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PubMed1977

Macrophage infiltration in the human retina.

The retinal tissues were examined by light microscopy and by scanning and transmission electron microscopy in a human eye in which there was extensive infiltration by macrophages. The stimulus to macrophagic infiltration was an immune response in a mixed sympathetic and lens-induced ophthalmitis which occurred after surgical treatment for glaucoma. The inflammatory infiltrate was so exuberant that the cells were considered to be predominantly exogenous and the sites of entry into the eye included the pars plana, the optic disc, and the retinal and choroidal blood vessels. Within the retina it appeared that the macrophages migrated via the nerve fibre layer and via the subretinal and subpigment epithelial spaces.

Glaucoma↗

PubMed1977

Renal failure secondary to leukemic infiltration of the kidneys.

Leukemic infiltration of the kidneys is a very rare cause of renal failure. A woman with acute lymphoblastic leukemia presented with nonliguric renal failure and was found to have massively enlarged kidneys. The size of the kidneys was dramatically reduced through the combined effects of local radiation therapy and systemic chemotherapy. Because this rapid shrinkage of the kidneys was associated with improvement in renal function, the uremia was ascribed to leukemic infiltration. As a consequence of rapid tumor lysis in the presence of renal failure, marked hyperphosphatemia and hypocalcemia developed. The literature experience with renal failure secondary to leukemic infiltration of the kidneys is reviewed.

Calcium↗

PubMed1977

Immunofluorescence study of lymphocytic infiltration in gliomas. Identification of T-lymphocytes.

Five human brain tumours (3 glioblastomas and 2 astrocytomas) and 5 rat brain tumours induced in Sprague--Dawley animals by systemic administration of N-methyl-N-nitrosourea (3 pleomorphic gliomas and 2 mixed gliomas) were studied. The human brain tumours were surgical specimens excised from patients with no cranial surgery prior to their disease. The experimental brain tumour had been adapted to tissue culture, propagated in vitro and then transplanted to immunocompetent and immunodeficient rats of the same stock. The above-described material was selected in consideration of the mononuclear cell infiltrates occurring in these tumours. Frozen sections of human and rat gliomas, the latter both primary and transplanted, were prepared and investigated as to the presence of T-lymphocytes within the mononuclear round cell infiltrates. This was done with the indirect immunofluorescence method using rabbit antisera against man and rat T-lymphocytes. With this technique a variable percentage of T-lymphocytes was demonstrated in the cell infiltrates of human and rat gliomas alike. The tumour transplanted in thymectomized rats showed only isolated, scattered, positive-reacting cells, i.e., cells recognizable as T-lymphocytes by the above method. The results can be interpreted as circumstantial evidence for the occurrence of tumour-specific and/or tumour-associated antigens in the parenchymal cells of spontaneous and chemically-induced gliomas.

Animals↗

PubMed1978

Lichen planus: immunologic and morphologic identification of the submucosal infiltrate.

The purpose of this investigation was to specifically identify T cells, B cells, and histiocytes in the infiltrate typically seen in lichen planus. In frozen tissue sections, AET-treated sheep erythrocytes formed immunologic rosettes with the lymphocytes in the infiltrate, designating them as T cells. Rosette assays with reagent erythrocytes, IgGEA, IgMEA, IgMEAC, and E resulted in nonadherence, indicating a lack of B cells and macrophages, and indirectly implicating them as T cells. Scanning electron microscopy of the cellular infiltrate, in situ, showed that the cells had smooth, nonvillous surfaces. These observations were consistent with a T cell origin and were considered supportive of the immunologic data. The results of this investigation support the hypothesis that lichen planus is a disease mediated by thymus-dependent lymphocytes.

Connective Tissue↗

PubMed2026

Zhiling Jiangya decoction treats hypertension in rats: An integrative study of network pharmacology, immune infiltration, molecular simulation, and 16S rDNA sequencing.

OBJECTIVE: This study integrated network pharmacology, immune infiltration analysis, molecular docking, molecular dynamics simulation, ADMET prediction, 16S rDNA sequencing, and rat experiments to elucidate the potential mechanisms underlying the antihypertensive effects of Zhiling Jiangya Decoction (ZLJYD). METHODS: Active compounds and their potential targets were screened from the PubChem, TCMSP, NovoPro, and SwissTargetPrediction databases. Hypertension-related targets were retrieved from the OMIM and GeneCards databases, and overlapping targets were identified. The STRING database and Cytoscape 3.10.1 software were used to construct a protein-protein interaction network and a herb-component-target-disease network. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to identify the key biological processes and signaling pathways involved. Using the CIBERSORT algorithm combined with correlation analysis, we investigated the association between key targets and immune cell infiltration. Molecular docking, molecular dynamics simulations, and ADMET predictions were performed to assess the binding stability and pharmacokinetic properties of the main compounds with their corresponding targets. Finally, the antihypertensive efficacy of ZLJYD was validated using a spontaneously hypertensive rat model, and alterations in gut microbiota were analyzed using 16S rDNA sequencing. RESULTS: A total of 123 active compounds and 267 hypertension-related targets of ZLJYD were identified. Enrichment analysis revealed that these targets were primarily associated with the PI3K-Akt signaling pathway and lipid and atherosclerosis pathways. Immune infiltration analysis suggested that the therapeutic effects of ZLJYD may involve the regulation of follicular helper T cells, naïve B cells, and naïve CD4⁺ T cells. Molecular docking and dynamics simulations supported the stable binding of key compounds to their target proteins, while ADMET predictions indicated favorable pharmacokinetic properties and safety profiles. Rat experiments demonstrated that ZLJYD significantly reduced blood pressure in spontaneously hypertensive rats, partially alleviated gut microbiota dysbiosis, and altered microbial community structure and phylogenetic diversity. CONCLUSION: This study systematically elucidates the potential mechanisms underlying the antihypertensive effects of ZLJYD through multiple components, targets, and pathways, particularly immune regulation and gut microbiota remodeling. These findings provide mechanistic insights into its potential therapeutic application.

16S rDNA sequencing↗

PubMed1977

Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma.

Whole body X-irradiation (400 rad) of C57BL mice, either before or after i.m. implantation of the syngeneic fibrosarcoma, FS6, influenced both the growth of the tumours and their cellular composition, particularly their macrophage content. Pre-irradiation resulted in slower initial growth of tumours, and a concomitant lack of host-cell infiltration, but when tumours began to grow at a rate parallel to controls infiltration by host cells was demonstrable. Similarly, irradiation of the tumour-bearing host resulted in a temporary cessation of growth, and a decrease in the macrophage content, which did not return to control levels for 2-3 weeks after irradiation. The significance of these results is discussed in relation to the possibility that infiltrating host cells, particularly macrophages, may stimulate the growth of this tumour.

Animals↗

PubMed1975

Formalin infiltration of the ductus arteriosus. A method for palliation of infants with selected congenital cardiac lesions.

To circumvent the decreased pulmonary blood flow associated with closure of the ductus arteriosus in newborns with heart defects, we infiltrated buffered formalin solution into the wall of that structure to delay its closure. In four infants with pulmonary atresia in whom shunts had been unsuccessful or were technically not feasible, this procedure produced rapid improvement of arterial oxygen tension that was maintained in three infants for one to nine months. The other died of complications of attempted shunt procedures. In an infant with interrupted aortic arch and a large ventricular septal defect, formalin infiltration of the ductus and pulmonary arterial banding alleviated cardiac failure and improved lower-body perfusion. Formalin infiltration of the ductus is an effective palliative technic for treating certain congenital cardiac defects. No adverse effects have been noted.

Aorta↗

PubMed1978

Detection by direct immunofluorescence of antibodies to Treponema pallidum in the cutaneous infiltrates of rabbit syphilomas.

By direct immunofluorescence, with use of fluorescein-labeled sonified Treponema pallidum, specific antibodies were detected in the tissue infiltrates of cutaneous syphilomas in rabbits. Specimens from cutaneous and mucosal inflammatory lesions induced by intradermal injection of a keratinous substance from an epidermal cyst served as controls. Granular fluorescence was detected in the dermis of 11 of the 12 syphiloma specimens and corresponded to areas of heavy plasma cell infiltrates, and some fluorescence was found directly on plasma cells identified by subsequent staining with hematoxylin and eosin. This fluorescence could be blocked by preabsorption. Control slides did not show any fluorescence. Immunopathologic techniques using labeled antigens may be of diagnostic value in syphilis and other infectious disorders which feature specific infiltrates.

Animals↗

PubMed1978

The multicellular spheroid as a model tumor allograft. II. Characterization of spheroid-infiltrating cytotoxic cells.

Alloimmune lymphoid cells infiltrating multicellular spheroids of EMT6 mammary sarcoma cells (a solid tumor allograft model) have been characterized according to their morphological and functional properties. Both lymphocytes and macrophages were found within spheroids at the time of peak tumor cell damage. Cytotoxic cells specific for allograft antigens were also present. Using a short-term 51-Cr release assay, the cells responsible for cytotoxicity were characterized as a nonadherent, nonphagocytic T cell population. Velocity sedimentation cell separation further demonstrated that these cytotoxic cells had the physical properties of small lymphocytes. Some evidence for selective spheroid infiltration by specifically alloimmune cells was also obtained. The possible relationship of this cellular infiltrate to graft damage is discussed.

Animals↗

PubMed1979

Partial characterization of cytotoxic cells infiltrating sponge matrix allografts.

Adapting the Roberts and Hayry sponge allograft model, we have demonstrated the presence of an enriched, specifically cytotoxic population of cells which infiltrate rejecting sponge allografts. The number of cells infiltrating a rejecting sponge allograft peaks on day 14 after transplantation. Utilizing a short-term 51chromium cytotoxicity assay, peak antiallogeneic killing was demonstrable on day 14 also. Only T cell killing was apparent for the first 15 days after transplantation. After day 20, specific cytolysis was present which was not sensitive to anti-theta serum and complement. The infiltrating cytotoxic cells are large, specifically cytotoxic, do not proliferate in culture, do not respond to mitogen, and do not respond in mixed lymphocyte culture even to the same alloantigen to which the animal had been sensitized. In contrast, spleens from sponge-bearing animals kill poorly, respond to mitogen, and respond vigorously in mixed lymphocyte culture to specific and nonspecific alloantigens. The following hypotheses are set forth with regard to the cytotoxic lymphocytes (1) Such cells may be end stage and cannot proliferate. (2) The cytotoxic cells may kill the stimulator cells more rapidly than they can be stimulated to proliferate. (3) The sponge cell population may be enriched for nonspecific supressor cells. (4) The sponge cells may be devoid of helper T cells.

Animals↗

PubMed1978

Surface markers and mitogen response of cells harvested from cutaneous infiltrates in mycosis fungoides and Sézary's syndrome.

It was the purpose of this study to characterize the proliferating cells in skin lesion of Sézary's syndrome and of mycosis fungoides by means of their surface markers and their response to Phytohemagglutinine mitogen stimulation. Viable infiltrating cells were freed from skin biopsy specimens by means of a disaggregating homogenizer and the cells yielded were tested with heterologius polyvalent anti-human Ig and with anti-human T-cell globulin, as well as for spontaneous rosette formation with sheep red blood cells (SRBC) and for their response to stimulation with Phytohemagglutinine. Most of the infiltrating cells in skin lesions of mycosis fungoides and Sézary's syndrome lack receptors for anti-human Ig but form spontaneous rosettes with SRBC and have receptors for anti-T-cell globulin, indicating the T-lymphocyte nature of the infiltrating cells; however, their response to Phytohemagglutinine is weak. The results indicate the atypical, presumably neoplastic, nature of T-lymphocytes proliferating in skin lesions of mycosis fungoides and Sézary's syndrome.

B-Lymphocytes↗

PubMed1977

Characterization of mononuclear cells in the inflammatory infiltrates of cutaneous tumours.

The identification of mononuclear cells extracted from cutaneous tumours (basal cell carcinoma, squamous cell carcinoma and superficial, spreading melanoma) has been investigated. The relative numbers of T cells and B cells have been determined using the E-rosette test and the EAC-rosette test. The results have been compared to those of delayed hypersensitivity type reactions. Different cell distribution patterns (E/EAC ratio) have been found in the infiltrates according to the type of tumour. An immunocytochemical technique has been developed for the identification in situ of immunoglobulin-producing cells in the inflammatory infiltrates. In each case the class of immunoglobulin (IgM, IgG or IgA) has been identified and the relative frequency of Ig-producing cells has been determined. The results indicate humoral and cellular immune responses with variations attributable to the type of tumour. In weakly malignant tumours, the infiltrate is characterized by an elevated number of T lymphocytes and numerous plasma cells which secrete all classes of Ig; in highly malignant tumours it is characterized by a reduced number of both T lymphocytes (E rosette) and plasma cells which do not secrete all classes of Ig.

B-Lymphocytes↗

PubMed1978

Rapid development of diffuse pulmonary infiltrates in histiocytic lymphoma.

A 24-year-old man with documented histiocytic lymphoma developed a nodular interstitial infiltrate, as shown by chest roentgenograms during a 10-day period of observation. He also developed fever, chills, and purulent sputum. Open-lung biopsy revealed histiocytic lymphoma without evidence of infection. This case demonstrates that lymphoma can cause rapid development of infiltrates observable by roentgenography. Because the infiltrate could be neoplastic or infectious, empiric therapy without an exact diagnosis is not warranted.

Adult↗

PubMedDate not supplied

Early x-ray diagnosis of occult infiltrating nasopharyngeal carcinoma.

The occult type of nasopharyngeal carcinoma (NPC) accounts for 30% of all nasopharyngeal carcinomas. The occult NPC is clinically difficult to visualize, because the tumor infiltrates and grows in the submucosa. It then metastasizes to the skull base or draining lymph nodes. When the NPC is finally diagnosed, the prognosis is poor. Three refined x-ray techniques are evaluated for their utilization in earlier diagnosis of the occult NPC: thin section tomography, nasopharyngography, and Eustachian tube function studies. In a consecutive series of 50 patients, these techniques detected 12 infiltrating carcinomas not visible on clinical examination. Five of these patients also had initially negative blind biopsies. Patients having diplopia, facial numbness, cervical adenopathy, and chronic serous otitis media are highly suspect for NPC. The described x-ray techniques, that are safe and noninvasive, can detect these occult infiltrative tumors earlier than clinical examination. Earlier detection and treatment of NPC has resulted in a significant increased cure rate.

Adolescent↗

PubMed2024

Identification of autophagy-related genes as potential biomarkers correlated with immune infiltration in bipolar disorder: a bioinformatics analysis.

BACKGROUND: Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. METHODS: The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. RESULTS: In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. CONCLUSIONS: Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD.

Bipolar Disorder↗

PubMed1975

Pathologic anatomy of the cardiomyopathies. Idiopathic dilated and hypertrophic types, infiltrative types, and endomyocardial disease with and without eosinophilia.

This presentation summarizes necropsy observations in patients with three types of cardiomyopathy: idiopathic, infiltrative, and endomyocardial disease. The idiopathic variety is subdivided into two types depending on the size of the ventricular cavity. In the dilated ventricular type the left ventricular wall is frequently less than 1.5 cm. thick, intracardiac thrombi are common, the atrioventricular valve rings usually are mildly dilated, and focal myocardial and endocardial scars are common. In the nondilated type (hypertrophic cardiomyopathy), the ventricular septum is usually thicker than the left ventricular free wall, which also is thick (greater than 1.5 cm.). When the septum is similar in thickness to the left ventricular free wall (symmetric), left ventricular outflow obstruction does not occur. When the septum is thicker than the left ventricular free wall (asymmetric), left or right ventricular outflow obstruction may or may not be present. The orientation of myocardial fibers one to another in the ventricular septum in the nondilated (hypertrophic) type is abnormal, whereas it is normal in the dilated ventricular type. Intracardiac thrombi are rare and atrioventricular valve rings are never dilated in the nondilated type of idiopathic cardiomegaly. The infiltrative types of cardiomyopathies include iron, calcium, lipids, mucopolysaccharides, granulomas, amyloid, and neoplasms. The first four usually are located within myocardial cells and the latter three, between myocardial cells. It is probable that all these myocardial infiltrates are capable of producing cardiac dysfunction, primarily on a restrictive basis. Endomyocardial disease may or may not be associated with eosinophilia. When the latter occurs, the eosinophils are structurally normal. Death is related to congestive cardiac failure. This category is actuality also in idiopathic.

Adolescent↗

PubMed1976

Lobular carcinoma of the breast in situ and infiltrating.

Lobular carcinoma in situ, while histologically delineated almost 35 years ago, is still being diagnosed and reported with differing qualitative and quantitative criteria. It is important to recognize this lesion because of its frequent bilaterality and risk of developing infiltrating carcinoma in the affected breast. Because of the apparent morphologic identity of the cell of ALH and the cell of LCIS, because both are associated with some increased risk of developing carcinoma, and because both have an increased propensity to be found simultaneously with carcinoma--especially lobular carcinoma--we believe these lesions should be looked upon as basically identical. Beginning with Ewing's astute intuition nearly 60 years ago18 and culminating with the 1967 report of McDivitt and others,50 pathologists and surgeons have gradually become aware of the long-term risk associated with this nonobligatorily, premalignant lesion (LCIS). As further studies have become available, it is clear that a large majority of women with lobular carcinoma in situ or atypical lobular hyperplasia retaining the involved breast will not develop infiltrating carcinoma. However, there is an increased risk of roughly 1 percent per year. Because of the increased risk, we believe that a meticulous long-term followup is mandatory, and suggest a physical examination every two to three months for the first few years supplemented with yearly mammography (as is now being done at Memorial Hospital for patients with atypical breast lesions6). With such a followup, we believe the mortality should fall well below 5 percent in a 20-year followup, and believe this is a risk that may be acceptable to the patient and her surgeon. The boundaries of the morphologic changes acceptable as ILC have been difficult for many pathologists (including ourselves) to delineate. This is borne out by widely varying incidence figures and is due, at least in part, to the frequent admixture of ILC with poorly differentiated duct carcinoma as well as problems in deciding how large and pleomorphic the cell nuclei may be, and still be designated as lobular in origin. We believe that about 4 to 6 percent of all breast carcinomas are infiltrating lobular, and incidence rates widely divergent from this should be scrutinized carefully. Prognostically, ILC behaves similarly to poorly differentiated duct carcinomas except for some increased risk of subsequent contralateral carcinoma. Future study of lobular disease should be directed toward its histogenesis, long-term risk, and the relative success of different treatment modalities. Hormonal studies and cell culture with chromosomal analysis might shed some light on the mechanism of what may be postmenopausal regression of LCIS.

Adenofibroma↗

PubMed1979

[Non-infiltrating intraductal carcinoma of the breast (author's transl)].

Non-infiltrating intraductal carcinoma may be considered a type of "carcinoma in situ" of the breast. In a review of 47 cases diagnosed and treated at Gustave-Roussy Institute between 1956--1972, it appears that the early symptoms of this rare type of breast carcinoma (it occurs only in 2.4% of all breast cancers) were a bloody discharge (38%) or Paget's disease of the nipple (11%). The histological examination was of the utmost importance in these cases due to the diagnostic uncertainties between benign hyperplastic lesions and authentic carcinomas as well as between infiltrating carcinomas and strictly intraductal carcinomas. Frozen section was only accurate in 30% of cases. The high frequency of multicentric foci (76%) contrasted with the absence of lymph node involvment (none of the 23 cases in which at least one node was excised, showed lymph node metastases). Treatment was only of ablation of the whole mammary gland, except in 6 patients who had a tumorectomy, two of whom also received radiotherapy. Local recurrence occurred in 4 patients, 3 of whom had only tumorectomy. The contralateral breast was affected in 2 cases. No patient under follow-up died of cancer within 5 years. The peculiar and highly favorable course of non-infiltrating intraductal carcinoma calls for an adequate therapy which could later be followed by a plastic reconstructive surgery should the patient wish to have this procedure.

Adult↗