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C Chapman

Publications and source records attributed to C Chapman.

At least 91 records · Page 5Linked to original sources
PubMed1993

Pharmacologic induction of posterior vitreous detachment in the rabbit.

OBJECTIVE: To assay the proteolytic activity of plasmin on the vitreoretinal junction and to assess a potential facilitating effect on posterior vitreous detachment. METHODS: We injected 1 U of plasmin into the vitreous of rabbits. Some eyes underwent vitrectomy after plasmin injection. Electroretinography and electron microscopy were performed. RESULTS: In plasmin-treated eyes, electroretinography displayed a transient (3 days) decreased b-wave amplitude. Histologic examination demonstrated posterior vitreous detachment in eyes that received intravitreal plasmin followed by vitrectomy. CONCLUSION: Plasmin may prove to be a useful biochemical adjunct to mechanical vitrectomy.

Animals↗
PubMed1993

Gene mutations and increased levels of p53 protein in human squamous cell carcinomas and their cell lines.

Using immunocytochemical and Western blotting techniques we have demonstrated the presence of abnormally high levels of p53 protein in 8/24 (33%) of human squamous cell carcinomas (SCC) and 9/18 (50%) of SCC cell lines. There was a correlation between the immunocytochemical results obtained with eight SCC samples and their corresponding cell lines. Direct sequencing of PCR-amplified, reverse transcribed, p53 mRNA confirmed the expression of point mutations in six of the positive cell lines and detected in-frame deletions in two others. We also detected two stop mutations and three out-of-frame deletions in five lines which did not express elevated levels of p53 protein. Several of the mutations found in SCC of the tongue (3/7) were in a region (codons 144-166) previously identified as being a p53 mutational hot spot in non-small cell lung tumours (Mitsudomi et al., 1992). In 11/13 cases only the mutant alleles were expressed suggesting loss or reduced expression of the wild type alleles in these cases. Six of the mutations were also detected in the SCCs from which the lines were derived, strongly suggesting that the mutations occurred, and were selected, in vivo. The 12th mutation GTG-->GGG (valine-->glycine) at codon 216 was expressed in line SCC-12 clone B along with an apparently normal p53 allele and is to our knowledge a novel mutation. Line BICR-19 also expressed a normal p53 allele in addition to one where exon 10 was deleted. Additionally 15 of the SCC lines (including all of those which did not show elevated p53 protein levels) were screened for the presence of human papillomavirus types 16 and 18 and were found to be negative. These results are discussed in relation to the pathogenesis of SCC and the immortalisation of human keratinocytes in vitro.

Base Sequence↗
PubMed1993

The relationship of haemoglobin to serum erythropoietin concentrations in the anaemia of rheumatoid arthritis: the effect of oral prednisolone.

Previous studies of the erythropoietin response to anaemia in RA have yielded conflicting findings. Some have found the response to be impaired and others have found a normal response. We have compared erythropoietin (EPO) levels measured by radioimmunoassay, in 54 anaemic rheumatoid patients and 55 patients with iron deficiency anaemia but no inflammatory disease. The erythropoietin response in the rheumatoid patients was impaired compared with the control group (P < 0.025) but only seven rheumatoid patients showed a response which fell below the 95% confidence intervals predicted for the control group. Rheumatoid patients who fell within the highest quartile for serum ferritin concentrations (i.e. those most likely to have anaemia of chronic disease) had significantly lower EPO levels compared with the control group (P < 0.01). EPO levels in rheumatoid patients within the lowest quartile for ferritin (i.e. those with iron deficiency anaemia) were not significantly different from the control group (P = 0.670). The difference in EPO response between the RA patients in the upper and lower quartile for ferritin approached but did not achieve significance (P = 0.056). In a second study 15 anaemic RA patients were given a 5-day course of oral prednisolone 1.5 mgkg-1. Hemoglobin did not rise significantly until day 4 but EPO levels fell by day 1 (P < 0.005) and remained lower than pretreatment values throughout the study. Thus, in RA patients, anaemia of chronic disease is associated with inappropriately low EPO concentrations but this does not appear to be the major cause of the anaemia and Hb response to prednisolone does not depend upon an increase in EPO concentration.

Administration, Oral↗
PubMed1992

Leeds inquiry.

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England↗
PubMed1992

Activation of kappa-opioid receptors inhibits depolarisation-evoked exocytosis but not the rise in intracellular Ca2+ in secretory nerve terminals of the neurohypophysis.

Nerve endings of the magnocellular neurohypophysial neurones possess kappa-opioid receptors. Using a preparation of isolated terminals from the neurohypophysis we studied kappa-opioid effects on secretion of oxytocin and vasopressin and on intracellular Ca2+ concentration ([Ca2+]i) measured fluorimetrically or using digital video imaging with Fura-2. The dihydropyridine Ca(2+)-channel antagonist nicardipine reduced [Ca2+]i responses to K(+)-depolarisation (30-40 mM K+) by 55-75% and inhibited evoked secretion of oxytocin and vasopressin to a similar extent. The selective kappa-receptor agonist D-Pro10 Dynorphin A 1-11 (DPDYN) substantially inhibited K+ evoked secretion of oxytocin by 40-90% and secretion of arginine vasopressin (AVP) by 20-50%. DPDYN caused only a 10% reduction in the average total population [Ca2+]i response to K+ depolarisation. No sub-population of inhibitory responses was observed when samples of individual terminal [Ca2+]i responses were examined with imaging. Although kappa-receptors are coupled to Ca(2+)-channels at neuronal somata our data suggest that alternative effector mechanisms operate in these secretory nerve endings.

Animals↗
PubMed1992

Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis. The Medical Research Council Working Party for Leukaemia in Adults.

Both melphalan and cyclophosphamide increase life expectancy in patients with myelomatosis, but few large randomised studies have compared combination chemotherapy regimens with these single agents. In the Vth MRC myelomatosis trial, the survival of 314 patients randomised to receive ABCM (adriamycin, BCNU, cyclophosphamide, and melphalan) as first-line treatment was significantly longer than that of 316 patients given intermittent melphalan (M7) (p = 0.0003). The 75%, median, and 25% survivals were 7, 24, and 42 months, respectively, with M7 and 10, 32, and 56 months, respectively, with ABCM. Stable disease with few symptoms (plateau) was achieved by 61% of patients given ABCM and 49% of those given M7 (p = 0.004). Myelotoxicity was comparable between regimens. Cross-trial analysis suggests that M7 is comparable to melphalan and prednisone or melphalan, prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth MRC trials is comparable; and that ABCM gave better survival than intermittent melphalan regimens in the prognostic groups analysed. The results indicate that ABCM is an acceptable regimen that is more effective than melphalan, with or without prednisone, for first-line treatment of myelomatosis.

Aged↗
PubMed1992

Naloxone prevents interruption of parturition and increases plasma oxytocin following environmental disturbance in parturient sows.

Experiments in rodents have suggested that environmental disturbance can disrupt parturition through an opioid-mediated inhibition of oxytocin secretion. To test this hypothesis in a large animal model, 14 primiparous female pigs were allowed to commence parturition in a strawed pen. Five of these gilts were allowed to continue parturition undisturbed in this pen, while the remainder were moved to a farrowing crate immediately after the birth of the first piglet. At this time, pigs were injected subcutaneously with either the opioid antagonist naloxone (n = 4; dose 1 mg/kg body weight) or saline (n = 5). Whereas the undisturbed pigs all gave birth to a second piglet within 53 min, in three of the five disturbed and saline-treated pigs no further births occurred for 2 h, at which time oxytocin was administered subcutaneously to restart parturition. By contrast, all of the naloxone-treated pigs gave birth spontaneously within 2 h, although mean interbirth intervals were still prolonged compared to undisturbed pigs. In a second experiment, nine primiparous female pigs with chronic catheters preplaced in the external jugular vein were similarly moved after the birth of their first piglet and either injected with naloxone (n = 5) or saline (n = 4). Again, parturition was interrupted in three out of four saline-treated animals for at least 2.5 h, but resumed promptly when exogenous oxytocin was administered. Plasma concentrations of oxytocin in these pigs were significantly lower than in naloxone-treated pigs, five out of six of which gave birth spontaneously to one or more piglets within 2.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of age, sex and the oral contraceptive on the platelet membrane fibrinogen binding site (glycoprotein IIb/IIIa).

1. We have studied the effects of age, sex and the oral contraceptive pill on platelet fibrinogen 'receptor' density (Bmax) and affinity (Kd). 2. [125I]-fibrinogen binding to gel-filtered platelets was assessed after stimulation with adenosine 5-diphosphate (ADP) and thrombin in 60 normal subjects; 37 females and 23 males. 3. For both agonists there was no significant difference in Bmax or Kd between the sexes. A trend towards increasing affinity (reduced Kd) with age was noted in the female group following ADP stimulation. This was not considered to be physiologically relevant. In the group as a whole no significant relationship of Bmax and Kd with age was demonstrated. 4. A further group of eight women taking low dose oestrogen combined oral contraceptive pill were studied on days 7, 14, 21 and 28 of the treatment cycle and compared with eight women with regular ovulatory cycles. No significant variations in Bmax or Kd were detected within or between cycles in these two groups.

Adenosine Diphosphate↗
PubMed1992

Reduced erythropoietin response to anaemia in elderly patients with normocytic anaemia.

We studied the effect of age on the relationship between haemoglobin and serum erythropoietin (EPO) levels in anaemic patients. 568 patients over 70 years of age were compared with 137 patients under 70 and a reference group of 144 patients of all ages with proven iron deficiency. EPO was measured using a radioimmunoassay. We found that elderly patients with a normocytic anaemia (N = 375) had a statistically lower EPO response than younger patients with normocytic anaemia (N = 61) (p < 0.05) or patients of all ages with iron-deficiency anaemia (p < 0.05). There was no difference between the sexes. Elderly patients with microcytic or macrocytic anaemia had a normal EPO response as compared to the "gold standard" of iron deficiency. These findings suggest that a proportion of elderly patients with normocytic anaemia has an impaired EPO response.

Adolescent↗
PubMed1992

Glomerular and tubular proteinuria in type 1 (insulin-dependent) diabetic patients with and without retinopathy.

We compared the urinary excretion of albumin, transferrin, N-acetyl-beta-D-glucosaminidase and alpha-1-microglobulin in 78 Type 1 (insulin-dependent) diabetic patients: 39 with retinopathy and 39 without. The two groups were matched for age, sex and duration of diabetes. The patients with retinopathy had increased excretion (median and range) of albumin [1.7(0.3-399.1) versus 1.0(0.3-116.6) mg/mmol creatinine, P less than 0.05], transferrin [114.2 (4.1-37126.2) versus 33.4 (1.0-4176.7) micrograms/mmol creatinine, P less than 0.01] and N-acetyl-beta-D-glucosaminidase [23.8 (1.1-119.1) versus 15.0 (0.1-65.1) mumol/h/mmol creatinine, P less than 0.05] but not alpha-1-microglobulin. Transferrin excretion correlated with albumin excretion. The prevalence of increased transferrin excretion (transferrinuria) was greater than that of microalbuminuria in patients both with and without retinopathy (P less than 0.01 in both cases). Urinary transferrin seems likely to be predominantly of glomerular origin and merits prospective longitudinal evaluation as a potential index of the microangiopathic process.

Acetylglucosaminidase↗
PubMed1991

125I-fibrinogen binding to platelets in myeloproliferative disease.

Recent reports have suggested a variation in the density and affinity of fibrinogen binding sites in platelets from patients with myeloproliferative disorders (MPD) which may reflect platelet functional abnormalities in these subjects. We have investigated the binding of 125I-fibrinogen (125I-Fb) to gel-filtered platelets from a large relatively homogeneous group of patients with MPD compared to normal age matched controls. Twenty-two of the patients investigated had polycythaemia vera and four essential thrombocythaemia. The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel-filtered platelets (GFP) stimulated with either 10 microM ADP or 150 mU thrombin. In addition the functional significance of the binding sites was studied by evaluating the response of GFP from the two experimental groups by assessing the effects of increasing concentrations of added fibrinogen on the response to 10 microM ADP using standard light transmission aggregometry. In both groups the density of fibrinogen binding sites expressed in response to thrombin stimulation was significantly higher (approximately 2-3 fold) than that found in response to ADP. However, fewer binding sites were detected in the MPD group as compared with the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower than that found in the MPD subjects. Although the 125I-Fb binding study results indicate a significant reduction in both the number and affinity of fibrinogen binding sites in patients with myeloproliferative disorders, the clinical and functional significance of these findings remain uncertain.

Blood Platelets↗
PubMed1991

Monozygotic twins with seizures. Shared characteristics.

Eleven sets of monozygotic twins with idiopathic seizure disorders seen at Children's Hospital, Boston, Mass, were reviewed Nine twin pairs were concordant for seizures. A marked correlation in the precise timing of onset of seizures was found; three sets of twins had their first clinical seizures within a 24-hour period of one another. The clinical features of the seizures and the electroencephalographic patterns, including the location of focal discharges, were strikingly similar in the twin pairs. The significance of these findings in suggesting aberrant processes that may contribute to epileptic syndromes is discussed.

Brain↗
PubMed1991

Role of medial preoptic GABA neurones in regulating luteinising hormone secretion in the ovariectomised rat.

The role of GABA neurones in the medial preoptic area (MPOA) in regulating the activity of the luteinising hormone-releasing hormone (LHRH) neurones projecting to the median eminence was investigated in the conscious ovariectomised rat. Plasma luteinising hormone (LH) concentrations were measured while (1) endogenous GABA release from the MPOA was monitored with the technique of microdialysis, or (2) activity at the GABA receptor was modulated by local infusions into the MPOA. Microdialysis studies revealed a fluctuating level of GABA release in the MPOA which did not correlate with pulsatile LH secretion. Infusion of 10 microM GABA (n = 8) or bicuculline methiodide (BMI, n = 6) into the MPOA, at a rate of 1 microliter/30 min, significantly inhibited mean LH concentrations (P less than 0.05-0.001) and LH pulse frequency (P less than 0.05-0.001) compared with controls (n = 8). LH pulse amplitude was not significantly altered by infusion of GABA (P greater than 0.05) while too few pulses were found after BMI treatment to enable statistical analysis. Infusions of GABA into the ventral half of the MPOA had a more significant inhibitory effect upon LH secretion compared with dorsal infusions (P = 0.012). A similar relationship did not exist for BMI infusions. These results show that acute changes in preoptic GABA receptor occupancy result in disruption of pulsatile LH secretion in the ovariectomised rat. This suggests that GABA neurones provide a tonic input important for the functional integrity of the neural network controlling LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A technique for managing terminally ill ovarian carcinoma patients.

A patient with terminal ovarian carcinoma was admitted with malnutrition, abdominopelvic pain, and an inoperable complete small bowel obstruction after failing standard therapy and several experimental regimens for her disease. Despite this serious situation, she had an overall high performance status. Instead of administering intravenous narcotics, providing nasogastric suction, and giving other supportive care to make her apparently imminent death as comfortable as possible, her malnutrition was treated with total parenteral nutrition administered through an indwelling central venous catheter during the night hours only. The pain was successfully treated with an indwelling epidural catheter with the continuous infusion of morphine through a portable pump carried by a shoulder strap. The intestinal obstruction was relieved by a percutaneous endogastric tube which drained spontaneously into a leg bag. This regimen allowed the patient complete daytime mobility. She remained active, largely at home, with slowly progressing tumor until her death 9 months after the institution of this supportive care.

Adult↗
PubMed1991

Storage and preparation of samples for erythropoietin radioimmunoassay.

The evaluation of a radioimmunoassay for erythropoietin developed using recombinant material as immunogen and radiotracer is presented. A series of serum samples prepared and stored under varying conditions showed that immunoreactive erythropoietin levels were stable at room temperature for at least 10 days and at -20 degrees C for 5 months. The optimum time for separating sera from samples was between 6 and 24 h after venepuncture. Serum EPO values were significantly higher than those measured in heparin or potassium EDTA plasma.

Antibodies↗