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Biomedical subjects

L Wood

Publications and source records attributed to L Wood.

At least 199 records · Page 11Linked to original sources
PubMed1985

Complement activation in type 1 human diabetes.

Complement activation was quantitated in serum and plasma of diabetic and normal subjects by sensitive competitive equilibrium radioimmunoassays (RIA) for C3a, C4a, C5a, Factor B, and a newly described C5 neoantigen (termed C5 activation antigen, and abbreviated C5-AA) in a stable 54-kDa fragment of C5. Plasma C3a levels were significantly elevated in 8 of 16 patients with newly diagnosed Type 1 diabetes (P less than 0.0005) with the mean C3a concentration for these patients being more than 10-times greater than the mean value of normal controls. C4a levels were also elevated in 2 of these patients (P less than 0.02), but C5a levels, although higher than normal, were not significantly increased. In contrast, the levels of C5-AA in the serum of all patients (11/11) with chronic Type 1 diabetes were significantly higher than in control Type 2 patients (noninsulin-dependent diabetes) (P less than 0.0005) and 4 of 7 patients with new onset insulin-dependent diabetes mellitus also had significantly higher levels of C5-AA than the Type 2 patients (P less than 0.01). The levels of Factor B in the serum of 5 of 9 patients with new onset diabetes were significantly higher than normal (P less than 0.0025). Five recent onset Type 1 diabetes patients were evaluated longitudinally for C3a, C4a, and C5a: in 3 the levels of C3a were elevated during new onset disease decreasing into the normal range during remission; in 2 of these patients C4a was also significantly elevated and the levels decreased during remission; and in 3 patients the levels of C5a were not significantly elevated but they decreased during remission. Purified human complement proteins and complement hemolytic assays were used to measure complement activation in serum during incubation with rat pancreatic islet cells. With diluted normal human serum, less than 20% of C3 or Factor B were consumed during 30 min at 37 degrees C, while with new onset Type 1 diabetic patient sera up to 90% of C3 and Factor B were consumed in 5/6 sera and 4/6 sera, respectively. These findings suggest (a) that complement activation fragments C3a, C4a, and C5a are generated in vivo in new onset Type 1 diabetes; (b) that both the classical and the alternative complement pathways may be activated; and (c) that this may result in a measurable activation of C5 generating biologically and immunologically active C5a and other C5 activation fragments.(ABSTRACT TRUNCATED AT 400 WORDS)

Complement Activation↗
PubMed1985

Transit of alpha-mannosidase during its maturation in Dictyostelium discoideum.

We proposed that Dictyostelium discoideum contains two linked pools of mature alpha-mannosidase (Wood, L., R. N. Pannell, and A. Kaplan, 1983, J. Biol. Chem., 258:9426-9430). To obtain physical evidence for these pools, cells were pulse-labeled with [35S]methionine, homogenized, and subjected to Percoll gradient centrifugation. After immune precipitation of alpha-mannosidase, its polypeptides were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and detected by fluorography. After a 30-min pulse with [35S]methionine, the precursor and small amounts of cleaved enzyme were detected in a low density fraction (1.04 g/ml). Subsequently, cleaved enzyme was transferred to higher density fractions (1.05 and 1.07 g/ml) that were enriched in lysosomal enzymes. The half time for formation of the 1.07 g/ml pool was approximately 45 min, whereas formation of the 1.05 g/ml pool was not detected until 1.5 h after the pulse. The transfer of mature forms out of the 1.04 g/ml pool was inhibited by monensin (3.5 microM). Thus, alpha-mannosidase precursor appears to be cleaved in a prelysosomal organelle. The data also indicate that starving cells secrete precursor directly from this organelle to the extracellular space, whereas cleaved forms are first transferred into lysosomes before they are secreted. Furthermore, 2 h after starvation, the secretion of mature forms ceases even though both transit of mature forms between the two pools and secretion of precursor continues. From this we inferred that the cessation of secretion of mature forms is due to a halt in fusion of lysosomes with the plasma membrane and that precursor follows a different route to the plasma membrane.

Biological Transport↗
PubMed1985

Cyclosporin A in the treatment of severe acute aplastic anaemia.

Twelve consecutive adults with severe acute aplastic anaemia, not having a bone marrow transplantation option, were prospectively randomized to receive either cyclosporin A alone or an equivalent amount of this immunosuppressive agent in combination with antilymphocyte serum. The minimum follow-up is 36 months, with half the patients developing nephrotoxicity, which was easily reversible in all but one. No response could be attributed to either regimen. Cyclosporin A does not appear to have a place as primary form of treatment for adults with severe acute aplastic anaemia, either on its own or in combination with antilymphocyte serum.

Acute Disease↗
PubMed1985

Fluid compartmentation and articular mechanoreceptor discharge in the cat knee joint.

Experiments were performed to determine the effect of alteration of intra-articular pressure in different areas of the cat knee joint on the discharge of slowly adapting mechanoreceptors in the posterior region of the joint. At physiological (subatmospheric) pressures the anterior and posterior regions of the knee joint are not hydraulically continuous. However, at supra-atmospheric pressures between 2.5 and 9 cmH2O there is free communication between these areas. The discharge of receptors in the posterior region of the joint is influenced by intra-articular pressure changes in the posterior region when these are supra-atmospheric. However, pressure changes in the anterior region of the joint have little effect on the discharge of these receptors until free communication occurs between anterior and posterior regions. It is suggested that articular mechanoreceptors detect tension changes in collagen fibrils rather than volume changes of the joint capsule.

Action Potentials↗
PubMed1985

Splenic pathology in immune thrombocytopenia.

Splenic pathology was analysed in 73 patients with immune thrombocytopenic purpura who underwent splenectomy for bleeding that had been resistant to adrenocorticosteroids. The mean splenic weight was 100 g. The only notable macroscopic feature was the prominence of Malpighian corpuscles in 15 cases. Microscopic examination showed formation of germinal centres in the lymphoid tissue of the white pulp in 40 cases, prominence of the histiocytes in the red pulp in 18 cases, and infiltration with neutrophils in the same area in 49 cases. Myeloid metaplasia throughout the splenic tissue was minimal in 58 cases, moderate in 15, and extreme in two. No distinguishing features were found in the spleen from patients who had not received previous immunosuppressive treatment (n = 3), those treated with prednisone (1 mg/kg/day) for a median of 14 days (n = 62), or those who had received the same dose of prednisone and additional azathioprine or cyclophosphamide (2 mg/kg/day) for a median of four weeks (n = 8). No correlation could be shown between histological features and the age of the patient or titre of antiplatelet antibodies. Similarly, no distinguishing features were found in patients with associated systemic lupus erythematosus (n = 8), hyperthyroidism (n = 6), immune haemolysis (n = 3), or recent viral illness (n = 3).

Adrenal Cortex Hormones↗
PubMed1985

Lipids in milk and the first steps in their digestion.

Human milk contains 3.0% to 4.5% fat. The fat is contained within membrane-enclosed milk fat globules. The core of the globules consists of triglycerides (98% to 99% of total milk fat) whereas the globule membrane (which originates from the mammary secretory cell's Golgi and cell membranes) is composed mainly of phospholipids, cholesterol, and proteins. Milk fat content and composition change during lactation. Whereas the triglyceride level rises, the phospholipid and cholesterol concentrations decrease during the transition from colostrum to mature milk, resulting in an increase in the size of the milk fat globules. Digestion of milk fat depends on the consecutive action of several lipases. The first step is the partial hydrolysis of the milk fat globule core by lingual and gastric lipases in the stomach. Hydrolysis continues in the duodenum, where the bile salt-stimulated lipase of human milk and pancreatic lipase complete the process initiated in the stomach.

Animals↗
PubMed1984

In adult acute nonlymphoblastic leukaemia extended maintenance chemotherapy has no benefit.

Fifty-two consecutive and previously untreated adults with nonlymphoblastic leukaemia underwent remission induction chemotherapy with a combination of the epipodophyllotoxin VP16-213, cytosine arabinoside, and doxorubicin (Adriamycin). Complete remission was achieved in 23 of the 52 patients (44%) by means of a single course of therapy in 20 individuals, two courses in two, and three courses in one; median duration of complete remission was 48 weeks. Failure to achieve remission status was due to primary drug resistance in 13 patients (25%), and adequate trial of therapy was not possible in 16 patients (31%) owing to their late referral and accounts for the low remission rate. Individuals achieving complete remission were randomly assigned to receive either 6 (n = 8) or 15 months (n = 13) of maintenance therapy; respective median survival was 95 and 78 weeks (P greater than 0.10). These data confirm previously reported results for complete remission induction with this three-drug combination and fail to show any difference between short (6 months) and long (15 months) maintenance chemotherapy.

Acute Disease↗
PubMed1984

Comparison of filtration to continuous-flow centrifugation for plasma exchange.

The Asahi Plasmaflo Hollow Nylon Fibre Filtration System (n = 13) was directly compared to the NCI-IBM 2990 Continuous-Flow Blood Fraction Separator (n = 10) for plasma exchange. The systems were equally efficient in achieving plasma separation. There were significant differences favouring filtration for clearance of fibrinogen (P less than 0.05), and the fourth component of complement (P less than 0.01). Greater loss of urea (P less than 0.05) was found after plasma exchange, using the cell separator. The flow characteristics were markedly different. In a standardised 4-L plasma exchange, filtration took place at 35 ml/minute, with a procedure time of 109 +/- 45 minutes in contrast to centrifugation at a plasma flow collection rate of 19 ml/minute, requiring 208 +/- 17 minutes. This time advantage for the former procedure was offset by 195 minutes required to regenerate the hollow nylon fibre unit and a further 90 minutes required for cleaning under strictly controlled aseptic techniques prior to reuse. Each filter was regenerated at least twice and reused without infection, but there was incremental loss of filtration efficiency demonstrated by decreasing clearance of an intravascular marker dye. In two of the 13 procedures using the Plasmaflo system, serious reactions necessitated termination of the procedure; this did not occur using the cell separator. Restriction of the number of times that the filter unit could be regenerated without loss of efficiency, the prolonged time required for regeneration and cleaning, coupled with the need for artificial vascular access to meet high blood flow rates required, limit the usefulness of this technique for plasma exchange.

Blood Chemical Analysis↗
PubMed1984

The function and structure of granulocytes collected using the IBM 2997 separator.

The effect of oral methylprednisolone and the sedimenting agent, hydroxyethyl starch, on granulocyte recovery, morphology, and function was studied in a volunteer donor programme. Using the IBM 2997, 10 litres of whole blood were processed, with an average procedure time of 2.4 hours and a collection volume of 300 ml. Donors not receiving methylprednisolone (n = 80) had a mean total granulocyte count of 3.5 X 10(9)/litre (range 1.6-5.3 X 10(9)/litre) and mean granulocyte yields were 1 X 10(10) (range 0.2-3.0 X 10(10)). Those receiving 48 mg oral methylprednisolone 6-8 hours before the procedure (n = 320) had a mean granulocyte count of 6.3 X 10(9)/litre (range 3.2-11.4 X 10(9)/litre) and significantly superior mean granulocyte yields of 2.0 X 10(10) (0.3-6.5 X 10(10)) (P less than 0.05). For both groups the mean packed cell volume of 0.08 litre/litre (range 0.02-0.17) and platelet contamination 1.9 X 10(11) (range 0.3-5.0 X 10(11)). In all these procedures, hydroxyethyl starch was added to the blood entering the centrifuge channel. In none of the procedures were any untoward symptoms experienced by the donors. Light microscopy and ultrastructural studies showed no difference between control granulocytes and those collected following the addition of hydroxyethyl starch or after oral methylprednisolone. Similarly, granulocyte function measured with a random migration, chemotaxis, phagocytosis, and intracellular killing was not significantly different between control cells and those exposed to the sedimenting agent or the adrenocorticosteroids (P greater than 0.10). It is concluded that donor premedication with methylprednisolone significantly enhances granulocyte yields in the presence of hydroxyethyl starch and neither agent has any demonstrable effect on granulocyte morphology or function.

Blood Donors↗
PubMed1984

Response of slowly adapting articular mechanoreceptors in the cat knee joint to alterations in intra-articular volume.

Recordings were obtained from slowly adapting mechanoreceptors innervating the posterior aspect of the cat knee joint capsule. It was observed that, with rising intra-articular volume, initially both intra-articular pressure and the neural discharge increased. This increase was dependent on the rate of fluid accumulation within the joint. However, the joint nerve discharge invariably levelled out despite increasing intra-articular volume and pressure. This suggests that there exists some limit to capsular distension in the posterior joint region beyond which fluid is diverted to other areas of the knee joint.

Action Potentials↗
PubMed1984

Acute locked facet syndrome and its treatment by manipulation under local periarticular anesthesia--Part I: Clinical perspective and pilot study proposal.

The clinical features of prolapsed intervertebral disc and facet joint pain are described and the condition referred to as "acute locked facet joint syndrome" is differentiated. Treatment by manipulation, with and without epidural or general anesthesia are considered, and a clinical trial of manipulation under local periarticular anesthesia is proposed.

Acute Disease↗