Mononuclear Cellular Infiltration Research Articles

Chronic inflammatory demyelinating polyneuropathy of infancy: a corticosteroid-responsive disorder.

We present the clinical, electrophysiological, and histopathological findings in 6 children with early-onset chronic inflammatory demyelinating neuropathy. The clinical features initially suggested a genetically determined disorder in each patient. Sural nerve biopsy showed changes of chronic demyelination with multifocal endoneurial edema and mononuclear cellular infiltrates. All children improved with corticosteroid therapy.

Beneficial effect of testosterone in the treatment of chronic autoimmune thyroiditis in rats.

Early thymectomy and sublethal irradiation of normal rats consistently induces a sex-dependent chronic autoimmune thyroiditis. Females are much more susceptible to this autoimmune disorder than are males. The possible therapeutic effects of testosterone (Te) on established autoimmune thyroiditis has been investigated in this model. The pathologic condition of the gland before treatment was monitored by a thyroid grafting and extirpation techniques. Te administration by either parenteral injection or implantation caused significant regression of established thyroiditis. Repeated doses of Te ester in oil were found to be more effective than powdered free-Te given by implantation, and frequently produced complete resolution of chronic lesions involving the entire gland. In these thyroids, there was reappearance of normal thyroid architecture and complete absence of mononuclear cellular infiltration. However, no inhibitory effect on serum autoantibody production to thyroglobulin was noted with any form of Te treatment. These observations strengthen the concept that cellular rather than humoral mechanisms are involved in the pathogenesis of thyroiditis.

Cyclosporine-associated renal arteriopathy resulting in loss of allograft function

Cyclosporine-associated arteriopathy was the cause of graft loss in 40 percent of all allografts that failed in a series of 200 consecutive cadaveric renal transplants. Arteriopathy was diagnosed by biopsy and renal uptake of indium 111m labeled platelets in the face of acute renal deterioration. A moderate thrombocytopenia and microangiopathic picture of hemolytic uremia was also present on peripheral blood smear. Immunofluorescence and histologic characteristics of the allograft biopsy specimens failed to show evidence for acute rejection: immunoglobulin M, immunoglobulin A, immunoglobulin G, C1q, C3, and C4 were not present, and there was no evidence of an interstitial or vascular mononuclear cellular infiltrate. Two clinical presentations have been described. In Group I (seven patients), anuria occurred rapidly within the first 2 weeks after transplantation. In Group II (nine patients) renal function gradually diminished 1 to 5 months after starting cyclosporine therapy. Fifteen of the 16 recipients had progressive and irreversible loss of renal function which was pathologically associated with fibrin deposition, intimal proliferation, and thrombotic occlusion of the cortical interlobular and arcuate arteries, with subsequent focal glomerular ischemia and cortical infarction. One recipient with rapid loss of renal function received an intraarterial allograft infusion of streptokinase and subsequent systemic heparinization, which resulted in return of normal allograft function. The syndrome of cyclosporine-associated arteriopathy has been linked to a lack of or reduced amounts of prostacyclin-stimulating factor or prostacyclin.

Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms.

Expression of histocompatibility antigens and the intensity of inflammatory cellular infiltrate were evaluated in frozen tissue sections from 70 human ovarian tumors and six normal ovaries using monoclonal antibodies and an avidin-biotin immunoperoxidase technique. In the normal human ovary, surface epithelial cells, mature granulosa cells and lutein cells reacted with anti-HLA-A,B,C (HLA) and beta2-microglobulin antibodies but not with anti-Ia (Ia-like, HLA-DR). Stromal cells and granulosa cells of the primordial follicles did not react with any of the antibodies. Among the neoplasms examined, all benign epithelial tumors, 86% of borderline an 81% of malignant epithelial tumors reacted with anti-HLA and/or beta2-microglobulin antibodies. HLA-negative epithelial tumors were of serous or endometrioid types. Although Ia was not found in normal ovarian surface epithelium, the antigen could be detected in 44% of benign, and 43% of borderline and malignant epithelial ovarian tumors. Mononuclear cellular infiltrate was generally scarce in ovarian tumors and consisted mainly of T cells. Malignant epithelial tumors contained significantly more T cells than did benign tumors. More T cells were observed in HLA-positive ovarian tumors than in HLA-negative neoplasms, but the difference did not achieve statistical significance. No correlation could be found between Ia expression and the intensity of T-cell infiltrate. Significantly more T8 and Leu-3a-positive cells were found in the tumor stroma than amongst neoplastic cells. HNK-I-positive natural killer cells, OK-MI-positive macrophages and BI-positive B lymphocytes were rarely encountered either in the tumor stroma or between adjacent tumor cells.

Immunohistologic Characterization of Major Histocompatibility Antigens and Inflammatory Cellular Infiltrate in Human Breast Cancer<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

The presence of major histocompatibility antigens [HLA-A,B,C; beta 2 microglobulin (beta 2)m; la-like] on tumor cells and the nature and distribution of mononuclear cellular infiltrates in benign and malignant human breast tumors were studied by the use of monoclonal antibodies and immunoperoxidase techniques on frozen tissue sections. Although all benign tumors expressed HLA-A,B,C or beta 2m, 20 of 53 primary breast cancers did not react with anti-HLA-A,B,C or anti-beta 2m antibodies. Expression of la-like antigens was rarely encountered on tumor cells. The intensity of the inflammatory mononuclear cellular response did not correlate with the expression of HLA-A,B,C or beta 2m by the tumor cells. Most of the mononuclear cells were identified as T-cells. T-cells with a cytotoxic-suppressor phenotype (T8+) were generally the predominant cell type among those found as single cells in the tumor stroma or invading tumor nests. However, infiltration of tumor nests by lymphocytes was infrequently seen and was usually limited to the periphery of the tumor. In contrast, lymphocytes with a helper-inducer phenotype (T4+, Leu-3a+) predominated in the lymphoid aggregates. Anti-Leu-7 (HNK-1) antibody, which reacts with natural killer cells, stained only a few mononuclear cells in the cellular infiltrate in most cases of breast cancer.

Pulmonary response to Mount St. Helens' volcanic ash

The pulmonary response to a sedimented sample of Mount St. Helens' volcanic ash from the first eruption was studied at 1, 7, 28, 90, and 180 days postintratracheal administration of 1 or 10 mg of ash in specific-pathogen-free rats. One day after administration of volcanic ash all animals exhibited a marked inflammatory cell response centered on respiratory bronchioles in which polymorphonuclear leukocytes predominated. At 7 days the reaction was characterized by mononuclear cellular infiltrates. The macrophages within the respiratory bronchioles and alveoli contained intracytoplasmic ash particles. At 28 days the intraalveolar aggregates of mononuclear cells had condensed to form granulomas. Most of the granulomas contained foreign body-type giant cells and some showed central necrosis. The granulomas enlarged in size from 28 days until the termination of the experiment at 180 days with progressive increase in the amount of collagenous tissue. The results of these studies suggest that the volcanic ash may pose a risk for pneumoconiosis in heavily exposed human populations.

Comparative Studies of Mitral Valves in Rheumatic Heart Disease

Mitral valve tissues from 195 patients with rheumatic heart disease removed at the time of cardiac surgery were studied by conventional histologic techniques. One hundred seven patients from a five-year period at All-India Institute for Medical Sciences in New Delhi were studied in conjunction with 88 patients undergoing cardiac surgery in Albuquerque during a similar period. In Indian patients a correlation was noted between degree of moderate or severe valvular calcification and extent of adjacent valvular mononuclear cellular infiltration often consisting of striking lymphocytic-plasma cell collections. Similar distinct correlations were not observed among the mitral valves from the Albuquerque patients. It is possible that mitral valve mononuclear cell infiltrates among Indian patients may reflect a chronic immune reaction influencing the natural course of rheumatic heart disease in this latter population.

Rhinitis medicamentosa. An experimental histopathological and histochemical study.

The deleterious effects of decongestant drops on the respiratory nasal mucosa of guinea pigs were studied histopathologically and histochemically. The histopathological changes included: initial goblet cell hyperplasia, squamous metaplasia, increased vascularity, oedema of the corium, mononuclear cellular infiltration and glandular hyperplasia. The histochemical changes indicated: increased secretory activity, increased phagocytic activity as well as disturbance of the vasomotor response.

A study of experimental hepatic amoebiasis in the rabbit.

Progressive acute and chronic hepatic amoebiasis was readily produced in rabbits by subcapsular intrahepatic inoculation of approximately 2 × 104 trophozoites of Entamoeba histolytica (along with their bacterial associates), at 0·05 ml per animal. Infant rabbits, one to four weeks old, were more susceptible to infection than those aged 8·12 weeks. Rabbits with hepatic lesions showed anorexia, reduced activity and significant loss in weight and death.The necrotic lesion appeared about two days post-infection; it was yellowish-pink and later became softer than the adjacent normal hepatic tissue from which it was sharply demarcated. Histological examination of the amoebic lesions showed extensive necrosis with polymorphonuclear and mononuclear cellular infiltration, with the presence of amoebae. In advanced cases, a fibrotic reaction was observed at the edge of the lesions.

Granulomatous enteritis in a thoroughbred horse

A case of granulomatous enteritis in a three-year-old thoroughbred horse is described. Onset of clinical signs succeeded pyrexia of unknown aetiology. The horse was emaciated, depressed and inappetent but diarrhoea was not a feature of the condition. There was hypoproteinaemia, anaemia, leucopaenia and abnormal small-intestinal carbohydrate absorption. Rectal biopsy revealed granulomatous changes in the rectal mucosa. As a result of these findings, euthanasia was performed and an autopsy was carried out. Histopathology showed marked villous atrophy in the small intestine with a diffuse mononuclear cellular infiltration involving mainly the submucosa and lamina propria. There were occasional granulomatous foci. The mononuclear cells consisted mainly of lymphocytes and histiocytes. No aetiological agent was isolated.

Early events following challenge of cattle with tsetse infected with Trypanosoma congolense: development of the local skin reaction.

A local skin reaction (chancre) was elicited in susceptible cattle after the successful feeding of Glossina morsitans morsitans infected with one of two different cloned isolates of Trypanosoma congolense. The chancre first appeared as a small 2 to 3 mm nodule at the site of the challenge as early as day 5 and reached maximum activity by days 10 to 13 when it had developed into a raised, indurated, hot, painful swelling measuring up to 100 mm in diameter. Thereafter it declined in size and activity and by days 20 to 30 was undetectable. Histologically the lesion was characterised by an intense inflammatory reaction and a four- to 10-fold increase in total cellularity. Initially, polymorphonuclear leucocytes were numerous but these were soon replaced by a mononuclear cellular infiltrate consisting mainly of small to medium lymphocytes. Development of the chancre and detection of parasites in the skin preceded by several days parasitaemia and other clinical signs. It was concluded that the skin was acting as a focus not only for establishment of infection but also as a site for localised proliferation of the parasite before dissemination into the bloodstream. The bite of an uninfected tsetse fly produced no detectable reaction and experimental intradermal inoculation of metacyclic T congolense resulted in chancre formation followed by infection. Bloodstream forms given by the same route caused infection but failed to induce a chancre.

Immunohistological study of the anatomic relationship of toxoplasma antigens to the inflammatory response in the brains of mice chronically infected with Toxoplasma gondii.

The relationship of toxoplasma antigen(s) to the origin and long-term persistence of the mononuclear cell inflammatory infiltrate that is present in the brains of mice chronically infected with Toxoplasma gondii was studied by using the peroxidase-antiperoxidase immunohistochemical staining technique. C3H/Km mice were infected with the avirulent C37 strain of T. gondii and sequentially sacrificed over the ensuing 107 days. Comparable sections of each brain were prepared for routine light microscopy. Antisera to toxoplasma made in rabbits were used for immunohistological staining, and adjacent slides were also stained with conventional histological stains. The peroxidase-antiperoxidase stain demonstrated toxoplasma tissue cysts, tachyzoites, and intra- and extracellular antigen-antibody reaction products. Early infection was characterized by small tight clusters of free tachyzoites gaining access to brain substance in the absence of an inflammatory response. Once there was disruption of neural parenchyma, a mononuclear cellular infiltrate rapidly ensued. After the first days of infection, mononuclear cells were always present in all infected brains and were anatomically associated with some component of toxoplasma antigen(s). The histological picture of late infection suggested that recurrent episodes of hematogenous dissemination of tachyzoites occurred in infected mice and that such episodes were at least partially responsible for persistence of an antigenic stimulus.

Effect of bleomycin on collagenolytic activity of the rat alveolar macrophage.

Bleomycin (0.5 unit/100 g of body weight) was instilled intratracheally into rats weighing 170 to 200 g. Microscopic examination of the lungs of these animals, as compared to the lungs of saline-in...

A radioisotopic technique for measuring the mononuclear inflammatory response in sindbis virus-induced encephalitis of mice

The mononuclear inflammation occuring in Sindbis virus-induced encephalitis of mice has been measured by means of pulse labelling with [ 125I]UdR at a defined time after infection. The method should be applicable to other studies of encephalitis and of mononuclear cellular infiltration occuring in other organs as a result of disease or infection.

Inverted Follicular Keratosis in a Dog

Inverted follicular keratosis is a benign epithelial tumor in man. It occurs most commonly as a single lesion on the head [I, 21 and is a firm, hairless growth that projects above the surface of the skin. All such lesions are asymptomatic without peripheral erythema or inflammation. The center of the lesion is scaly, and the periphery is smooth and shiny. A 1-year-old female miniature Poodle dog had a small, raised, crusted nodule on the dorsum of the nose. The lesion had been present for about 6 weeks. Onset had been acute with periodic serous discharge and scale formation. There was no pruritis nor self trauma associated with the lesion which was 3 millimeters wide and protruded 3 millimeters above the surrounding skin (fig. I). The nodule consisted of a papillomatous epithelial tumor growing above the surrounding skin. The epidermis at the periphery was raised, blended with the edges of the tumor, and appeared to buttress the central tumor mass. The tumor had several elongated, papilliferous projections, some fused at the bases. The cells at the periphery of the tumor were cuboidal basal epithelial cells with prominent vesicular nuclei, separated from the underlying corium by a basement membrane. Numerous large dendritic melanocytes were scattered throughout the peripheral areas of the tumor; these melanocytes contained great amounts of melanin but little was in the epithelial cells. The cells in the centers of the papilliferous projections showed squamous differentiation and contained abundant eosinophilic cytoplasm and keratohyaline granules. Occasionally formations of squamous eddies were noted. There was little evidence of mitotic activity and no nuclear or cellular atypia. The surface was covered by a parakeratotic scale, and within the center of the tumor small aggregates of keratinous material were present. Dilated and congested vessels and a mild mononuclear cellular infiltrate were in the corium. Although numerous hair follicles were adjacent to the base of the tumor, none penetrated the tumor mass to reach the surface (fig. 2). This lesion has many features associated with inverted follicular keratosis in man, namely the papillomatous surface, one or several invaginations that resemble hair follicles and fingerlike tumor masses with peripheral small basal cells and with small squamous eddies in their centers. The feature that distinguishes this tumor from that in man is a lack of palisading of the peripheral basal cells [2]. Clinically the lesion in our dog resembles that in man. Both are on the head and have scales in the center of the tumor. In man, these tumors are thought to arise from hair follicle infundibulum; the infundibulum is that part of the hair follicle above the opening of the sebaceous gland [2,4]. Tumors of hair follicle origin in the dog [5, 61 do not resemble the tumor in our dog. Inverted follicular keratosis has not been described previously in animals [6]. Inverted follicular keratosis must be differentiated from canine cutaneous papillomatosis which is a solitary growth 151. These two tumors are distinguishable histologically. In canine cutaneous papillomatosis the hyperplastic epidermis is thrown into folds by an ingrowth of hyperplastic dermal tissue and lacks the dermal invasion by epidermal tissue which is a feature of inverted follicular keratosis. Papillomas also lack the squamous eddies and are covered on the surface by hyperkeratotic scale. Inverted follicular keratosis must be further distinguished from squamous cell carcinoma,

Morphological Evidence of the Interaction Between Plasma Cells and Macrophages in Beagle Dogs

The interplay and the close physical contact between lymphocytes and macrophages during the course of immunological reactions involving antigen recognition have been described by many authors. There have been only a few reports, however, on contact between plasma cells and macrophages and these were only in the lymph nodes and spleen of rodents [2, 5, 61 and in people with multiple myeloma [I]. In several independent toxicological experiments in which different substances were used on Beagle dogs over 3 to 9 months, close physical contact between plasma cells and macrophages was found in non-lymphatic organs such as kidneys and mitral valves. Nephropathy induced by K2HP04 [4] was used to show the relationship between such cells. In the kidneys of dogs treated with 0.8 g/kg bodyweight K2HP04 added to the food, different regressive changes in the tubules, a high degree of basement membrane thickening and less frequently mononuclear cellular infiltrates could be shown. Electron microscopically in such areas plasma cell-macrophage complexes occasionally were seen in proximity to the basement membrane of proximal tubules. Generally single plasma cells are encircled by one or more macrophages (fig. I) or cell clusters appear sporadically (fig. 2) in which a macrophage in the center is encased in a rosette of plasma cells. The space between the plasma cells and macrophages is 100 to 200 x lo-' mm (mean 120 x lo-' mm). The intercellular gap was decreased by dot-shaped intracytoplasmic thickenings, especially in the periphery of the plasma cell-macrophage complexes. The plasma cells often had finger-like or pedunculate and mostly plump pseudopods that penetrated the very thick basement membrane of atrophic renal tubules (fig. 2). My findings were distinctive in that the close apposition between the plasma cells and the macrophages in nonlymphatic tissues such as the kidneys and heart valves could be demonstrated. This was frequently found in isolation. An accidental contact, as would be possible in the lymphatic organs [3] which are densely populated with immunocompetent cells seems unlikely. I believe that the plasma cells in the course of their contact with the macrophages carry out immunospecific functions that could arise from an antigen transfer. Evidence for this is the close topographical relationship of the plasma cells to the basement membrane of the atrophied renal tubules. The plasma cells with their finger-like pseudopods penetrate the basement membranes, which form lacunae at these points (fig. 2). As the mature plasma cells doubtless are secretory cells, the possibility should be considered that they secrete particular antibodies directed against basement membrane antigens; this could lead to lysis of the basement membrane.

Graft-versus-host disease impairs cerebellar growth.

Graft-versus-host disease impairs cerebellar growth.

Interstitial nephritis with acute renal failure following cardiac surgery and treatment with methicillin.

Six patients developed acute renal failure 13-19 days after cardiac surgery with extracorporeal circulation. None of the patients had suffered from postoperative hypotension; slight hemolysis was present for only 1-2 days post-operatively. Acute renal failure lasted for 11-80 days in four patients. In two patients creatinine clearance stabilized at reduced values. Seven renal biopsies from the six patients showed severe acute interstitial nephritis with mononuclear cellular infiltration and distal tubular damage. No immune deposits were detected in glomeruli or tubular basement membrane. All six patients had been treated prophylactically with methicillin and the acute renal disease was probably elicited by this drug.

A receptor for the third component of complement in the human renal glomerulus.

In the course of studying the nature of mononuclear cellular infiltrates in tissue sections of human kidney it was noted that indicator sheep erythrocytes densely coated with the third component of complement (C3) specifically adhered to all of the glomeruli in the tissue sections. The deposition of complement (C) within the glomerulus is a feature of many immunologically related renal diseases (1,2), yet the precise mechanism by which C is deposited remains unexplained. We feel that this observation, suggesting the presence of a receptor for C, is, therefore, of particular interest.

Ultrastructural glomerular changes associated with filariasis.

Abstract Renal glomeruli of 9 dogs and 5 cats infected with Dirofilaria immitis and 19 hamsters infected with Dipetalonema viteae were studied ultrastructurally. Other major organs from infected hamsters were studied with the light microscope. One or more of the following pathological changes were found in the infected dogs: glomerular basement membrane (GBM) thickenings, GBM dense deposits, GBM holes, fusion of epithelial cell foot process, increased numbers of epithelial cell microvilli, increased numbers of mesangial cells, and occurrence of lysosome-like residual bodies in mesangial cells. Glomerular basement membrane thickenings, GBM dense deposits, GBM holes, GBM nodules and subendothelial dense deposits occurred in heavily infected hamsters. Amyloid fibrils and virus-like inclusions were also found in some infected hamster glomeruli. The pathological changes in hamster glomeruli appear to be associated with microfilaremia. Abnormalities were not found in cat glomeruli examined. Light microscopy revealed mononuclear and eosinophilic cellular infiltrations in the liver of all infected hamsters. These liver lesions were not found in any of 12 control animals examined. The observations made in this study suggest that glomerular lesions are another complication of filariasis.