Stage specific gene expression in the post-infective L3 of the filarial nematode, Brugia pahangi.
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Age Factors↗
Biomedical subjects
S J Hunter
Publications and source records attributed to S J Hunter.
Anti-interleukin-4 modulation of the Th2 polarized response to the parasitic nematode Brugia pahangi.
Lymphatic filariasis is a chronic disease characterized by a pronounced Th2 bias in the immune response and impaired antigen (Ag)-specific Th1 responses. We have used a mouse model of filariasis to investigate the role of the infective form (the third-stage larvae [L3]) in modulating the immune response. Subcutaneous infection of BALB/c mice with L3 of Brugia pahangi has a profound effect on Th cell function. By day 12 post-infection, spleen cells from these mice exhibited a dramatic reduction in concanavalin A-driven proliferation and interleukin-2 (IL-2) and gamma interferon (IFN-gamma) secretion in comparison with uninfected controls. However, exposure to L3 did not render the mice completely unresponsive; these animals mounted a strong Th2 response to the parasite, characterized by elevated levels of IL-4, IL-5, and IL-10 and parasite-specific serum immunoglobulin G (IgG), IgG1, and IgE. Treatment of spleen cells from L3-infected mice with neutralizing anti-IL-4 or recombinant IL-2 resulted in a dramatic increase in concanavalin A-induced proliferation and IL-2 and IFN-gamma production. Despite their defective polyclonal Th1 response, cells from L3 infected mice proliferated when stimulated with Ag, and this response was blocked by anti-IL-4. However, anti-IL-4 treatment failed to induce Ag-specific IL-2 or IFN-gamma production, indicating that B.pahangi-primed Th1 cells do not appear to be present or are still unable to respond even in the absence of IL-4.
Animals↗
Association between insulin secretory pulse frequency and peripheral insulin action in NIDDM and normal subjects.
Abnormalities of both insulin secretion and insulin action occur in NIDDM. It is not clear, however, which is the primary defect. Recently, it has been suggested that the frequency of insulin pulses is an important factor regulating insulin action in normal humans. We examined the relationship between pulsatile insulin secretion and insulin action in eight NIDDM subjects and eight health matched control subjects. Insulin action was assessed prevailing fasting glucose levels before and after hype insulinemia (2-h insulin infusion at 2.0 mU / kg / min). Pulsatility of insulin was assessed by sampling every 2 min for 90 min after an overnight fast and identifying insulin pulses using the computer program Pulsar. Fasting plasma glucose and postabsorptive endogenous glucose production were both greater in diabetic subjects compared with control subjects (10.1 +/- 1.2 vs. 5.4 +/- 0.1 mmol/l, P < 0.01; 11.8 +/- 0.8 vs. 9.9 +/- 0.4 micromol / kg / min, P < 0.05). During the 2.0 mU insulin infusion, glucose clearance was lower in the diabetic subjects (3.6 +/- 0.7 vs. 6.9 +/- 0.5 ml / kg / min), P < 0.05), whereas endogenous glucose production was suppressed to a similar degree in both groups (4.5 +/- 0.8 vs. 3.6 +/- 0.7 micromol x kg(-1) x min(-1), NS). The frequency of insulin pulses and glucose clearance were negatively correlated in both diabetic subjects (r = -0.75, P < 0.05) and normal control subjects (r = -0.82, P < 0.01). This negative correlation was also present in both groups taken together (r = -0.72, P < 0.001). There was no correlation between insulin pulse frequency and endogenous glucose production either in the fasting state or during hyperinsulinemia. We concluded that the frequency of insulin pulses and peripheral insulin sensitivity are closely linked in NIDDM and normal subjects.
Activity Cycles↗
Elderly women in northern New England exhibit seasonal changes in bone mineral density and calciotropic hormones.
A seasonal component to bone loss has been reported in some postmenopausal women. We hypothesized that elderly women in northern New England would be at high risk for bone loss during winter because of their age, diet and lack of sunlight. Eighteen elderly but healthy women (mean age 77 years) started a 2-year observational study in a remote area of northwestern Maine (Greenville: 45.5 degrees N latitude). Fifteen women completed the study. Bone mineral density of the spine (L-BMD) and hip (F-BMD) and biochemical markers of bone turnover were measured biannually. In vitro photo-conversion of provitamin D3 to previtamin D3 was determined in the winter and spring. Initial calcium and vitamin D intake averaged 700 +/- 72 mg/day and 6.2 +/- 1.2 micrograms/day, respectively. During the first year L-BMD dropped 4.2% (P = 0.002) while F-BMD dropped 2.4% (P = 0.09), primarily because of steep declines during the fall and winter (August to February: L-BMD: 3.6%, P = 0.001; F-BMD: 3.0%, P = 0.04). In that 6-month period, serum 25 hydroxyvitamin D (25(OH)D) fell 13 +/- 6% (P = 0.06) and PTH rose 27 +/- 11% (P = 0.01). Additionally, there was no detectable in vitro conversion of provitamin D to previtamin D over 8 h of one sunny winter day. In the summer, PTH and 25(OH)D reverted to basal levels and significant in vitro photoconversion of provitamin D to previtamin D was detected. In the 2nd year of the study, vitamin D consumption increased (+2.0 +/- 1.2 micrograms/day, P = 0.03 vs. baseline), L-BMD increased slightly (+1.8%, P = 0.05) and F-BMD did not change (+0.5%, P = NS). Again, changes in BMD and vitamin D were seasonal: L-BMD and F-BMD were constant during fall and winter but both sites showed increases during summer (L-BMD: +1.7%, P = 0.04, F-BMD: +1.6%, P = 0.25). In the second winter, serum 25(OH)D fell nearly 20% and PTH rose 17%. Increased dietary consumption of vitamin D was positively correlated with changes in F-BMD at 18 months (r = 0.61, P = 0.02) and resulted in slightly greater serum 25(OH)D concentrations during the second winter than the first. The difference in serum 25(OH)D between the first and second winter was the strongest predictor of lumbar bone accretion during the second year of the study (r = 0.59, P = 0.04). In this 24-month observational study, significant seasonal changes in BMD, 25(OH)D and PTH were reported.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin.
We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Topical↗
Variable patterns of atrial natriuretic peptide secretion in man.
Peripheral circulating levels of atrial natriuretic peptide may exhibit short-term variation compatible with a pulsatile pattern of secretion. We obtained samples every 2 min for 90 min from the antecubital vein of 16 patients with chronic cardiac failure and 13 controls. Overall levels were higher in the patients (median and quartiles 230 (125,325) vs. 26 (16,48) ng l-1; P < 0.001). In both groups there was considerable variability, with 10 (2-12) peaks, 9 (7-15) troughs (both defined as > 2 SD from the mean) and 16 (13-18) pulses (defined by computer) during the sampling period in controls, and a similar number in patients. We then carried out simultaneous sampling in the pulmonary artery, femoral artery and peripheral vein in eight subjects with normal cardiac function and six patients with impaired function due to valvular heart disease. The pattern of variability was preserved in all three sites in both groups, suggesting intermittent secretion rather than variable breakdown of the peptide in the lung. No changes in right atrial pressure or heart rate were observed to coincide with the variations, but levels of the peptide in the pulmonary artery correlated with right atrial pressure in patients (r = 0.87; P < 0.05). The mechanism of such periodicity and its pathophysiological importance remain unknown.
Adult↗
Insulin-like growth factors and bone: the osteoporosis connection.
In the last five years significant progress has been made defining the role of insulin-like growth factors (IGFs) in the process of bone remodeling. In this paper, we present critical evidence that IGF-I and IGF-II are produced by bone cells and regulate specific osteoblastic and osteoclastic functions. In addition, we review work from several laboratories establishing the role of the skeletal IGF binding proteins as an integral component of a unique IGF regulatory system. Data presented suggest that the calciotropic hormones active in the bone remodeling process may exert their effects through the IGF regulatory system. In contrast to the well-defined local action of IGF-I and IGF-II on the skeleton, the relationship between circulating IGF-I and bone remodeling is less certain. Newer data are presented which suggest the potential utility of serum growth factor measurements in certain clinical states. Finally, this paper presents an overview of the most current efforts to stimulate bone formation using recombinant IGFs. However, work on the beneficial aspects of IGFs for the skeleton remains preliminary at best with the eventual therapeutic role of IGF-I in osteoporosis yet to be defined.
Animals↗
Secondary patient transfer by air: an audit of 3 years' experience of the Royal Air Force in the world-wide transport of critically ill patients.
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Aerospace Medicine↗
A comparison of bupivacaine instillation and inguinal field block for control of pain after herniorrhaphy.
In a single-blind, randomised trial, 50 consecutive adult patients for inguinal herniorrhaphy under general anaesthesia received either an inguinal field block or bupivacaine instilled into the wound to provide postoperative analgesia. Bupivacaine instillation was found to be simple, safe and effective. The method is particularly appropriate for day-case surgery.
Adolescent↗
In vitro resorptive activity of isolated chick osteoclasts: effects of carbonic anhydrase inhibition.
A potent inhibitor of carbonic anhydrase, 5-[3-hydroxybenzoyl]thiophene-2-sulfonamide (HTS), was shown to cause a 37% reduction in the area of resorption pits formed by isolated chick osteoclasts when used at a dose of 10(-7) M. HTS at doses of 10(-9) and 10(-7) M was also effective in reducing acid formation by the osteoclasts (14 and 36%, respectively). Additionally, the effect of HTS was found to be readily reversed by removing the agent, showing that it does not exert a toxic effect on the cells. This study indicates that the inhibitory effect of HTS on bone resorption is at the level of the acid-forming mechanism in osteoclasts and supports the view that carbonic anhydrase has a central role in the process.
Acid Phosphatase↗
The pneuPAC hyperbaric variant HB: a ventilator suitable for use within a one-man hyperbaric chamber.
We describe the performance of the pneuPAC hyperbaric variant HB, a ventilator designed for use in a one-man hyperbaric chamber. The ventilator delivered minute volumes of 11-23 litre at 1 atm abs to 7.6-16 litre at 2.5 atm abs. The delivered minute volume may be controlled easily from outside the chamber by manipulation of the ventilator rate, 11.5-31 b.p.m.
Evaluation Studies as Topic↗
Two incidents of complete failure of OAV 7750 ventilators.
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Anesthesiology↗
Primary malignant melanoma of the oesophagus. Report of a case with flow cytometric DNA analysis.
Primary malignant melanoma is a very rare tumour of the oesophagus, and although this is the first case reported in a black patient in South Africa, the clinical, radiographic and histopathological features were characteristic of this malignancy. Primary oesophageal melanoma is a highly lethal tumour--fewer than 2% of patients are surviving 5 years after diagnosis. Flow cytometric DNA analysis of the resected specimen in this case revealed two populations of malignant cells, one of which had grossly abnormal DNA. Existence of two clones of malignant melanoma cells supports the observations that this tumour is biologically aggressive, radioresistant and almost always incurable.
DNA, Neoplasm↗
Age-related changes in serum insulin-like growth factor-binding proteins in women.
Plasma insulin-like growth factor-I (IGF-I) concentrations are reported to decline with advancing age. Five IGF-binding proteins (IGF-BPs) have recently been characterized in human serum, although their biological role beyond circulatory transport of IGF-I is unknown. We studied plasma IGF-I (by RIA) and serum IGF-BPs (by Western ligand blotting) in healthy elderly (n = 21) and healthy young (n = 22) women to determine if aging alters IGF-I and its high affinity BPs. Plasma IGF-I was significantly lower in the elderly than in the young group (0.78 +/- 0.08 vs. 1.22 +/- 0.11 U/ml; P less than 0.005). The number and size of IGF-BPs did not differ between age groups, but the IGF-BP binding ratios (binding of one BP fraction/binding of all fractions) for the BP-53 acid-stable complex (41.5K and 38.5K BPs), the 30K IGF-BP, and the 24K IGF-BP were all lower in the elderly than in the young group (P less than 0.01 for each fraction, elderly vs. young). In contrast, the 34K IGF-BP binding ratio was significantly greater in the elderly than in the young (0.30 +/- 0.03 vs. 0.12 +/- 0.01; P less than 0.001) and correlated closely with advancing age (r = 0.64; P less than 0.01). The changes in IGF-BPs found in the elderly are quite similar to alterations in serum IGF-BPs previously reported in GH deficiency. Since several IGF-BPs in vitro have been shown to modulate the mitogenic activity of IGF-I, the serum IGF-BP changes noted above may be important for the growth and maintenance of connective tissue, muscle, and bone during the aging process.
Adult↗
DNA ploidy in oesophageal cancer. A preliminary report.
Prognosis in oesophageal cancer is directly related to depth of invasion and lymph node metastases. However, without surgical exploration, assessment of the spread of oesophageal cancer is notoriously inaccurate and there is a need for another objective measurement of prognosis. In this study, the relationship of DNA-ploidy status to tumour length, histological appearance, extra-oesophageal spread and survival was examined in 42 patients with squamous oesophageal cancer. No correlation was found between DNA-ploidy status and tumour length or histological appearance. But the DNA-aneuploidy rate in cancers with extra-oesophageal spread was significantly greater than the rate in tumours localised to the oesophagus (P = 0.038). Short-term survival was poorer in patients with DNA-aneuploid cancers than in those with a DNA-diploid pattern. DNA analysis may prove to be a more accurate guide to prognosis in oesophageal cancer than either clinical or operative staging.
Carcinoma, Squamous Cell↗
Characterization of the cytoskeleton of isolated chick osteoclasts: effect of calcitonin.
We investigated the effects of calcitonin (CT) and parathyroid hormone (PTH) on the distribution of actin, tubulin, vimentin, and on cell size in cultured chick osteoclasts. In addition, we studied the effects of colchicine on intracellular acidity. Osteoclasts were isolated from the endosteum of 2-3-week chick tibias and were maintained under culture conditions for 5 days. The cells were treated with CT for 30 min or PTH for 60 min and were observed after immunocytochemical staining of cytoskeletal proteins. In untreated cells, actin was found in both a filamentous and a punctate staining pattern, with indented or invaginated regions free of punctate spots. The tubulin distribution in untreated cells was characterized by a pattern of microtubules radiating from the cell center and running parallel to the cell edge. Vimentin staining was usually localized to the perinuclear area. There were no changes in cytoskeletal element distribution or morphology attributable to PTH treatment. Osteoclasts treated with CT were more irregularly shaped, contained more retraction fibers, and were more rounded, with a denser array of cytoskeletal elements in the cell center. In addition, the mean area of the CT-treated cells was significantly less than that of the untreated cells. The actin distribution after CT treatment was still characterized by both a filamentous and a punctate pattern. After CT treatment, vimentin staining appeared more centrally localized than in untreated cells and tubulin staining revealed microtubules which now extended to the retracted cell margin. These results indicate that isolated osteoclasts respond to CT by significant morphological changes which are reflected in the distribution of the major cytoskeletal elements. Disruption of the microtubular system by colchicine treatment also resulted in an initial increase in intracellular acidity, suggesting the involvement of microtubules in the movement of acid-laden vesicles to the exterior.
Acid Phosphatase↗
Characterization of isolated and cultured chick osteoclasts: the effects of acetazolamide, calcitonin, and parathyroid hormone on acid production.
The effects of acetazolamide, calcitonin (CT), and parathyroid hormone (PTH) on acid production in isolated osteoclasts has been investigated. Osteoclasts were isolated from the endosteum of 3-week chick tibias and were maintained under culture conditions for 5 days. The cells were treated with acetazolamide (10 x 4 M and 10(-7) M), CT (1 mU/ml and 0.31 mU/ml) and PTH (6.5 U/ml and 0.40 U/ml) for 1, 3, 6, and 18 hr. The cells were stained with acridine orange and the intensity of fluorescence measured by a light microscope photometer. Acetazolamide treatment resulted in a steady decline in intracellular acidity, suggesting that carbonic anhydrase plays a major role in acid production in isolated osteoclasts. Treatment with PTH produced a decline in acidity at 1 hr, followed by a peak at 3 hr and then a decline at 6 and 18 hr. The transient increase in acidity may be due to activation of carbonic anhydrase by PTH. Calcitonin treatment also resulted in a decline in cell acidity which was similar, but less pronounced than that resulting from acetazolamide treatment. These results indicate that calcitonin may mediate osteoclast activity by alterations in intracellular acid production.
Acetazolamide↗