Perivascular Mononuclear Infiltrates Research Articles

Immunoglobulin Deposition in Skeletal Muscle in Primary Muscle Disease

Using direct immunofluorescence the deposition of IgG, IgM, IgA, Clq and C3 was studied on muscle biopsies from 39 patients with polymyositis/dermatomyositis, 21 patients with muscular dystrophy, 57 other disease controls and 10 healthy volunteers. Three staining patterns were observed, sarcolemma/basement membrane blood vessel wall and intrafibrous. Sarcolemma/basement membrane staining, but not blood vessel wall or intrafibrous staining, occurred more frequently (p less than 0.05) in the polymyositis/dermatomyositis group compared with the two other disease groups. Immunoglobulin deposition was useful in distinguishing myopathic from neuropathic disorders. Grouping the patients into those with connective tissue diseases and those without, sarcolemma/basement membrane and blood vessel wall staining were shown to distinguish the two groups (p less than 0.05). An analysis of the histological abnormalities in the polymyositis/dermatomyositis group was performed and related to immunoglobulin/complement deposition. Fibre damage, rather than the presence of a mononuclear perivascular infiltrate, was shown to be the best correlate with each of the three staining patterns. Immunoglobulin and/or complement deposition in skeletal muscle is an abnormal finding and the results described support the notion that humoral abnormalities may be detected frequently in polymyositis/dermatomyositis. In addition, the inability to distinguish polymyositis/dermatomyositis from muscular dystrophy limits the potential value of direct immunofluorescence as a diagnostic tool.

Eosinophil leukocytic response in dinitrochlorobenzene skin hypersensitivity reaction in the chicken

The cutaneous inflammation evoked by topical application of dinitrochlorobenzene in sensitised chickens was studied at 24- and 48-hours post-challenge. A slight increase in vascular permeability was present at 24 hours but absent at 48 hours. Histologically, the reaction comprised oedema and a diffuse infiltration of polymorphonuclear granulocytes in the superficial dermis, and intense perivascular mononuclear infiltrations in the deep dermis. The apparent participation of eosinophils was a noteworthy feature of the reaction.

Unusual Cutaneous Manifestations of Systemic Lupus Erythematosus: I. Urticaria-like Lesions. Correlation with Clinical and Serological Abnormalities

Ten of 143 systemic lupus erythematosus patients demonstrated urticaria-like lesions. Lesional biopsies in 7 of 9 patients tested revealed a leukocytoclastic angiitis and in 2, a mononuclear perivascular infiltrate. Direct immunofluorescent studies in 2 of 6 patients tested revealed IgM and C3 deposition in and about dermal blood vessels. Nine of the 10 systemic lupus erythematosus, patients displayed active clinical disease (e.g., arthritis, renal disease, etc.), a positive lupus band test, antibodies against deoxyribonucleic acid or Sm macromolecules, serum hypocomplementemia and markedly elevated quantities of serum immune complexes as determined by an immunoradiometric assay employing Raji cells. Similar lesions were not detected in 35 discoid lupus erythematosus patients. These studies strongly suggest: (1) urticaria-like lesions are uncommon cutaneous manifestations of systemic lupus erythematosus. (2) These urticaria-like lesions do not represent a classic IgE mediated urticaria. (3) These urticaria-like lesions generally occur in lupus erythematosus patients demonstrating clinical and/or serological evidence of systemic disease activity. (4) These lesions are probably secondary to immune complex deposition. We, therefore, conclude that all urticarial lesions in lupus erythematosus patients should be biopsied and the patient evaluated for active systemic disease.

Epidermolysis bullosa acquisita: A clinical disorder of varied etiologies: Two cases and a review of immunologic and other reported findings

Epidermolysis bullosa acquisita (EBA) is an acquired mechanobullous disorder characterized by traumatically induced bullae in skin subjected to frictional injury, i.e., acral extensor surfaces or any point of sufficient mechanical distress. Two new patients with EBA are reported. Histopathologic findings were subepidermal ballae with sparse superficial perivascular mononuclear cell inflammatory infiltrates. The periodic acid-Schiff (PAS)-positive basement membrane zone (BMZ) was split between the floor and roof of the blisters with most attached to the blister roof. Electron microscopy of normal skin from one patient revealed a bandlike zone of granular material within the dermis immediately beneath the basal lamina. Nonbranching filaments were embedded in the granular material. Electron microscopy of normal skin from the second patient revealed a markedly diminished density of anchoring fibrils but no granular material. Immunologic findings in skin biopsies were C'3, IgG, and other immunoglobulins in varying combinations in both cases and in all reported cases. Comparisons of direct immunofluorescent (IF) findings in nine reported cases with 223 cases of bullous pemphigoid (BP) suggest that BMZ deposits of IgG plus IgA and/or IgM occur more frequently in EBA than in BP. Indirect IF studies of patients' sera revealed antibodies to the BMZ in two samples of one of our two cases and in one of seven cases reported by others. While both EBA and BP characteristically yield positive IF findings in the BMZ, clinical, electron microscopic, and some immunopathologic findings indicate that the two diseases are distinct.

Papular Eruption in Black Men

A persistent papular eruption in black men characterized clinically by small, pruritic papules and histologically by a mononuclear cell-eosinophil perivascular infiltrate is described. This disorder, seen only in young black men, is not readily classifiable within existing dermatologic taxonomy.

Erythema Chronicum Migrans With Purpura and Polymorphonuclear Infiltrates

Erythema chronicum migrans with an intensely purpuric border developed in a 70-year-old woman. A biopsy specimen, in addition to showing the usual perivascular mononuclear infiltrate, demonstrated numerous polymorphonuclear leukocytes associated with leukocytoclasis. Immunofluorescence study showed vascular deposition of IgM and C3.

Virus-induced demyelination: Production by a viral temperature-sensitive mutant

Infection of mice with a temperature-sensitive ( ts) mutant of Chandipura virus (CV) ts472 CV, induced a slower disease than the respective parental virus and white matter lesions characterized by perivascular mononuclear infiltrates accompanied by primary demyelination. The pattern of these lesions was very similar to that in EAE, a prototypic autoimmune disease and in Theiler's virus infection in which an immunopathologic mechanism of myelin injury is strongly suggested. Results obtained in nude mice supported the possible immunopathological nature of myelin injury in ts472 CV infection. No inflammatory response was elicited in either grey or white matter. However, whereas grey matter presented extensive necrosis, no alterations were present in white matter. Such data suggest that whereas grey matter lesions are produced by direct viral cytolytic activity, white matter pathology is probably dependent on the host immune response for its development. The finding of additional models of virus-induced demyelination with a possible immunopathologic mechanism of myelin injury is significant as it suggests that this type of virus-induced myelin degeneration is not restricted to a single virus like Theiler's, but it may represent a more general mechanism of virus-induced demyelination.

Delayed-Type Hypersensitivity Skin Reactions in Congenital Afibrinogenemia Lack Fibrin Deposition and Induration

Induration is a characteristic feature of delayed-type hypersensitivity skin reactions and is the usual measure of their intensity. The precise basis of induration has not been established, although activation of the clotting system with consequent fibrin deposition has been clearly implicated. In this study, two subjects with congenital afibrinogenemia, a genetic defect in fibrinogen synthesis, were skin tested with standard microbial antigens: streptokinase-streptodornase, monilia, mumps, and tuberculin purified protein derivative. One positive delayed reaction from each subject was biopsied at 40-48 h and compared with 23 biopsies of similar skin tests in normal volunteers. The eight skin tests in the afibrinogenic subjects lacked induration, although the erythema was similar in size (10-34 mm in diameter), intensity, and time-course to those in normals. Biopsies from the two strongest reactions from the afibrinogenemic subjects showed a typical perivascular mononuclear infiltrate. No more than traces of fibrin/fibrinogen were detected by immunofluorescence, in striking contrast to the abundant fibrin/fibrinogen deposition in 23 positive, indurated reactions in normal subjects. These findings indicate that fibrinogen itself is essential for the development of induration in delayed-type skin reactions in man. As judged by 1-mum sections and fluorescence, this is probably a result of the formation of an extravascular fibrin gel.

CNS disease following dissemination of SSPE measles virus from intraperitoneal inoculation of suckling hamsters.

Acute encephalitis was observed in suckling Golden Syrian hamsters following intraperitoneal (ip) inoculation of a hamster brain adapted strain of subacute sclerosing panencephalitis (SSPE) measles virus (HBS). Virus was isolated from the brains of all encephalitic animals by cocultivation of tissue with Vero cells. The histopathology of the encephalitis was characterized by perivascular mononuclear infiltrates, necrosis, eosinophilic inclusion bodies, and rare giant cells. Association of encephalitis with systemic viral infection was observed with virus present in lung and a kidney-spleen pool in addition to brain. Viral dissemination in asymptomatic animals was documented with virus being isolated from multiple non-neural tissues (spleen, lung, liver) of animals having no recoverable virus in their brains and no signs of encephalitis. Treatment of animals with cyclophosphamide prior to ip virus inoculation did not increase dissemination to brain. Absence of encephalitis in asymptomatic animals with proven viral dissemination to parenchymal organs indicates that neither viremia alone, nor viremia in conjunction with dissemination are sufficient conditions to establish central nervous system disease. The association of encephalitis with systemic viral infection and the dissemination to brain establish this model's potential value for the study of the pathogenesis of measles encephalitis.

Reactions in canine skin with human leukocyte lysates.

SummaryTwo types of local reactions in canine skin were observed after intradermal injection of chromatographically prepared fractions of human perpheral blood leukocyte lysates. The first reaction peaked within 4 hr after injection, appeared unrelated to antigen, and was characterized by a mild diffuse mononuclear and polymorpho-nuclear infiltrate in the subcutaneous tissue. The second response peaked 30 hr after the injection of antigen onto the site previously prepared with leukocyte lysate. This response appeared to be antigen specific, and was characterized by an early perivascular mononuclear infiltrate followed by a diffuse mononuclear and polymorphonuclear accumulation in the subcutaneous region. PeaksI and IV most consistently gave positive results.

Clinico-pathological and pathomorphological observations in trypanosoma vivax infection cattle

Abstract During infection with T. vivax (strain Y 58) four stages can be distinguished: (a) A prepatent period of about 1 week. (b) An acute or fulminating disease characterized by an almost continuous, fluctuating parasitaemia, a decrease of the number of thrombocytes, blood serotonin level, packed cell volume (PCV) and Hb, serum albumin and γ-globulin fractions, a low serum total lipid content and an initial rise with subsequent decrease of the blood bradykinin level. (c) A critical stage of about 4–5 weeks post infection (pi) during which the animal may develop a progressive parasitaemia and may die from disseminated intravascular coagulation. At necropsy microthrombi were a consistent and most significant observation. Accompanying features were oedema and haemorrhages in the various tissues, pulmonary oedema and lobular infarction, patches of necrosis in liver, spleen and adrenals and nephrotic changes in the kidneys. Perivascular mononuclear infiltrates, resulting in local granuloma formation (heart liver), were a constant feature. Related biochemical changes were an increase of the blood urea and serum lactate dehydrogenase levels. (d) A post-critical stage characterized by an ameliorating condition, periods with no or few trypanosomes in the peripheral blood alternating with relatively high peaks of parasitaemia. This was associated with increased blood bradykinin levels, an increase of the PCV and Hb, serum albumin and γ-globulin fractions, number of thrombocytes and blood serotonin level. A return to normal values of the serum total lipids was observed at this stage. Despite this clinical recovery of the animals, at necropsy (on days 90, 98, and 99 pi) there was a moderate to massive histiocyte-lymphocyte-plasma cellular infiltration of the heart, which led to cardiac insufficiency in two heifers. The rise of the d-amino laevulinic acid dehydratase levels of erythrocytes during the decline of the PCV and Hb values is an indication for the production of many young erythrocytes and thereby for the haemolytic nature of the anaemia.

Zytoplasmatische tubuloretikuläre Komplexe und Kernsphäridien in Zellen rötelninfizierter menschlicher Embryonen und Feten

The range of single or multiple defects which might develop in the human embryo of fetus after an intra-uterine rubella infection has been documented by means of a large number of epidemiological, clinical and pathological investigations. Newborns with congenital rubella carry a number of defects, some of which could be the direct result of a virus-induced, intra-uterine vascular damage. In rubella-infected embryos and fetuses, vascular lesions are the most frequently observed histopathological finding. These changes have already been systematically investigated by means of the light microscope. Ultrastructural data are, however, not available at present.

Pathogenesis of Trypanosoma brucei infection in sheep : III. Hypophysial and other endocrine lesions

Sheep experimentally infected with Trypanosoma brucei for 2 to 5 months developed lesions in the pituitary body, thyroid and adrenal cortex, but not in the adrenal medulla, pancreas and parathyroid. Neurohypophysial lesions were characterized by gliosis and perivascular mononuclear infiltration extending to the surrounding meninges. In the adenohypophysis, oedema, acute coagulative necrosis and fibrosis were observed. Adrenal cortical hypertrophy and atrophy of the thyroid were the other endocrine lesions. There was massive localization of trypanosomes (so-called amastigote forms) in the interstitial tissue of the adeno- and neuro-hypophysis, but not in the other endocrine glands. It was suggested that trypanosome-induced pituitary damage might explain some of the clinical signs in animal trypanosomiasis, as is the case in human sleeping sickness.

The mast cells of the mammalian central nervous system: Part 2. The effect of proton irradiation in the monkey

Young adult monkeys ( Macaca mulatta) were irradiated with protons variable in energy and dosage and given at different rates. They died or were killed at intervals and their brains and spinal cords were examined for several changes including the status of the mast cells (MCs) (see Ibrahim 1974). Depending on the animal and the dosage, initial changes in these cells included various combinations of partial or complete degranulation, anisogranulation, hypertrophy and moderate to marked increase in number. These changes are similar to changes recorded in the literature respecting MCs outside the CNS; they resolved, but incompletely, within a few days. When delayed radionecrosis occurred a few months later, the same changes recurred but generally more intensely and were sometimes accompanied by parenchymal perivascular or leptomeningeal mononuclear cell inflammatory infiltrates. Calcification and pigment transformation of some MCs occurred. Also, in 3 cases marked oligodendroglial proliferation in central white matter was seen accompanied by intense MC damage. This proliferation is of interest in relation to experimental and human demyelination. An aetiological relationship between MC changes and both early and delayed vascular and parenchymal damage is possible. The suggestion made by others, that many features of delayed radionecrosis are due to a delayed hypersensitivity reaction, is here reiterated, but in addition there seems also to be a possibility that the MCs are involved in providing the antigen either directly or indirectly. Vascular damage must be responsible for many features of delayed radionecrosis.

Experimental immunity to a metabolite of halothane and fluroxene: cutaneous delayed-type hypersensitivity.

Trifluoroacetate (TFA), a common metabolite of halothane and fluroxene, conjugated to human and guinea pig albumin induces specific delayed-type hypersensitivity in guinea pigs. Histologic examination of cutaneous hypersensitivity reactions characterized by erythema and induration 24–48 hours after intradermal challenge with antigen revealed perivascular mononuclear infiltration. These findings support the hypothesis that trifluoroacetate, a metabolite of halothane and fluroxene, can serve as a hapten to elicit specific cellular immune responses.

Oedemerid beetle dermatitis.

This is the first report of a pruritic, vesicular dermatitis due to the beetle Oxycopis vittata (Fabricius). Experimental reproduction of the disease was achieved in volunteer subjects. Histologic examination of biopsy material revealed subepidermal vesicle formation and moderate mononuclear perivascular infiltrate in the mid and upper dermis.

Transplantation Antibody Associated with First-Set Renal Homografts

Summary Antibodies were detected in the circulation of rats undergoing first-set renal homograft rejection as early as 3 days after transplantation. These antibodies were shown to be present in both purified IgG and IgM fractions of serum and to adhere primarily to the ultracentrifuged sediment of homogenized kidney, presumably to histocompatibility antigens. Parenteral injection of IgG fractions produced perivascular mononuclear infiltrates in the kidney. The lesions were indistinguishable from those accompanying early rejection.

Some Observations on the Histopathology of Mulberry Heart Disease in Pigs

SUMMARY Material from 37 pigs with suspected mulberry heart disease was examined histologically. Thirty-two cases fell into a group characterized by widespread myocardial congestion and haemorrhage with parenchymal degeneration, mild perivascular mononuclear infiltration and frequently the presence of groups of iron-containing granules. Unusual abnormalities were found in 2 out of 12 brains examined, but changes in liver, kidney, thyroid, lung, spleen, adrenal and skeletal muscle were considered to be non-specific. Mulberry heart disease does not resemble the classical European herztod.