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Biomedical subjects

J B Allen

Publications and source records attributed to J B Allen.

106 records · Page 6Linked to original sources

Relationship of complement to experimental arthritis induced in rats with streptococcal cell walls.

Experimental arthritis developed in rats injected intraperitoneally with aqueous suspensions of peptidoglycan-polysaccharide complexes (PG-APS) isolated from group A streptococcal cell walls. Reduction of serum complement by pretreatment with cobra venom factor (COV) reduced acute joint inflammation over the first 3 days following injection of PG-APs. Thereafter, the course of the disease was not different in the COV-treated rats. The serum levels of complement were depressed below detectable levels by 24 hr in rats injected only with cell walls, but rebounded to normal levels or above 3 days after injection. In rats injected with COV before cell walls, the complement levels also increased 3 days after injection of cell walls, in contrast to sustained depressed levels in rat injected only with COV. The correlation between severity of joint inflammation and serum complement levels at day 3 was positive in COV-treated rats. The quantity of cell wall per joint at day 3 correlated with the severity of joint disease. However, COV treatment did not alter the amount of cell wall localized in joint tissue. Therefore, although complement does appear to have a role in early joint inflammation, its effect is not upon the transport of cell wall into joint tissue.

Animals↗

Irradiation decreases vascular prostacyclin formation with no concomitant effect on platelet thromboxane production.

Effects of irradiation on vascular tissue include endothelial cell degeneration, vasoconstriction, and thrombus formation. The effect of irradiation on the in-vitro production of prostacyclin (PGI2) was evaluated, since it is a potent antithrombotic metabolite and vasodilator. After a single dose of 200 rad, umbilical artery PGI2 levels were much decreased when estimated both be bioassay and by evaluation of the stable end-product of PGI2, 6-keto-prostaglandin in Fl alpha. The mean PGI2 production in control tissue was 0.94 +/- 0.14 (1SEM) ng/mg vascular tissue compared with 0.18 +/- 0.07 ng/mg in paired irradiated vessels (p less than 0.001). However, irradiation had no effect on platelet thromboxane formation in a dose rage of 200-2000 rad. Since radiotherapy is routinely administered for the whole period of therapy in daily dose fractions similar to the in-vitro experimental dose used in this study, recovery of vascular PGI2 production may be inhibited for the total period of radiotherapy.

Blood Platelets↗

Decrease prostacyclin production: a characteristic of chronic placental insufficiency syndromes.

Prostacyclin production in neonates born at various gestational ages (28 weeks to term) was compared with that in neonates born of pregnancies complicated by various acute and chronic placental insufficiency states. Prostacyclin levels were reflected by the amount of conversion of 14C arachidonic acid to 6-keto-PGF1 alpha (the stable end-product of prostacyclin) by umbilical arteries. The uptake of 14C arachidonic acid by the umbilical arteries was also determined, and since this was similar for all groups it was not the cause of the differences noted in prostacyclin production. Neonates born of normal pregnancies had similar levels of prostacyclin production regardless of gestational age. Prostacyclin production was very low in neonates born of pregnancies complicated by chronic placental insufficiency (intrauterine growth retardation, essential hypertension, and pre-eclampsia), but normal with acute placental insufficiency (abruptio placentae). Hence the decrease in fetal prostacyclin production in pre-eclampsia is not related to gestational age; furthermore, it is also seen in other chronic placental insufficiency states.

6-Ketoprostaglandin F1 alpha↗

Abnormal platelet function and arachidonate metabolism in chronic idiopathic thrombocytopenic purpura.

We observed several patients with chronic idiopathic thrombocytopenic purpura (ITP) whose bleeding times were more prolonged than would have been expected from their platelet counts. To investigate this further, we performed in vivo and in vitro platelet function studies, assessed arachidonate metabolism, and measured platelet-associated IgG (PAIGG) in seven patients with chronic ITP. The bleeding times of three of the patients were prolonged for greater than 7 min, and all of these patients had impaired platelet aggregation and abnormal platelet arachidonic acid metabolism as reflected by increased production of the lipoxygenase product HETE and a concomitant decrease in cyclooxygenase products, TXB2 and HHT (p less than 0.001). The abnormalities noted were not due to concomitant drug ingestion, since they were present on repeated evaluation. There was no relationship between the platelet count and the bleeding time; however, there was a significant inverse correlation between the bleeding time and TXB2 production in all patients evaluated (r = 0.81; p less than 0.05). There was no relationship between the level of platelet-associated IgG and any parameter of platelet aggregation or arachidonate metabolism. The abnormalities noted should be looked for in the individual patient with chronic ITP, since the bleeding tendency is exacerbated by the superimposed impairment of platelet function even at platelet counts of greater than 50,000/cu mm, levels generally regarded as "safe."

Adolescent↗

Decreased prostacyclin production in the infant of the diabetic mother.

Maternal diabetes mellitus is recognized to be a predisposing factor to thrombosis in the neonate. In the adult with diabetes, abnormalities in the metabolism of AA by the platelet and vessel wall occur, which result in an increase in proaggregatory platelet thromboxane A2. A decrease in antiaggregatory vascular PGI2 has been demonstrated in the diabetic rat, although conclusive proof of a similar abnormality is lacking in humans. We evaluated vascular AA metabolism in 10 IDM (groups II and III comparison to 20 control neonates of gestational ages 32 to 40 weeks (group I). Mean uptakes of labeled AA into vascular tissue of both controls and IDM were similar. The conversion of [14C] AA to 6-keto-PGF1 alpha was not dependent on gestational age (r = 0.223) in the control neonates, with a mean value of 5.2% +/- 1.3 (1 S.D.). A marked decrease (p less than 0.001) in 6-keto-PGF1 alpha formation to 1.7% +/- 0.3 was found in the group II IDM of mothers with poor diabetic control (HbA1c = 9.3% +/- 0.5). In the group III neonates whose mothers had normal HBA1c levels (6.1% +/- 0.9), 6-keto-PGF1 alpha production was normal at 4.9% +/- 0.8. Although no correlation between maternal fasting blood glucose and neonatal 6-keto-PGF1 alpha was demonstrable, a significant inverse correlation (r = 0.872; p less than 0.02) was observed between maternal HbA1c levels and the conversion of AA to 6-keto-PGF1 alpha in the vascular tissues of the IDM. It appear possible that abnormalities in platelet-vascular AA metabolism may play an etiologic role in the vascular complications present in some IDM.

Adolescent↗

Pneumococcal sepsis in childhood leukemia and lymphoma.

Forty episodes of sepsis in 28 patients with leukemia or lymphoma were reviewed. Streptococcus pneumoniae accounted for 14 episodes and was the most frequent etiologic agent isolated. Escherichia coli and Staphylococcus aureus accounted for an additional 16 episodes. No patients with pneumococcal sepsis died whereas the overall mortality was 25%. Five of the patients with pneumococcal sepsis had polymorphonuclear leukocyte counts less than 500/cu mm. All patients in remission who had pneumococcal sepsis had a leukocytosis in response to their infection. Foci in patients with pneumococcal sepsis were identified in 50% of the episodes and all were confined to the respiratory tract.

Escherichia coli Infections↗

Cochlear micromechanics--a physical model of transduction.

One of the basic questions which has persisted in the field of hearing theory is the still unresolved mechanical action of hair-cell transduction. The fundamental problem that has historically plagued researches is the discrepancy between mechanically measured tuning of basilar membrane motion and neurally measured tuning. In this paper we show that the difference between these two measures appears to be accounted for by a specific, physically motivated, micromechanical model. This model gives rise to a spectral zero which we identify as the "second-filter" of cochlear transduction. For high-frequency fibers this zero resides at a fixed frequency ratio below CF (characteristic frequency) while for fibers having low-frequency CF's the zero appears to go to zero frequency faster than CF. In this paper we first present and analyze the assumed mechanical model. We then briefly discuss a possible specific physical realization for the nonlinearity of cochlea mechanics. The nonlinear model is based on dynamical variations in outer hair cell stereocilia stiffness.

Basilar Membrane↗

Cochlear macromechanics: time domain solutions.

In this paper we report on a new method of solving a previous derived, two-dimensional model, integral equation for basilar membrane (BM) motion. The method uses a recursive algorithm for the solution of an initial-value problem in the time domain, combined with a fast Fourier transform (FFT) convolution in the space domain at each time step. Thus, the method capitalizes on the high speed and accuracy of the FFT yet allows the BM to have nonlinear mechanical properties. Using the new method we compute (linear) solutions for various choices of model parameters and compare the results to the experimental measurements of Rhode. [J. Acoust. Soc. Am. 49, 1218-1231 (1971)]. We also demonstrate the effect of including longitudinal stiffness along the BM and conclude that it is useful in matching the high-frequency slope as measured by Rhode.

Basilar Membrane↗

Cochlear models - 1978.

Two important concepts at the forefront of most cochlear modeling work today are the need for nonlinear basilar membrane mechanics and the need for a "second-filtering" mechanism at the transduction site of the hearing system. Other less controversial topics are one vs. two-dimensional models and the use of the WKB method for obtaining analytical results for frequencies below the cut-off frequency.

Biomechanical Phenomena↗

Cochlear micromechanics--a mechanism for transforming mechanical to neural tuning within the cochlea.

A linear mathematical model is proposed which will account for the differences observed between mechanically measured data of Rhode (1971) for basilar membrane motion, and the responses of neural tuning curves (Kiang et al., 1974). We show that theoretical tuning curves may be derived from mechanical responses by forming the difference between the pressure across the basilar membrane and its displacement. Some ramifications of this proposal are discussed. We then propose a hypothetical physical model which could perform such a function.

Acoustics↗

Depression among the head-injured and non-head-injured: a discriminant analysis.

Neuropsychologists often use traditional psychological tests to assess depression following a head injury; but the assumption that depression with a head injury resembles that in an uninjured person is suspect. The current study attempts to examine the cognitive manifestations of depression with and without a coexisting head-injury. Advanced statistical methods are used to assess whether or not the two depressions 'look alike' with respect to the neuropsychological sequelae of the disorders. A total of 1182 people were entered into one of two discriminant function analyses (DFA) for depression. Each person was a member of one of the following groups: (a) depressed, (b) non-depressed, (c) head-injured, or (d) head-injured and depressed. Two functions were performed for depression, one on the population of head-injured people and one on the population of uninjured people. Cross-validations were performed for each population and across populations in order to assess the utility of each population's function for the opposite group. This comparison allows the researcher to indirectly compare depression in the two populations. Both functions were successfully applied to either population when MMPI variables were included in the analyses. However, when only cognitive variables were included the function performed on the non-head-injured population did not correctly classify head-injured people as depressed or non-depressed. One explanation for this is that the range of cognitive scores in head-injured people is so great that it allows for a less accurate but more generalizable function. Suggestions for future research are discussed.

Adult↗

Multiple thromboses in a premature infant associated with maternal phospholipid antibody syndrome.

Phospholipid antibodies (lupus anticoagulant, cardiolipin) are associated with a syndrome of repeated fetal loss. Mothers with phospholipid antibodies are currently being treated with either prednisone, aspirin, or heparin to prevent fetal death. We describe a neonate whose mother had cardiolipin antibody and recurrent fetal loss and was treated with prednisone and aspirin. Thrombosis was noted in placental fetal vessels. Thromboses developed in the infant's aorta, left renal artery, middle cerebral artery, and superior sagittal sinus. Infants of phospholipid-positive mothers may have vascular thrombosis and should be carefully monitored for signs of thromboembolism.

Antiphospholipid Syndrome↗