Search PubMed⌕ Search

Biomedical subjects

C Allen

Publications and source records attributed to C Allen.

At least 181 records · Page 10Linked to original sources

Prevalence and clinical associations of intraocular pressure changes in Graves' disease.

We investigated an unselected series of 55 patients with treated or untreated hyperthyroid Graves' disease, assessing their clinical and laboratory status and ophthalmological findings, including the difference in intraocular pressure (dIOP) between upgaze and straight gaze using applanation tonometry. An increased dIOP (greater than 2 mm Hg) was detected in only 22% of Graves' patients [who had a mean dIOP of 3.5 +/- 1.6 (+/- SEM) mm Hg]. dIOP did not correlate with age, sex, age at disease onset, duration of disease, mode of antithyroid treatment, or thyroid function testing at the time of examination. Mean Hertel exophthalmometry measurements in patients with a dIOP greater than 2 mm Hg were 22.0 +/- 2.9 mm compared with 18.4 +/- 3.7 mm in those with a dIOP less than 2 mm Hg (P less than 0.027, by Wilcoxon rank sum test). Only 58% of patients with increased dIOP had clinical exophthalmos, but all had other evidence of Graves' eye disease. Computed tomographic scanning revealed significant proptosis and/or orbital muscle involvement in all of the patients with increased dIOP.

Adult↗

Ancrod: normalization of fibrinolytic enzyme abnormalities in patients with systemic lupus erythematosus and lupus nephritis.

Ancrod is a thrombinlike enzyme from Malayan pit viper (Agkistrodon rhodostoma) venom that has a selective enzyme substrate specificity for fibrinogen. Unlike thrombin, it splits only fibrinopeptide A from the fibrinogen molecule and does not activate factor XIII. Simultaneously with the occurrence of hypofibrinogenemia there is a reduction of plasma plasminogen and a rise in fibrin degradation products, suggesting secondary recruitment of the fibrinolytic enzyme system. Ancrod was given to 18 patients with systemic lupus erythematosus and glomerular and vascular microthrombi. Before treatment vascular plasminogen activator (VPA) was low or unmeasurable in 14, an inhibitor of urokinase-induced plasminogen activation (IPA) was elevated in 18, and an inhibitor of plasmin (PI) was elevated in five. Ancrod treatment resulted in prompt normalization of IPA levels in 13 patients; they were classified as fibrinolysis responders. In five patients IPA levels remained elevated throughout treatment with ancrod; they were classified as fibrinolysis nonresponders. In these five the PI level was elevated before treatment and decreased slowly toward the normal range during ancrod administration. The PI did not appear related to the nonspecific serine protease inhibitors, and was shown to be identical with alpha 2-antiplasmin. In the fibrinolysis responders serial histologic studies showed a striking decrease of disappearance of microvascular thrombosis; in the fibrinolysis nonresponders microvascular thrombosis persisted. The action of ancrod is discussed.

Adult↗

Features of synovial membrane identified with monoclonal antibodies.

As part of a study of the characteristics of the synovial membrane which make it susceptible to inflammatory reactions, we tested a number of monoclonal antibodies (MoAb) which revealed novel features of the synovium using tissue from rheumatoid, osteoarthritic and traumatized (mechanically deranged) joints. In a previous study we detected macrophages (Mph) lining the synovial membrane by means of Mph specific and HLA-DR specific MoAb. These may account for the type A synoviocytes. Type B synoviocytes are thought to be fibroblastic and we used an anti-Thy 1 MoAb to identify these cells. Many fibroblasts were seen in a subintimal position but only few in the lining layer, not in sufficient numbers to account for the type-B category of synoviocyte. Staining with a new MoAb, 67, was found to precisely delineate the lining layer. This MoAb was previously seen to react with dendritic reticulum cells (DRC) of germinal centres, cells involved in B lymphocyte activation. However, other MoAb which react with germinal centre DRC did not label the synovial lining layer. Several MoAb revealed features of the vasculature not previously recognized. In rheumatoid samples, MoAb10 labelled small capillaries near the synovial surface and larger vessels deeper in the intima were labelled with a second MoAb, SM phi. This dichotomy of staining was not so apparent in synovium from control osteoarthritis and trauma (OA/T) samples. In addition, the Thy 1 epitope, identified previously on a variety of human cells, was strongly expressed on all vascular endothelium. Finally a new vessel or duct like structure was identified in OA/T samples, located subintimally. These ducts contained keratin, detected with MoAb LE61 and may be the normal counterpart for the rare malignancy, biphasic synovial sarcoma.

Adult↗

Monocytes and other infiltrating cells in human colorectal tumours identified by monoclonal antibodies.

Monoclonal antibodies have been used to examine the patterns of infiltrating cells in colorectal tumours staged according to Dukes' classification. MAbs reacting with monocytes, but not tissue Mph, revealed a six-fold increase in monocytes in metastasizing C tumours compared to normal gut. The non-metastasizing B tumours could be divided into one group containing increased numbers of monocytes, and a second group comparable to control gut. T-cell numbers were increased in all tumour stages by an average 1.4-fold, which disguised the lack of consistent pattern in T-cell subset ratios in the tumour stromal tissue. However, in the tumour epithelium, there was a constant decrease in the Ts + c cell subset and a subsequent alteration in T-cell subset ratio in favour of Th + i cells. With the progression from Dukes' Stage B to C, there was an increase in the proportion of monocytes and T cells which were activated as detected by mAbs to the C3b receptor and IL-2 receptor, respectively. These observations suggest that an immune response is in progress in these colorectal tumours and that it is most active in the metastasizing Dukes' C tumours. Whether this response is elicited by the tumour or other elements, whether it is detrimental to tumour growth, or whether it is actively assisting tumour growth and possibly dissemination, are matters of conjecture.

Antibodies, Monoclonal↗

Ranitidine in the control of acute upper gastro-intestinal haemorrhage. A prospective randomized trial.

Fifty patients with acute upper gastro-intestinal haemorrhage were given either oral or intravenous ranitidine ( Zantac ; Glaxo), the route of administration being allocated on a random basis. Two patients were excluded from the oral group and 5 were excluded from the intravenous group. The two groups were similar as regards age, sex, number of patients aged over 60 years and severity of bleeding. All the patients were carefully monitored for rebleeding, which occurred in a total of 7 cases (16,3%), 6 in the oral group (26%) and 1 in the intravenous group (5%). Statistically this represented a marked tendency towards a significantly lower incidence of recurrent haemorrhage in the patients treated with intravenous ranitidine (P = 0,07, tested according to Fisher's exact method). No patient in the intravenous group who bled again came to surgery, while 3 of the 23 patients in the oral group (13%) required surgery.

Acute Disease↗

Hereditary retinal degeneration in the Rhode Island Red chicken. I. Histology and ERG.

Hereditary blindness in Rhode Island Red chickens was analyzed at various post-hatching stages by light microscopy and electrophysiological recordings. At the time of hatching the retina of affected chicks appeared morphologically normal and identical to that of control, non-affected chicks. Whereas the electroretinographic (ERG) response to light stimulus in normal chicks was near the adult level at the time of hatching, no ERG either under light- or dark-adapted conditions was measurable in affected chicks at any stage examined. Photoreceptor cells of affected animals were seen to undergo degenerative changes after about one week post-hatching. Decrease in number of outer segments, spaces between inner segments and large spaces in the outer nuclear layer were apparent by Day 10. By Day 21, most of the photoreceptor inner segments appeared swollen, and the decrease in number of outer segments and photoreceptor nuclei was noteworthy. By the end of the second month no outer segments were seen and the majority of identifiable inner segments were from cones, a larger proportion than normally present being double cones. By six months, very few photoreceptor inner segments and nuclei remained; most inner segments were deformed and diminutive but usually contained a clearstaining oil droplet characteristic of the principal member of the double cone. In all stages after one week of age, pycnotic nuclei and thinning of inner retinal layers accompanied photoreceptor degeneration. In all specimens examined, degeneration of retinal cells was more pronounced in the superior central retina than in the periphery. Pathological changes were frequently also noted in the pigment epithelium overlying degenerating retina. Because the chick retina is well developed at birth, contains a fovea and a significant cone population and because cones (particularly one specific type) survive rods, we believe that this congenitally-blind chicken may be a useful model for studies on human hereditary retinal degenerations.

Age Factors↗

Influence of polyunsaturated and saturated fats on plasma lipids and lipoproteins in man.

The effects of varying polyunsaturated/saturated (P/S) fat ratios on the plasma levels of lipids, lipoproteins, and apolipoprotein A-I were assessed in six normal healthy subjects (three males, three females) with a particular focus on the P/S ratio which would offer optimal concentrations of both low-(LDL) and high-density lipoproteins (HDL). The isocaloric experimental diets contained 40% of calories as carbohydrate, 40% fat, and 20% protein; dietary cholesterol was 400 mg/day. The P/S ratio for the diets was 0.4, 1.0, or 2.0. Each diet was sequentially consumed for periods of 2 wk each. At the end of each 2-wk study period, plasma lipid, apolipoprotein A-I, and LDL and HDL cholesterol concentrations were determined; HDL were fractionated by zonal ultracentrifugation and lipid and protein composition determined. Compared to the P/S = 0.4 diet, mean plasma total cholesterol fell by approximately 6 and 12% on the P/S = 1.0 or P/S = 2.0 diets, respectively; plasma concentrations of LDL-cholesterol, HDL-cholesterol, and apolipoprotein A-I were also decreased on the polyunsaturated fat diets. The mean +/- SEM concentration (mg/dl) of HDL-cholesterol was 49.0 +/- 5.2 (P/S = 0.4), 44.0 +/- 3.8, (P/S = 1.0) and 41.0 +/- 3.7 (P/S = 2.0). As a result of a reduction in both LDL- and HDL-cholesterol on the polyunsaturate-rich diets, the ratios of HDL-cholesterol to plasma total cholesterol and HDL- to LDL-cholesterol were not significantly changed on the three diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Electrophoretic and cytochemical characterization of alpha-naphthyl acetate esterases in acute myeloid leukemia: relationships with membrane receptor and monocyte-specific antigen expression.

Alpha-naphthyl acetate esterases (ANAE) were examined by cytochemical and isoelectric focusing (IEF) techniques in 48 cases of acute myeloid leukemia that were classified by conventional morphological criteria. Four main types of ANAE isoenzyme patterns were found by IEF, and comparisons with the expression of membrane receptors (Fc-IgG and C3b) and monocyte-specific antigens (UCHM1, UCHALF, and E11) suggest relationships between ANAE isoenzyme synthesis and distinct myeloid maturational stages. The results further indicate that the blast cells of acute myelomonocytic leukemia (AMML) may represent an immature variant of monocytic leukemia (AMoL) and that morphological examination alone is inadequate in the assessment of monocytic differentiation in acute myeloid leukemias. Inhibition studies of cytochemical ANAE activity with sodium fluoride (NaF) show that the presence of NaF-sensitive or NaF-resistant ANAE enzymes is often unrelated to the diagnostic category of acute leukemia. The results of this study are examined in relation to current concepts of myeloid differentiation, and the application of these findings to the subclassification of acute myeloid leukemias is discussed.

Antibodies, Monoclonal↗

Fibrinolysis in health and disease: severe abnormalities in systemic lupus erythematosus.

Methods are described to measure fibrinolysis in healthy persons and in patients with systemic lupus erythematosus. Using the fibrin plate method, total fibrinolytic activity and vascular plasminogen activator were measured. (Total fibrinolytic activity expresses the fibrinolytic potential and consists of both the intrinsic [factor XII-dependent and independent] activities and the extrinsic activities [vascular or tissue type]. Vascular plasminogen activator, assessed in a separate assay, refers to the endothelium-derived component only.) In addition, the degree of inhibition by plasma of both urokinase-induced and of plasmin-induced fibrinolysis were analyzed. Vascular plasminogen activator levels were low in 63% of plasma samples from 55 patients with systemic lupus erythematosus. The level of an inhibitor of plasminogen activation was significantly elevated in 87% of patients and levels of an inhibitor of plasmin were significantly elevated in 29%. The nonspecific serine protease inhibitors, including alpha 2-macroglobulin, were within the normal range in all patients. The natures of inhibitor of plasminogen activation and plasmin inhibitor were studied further. Using both the fibrin plate and the lysis time methods, the data indicated that the urokinase-inhibiting activity increased with time of incubation of plasma-enzyme mixtures, whereas the plasmin inhibiting activity did not. Elevated levels of plasmin inhibitor measured with the fibrin plate method correlated well with prolonged lysis times. Results using the chromogenic substrate S-2251, commonly used as a simple and specific assay for antiplasmin, agreed reasonably well with those using the fibrin plate method, but elevated plasmin inhibitor levels could be quantitated with greater accuracy and sensitivity by the fibrin plate method. Studies with an antiserum directed against alpha 2-antiplasmin showed that inhibitor of plasminogen activation and plasmin inhibitor were different inhibitors, and that plasmin inhibitor was identical to alpha 2-antiplasmin. The abnormalities are discussed in the light of current knowledge on fibrinolysis and as possible mediators in the pathogenesis and perpetuation of lupus glomerulonephritis.

Adult↗

Monoclonal antibodies differentiating between monocytic and nonmonocytic variants of AML.

Blast cells from 70 cases of acute myeloid leukemia (AML), with a preponderance of monocytic variants (M4 and M5), were stained with a panel of 10 monoclonal antibodies (MoAb) that react with normal myeloid cells. Two McAb, UCHMI and UCHALF, stained cells from nearly every case of M4 and M5 leukemia, but not cells from cases of M1/M2 leukemia. Two other antibodies, E11 and UC45, were also specific for the monocytic leukemias, but stained cells from a lesser proportion of cases. The antibodies TG1, OKM1, Smø, DA2, 28, and 5.5 stained a differing proportion of cases in both the M1/M2 and M4/M5 subtypes. Routine morphology and alpha-naphthyl acetate esterase (ANAE) staining were largely in agreement with the antibody findings, though the interpretation of the fluoride sensitivity of ANAE was apparently misleading in 10% of cases. It is concluded that these antibodies, particularly UCHMI and UCHALF, will be of considerable value in the more precise subtyping of AML and that some of this panel of antibodies will be valuable tools for the investigation of normal monocytic differentiation.

Antibodies, Monoclonal↗

Intrastromal noninflammatory bacterial colonization of a corneal graft.

Progressive branching, needlelike stromal opacities were observed within a corneal transplant. Analysis of the corneal button by light microscopy and transmission electron microscopy disclosed a localized epithelial ingrowth into the stroma at a suture tract accompanied by intrastromal pockets of gram-positive cocci extending across the cornea. No inflammatory reaction was found in the areas of bacterial colonization. To our knowledge, noninflammatory bacterial colonization of the stroma of a corneal transplant has not been previously described.

Aged↗

Alimentary lipemia: plasma high-density lipoproteins and apolipoproteins CII and CIII in healthy subjects.

Three healthy male and three female inpatient volunteers consumed isocaloric diets for 4 wk. At weekly intervals, a fatty meal (100 g fat) was consumed by each fasting subject and blood drawn at 2 h intervals for 12 h. Of the four oral fat loads, two contained saturated fat (polyunsaturated/saturated fat ratio = 0.34) and two contained unsaturated fat (polyunsaturated/saturated fat = 2.21). The magnitude of alimentary lipemia, expressed as area under the plasma triglyceride curve, was 3- to 4-fold higher in males than females. Alimentary lipemia was inversely related to the subjects' fasting plasma high-density lipoprotein (HDL)-cholesterol, HDL apolipoprotein (apo) CIII and directly related to plasma triglycerides. The P/S ratios of the daily diet or the fat meal did not significantly influence the plasma triglyceride curve. After fat intake, mean (+/- SEM) plasma total apoCII and CIII fell to 54 +/- 20% and 73 +/- 5% of base-line, respectively, at 12 h in five of six subjects. After oral fat, an initial fall and a subsequent rise in apoCII and CIII in HDL was associated with reciprocal changes in apoC concentrations in very low-density lipoproteins. We speculate from the data that 1) plasma HDL and their apoC concentrations are important determinants of chylomicron clearance and 2) transfer of apoCs from HDL to triglyceride-rich lipoproteins in the early phase of fat absorption does not result in the total recycling of apoCs from these lipoproteins to HDL during the late phase of alimentary lipemia.

Adolescent↗

Sucrose polyester: substitution for dietary fats in hypocaloric diets in the treatment of familial hypercholesterolemia.

In five obese women heterozygous for familial hypercholesterolemia, we assessed the combination of weight loss and sucrose polyester (SPE) in lowering low-density lipoprotein cholesterol (LDLC). After a 10-day basal hypocaloric (1426 cal/day), 270 mg cholesterol, P/S 1.2:1 diet, an average of 36 g of dietary fat/day was replaced by 36 g of an 80/20 SPE-hydrogenated palm oil mixture, providing 30 g SPE for 30 days; during the SPE substitution period mean dietary cholesterol and P/S were unchanged, mean caloric intake was 1104 cal/day. During the hypocaloric basal diet, mean weight fell 1.2 kg, p less than 0.02, total plasma cholesterol fell 8% from 358 +/- 46 to 330 +/- 47 mg/dl, p less than 0.01, LDLC fell 4% from 264 +/- 37 to 254 +/- 44 mg/dl, p greater than 0.1, and mean high-density lipoprotein cholesterol fell 11%, from 52 +/- 4 to 46 +/- 4, p less than 0.05. Over the 30-day SPE substitution, mean cholesterol fell 20% from 330 +/- 47 at the end of the basal diet to 265 +/- 42 mg/dl, p less than 0.001; mean LDLC fell 23%, from 254 +/- 44 to 195 +/- 41 mg/dl (p less than 0.01); weight fell 4%, p less than 0.01, from 91 +/- 7 to 87 +/- 7 kg, and mean high-density lipoprotein cholesterol fell 11% from 46 +/- 4 to 41 +/- 2, p less than 0.05. Hypocaloric removal of dietary fat by SPE, an artificial fat with culinary properties of conventional dietary fats, effectively reduces LDLC (by 23%) in familial hypercholesterolemia subjects, with additive effects of SPE and weight loss.

Body Weight↗

Membrane Fc-IgG and C3b receptors on myeloid leukaemia cells: a comparison with cytoplasmic acid naphthyl acetate esterase cytochemistry.

Membrane receptors for IgG and C3b were examined on blast cells from 57 cases of acute myeloid leukaemia. These acute leukaemias were classified as myeloblastic, myelomonocytic or monocytic following morphological, cytochemical, and immunological investigations. The membrane receptors of leukaemic blast cells appear to be directly related to the degree of monocytic differentiation with the lowest receptor activities found in acute myeloblastic leukaemia. A comparison was also made between receptor and cytoplasmic acid naphthyl acetate esterase (ANAE) activities in 29 morphologically and immunologically-defined myelomonocytic and monocytic leukaemias. This study revealed that the receptor-positive "monocytic component" in a significant proportion of cases showed unexpectedly weak or negative ANAE reactions suggesting a more cautious approach to the interpretation of ANAE cytochemistry in acute leukaemias. The normal development of cytoplasmic ANAE and membrane receptors is also discussed and compared with their abnormal patterns of expression associated with leukaemic transformation.

Carboxylic Ester Hydrolases↗

Sucrose polyester and covert caloric dilution.

Total daily caloric intake was measured in 10 obese subjects when sucrose polyester (SPE), a nonabsorbable synthetic fat, covertly replaced conventional fats in a single crossover study consisting of three periods: a period of 7 to 14 days to determine baseline caloric intake and two 20-day study periods. An average of 60 g SPE/day replaced conventional fat in one of the two study periods. During both study periods, 60% of the base line caloric intake was "required intake" at mealtime; an additional 60% of base line caloric intake was allowed as "free choice" foods at a specified snacktime. It was thus possible during both study periods to consume more than 100% of the base line caloric intake. In the SPE study period, 40 g SPE replaced 40 g conventional fat for every 1200 kcal of required intake, resulting in a 30% reduction in mealtime caloric intake. Mean total caloric intake (meal and snack) fell 23% during the SPE period (p less than 0.05), despite an average daily weight loss of 0.18 kg. Snack caloric intake did not increase significantly to compensate for caloric dilution of the meals during the SPE period. These results indicate that the obese may not detect or may not compensate for covert dilution of fat calories with SPE. In addition, during the SPE period, there was a 10% reduction in total plasma cholesterol, a 14% reduction in low-density lipoprotein cholesterol, and a 10% reduction in triglyceride concentration. Thus, fat replacement with SPE may benefit weight reduction regimens in obese subjects by facilitating decreased caloric intake and by improving the circulating lipoprotein profile as well.

Adult↗