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Biomedical subjects

D M Lewis

Publications and source records attributed to D M Lewis.

At least 127 records · Page 7Linked to original sources
PubMed1982

Functional evidence for complement-activating immune complexes in the skin of patients with bullous pemphigoid.

Previous immunofluorescent studies showing deposits of immunoglobulin and complement at the cutaneous basement membrane zone have provided evidence supporting a role for immune complexes in the pathogenesis of bullous pemphigoid. In this study the functional activity of the deposits has been examined using leukocyte attachment, a method for detecting and quantitating the biological activity of complement-activating immune complexes in tissues. When peripheral blood leukocytes suspended in serum complement were incubated with cryostat sections of lesional and adjacent normal-appearing skin from 9 patients with pemphigoid, skin from 11 normal controls and lesional skin from 14 nonpemphigoid disease controls there was significantly greater attachment of leukocytes to the basement membrane zone of lesional bullous pemphigoid skin compared to normal-appearing pemphigoid skin and skin of both control groups. A significant reduction in attachment in the absence of serum complement suggested the reaction was dependent on activation of complement by tissue-deposited complexes. Although leukocyte attachment was greater in lesional than normal-appearing pemphigoid skin, a comparison of the incidence and intensity of cutaneous IgG and complement immunofluorescence between the 2 groups showed no significant differences. Furthermore, no correlation between leukocyte attachment and serum titers of immunoglobulin G or complement-binding anti-basement membrane zone antibodies was observed. These results suggest that immune reactants in lesional pemphigoid skin are functional complement-activating immune complexes, that differences exist between the activity of complexes in lesional and normal-appearing pemphigoid skin and may explain why lesions develop at some sites and not others.

Antigen-Antibody Complex↗
PubMed1982

An in vitro model of immune complex-mediated basement membrane zone separation caused by pemphigoid antibodies, leukocytes, and complement.

In this study, an in vitro model of immune complex-mediated basement membrane zone separation caused by periphigoid antibodies, serum complement, and peripheral blood leukocytes is described. When cryostat sections of fresh-frozen normal human skin were treated with either of 4 bullous pemiphigoid sera containing complement-activating anti-basement membrane zone antibodies and subsequently incubated at 37 degrees C with normal human peripheral blood leukocytes and fresh human serum, leukocytes attached to 96% of the basement membrane zone in 100% of sections. Sixty-seven percent of the sections developed focal areas of basement membrane zone separation resembling dermal-epidermal separation described in early pemphigoid lesions. In control sections in which either leukocytes, pemphigoid antibody or fresh human serum were omitted, significantly less leukocyte attachment and basement membrane zone separation occurred. Evidence that leukocytes caused separation was supported by an absolute requirement for viable leukocytes during incubation, a high correlation between leukocyte attachment and separation and experiments showing that leukocytes attached to the basement membrane zone were activated. This study provides the first in vitro evidence directly supporting a functional role for immune-complex mediated inflammation in the pathogenesis of basement membrane zone separation and blisters in bullous pemphigoid.

Antibodies↗
PubMed1982

Isometric contractions of motor units and immunohistochemistry of mouse soleus muscle.

1. Isometric contractions of motor units, isolated functionally by ventral root splitting in vivo, were recorded from mouse soleus muscle. 2. Motor unit tensions varied over a narrow symmetrical range and averaged 4.7% of whole muscle tension, corresponding to twenty-one motor units per muscle. 3. There was considerable variation between muscles in isometric twitch times-to-peak and even greater variation for the motor units. The distribution of motor unit times-to-peak was apparently unimodal and could be fitted by a single normal population. A slightly better fit was, however, obtained with two normal populations, as suggested by the histochemistry. 4. Twitch time-to-peak decreased in proportion to axonal conduction velocity in individual animals. The whole population of motor units could be fitted by a linear relation between time-to-peak and the reciprocal of conduction time in the motor axon. Motor unit tension was also linearly related to the reciprocal of conduction time. 5. Histochemistry showed clear division between Type I and Type IIa fibres. Type I fibres reacted strongly with antibody against slow myosin of cat soleus muscle; Type IIa gave a reaction no stronger than the background. The division was as clear as in the cat or rat.

Animals↗
PubMed1982

Motor units and immunohistochemistry of cat soleus muscle after long periods of cross-reinnervation.

1. Cat soleus (slow twitch) was cross-reinnervated with nerve to flexor hallucis or digitorum longus muscle (fast twitch). More than 3 years later motor unit isometric contractions and muscle immunohistochemistry and histochemistry were investigated. All muscles differed from normal fast or slow muscle.2. The motor units could be divided into two groups: one with fast twitches and low tetanic tension, the other with slow twitches and high tension. This is the reverse of the relation between motor unit twitch time and tetanic tension in normal muscle (fast or slow).3. Motor unit twitch time to peak decreased with axonal conduction velocity, as in normal muscle, but so did tetanic tension, which is abnormal.4. Twitch-tetanus ratio increased with twitch time to peak in the group of slow units but not in the fast group (although the range of ratios was as great).5. A tetanus depressed the twitch tension of slow motor units and potentiated fast ones as in normal muscle but the potentiation was often accompanied by an abnormal prolongation of the twitch.6. The mean conduction velocity of axons was slightly higher than at 6 months' reinnervation but below the normal value for fast muscle.7. Antibody to slow myosin was bound strongly to Type I fibres but not to Type II fibres, confirming the histochemical division of fibres into Types I and II.8. More than 95% of the fibres were oxidative, with Type I predominating over Type II a in the ratio of about 2:1.9. The higher tension of the slow motor units was the result of three factors: the number of fibres per motor unit was at least three times that in the fast; Type I fibres had cross-sectional areas little less than Type II (a and b together) and were estimated to develop more tension per unit area. All three findings were different from those in normal fast muscle.10. One flexor hallucis longus muscle was self-reinnervated and examined histochemically. This muscle was abnormal in that a large majority of the fibres were Type I.

Adenosine Triphosphatases↗
PubMed1981

Motor units in cross-reinnervated fast and slow twitch muscle of the cat.

1. Isometric contractile properties of motor units were measured in cross-reinnervated fast (flexor digitorum longus) and slow (soleus) twitch muscles of the cat. All but one cross was at least 95% pure. 2. There was a reduction in the number of motor units in all muscles, but totals remained about equal in cross-reinnervated soleus and flexor digitorum longus. 3. Motor unit tensions (mean and maximum values) were higher in cross-reinnervated soleus than in cross-reinnervated flexor digitorum longus, reversing the differences between normal muscles. This was due to increases in muscle mass and in the tension developed per unit cross-sectional area. There were motor unit tensions larger and smaller than those seen in normal muscle, but the range was comparable with that seen in self-reinnervated muscle. 4. The changes in twitch time to peak of whole muscle following cross-reinnervations resulted from a change over the whole range of motor units. The conversion of soleus was less complete than that of flexor digitorum longus, and the time to peak of its fastest motor unit was twice as long as any seen in normal flexor digitorum longus. 5. In neither of the cross-reinnervated muscles were the fast contracting motor units larger than the slow contracting ones, and in cross-reinnervated soleus they were smaller. 6. Axonal conduction velocity was correlated with motor unit tension in both muscles and with twitch time to peak in cross-reinnervated flexor digitorum longus, but in all cases less clearly than in normal muscles. 7. The ratio of twitch to tetanic tension increased with increasing twitch time to peak, as in normal muscles.

Animals↗
PubMed1981

The effects of denervation on contractile properties or rat skeletal muscle.

1. Isometric contractions of fast and slow twitch muscles of rats were recorded 1-42 days after denervation. 2. The major changes occurred over the period from 2 to 6 days after denervation. These changes were qualitatively similar in the two types of muscle. The most important effects were on the twitch: times to peak and half relaxation were prolonged, active tension and peak rate of rise of tension were increased. Tetanic tension per unit cross-sectional area and the maximum rate of rise of tension decreased during this period but, in the second week, the tension recovered substantially and the maximum rate recovered completely. 3. Very small differences were seen between muscles denervated with short and long nerve stumps at day 4. 4. In the late stage of denervation (7-42 days) twitch and tetanic tension fell more than cross-sectional area, but this may have been due to greater atrophy of fibres compared with other muscle tissue. 5. Apart from this tension fall, there were only small changes in the fast muscle in the late stage of denervation. These were a fall in twitch-tetanus ratio and a prolongation of relaxation. 6. In more than half of the soleus muscles there was a late reversal of some of the denervation changes, and these muscles showed a greater degree of atrophy. The less atrophied soleus muscles maintained a prolonged twitch and a low rate of development of tension. 7. It is concluded that denervation affects the contractile properties of muscle as early and as abruptly as it does the membrane properties, and that most of the contractile changes are a direct consequence of changes in excitation-contraction coupling alone.

Animals↗
PubMed1980

Intraosseous angiolipoma of the mandible.

A case of intraosseous angiolipoma of the mandible is reported. To our knowledge, this represents only the second case involving the jaw to be reported in the literature.

Adipose Tissue↗
PubMed1980

Pemphigoid antibody mediated attachment of peripheral blood leukocytes at the dermal-epidermal junction of human skin.

It has been proposed that cutaneous inflammation and blister formation in bullous pemphigoid is caused by antibodies to the cutaneous basement membrane zone which active complement, thereby, attracting leukocytes to the dermal-epidermal junction. There is, however, no functional evidence which supports a role for pemphigoid antibodies in complement activation or leukocyte activity in skin. This study describes the in vitro attachment of human peripheral blood leukocytes to the dermal-epidermal junction of cryostat skin sections treated with 9/13 pemphigoid sera containing antibodies to the cutaneous basement membrane zone. A requirement for complement in the reaction was supported by the findings that only complement-fixing pemphigoid sera mediated the leukocyte response, a strong correlation existed between complement-fixation titers and leukocyte attachment titers and only leukocytes suspended in fresh serum but not buffer or heat inactivated serum attached at the junction. A requirement for antibody was supported by the observation that IgG fractions of 4 pemphigoid sera were as effective as whole sera in mediating leukocyte attachment. The leukocyte response was shown to be specific for complement-fixing pemphigoid sera since it was not observed with noncomplement-fixing sera or sera from 15 normal human and 22 nonpemphigoid disease controls. This study offers functional evidence for an interaction between pemphigoid antibody, complement and leukocytes in the immunopathogenesis of bullous pemphigoid and demonstrates that complement-fixing antibasement membrane zone antibodies may be important in initiating the cellular inflammatory events observed near the dermal-epidermal junction in vivo.

Adult↗
PubMed1979

Otitis media with effusion. Cytological and microbiological correlates.

A quantitative cytologic study of 83 middle ear effusions from children with otitis media with effusion (OME) was made with the use of cytocentrifuge-prepared smears and was correlated with bacteriological findings. The identification of the types of cell present in an effusion was confirmed by electron microscopic findings. The most common cell types were neutrophilic leukocytes, lymphocytes, and macrophages, but a few eosinophils were found in only one case. The cytologic profile of an effusion correlated well with the bacterial culture results. Neutrophil counts were significantly higher in effusions that contained pathogenic bacteria (P less than .01) than in culture-negative effusions. Lymphocytes were the dominant cell type in culture-negative effusions. The results support the idea that bacteria are involved in the pathogenesis of many cases of OME.

Cell Count↗
PubMed1979

Intraoral rhabdomyomas.

Review of the world literature revealed 16 cases of intraoral rhabdomyomas. Thirteen additional cases of intraoral rhabdomyomas from the files of the Armed Forces Institute of Pathology are reported. The neoplasm occurred principally in adults (mean age 56 years), and the male-female ratio was greater than 2:1. The majority of cases occurred in the floor of the mouth, followed by the soft palate, tongue, and buccal mucosa. Recurrences occurred in four (30 percent) cases, and there was one multiple recurrence. One residual tumor, the result of incomplete surgical removal was noted. Although these tumors have a characteristic microscopic appearance, they were frequently misinterpreted. The size, clinical presentation, and growth pattern of these tumors may reflect their ultimate behavior and prognosis.

Adolescent↗
PubMed1979

Histochemical reactions of fibres in a fast twitch muscle of the cat.

1. Serial sections of flexor digitorum longus muscle (f.d.l.) of the cat were examined histochemically for four enzyme systems: adenosine triphosphatase (ATPase) with alkaline and acid pre-incubation, phosphorylase and succinic dehydrogenase (SDHase).2. The number of types into which fibres should be divided was assessed by estimating enzyme reaction intensity from measurements of light transmission through photomicrographs. It was concluded that in general the enzyme reaction intensities of fibres were distributed continuously. However, the distribution histograms showed two (phosphorylase and SDHase) or three (acid and alkaline ATPase) clear peaks. Eighteen combinations of reaction intensities (profiles) were seen of which eight were very rare. The distribution of profiles differed between individuals but were similar in right and left muscles.3. Areas of fibres were measured from muscles which had been fixed at the length at which twitch tension was maximal. The variance in fibre area with any one profile was significantly less than the variance in fibre area of all fibres within a muscle. There were significant differences between the mean areas of fibres with different profiles.4. If only three enzyme reactions are considered (acid and alkaline ATPase and phosphorylase) the majority of fibres fall into one of the three classes commonly accepted for other muscles. The remainder would fit into this classification with the minimal assumption of only one error of fibre typing resulting from the continuous distributions of enzyme reaction intensities. The SDHase reaction was not strongly correlated with the three classes and could be used to divide the fibres further into six groups. Differences between means of fibre areas were significant for all pairs out of these six groups except one.5. The grouping may be considered to reflect a dual system of enzymes, the two systems being (a) ATPases and phosphorylase, (b) SDHase. A possible role of nervous activity in determining this dual system is discussed. The hypothesis involves two partly independent characteristics of motoneuronal activity: (a) the frequency of impulses, and (b) the total number of impulses.6. The measurements are correlated with other physiological variables in the individual animals. The mean areas of fibres in all groups increased with body weight. There were changes in the proportions of light and dark SDHase fibres related to weight. The total area contributed by dark alkaline ATPase fibres decreased and that by intermediate alkaline ATPase fibres increased with increasing twitch time to peak.7. Specific tension of the group of slower muscle fibres in f.d.l. was estimated to be 0.29 N.mm(-2) compared with 0.39 N.mm(-2) for the faster fibres.

Adenosine Triphosphatases↗
PubMed1978

Localization of the guinea pig eosinophil major basic protein to the core of the granule.

The localization of the guinea pig eosinophil major basic protein (MBP) within the cell was investigated by the use of immunoelectron microscopy and by isolation of the granule crystalloids. First, by immunoperoxidase electron microscopy, we found that the MBP of eosinophil granules is contained within the crystalloid core of the granule. Specific staining of cores was present when rabbit antiserum to MBP was used as the first stage antibody in a double antibody staining procedure, whereas staining was not seen when normal rabbit serum was used as the first stage antibody. Second, crystalloids were isolated from eosinophil granules by disruption in 0.1% Triton X-100 and centrifugation through a cushion of 50% sucrose. Highly purified core preparations yielded essentially a single band when analyzed by electrophoresis on polyacrylamide gels containing 1% sodium dodecyl sulfate (SDS). The E1%1cm of the core protein was 26.8 +/- 1.0 (X +/- SEM); the E1%1cm for the MBP was 26.3. The core protein could not be distinguished from the MBP by radioimmunoassay (RIA) and essentially all of the protein in the core preparations could be accounted for as MBP. The results indicate that the MBP is contained in the core of the guinea pig eosinophil granule and that it is probably the only protein present in the core.

Animals↗