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Biomedical subjects

J B Allen

Publications and source records attributed to J B Allen.

At least 91 records · Page 5Linked to original sources
PubMed1985

Bacterial cell wall composition, lysozyme resistance, and the induction of chronic arthritis in rats.

Bacterial cell wall induced arthritis is an experimental model of chronic erosive synovitis in which arthritis is induced in rats by a single injection of an aqueous suspension of cell wall fragments from selected Gram-positive bacteria. To understand better the Gram-positive bacterial cell wall characteristics necessary for the induction of chronic arthritis we tested the arthritogenicity of five Gram-positive bacteria which were (1) lysozyme resistant and contained a polyrhamnose peptidoglycan side chain moiety, (2) lysozyme resistant, but had little or no rhamnose in the peptidoglycan, polysaccharide, or (3) neither lysozyme resistant, nor contained rhamnose in their peptidoglycan, polysaccharide. All of the lysozyme resistant cell walls tested induced acute arthritis, but only those cell walls which were both lysozyme resistant and contained rhamnose in their polysaccharide side chain were able to induce chronic arthritis. Cell walls which were neither lysozyme resistant nor contained rhamnose were not arthritogenic. These data suggest that both lysozyme resistance and the rhamnose moiety in the peptidoglycan, polysaccharide side chain play an important role in the induction of chronic arthritis by Gram-positive bacterial cell walls in aqueous suspension.

Animals↗
PubMed1985

Dose-dependent suppression by the synthetic retinoid, 4-hydroxyphenyl retinamide, of streptococcal cell wall-induced arthritis in rats.

We studied the effects of oral administration of the retinoid, 4-hydroxyphenyl retinamide (4-HPR), on group A streptococcal cell wall-induced polyarthritis in the rat, a model characterized initially by exudative inflammation of peripheral joints followed by chronic proliferative/erosive synovitis. Experimental arthritis was induced in female LEW/N rats by i.p. injection of streptococcal cell walls in saline (15 micrograms/g body weight). Depending upon the experiment, continuous daily oral administration of the retinoid was begun either 14 days prior to induction of the disease, at the time of cell wall administration and/or 11 days and 31 days after cell wall injection. Dosage was either 1 or 2 mmol 4-HPR/kg of chow. During the course of the disease, severity of clinical illness was assessed by determination of clinical severity index, by histological or radiologic examination, and by measurement of production in vitro of collagenase and prostaglandin E2 by excised synovial tissue. In rats fed the retinoid prior to cell wall injection, both the acute and the chronic responses were suppressed. In rats given the retinoid at the time of cell wall injection, the acute inflammatory response was only partially suppressed on the diet containing 2 mmol 4-HPR/kg chow, but the chronic disease was impressively inhibited in a dose dependent manner. Similarly, in animals with established disease, the drug was also effective; however, the more advanced the illness, the less effective the drug. Clinical observations were paralleled by the histological, radiographical and biochemical analyses. Treated animals showed far less synovial proliferation and joint destruction, and synovial tissues taken from these rats produced lesser amounts of collagenase and prostaglandin E2. No significant toxicity of the retinoid was noted. We conclude that oral administration of 4-HPR suppresses, in a dose and time dependent manner, both the acute and chronic stages of streptococcal cell wall-induced arthritis in rats without apparent significant toxicity. Our data suggest that studies of the effects of this retinoid on patients with chronic inflammatory synovitis are warranted.

Animals↗
PubMed1985

Nonlinear phenomena as observed in the ear canal and at the auditory nerve.

We report here several measures of nonlinear effects in the mammalian ear made in the external auditory meatus and in single neurons of the auditory nerve. We have measured the 2f1-f2 and the f2-f1 distortion products and we have found that the neural distortion product threshold curve for 2f1-f2 mirrors the low-frequency side of the frequency threshold curve, when the neural distortion product threshold curve of 2f1-f2 is plotted versus log(f2/f1) its slope is about 50 dB/oct and its intercept is 10-20 dB above the frequency threshold at the characteristic frequency CF, substantial 2f1-f2 distortion was seen in all animals studied while the f2-f1 distortion product was only rarely found at substantial levels, and the distortion product pressure observed in the ear canal was at a level equal to that detected at threshold by the neural units under study. We have also made measurements of two-tone rate suppression thresholds using two new and consistent threshold paradigms. We find that for high and intermediate characteristic frequency neural units the suppression threshold is independent of frequency and at a level of about 70 dB SPL, the suppression above CF is much less than below CF, and the tip of the frequency tuning curve can be suppressed by up to 40 dB by a low-frequency suppressor.

Animals↗
PubMed1985

Measurement of streptococcal cell wall in tissues of rats resistant or susceptible to cell wall-induced chronic erosive arthritis.

The quantity of streptococcal cell wall localized in the joints of rats of strains which are either susceptible (Sprague-Dawley, LEW/N, M520/N) or resistant (Buffalo, WKY/N, F344/N) to cell wall-induced chronic erosive arthritis was measured after intraperitoneal injection of group A streptococcal cell wall fragments. Susceptibility or resistance was not associated with a difference in the amount of cell wall localized in limbs or other tissues. It is concluded that although localization of cell wall in joint tissue is essential for development of arthritis, the relative resistance of certain rat strains reflects genetic regulation of inflammatory response rather than a quantitative difference in localization of cell wall in joints.

Animals↗
PubMed1985

Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats.

Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments to susceptible rats induces acute and chronic polyarthritis, as well as noncaseating hepatic granulomas. To gain insight into the role of the thymus in the pathogenesis of this experimental model, pathologic responses and cell wall tissue distribution were compared in congenitally athymic rats (rnu/rnu) and their euthymic littermates (NIH/rnu). Within 24 h, both rat strains developed acute arthritis, characterized by polymorphonuclear leukocytic exudate in the synovium and joint spaces. This acute process was maximal at day 3 and gradually subsided. Beginning 2-3 wk after injection, the euthymic, but not the athymic, rats developed the typical exacerbation of arthritis, characterized by synovial cell hyperplasia with villus formation and T helper/inducer lymphocyte-rich mononuclear cell infiltration. This process eventually resulted in marginal erosions and destruction of periarticular bone and cartilage. Parallel development of acute and chronic hepatic lesions was observed. Bacterial cell wall antigen distribution and persistence were similar in the athymic and euthymic rats. Cell wall antigens were demonstrated in the cytoplasm of cells within subchondral bone marrow, synovium, liver, and spleen, coincident with the development of the acute lesions, and persisted in these sites, although in decreasing amounts, for the duration of the experiment. Our findings provide evidence that the acute and chronic phases of the experimental model are mechanistically distinct. The thymus and functional thymus derived-lymphocytes appear not to be required for the development of the acute exudative disease but are essential for the development of chronic proliferative and erosive disease. Induction of disease is dependent upon cell wall dissemination to and persistence in the affected tissues.

Acute Disease↗
PubMed1984

Leukapheresis and pathogenetic mechanisms in rheumatoid arthritis.

Rheumatoid Arthritis is a chronic, usually progressive inflammatory disorder of joints in which the immune system plays a central role in the pathogenesis. In its classic form, the synovial tissues from severely affected joints are densely infiltrated with HLA-DR bearing T-lymphocytes (primarily OKT4+/Leu3+ subset) and macrophage-like cells. Moreover, these tissues, as demonstrated by ex vivo culture, spontaneously produce high levels of a multitude of inflammatory mediators, such as collagenase, PGE2, interleukin 1 and fibroblast activating factors, indicating that the cells infiltrating the synovium are "activated". The action of these various inflammatory mediators on different target substances or cells (collagen, fibroblasts, chondrocytes, osteoclasts, etc.) most likely produce the characteristic pattern of joint pathology. Recent data indicate that this classic form of synovitis tends to be associated with peripheral anergy and other qualitative and quantitative abnormalities in the peripheral blood mononuclear cells. Repeated leukapheresis can induce substantial, although transient, clinical improvement in patients with these classic features, probably as a consequence of disrupting T-lymphocyte traffic. Rheumatoid synovitis, however, is highly heterogeneous, but can be categorized into subsets. For example, a subset of patients with highly active clinical rheumatoid arthritis exists which do not exhibit the classic features of disease. Synovial tissues from this patient subset are sparsely infiltrated by T-lymphocytes but contain mainly macrophages and fibroblasts, as well as prominent lining layer fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1984

A behavioral technique for recovery from the psychological trauma of hysterectomy.

Three groups of women (ns = 10) undergoing hysterectomy were subjects in an evaluation of biofeedback and relaxation techniques applied to recovery from psychological trauma of hysterectomy. Dependent measures included requests of pain medications, anxiety levels, finger-tip temperature, subjective units of discomfort, and number of days post-operative care. Although the results were mixed on most variables, the number of days post-operative care was significantly less in the relaxation/biofeedback group.

Adaptation, Psychological↗
PubMed1984

Immune function in severe, active rheumatoid arthritis: a relationship between peripheral blood mononuclear cell proliferation to soluble antigens and mononuclear cell subset profiles.

We have previously reported that patients with active rheumatoid arthritis and depressed in vitro peripheral blood mononuclear cell proliferation to soluble recall antigens (anergic subgroup) improve clinically after repeated short-term leukapheresis, whereas patients with normal responses (nonanergic subgroup) do not. This observation prompted us to examine the mononuclear cell subset profiles in the peripheral blood of anergic and nonanergic seropositive rheumatoid arthritis patients with severe, active, clinically similar disease not taking long-acting anti-rheumatic drugs. In the present study, 42 patients were categorized as anergic (n = 14) or nonanergic (n = 28) on the basis of in vitro peripheral blood mononuclear cell proliferation to soluble recall antigens. The anergic patients had a decreased frequency of OKT4+ mononuclear cells (p less than 0.01), and an increased frequency of OKT8+ cells (p less than 0.02), with a lower OKT4+ :OKT8+ ratio (p less than 0.01) than the nonanergic patients. Anergic patients also had a higher frequency of HLA-DR+ mononuclear cells and HLA-DR+ T cells (p less than 0.001). About 50% of the OKT8+ cells were HLA-DR+, whereas only about 20% of the OKT4+ population expressed HLA-DR antigens. These data suggest that the decreased lymphocyte function described in the anergic patient subgroup is associated with characteristic peripheral blood mononuclear cell subset profiles. Moreover, when considered in the context of other data indicating that anergic patients have characteristic synovial immunopathologic abnormalities, these data provide insight into potential pathogenic mechanisms of this disorder.

Adult↗
PubMed1983

Leukapheresis in rheumatoid arthritis. Association of clinical improvement with reversal of anergy.

In order to study the clinical and immunologic effects of a brief course of leukapheresis, 14 patients with clinically similar rheumatoid arthritis were segregated into 2 subgroups. Group A (7 patients) had subnormal lymphocyte tritiated thymidine incorporation to soluble antigens. After a brief course of leukapheresis, 6 of these 7 patients demonstrated substantial clinical improvement associated with significantly enhanced lymphocyte tritiated thymidine incorporation to soluble antigens. In contrast, none of the 7 patients in group B (normal immune functions) demonstrated similar changes in articular indices or lymphocyte proliferation. Thus, clinical improvement induced in a subset of rheumatoid arthritis patients appears to reflect modulation of function, and not simply immunosuppression.

Adolescent↗
PubMed1983

Polyarthritis in rats following the systemic injection of Lactobacillus casei cell walls in aqueous suspension.

Postdysenteric Reiter's syndrome and the arthritis associated with jejunal bypass surgery for obesity suggest that the gastrointestinal tract is a possible source of bacterial products capable of initiating chronic inflammatory arthritis. Lactobacillus casei, a common component of the enteric flora, has a cell wall structure similar to that of arthritogenic streptococci. In this study we have demonstrated that a single intraperitoneal injection of an aqueous suspension of the cell walls of Lactobacillus casei induces a dose-dependent, chronic, symmetric, erosive, peripheral polyarthritis in inbred LEW/N female rats. This model suggests that bacteria in the "normal enteric flora" may be a source of inflammatory products capable of inducing chronic erosive polyarthritis.

Amino Acids↗
PubMed1983

The pathogenesis of group A streptococcal cell wall-induced polyarthritis in the rat. Comparative studies in arthritis resistant and susceptible inbred rat strains.

This report addresses the host mechanisms which regulate susceptibility and resistance to group A streptococcal cell wall-induced polyarthritis in the rat. We have compared cell wall tissue distribution and persistence following a single intraperitoneal injection of an aqueous suspension of the cell walls into arthritis susceptible LEW/N and resistant F344/N female rats. Selected aspects of the induced inflammatory reaction were also compared. Our results suggest that development of chronic erosive polyarthritis in this model is dependent, in variable degrees, upon 1) deposition and persistence of the cell walls in synovial tissues, and 2) a relative inability of arthritis susceptible rats to neutralize the proinflammatory properties of the cell walls.

Animals↗
PubMed1983

Magnitude and phase-frequency response to single tones in the auditory nerve.

In this paper we describe magnitude and phase measurements obtained from primary single unit recordings in the cat auditory nerve. Levels range from threshold to 100 dB SPL, with frequencies from 0.1-30.0 kHz. The upper limit on the phase measurements was limited by the loss of neural phase locking at 4-5 kHz. For each unit, the frequency tuning curve (FTC) was measured by the method of Kiang and Moxon [M.C. Liberman, J. Acoust. Soc. Am. 63, 442-445 (1978)] to establish the threshold frequency response of the unit. Data from several selected animals, organized by characteristic frequency (CF), are presented showing phase response, group delay, frequency tuning, and tuning slope for each CF range. The major emphasis in this paper is on the "linear" aspects of the data as characterized by the filter properties of the single unit response, however a number of nonlinear (level-dependent) effects are described. Data are presented showing the phase response normalized by the cochlear microphonic (CM) recorded at the round window membrane. This normalization simplifies the phase data since it produces a constant phase slope with respect to frequency (constant group delay) for high CF units (f CF greater than 1 kHz) for frequencies more than one octave below their characteristic frequencies. A model of CM, as measured at the round window (RW), is presented and compared to experimental CM measurements. The CM model gives a reasonable fit to the experimental data above 500 Hz. Our interpretation of the CM normalization is that it removes driver and middle ear effects. In the model we assume that the CM is generated by the displacement of the basilar membrane near the round window recording site.

Animals↗
PubMed1983

Cutaneous inflammatory reactions to group A streptococcal cell wall fragments in Fisher and Lewis inbred rats.

Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments induces severe, chronic erosive polyarthritis in LEW/N female rats, but rarely in F344/N female rats. In the present study, we attempted to exclude unresponsiveness to the cell walls as a mechanism for arthritis resistance in F344/N females. Cutaneous inflammatory reactions were assessed in both strains at various time points after direct injection of cell wall fragments of three different average molecular weights. Fragments of all sizes induced an acute inflammatory reaction, with infiltration of polymorphonuclear leukocytes and a few mononuclear cells. Small fragments (approximately 5 megadaltons) induced a transient response which resolved by day 14. Large fragments (approximately 500 megadaltons) induced severe inflammation characterized by prominent mononuclear leukocyte infiltration, whereas the intermediate-sized fragments (approximately 50 megadaltons) induced inflammation of intermediate intensity and duration. The intensity and severity of the lesions paralleled the persistence of cell wall antigens at the site of deposition. F344/N female rats responded acutely to the cell walls, with an intensity equal to or greater than that of LEW/N female rats, but the lesions tended to resolve more rapidly. These findings indicate that severity and chronicity of streptococcal cell wall-induced inflammation are dependent on the size of the fragment and provide evidence that arthritis resistance in F344/N female rats does not result from a completely unresponsive state to the proinflammatory effects of the cell walls.

Animals↗
PubMed1982

Arachidonic acid metabolism in the neonatal platelet.

An assessment of arachidonic acid metabolism in the platelet of the neonate was performed. The uptake of [14C]arachidonic acid into platelets of both the neonate and the adult were similar. Neonatal platelets, however, released a significantly greater amount (P less than .001) of prelabeled arachidonic acid (24.7% +/- 2.8%) in response to the physiologic agent thrombin when compared with platelets from adult control subjects (14.6% +/- 0.8%). When the activities of the lipoxygenase (12-L-hydroxy-5,8,10,14-eicosatetraenoic acid) and cyclooxygenase pathways (12-L-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2) were evaluated following incubation of platelets with [14C]arachidonic acid, significant differences were observed between adult and neonatal platelets. Platelets from the neonate produced less (P less than .01) thromboxane B2 (11.1% +/- 1.7%) when compared with platelets from adult control subjects (19% +/- 1.7%). In contrast, the lipoxygenase product 12-L-hydroxy-5,8,10,14-eicostatetraenoic acid was increased (P less than .005) in the platelet from the neonate (41.5% +/- 2%), when compared with the adult (31.2% +/- 2.1%). The observation that the availability of substrate arachidonic acid is increased in the platelet of the neonate may have general implications in neonatal pathophysiologic processes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗