Biomedical subjects
Publications and source records attributed to V Tricottet.
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The localization of immunoreactive angiotensin I-converting enzyme (ACE) has been investigated at the optical and ultrastructural level with anti-human ACE antibodies in the human kidney and small intestine. In both tissues ACE was found in blood vessels and in extravascular situation in the absorptive epithelial cells of intestinal mucosa and renal proximal tubules. Ultrastructural immunohistochemistry showed that in intestinal and renal proximal tubular cells ACE was prominent in microvilli and brush borders. In the kidney ACE was also present on the basolateral part of the plasmalemmal membrane, where it may contribute to the regulation of angiotensin II-dependent absorption processes. Intracellular positivities were also observed inside the renal vascular endothelial and proximal tubular cell in endoplasmic reticulum and nuclear envelope reflecting the synthesis and the cellular processing of ACE. The intestinal microvascular endothelium was strongly labeled suggesting that the mesenteric circulation is an important site for the production of angiotensin II. Vascular endothelial ACE was also detected in the peritubular but not glomerular capillaries of the kidney.
The detection of LAV- or HTLV III-type viral particles in lymph node germinal centers from patients with the persistent lymphadenopathy syndrome (LAS) or the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) is an important diagnostic factor in the prodromal stages of AIDS. These particles, the morphology of which is defined, are situated solely in the extracellular spaces delimited by cytoplasmic extensions of the dendritic reticular cells. Often few in number, they were found in 26 of the 30 lymph nodes studied, selected uniquely on the basis of light microscopic criteria (predominantly follicular lymphoid hyperplasia). The four negative nodes contained no, or fewer than two, germinal centers in the samples taken for ultrastructural study. The diagnosis of the LAS or the ARC was always confirmed clinically and biologically. Thus, lymph node biopsy and the corresponding ultrastructural study are important steps in the diagnosis of AIDS.
A prospective light and electron microscopic study of repeated endoscopic gastric biopsy specimens obtained from 10 patients presenting at the first examination for long-standing erosive gastritis was performed. In nearly all specimens from 7 patients, spiral bacteria were found in close contact to the surface epithelial cells and associated with active inflammatory changes. These organisms appeared similar to those recently described as gastric "campylobacter-Like organisms" (GCLO). It is possible that they are related to unusual anaerobic spirochetes. In the specimens obtained after antibiotic-therapy the bacteria were few in number and damaged. At the ultrastructural level, the presence of cell necrosis and autolytic intracytoplasmic vacuoles combined with damaged bacteria may suggest a relationship between GCLO surface colonization and erosive epithelial abnormality. Such colonization does not occur in normal mucosa.
Ultrastructural study of rectal mucosa was performed in 6 patients with AIDS related complex (ARC) and in 10 patients with AIDS. There were 16 men (mean age: 39.1 years): 8 homosexuals, 3 Haitians, 2 Africans and 3 IV drug abusers, all having significant titers of LAV antibodies. Two types of ultrastructural markers were observed: tubuloreticular structures (TRS) were found in endothelial cells, lymphocytes and macrophages in 1/6 ARC patients and 10/10 AIDS patients. TRS have already been described in various pathological situations and seem to be related to alpha-interferon, test tube and ring shaped forms (TRF) were observed in lymphocytes and macrophages in 0/6 ARC patients and 6/10 AIDS patients. TRF have been rarely reported previously. The 6 AIDS patients with TRF were 4 homosexuals and 2 Haitians. In two of three of these patients in whom repeated ultrastructural studies were performed, the same markers were found. All AIDS patients with TRF died within a mean time of ten months after the diagnosis had been established, whereas 1/4 AIDS patients without TRF died within seven months and the three others survived for more than 14 months. These data suggest that the association of TRS and TRF in the rectal mucosa could be specific of AIDS. In LAV/HTLV III retro-virus infection, this association is an aggravating factor.
The authors report their ultrastructural findings of 36 involved lymph-nodes in Hodgkin's disease (HD), before any treatment. More than 400 tumour cells were studied. An analytical study was carried out on the different aspects presented by the nuclei (uni or multi-lobated); the nucleoli (compact, reticulate or dispersed); and the cytoplasm (immunoblastic, complex, intermediate). No cellular structure evoking phagocytic activity with digestion, and consequently an eventual histiomonocytic origin, could be detected even on serial sections. The presence of lipid inclusions, sometimes of glycogen, as well as certain peculiar structures are described and discussed. The ultrastructural aspects could be easily correlated with the different types of tumour cell described in HD using light microscopy. The various kinds of cells which could could be detected in the same lymph node, may correspond to a real tumour cell lineage, consisting, firstly, of a cell of immunoblastic type with a mono- or bilobated nucleus, then an intermediate type with a bilobated or multisegmented nucleus, and finally a complex cell type with a multisegmented nucleus. The lacunar cells are characterised by a fragile hyaloplasm, without cellular organelles at their periphery, these being concentrated around the nucleus. This special organisation explains the aspects observed in light microscopy. However, no explanation could be offered to understand this particular aspect of the cytoplasm. The ultrastructural characteristics of the Reed-Sternberg cells and their variants did not allow a precise cellular origin to be proposed. The absence of phagolysosomes pleads against a histiocytic origin. However their similarity of the interdigitated reticular cells did not seem sufficient to propose this origin. The likeliness of the cytoplasm of cells with mono- or bilobated nuclei with that of immunoblasts, constitutes the most interesting morphological feature. This fact, associated with the appearance of immunoblasts similar to Reed-Sternberg cells of infectious mononucleosis, suggests a lymphoid origin. The study of the reactive cells around the tumor cells did not allow any consequences to be drawn. One could simply note that the Reed-Sternberg cells and their variants were surrounded by lymphocytes, forming a kind of crown. No etiological agent could be detected. These data are compared to those of other publications, and discussed. This ultrastructural study, therefore, does not offer the solution to most of the questions which still remain to be answered as to the origin of the Reed-Sternberg cells.(ABSTRACT TRUNCATED AT 400 WORDS)
The authors present the results of a histopathological study on the lymph-nodes taken from 45 subjects suffering from either an AIDS or from a chronic adenopathy corresponding to the definition of AIDS related complex (ARC). The various aspects observed were classed as type I to type IV. The lymph-node modifications observed in the 29 patients with an ARC could be divided into three principle groups: an extensive follicular hyperplasia associated with other elementary lesions or type IA (25 lymph-nodes from 23 patients); changes resembling a multicentric Castleman syndrome or type IB (1 case); angioimmunoblastic-like (AIL) lesions or type II (2 cases) and an association of lesions of type II (7 lymph-nodes from 6 patients). During AIDS, the adenopathy usually disappears, and the small lymph-nodes removed, especially on autopsy, show an extensive lymphoid depletion (type III) with systematic sclerosis (15 lymph-nodes from 14 patients). When adenopathy persists, it is due to infections complications (tuberculosis, cryptococcosis, avian mycobacteriosis and Whipple's disease like lesions). Of the 10 patients in whom a Kaposi's sarcoma was observed, only 6 showed lymph-node involvement, or type IV. The different histopathological lesions seem to appear according to an evolving succession, proven by certain association of lesions and by successive biopsies. In our series, 17% of subjects with an ARC evolved to AIDS. Lymph-node biopsy allows a possible ARC to be implicated on the association of the following simple lesions: follicular hyperplasia with partial or total destruction of the perifollicular lymphocytic cisterna, infiltration of the germinative centres by streams of small lymphocytes, evolving to an aspect of a "burst" germinative centre and various sinusal reactions with, in particular, the presence of neutrophilic polynuclear cells. The biopsy also allows the forms with bad prognosis to be recognized: those with AIL-like aspect or multicentric Castleman-like syndrome, which seems to represent a particular evolutive form. Finally, it also detects, in certain cases, the localization of a Kaposi syndrome, signalling the passage to AIDS. The immunopathological studies present a double interest. Firstly, they offer arguments in favour of the diagnosis: increase in the number of T8 lymphocytes in the germinative centres with the formation of small clusters and disruption of the network of dendritic reticular cells, and the inversion of the T4/T8 ratio in the extra-follicular cortical regions, by either a decrease in T4 lymphocytes or by an increase in T8 lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Up to now, light chain deposition disease (L.C.D.D.) and amyloidosis have been shown to occur in different individuals. A case of association is described in a 76 year old man with terminal renal failure and normal size kidneys. Percutaneous renal biopsy showed glomerular and peritubular fixation of labeled antikappa light chain serum. Stains for amyloidosis were positive in small vessels. Kappa free chains were found in both serum and urine and the bone marrow showed predominantly kappa-containing plasma cells. By electron microscopy both electron-dense granular deposits and amyloid like fibrils were found in the wall of arterioles and small arteries.
The expression of complement receptors by human follicular dendritic cells (FDC) was investigated by immunohistochemical techniques by using polyclonal and monoclonal antibodies to antigenic determinants of CR1, CR2, and CR3. Upon optical immunohistochemical examination of frozen sections from human reactive lymph nodes and tonsils by a three-step immunoperoxidase technique, a strong staining of cell bodies and cytoplasmic extensions of FDC was observed in germinal centers with anti-CR1 and anti-CR2 antibodies. Staining for these antigens was also found on cytoplasmic extensions of FDC in the mantle zone and on the plasma membrane of B cells in the entire follicles. Staining of FDC with anti-CR2 antibody was more intense than that of B lymphocytes. Monoclonal antibodies directed against epitopes of the alpha-chain of CR3 weakly stained FDC in follicles in a similar pattern to that which was observed on adjacent sections with mouse monoclonal antibody KIM4 that only recognizes FDC in human lymph nodes. Immunoelectron-microscopy was performed on frozen sections of a lymph node involved with a centroblastic centrocytic B malignant lymphoma and a reactive tonsil with the use of rabbit F(ab')2 anti-CR1 antibodies and mouse monoclonal anti-CR2 antibody. All the plasma membrane of the cell body and cytoplasmic extensions of FDC in germinal centers and in the mantle zones homogeneously stained for CR1 and CR2 antigens. Fibroblastic reticulum cells were negative. The plasma membrane of tumoral B lymphocytes strongly stained with anti-CR1 and weakly stained with anti-CR2 antibodies. The presence of CR1, CR2, and CR3 on FDC is a unique surface characteristic of these cells that should optimally allow the cells to bind antigen/antibody complexes bearing any type of C3 fragment.
Histologic, transmission, and scanning electron microscopic observations were made of 26 biopsy specimens from patent polytetrafluoroethylene grafts that had been implanted as arterial bypasses for up to 60 months. The results showed the rarity of host connective tissue ingrowth, the absence of neovascularization, and the limited neointimal proliferation. The defect of staining for factor VIII-related antigen by immunohistochemistry confirmed the absence of true endothelial cells at a distance from the anastomoses. Under electron microscopy the thin neointimal layer consisted mainly of fibrin, platelets, blood cells, and cellular debris. Even in prostheses implanted for the longest periods, mature collagen and elastin were not found. Tubular microfibrils (9- to 12-nm thick) could be observed. The source of such microfibrils, probably glycoproteins, remains under investigation.
Three renin-secreting juxtaglomerular cell tumors were studied by ultrastructural and immunocytochemical methods. Both active and inactive renins were identified in tumor extracts. By immunofluorescence and the peroxidase-antiperoxidase (PAP) method with antirenin antiserum, immunolabeling was intracytoplasmic and irregularly distributed throughout the tumor tissue. Electron microscopic examination revealed various types of secretory granules, including atypical giant crystalloid protogranules in one case, and the postembedding PAP procedure showed labeling of all types of granules. Acid phosphatase staining was observed within secretory granules and autophagic vacuoles. The process of renin storage and release is discussed. The presence in one case of a neural component and a distal tubular structure supports the view of a hamartomatous lesion.
An immunoelectronmicroscopic method using Fab fragment of anti human IgG (H + L) has been employed to study the localization of cytoplasmic immunoglobulins in the tumoral cells of 12 B non Hodgkin's malignant lymphomas (B-M.L.). A comparison with normal homologous B lymphoid cells was performed on 10 non tumoral reactive lymph nodes. Immunostaining was observed in PNC, RER and Golgi complex. The criterions of differentiation were discussed in the different B-M.L.. Because of a granular hyaloplasmic immunostaining in normal and tumoral centroblasts and immunoblasts, monospecific antibodies against gamma, mu, alpha heavy chains were used to rule out a non specific uptake. Presence of mu heavy chain was discussed as an argument for immunoglobulin free ribosomal synthesis.
Capillary abnormalities were found by electron microscopy in labial salivary gland biopsies obtained from 20 patients with progressive systemic sclerosis (PSS). They consisted of marked thickening and multilayering of basal lamina, degenerative and adaptative endothelial cell changes, alterations of pericytes and perivascular mononuclear cell infiltration. There was no correlationship between the intensity of the capillary abnormalities and the duration of the disease. In 12 patients with Raynaud's disease (RD) such changes were not found. Thus capillaries displayed normal-looking ultrastructural appearances. Mean capillary basal lamina width was consistently thicker in the PSS group than in the RD group (p less than 0.001). These observations are consistent with the hypothesis that the primary event in PSS occurs in the microvessels. It is suggested that labial salivary gland biopsy may be helpful for early recognition of PSS among subjects with Raynaud's syndrome.
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3 cases of hairy cell leukaemia were studied with ultrastructural immunocytochemical methods using an anti human Ig HRPO-Fab fragment. Ig were detected on the cell surface, in the perinuclear cisterna and endoplasmic reticulum of hairy cells. Evidence of Ig in these sites demonstrates a B-lymphoid differentiation of the leukaemic cells.
An ultrastructural cytochemical study of lysosomal acid phosphatase was performed on leukemic cells in a case of chronic lymphocytic leukaemia of T cell origin (T-CLL). The cells showed inclusion bodies known as parallel tubular arrays, which often lay within acid phosphatase-positive, membrane-bound spaces. This suggests their lysosomal location.
Epidermolysis bullosa acquisita (EBA) is a rare non hereditary bullous disease. One case is described with a morphological, and immunocytochemical ultrastructural study. The plain ultrastructural morphology showed a dense amorphous deposit in the superficial dermis, under the basal lamina. Immunofluorescence showed IgG and C3 deposits. The ultrastructural study (direct immunoperoxidase technique using Fab) showed a dense labelling associating : dark dots spaced under the basal lamina and fogging less dense labelling in the clarified superficial dermis. Using the patient's antibodies an indirect reaction on normal human skin performed : the same dotted sub laminal labelling was found but with no dermal diffuse reaction product. The study shows the site and the aspect of the Ig deposit in EBA and indicates that the antibodies demonstrated in some patients are reactive with a constituent of the normal superficial dermis.
The light chain deposition disease was recently identified as a systemic clinicopathological entity characterized by amorphous extracellular deposits which differ from the amyloid substance. Various organs may be involved, notably the kidney, the liver, the myocardium and the skin. The histopathological aspects were investigated in 3 cases. By immunofluorescence using frozen sections the deposits were shown to contain monoclonal light kappa or lambda chains. By electron microscopy they appeared to be granular and usually located close to epithelial and/or vascular basal lamina. There was in every case a monoclonal lymphoplasmacytoid proliferation. In one case amyloid deposits were associated in small vessels. In another one, follow-up study after chemotherapy showed improvement of hepatomegaly, stabilization of renal function, and regression of light chain deposits in skin biopsy specimens.