Showing papers in "The Journal of Pathology in 1987"
TL;DR: Using a silver staining technique, nucleolar organizer region‐associated proteins (Ag‐NORs) have been studied in paraffin sections of 90 non‐Hodgkin's lymphomas, five palatine tonsils and five ‘reactive’ lymph nodes.
Abstract: Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 90 non-Hodgkin's lymphomas, five palatine tonsils and five 'reactive' lymph nodes. The method was readily applicable to these preparations and the Ag-NORs were enumerated with ease. A significant difference was found between the numbers of Ag-NORs in the nuclei of low-grade lymphomas (from a mean of 1 to 1.5 per nucleus) and those of high-grade lymphomas (a mean of 4.4 to 6.8 per nucleus). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were not visible. It is suggested that this method, previously largely the province of the cytogeneticist, should find widespread applications in the field of tumour histopathology.
551 citations
398 citations
TL;DR: The Ki67 score may prove to be an objective indicator of biological behaviour and thus be of clinical significance, particularly since it is not strongly related to other clinical and pathological parameters used in predicting outcome in breast carcinoma.
Abstract: Sixty cases of primary breast carcinoma have been studied using a monoclonal antibody, Ki67, which recognizes an antigen expressed by cells in G1, S, G2, and M phases of the cell cycle but not Go. A Ki67 score (positive cells/total tumour cells) was determined, and possible relationships between this index of cellular proliferation and a number of clinical and pathological parameters were investigated. There was a strong positive correlation between the Ki67 score and mitotic index (p less than 0.001), a weak negative correlation with age (p less than 0.02), and weak positive correlations with histological tumour grade (p less than 0.03), tumour necrosis (p less than 0.01), and cellular reaction (p less than 0.01). No relationship was noted between the Ki67 score and tumour size, nodal status, tumour oestrogen receptor levels, or menopausal status. The Ki67 score may prove to be an objective indicator of biological behaviour and thus be of clinical significance, particularly since it is not strongly related to other clinical and pathological parameters used in predicting outcome in breast carcinoma.
247 citations
TL;DR: DNA content and cell proliferation were studied retrospectively in 125 patients presenting from 1974–1981 with rectal adenocarcinoma and when combined were the best predictor of survival after Dukes's stage excluding all other pathological assessments investigated.
Abstract: DNA content and cell proliferation were studied retrospectively in 125 patients presenting from 1974–1981 with rectal adenocarcinoma. The presence of DNA aneuploidy or a high level of cell proliferation were associated with a poor prognosis and when combined were the best predictor of survival after Dukes's stage excluding all other pathological assessments investigated. High cell turnover was significantly associated with an infiltrative pattern of growth, an observation that might explain the poorer prognosis of this pattern in rectal adenocarcinomas.
173 citations
TL;DR: Although alcoholic hepatitis is now recognized as the transitional link between alcoholic fatty liver and advanced alcoholic liver disease, the aetiology of liver cell necrosis inalcohol hepatitis is not known.
Abstract: The role of endotoxin in the pathogenesis of progressive liver disease is receiving increasing attention, but remains controversial. Similarly, although alcoholic hepatitis is now recognized as the transitional link between alcoholic fatty liver and advanced alcoholic liver disease, the aetiology of liver cell necrosis in alcoholic hepatitis is not known. Rats fed a nutritionally adequate liquid alcohol diet according to the formula of Lieber and DeCarli developed fatty livers. Littermates fed an identical diet and challenged with small IV doses (1 microgram/g body weight) of E. coli lipopolysaccharide endotoxin (LPS) developed focal necrotizing hepatitis. Control littermates fed an identical calorie balanced but alcohol free diet and challenged with identical doses of LPS did not develop any liver lesions. The hepatocyte necrosis with associated inflammatory changes induced by LPS in fatty livers has some features of early human alcoholic hepatitis and suggests that progressive alcohol induced damage may be multifactorial in origin.
162 citations
TL;DR: Measurement of EGF receptor expression in lung tumours can be of diagnostic value and may prove to be useful in the development of antibody‐directed therapy.
Abstract: Immunocytochemical analysis of epidermal growth factor (EGF) receptor expression was carried out on frozen sections of 109 primary lung tumours resected at the Brompton Hospital from February 1984 to May 1985. Tumours with detectable levels of this proto-oncogene protein were significantly more frequent among squamous cell carcinomas than among other types of lung tumour. No truncated EGF receptors were detected in the tumours using two monoclonal antibodies (Mabs) directed against different portions of the receptor (EGFR1 and F4). Mab F4 is the first antibody to the EGF receptor to show reactivity in paraffin sections. Southern blot analysis of a subset of the tumours detected amplification of the EGF receptor gene in squamous cell carcinomas but not in adenocarcinomas. The one carcinosarcoma examined had a re-arranged and amplified EGF receptor gene. Measurement of EGF receptor expression in lung tumours can be of diagnostic value and may prove to be useful in the development of antibody-directed therapy.
145 citations
TL;DR: Rat parotid gland atrophy after unilateral duct ligation was studied by light and electron microscopy and compensatory hyperplasia, involving proliferation of duct and acinar cells, was demonstrated in the contralateral glands.
Abstract: Rat parotid gland atrophy after unilateral duct ligation was studied by light and electron microscopy. Death of secretory acinar cells, which took the form of apoptosis, resulted in their complete disappearance within 5 days. The remnants of the dying cells were mostly phagocytosed and degraded by macrophages within the glandular epithelium; a few were taken up by adjoining epithelial cells. The acinar cell deletion was accompanied by increased mitosis of striated and intercalated duct epithelial cells. However, over many weeks, there was enhanced apoptosis of duct cells, which eventually led to marked shortening of intercalated ducts. Apoptosis of capillary endothelial cells was observed and may account for the reduction in the capillary bed known to accompany gland atrophy. The end-stage lesion comprised small numbers of ducts in a condensed stroma. Compensatory hyperplasia, involving proliferation of duct and acinar cells, was demonstrated in the contralateral glands.
143 citations
TL;DR: This work injected rats intramuscularly with toxin and killed at time intervals to find whether ricin and abrin caused any apoptotic changes in rapidly dividing tissues where they believed that these toxins concentrate.
Abstract: The toxins ricin and abrin are potent inhibitors of protein synthesis. Apoptosis has been shown to be induced in some cells by cycloheximide and actinomycin D whereas the process is prevented in other cells by the same agents, both inhibitors of protein synthesis. We were interested to find whether ricin and abrin caused any apoptotic changes in rapidly dividing tissues where we believed that these toxins concentrate. Rats were injected intramuscularly with toxin and killed at time intervals, tissues being removed and examined by light and electron microscopy.
Apoptotic-like bodies were abundant in para-aortic lymph nodes, Peyer's patches and ileal crypts of ricin or abrin intoxicated rats. Abrin was found to cause markedly more pronounced changes in these tissues, when compared with a similar dose of ricin. Prior to this, these toxins have been reported as causing necrosis in animal tissues.
143 citations
TL;DR: In four preterm infant brains, four contained early intraparenchymal haemorrhage supero‐lateral to the angles of the lateral ventricles which were associated with large germinal layer and intraventricular haem orrhage, the anatomical distribution and histological features suggested that they resulted from venous infarction.
Abstract: Haemorrhage into cerebral parenchymal tissue supero-lateral to the angles of the lateral ventricles is a major cause of death and disability in preterm infants. It is frequently associated with germinal layer and intraventricular haemorrhage but the mechanism by which parenchymal haemorrhage occurs is uncertain. Recent studies have suggested that it is due to bleeding into tissue previously damaged by ischaemia following cerebral hypoperfusion. We have studied 68 preterm infant brains, of which four contained early intraparenchymal haemorrhage supero-lateral to the angles of the lateral ventricles which were associated with large germinal layer and intraventricular haemorrhages. The anatomical distribution and histological features of these haemorrhages suggested that they resulted from venous infarction and that the venous drainage of the periventricular tissues had been obstructed by the germinal layer haemorrhages. In these four infants, bleeding into parenchymal tissues could be regarded as a complication of germinal layer and intraventricular haemorrhage rather than of cerebral hypoperfusion.
140 citations
TL;DR: Part A. the ear, part B. the nose and paranasal sinuses, part C. the nasopharynx, and part D the palatine tonsil.
Abstract: Part A. The ear.- Part B. The nose and paranasal sinuses.- Part C. The nasopharynx.- Part D. The palatine tonsil.- Part E. The larynx and hypopharynx.- Part F. Major salivary glands.- Part G. The neck.
140 citations
TL;DR: It is evident that the elucidation of the mechanism(s) which governs the onset and progression of the amyloidoses will allow future regulation and treatment of these all too often complex disorders.
Abstract: The transformation of serum proteins into Congo red-sensitive fibrillar material is requisite for the onset and progression of amyloid disease. All the mechanisms which lead to the disease itself have not been elucidated, but our knowledge has increased significantly. It is apparent that in all types of amyloid fibrils, three common features are displayed by the major protein constituents. These are that the fibril protein has (1) a serum precursor, (2) a high degree of anti-parallel beta-sheet conformation and (3) a distinctive ultrastructure on electron microscopy. In the AL and AA forms of amyloidosis, the putative precursors appear to undergo limited degradation to form the protein component of amyloid fibrils. It has been suggested that there may be certain primary structural characteristics inherent in precursor molecules which make them amyloidogenic, thus predisposing them to amyloid fibril formation.33 This would include certain subtypes of immunoglobulin light chains, possibly kappa I and lambda VI, in the AL type of amyloidosis and one of the polymorphic SAA species, SAA2, which has been identified as the predominating isotype found in AA amyloid fibrils.32,33,110 In AH amyloidosis, the mechanism of amyloid fibril formation appears to be simply a concentration phenomenon where elevated concentrations of B2-M are not handled normally and amyloid deposition is the result. Amyloidogenesis in the hereditary form of systemic amyloidosis may involve other factors in addition to the presence of a variant precursor prealbumin as indicated by the delayed onset of the disease. It is evident that the elucidation of the mechanism(s) which governs the onset and progression of the amyloidoses will allow future regulation and treatment of these all too often complex disorders.
TL;DR: A new monoclonal antibody, 11‐5F, against desmosomal proteins 1 and 2 (desmoplakins) is described and its usefulness in the diagnosis of meningiomas and other intracranial tumours is assessed and emphasized.
Abstract: Immunocytochemistry has been applied extensively to the diagnosis of intracranial tumours, but meningiomas still present a diagnostic problem. However, desmosomes have been shown by electron microscopy to be present in meningiomas, and this distinguishes them from gliomas. This paper describes a new monoclonal antibody, 11-5F, against desmosomal proteins 1 and 2 (desmoplakins) and assesses its usefulness in the diagnosis of meningiomas and other intracranial tumours. A total of 74 surgically removed intracranial tumours were examined by fluorescent antibody staining with 11-5F on frozen sections. In addition, a panel of antibodies against cytokeratin, vimentin, glial fibrillary acidic protein, and S100 protein was used. 11-5F stained 30/30 meningiomas and 14/14 metastatic carcinomas but 0/30 gliomas, thus distinguishing meningiomas and metastatic carcinomas from gliomas. The distinction between meningiomas and metastatic carcinomas on the basis of intermediate filaments staining was more difficult because neither the anticytokeratin nor the antivimentin antibody was specific for either tumour type. This study emphasizes the value of antidesmosomal antibodies as an important adjunct to the diagnosis of intracranial tumours.
TL;DR: This article showed that primary gastric lymphoma (PGL) is a tumour of CCL cells with plasma cell differentiation in a minority of cases, but selective invasion of reactive follicles by neoplastic cells often led to a misleading appearance of malignancy.
Abstract: Primary gastric lymphoma, (PGL), is thought to be a tumour of follicle centre cell origin containing centrocyte-like (CCL) cells, and plasma cell components. The advent of novel leucocyte antibodies reactive in paraffin sections and improved techniques for the demonstration of immunoglobulin (Ig) in tissues has permitted a reassessment of the histogenesis of PGL. Our results have shown that PGL is a tumour of CCL cells with plasma cell differentiation in a minority of cases. Follicles were reactive, as defined by polytypic expression of Ig, in each case but selective invasion of reactive follicles by neoplastic CCL cells often led to a misleading appearance of malignancy. CCL cells bear close similarities to marginal zone cells which have been defined as a distinct non-circulating B-cell lineage. This could account for the favourable clinical behaviour of PGL.
TL;DR: It is shown that genetic factors rather than the age of mice influenced phagocytosis and muscle formation in grafts, and that macrophage stem cell function is unimpaired with age.
Abstract: In grafts of skeletal muscle the implanted muscle becomes necrotic, is phagocytosed and replaced by new muscle cells. This study investigates the hypothesis that removal (phagocytosis) of necrotic implanted muscle is impaired in grafts made into old Swiss mice. Isografts (154) of minced muscle were made between young (20 day) and old (140 day) mice of the strains Swiss, AKR, BALBc, C3H and C57BL. Grafts were examined histologically after 7 days. A relationship between impaired phagocytosis and increasing host age was confirmed for male Swiss mice but was not seen with female Swiss mice or the other four strains. The proposal that ageing of bone marrow was responsible for diminished phagocytosis in old Swiss mice was investigated by replacing the marrow of 33 lethally irradiated male Swiss mice with marrow cells from mice of different ages (20 and 140 day), before isografting minced muscle. The results clearly show that macrophage stem cell function is unimpaired with age. Testosterone levels might account for the impaired phagocytosis seen in many sexually mature male Swiss mice. Support for this proposal came from experiments in which 15 mice were castrated before implanting muscle isografts. This study shows that genetic factors rather than the age of mice influenced phagocytosis and muscle formation in grafts.
TL;DR: The results imply, however, that tumours acquire their vasculature by infiltration into, and expansion between, a network of newly formed vessels in the surrounding connective tissue.
Abstract: This study was designed to investigate the early development of tumour circulation using a transplantable mouse mammary adenocarcinoma. Tumour cells (10(6] were injected subcutaneously into the flank and groups of treated mice were killed at 24 h intervals up to 12 days; the tumours and surrounding tissues being processed by standard histological methods. Sections of tumour were sub-divided into neoplastic tissue, vessels and connective tissue using computer-assisted morphometric techniques: the host tissue around the tumour was similarly quantified for vessels and connective tissue. With increasing tumour size, the proportion of vessels within tumours rapidly increased to reach a plateau of approximately 1.5 per cent of tumour volume, a 400 per cent increase on the vascular density of normal subcutaneous tissue. Within tumours, vascular density was always higher at the periphery than the centre. The most pronounced increase in vascular density affected the host tissue around the tumour. It is not clear why vascular development is most prominent outwith the tumour when postulated angiogenic factors, such as tumour angiogenesis factor, are presumably released within. Our results imply, however, that tumours acquire their vasculature by infiltration into, and expansion between, a network of newly formed vessels in the surrounding connective tissue.
TL;DR: Endometrial stromal granulocytes were LCA+, CD2+, MT1+, and UCHL1+, which provides evidence that they are leucocytes, and EGs are probably members of the large granular lymphocyte series and may have an essential role in normal implantation and placentation.
Abstract: Endometrial stromal granulocytes (EGs) are prominent in late luteal phase human endometrium and in early pregnancy decidua. They have been believed to develop from endometrial stromal cells and to secrete relaxin. Recent immunohistochemical studies have suggested that EGs are derived from bone marrow but this has been difficult to prove, mainly because the characteristic cytoplasmic granules are not preserved in frozen tissues. Two separate approaches have now been employed to investigate the cellular lineage of EGs. Formalin-fixed paraffin-embedded sections of first trimester decidua were labelled by an immunoperoxidase method with four monoclonal antibodies (mAbs) reactive with routinely fixed and processed tissues. In addition, acetone-fixed smears of decidual cell suspensions were labelled with a panel of mAbs. Sections and smears were counterstained to demonstrate the characteristic cytoplasmic granules of EGs. Endometrial granulocytes were LCA+, CD2+, MT1+, and UCHL1+, which provides evidence that they are leucocytes. EGs are probably members of the large granular lymphocytes series and may have an essential role in normal implantation and placentation.
TL;DR: It is demonstrated that a simple assessment of lectin binding can provide prognostic information in breast cancer and may be useful particularly when conservational surgical practice restricts the amount of nodal tissue for staging.
Abstract: Formalin fixed, paraffin embedded tissue from 100 consecutive cases of breast carcinoma were studied for binding with Helix pomatia (HPA) and Ulex Europeus (UEA1) lectins. Serial sections were pretreated with trypsin or neuraminidase to determine the effect of these enzymes on lectin binding. The lectins were visualized by the peroxidase antiperoxidase technique and the cell staining proportion assessed in a semi-quantitative manner under the light microscope. Correlating staining with prognostic factors and patient follow-up details showed that UEA1 related to disease-free interval and survival, and HPA to lymph node stage, time to loco regional recurrence and to survival. Relationships with both lectins were abolished by pretreatment with neuraminidase. The study demonstrates that a simple assessment of lectin binding can provide prognostic information in breast cancer. This may be useful particularly when conservational surgical practice restricts the amount of nodal tissue for staging.
TL;DR: CTP is of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell‐small cell carcinoma.
Abstract: A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non-small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron-specific enolase (NSE), protein gene product (PGP) 9.5, human bombesin, and the C-terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9.5 but a significant number of non-small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non-small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell-small cell carcinoma.
TL;DR: Using immunohistochemistry, the epithelial expression of HLA Class I and II antigens (and β2 microglobulin) was compared in benign and malignant breast, and the stromal lympho‐histiocytic infiltrate of these tissues quantified.
Abstract: Using immunohistochemistry, the epithelial expression of HLA Class I and II antigens (and beta 2 microglobulin) was compared in benign and malignant breast, and the stromal lympho-histiocytic infiltrate of these tissues quantified. The findings were compared with certain characteristics of the carcinomas. In contrast to other studies, malignancy was found to be associated with a far greater infiltrate of both lymphocytes and macrophages. In carcinomas, lymphocyte but not macrophage numbers showed a positive correlation with epithelial HLA ABC and HLA DR expression. This was particularly striking for T lymphocytes, and especially for the T4 subset. The histological grade of carcinoma is closely related to the degree of HLA ABC and beta 2 microglobulin expression, but no such relationship was found for HLA DR. There were greater numbers of mononuclear cells in the poorer differentiated tumours compared with other grades. Those carcinomas with evidence of lymph node metastasis contained greater numbers of macrophages identified by the antibody Y1/82A, but none of the other parameters studied was found to be associated with local lymph node status. The use of a large panel of monoclonal antibodies against various cellular subtypes has allowed a more detailed analysis of the interaction between breast epithelium and the host response.
TL;DR: A study is reported in which an in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin–streptavidin polyalkaline phosphatase complex has been successfully applied to formalin‐fixed paraffin‐processed tissue obtained from ten patients with juvenile laryngeal Papillomatosis.
Abstract: A study is reported in which an in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin--streptavidin polyalkaline phosphatase complex has been successfully applied to formalin-fixed paraffin-processed tissue obtained from ten patients with juvenile laryngeal papillomatosis. In all cases, positive results were obtained for either HPV type 6 or 11. Normal vocal cord epithelium was negative.
TL;DR: It is suggested that this simple histochemical technique may be a useful adjunct to the range of special techniques now available to assist the pathologist in the diagnosis of small round cell tumours.
Abstract: A silver colloid technique for nucleolar organizer regions (AgNORs) was applied to paraffin sections of 50 small cell tumours of childhood. These comprised 20 neuroblastomas, 10 Ewing's sarcoma, and 20 rhabdomyosarcomas, including spindle cell, myxoid, and round cell variants. On the basis of the number of AgNORs, one could differentiate between the three groups. The differences observed were statistically significant (P = 0.01-0.001). The subtypes of rhabdomyosarcoma could not be distinguished from one another on the basis of AgNOR counts. We suggest that this simple histochemical technique may be a useful adjunct to the range of special techniques now available to assist the pathologist in the diagnosis of small round cell tumours.
TL;DR: It is suggested that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage‐fibroblast interactions result in a severe fibrotic reaction that resembles the bronchioar component of human asbestosis.
Abstract: To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage-fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.
TL;DR: The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis.
Abstract: The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord-stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli-Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli-Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non-neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co-expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli-Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.
TL;DR: Both abnormalities of MHC expression appeared to precede insulitis within a given islet and appeared to be unique to Type I diabetes, being absent in pancreases of patients with Type II diabetes, chronic pancreatitis, cystic fibrosis, graft‐versus‐host disease and Coxackie B viral pancreatitis.
Abstract: In a study of pancreases from 75 patients who died at presentation of Type I diabetes there was selective destruction of beta cells associated with islet inflammation (insulitis). According to a recent hypothesis, aberrant expression of Class II major histocompatibility complex (MHC) products on a target cell may allow presentation of organ specific surface antigen(s) to potentially autoreactive T helper lymphocytes and thus lead to autoimmunity. Aberrant expression of Class II MHC was demonstrated immunohistochemically on beta cells in 21 out of 23 patients with recent onset diabetes. No such expression was seen on the other pancreatic endocrine cells. Ninety-four per cent of insulin-containing islets in these patients had marked hyperexpressions of Class I MHC affecting all endocrine cells in these islets. Insulin deficient islets were not thus affected. Both these abnormalities of MHC expression appeared to precede insulitis within a given islet and appeared to be unique to Type I diabetes, being absent in pancreases of patients with Type II diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to beta cells in Type I diabetes may be a 'multistep' process in which abnormalities of MHC expression are crucial events.
TL;DR: Experimental data suggest that disturbance of hepatic microcirculation by sinusoidal thrombosis is the necessary and sufficient condition for the development of endotoxin‐induced hepatic injury.
Abstract: The present study was undertaken in rats to examine the significance of sinusoidal circulatory disturbance by microthrombosis in the pathogenesis of hepatic damage and dysfunction due to endotoxin. Administration of endotoxin induced fibrin deposits and infiltration of polymorphonuclear leukocytes in the sinusoids, focal random coagulative hepatocellular necrosis and elevation of serum transaminase activities. When heparin was given simultaneously with endotoxin, the formation of fibrin thrombus in the sinusoids was prevented, and the endotoxin-induced morphological and functional changes in the liver were markedly inhibited. Infusion of thrombin into the portal vein induced a large amount of fibrin thrombi in the sinusoids, focal random necrotic foci resembling the lesions produced by endotoxin and elevation of levels of serum transaminases. These experimental data suggest that disturbance of hepatic microcirculation by sinusoidal thrombosis is the necessary and sufficient condition for the development of endotoxin-induced hepatic injury.
TL;DR: A monoclonal antibody is described to a major desmosomal glycoprotein (dg1) which reacts with human tissues in paraffin sections and reacted with all epithelia tested and with every specimen of a wide range of carcinomas.
Abstract: Desmosomes are intercellular adhesive junctions that occur in almost all epithelia and should therefore be useful as epithelial markers in tumour diagnosis. Here, we describe a monoclonal antibody, 32-2B, to a major desmosomal glycoprotein (dgl) which reacts with human tissues in paraffin sections. This antibody was tested for its ability to stain epithelia and tumours. It reacted with all epithelia tested and with every specimen of a wide range of carcinomas. It also stained meningiomas, another desmosome-containing tumour. It did not stain other types of tumours including lymphomas, melanomas, and various sarcomas, or normal tissues which lack desmosomes. These characteristics demonstrate that 32-2B is a reliable epithelial marker that may have a useful role in diagnostic histopathology.
TL;DR: Cervical scrapes were obtained from 215 women with cytologically normal cervices and 74 women with cervical intraepithelial neoplasia and probed for HPV 6, 11, 16, and 18 by dot‐blot hybridization.
Abstract: Cervical scrapes were obtained from 215 women with cytologically normal cervices and 74 women with cervical intraepithelial neoplasia (CIN) and probed for HPV 6, 11, 16, and 18 by dot-blot hybridization. Viral copy numbers were determined by densitometric scanning of autoradiographs.
The prevalence of HPV DNA in women with normal smears was as follows: 23 per cent of women attending a Family Planning Clinic (FPC), 16 per cent of women attending a Sexually Transmitted Diseases (STD) clinic, and 48 per cent of women attending a laser follow-up clinic after treatment of CIN. Ten per cent of women with normal cervices harboured HPV 16. Viral copy numbers ranged from 1300 to 52 800 genome equivalents per cell. Twenty-seven HPV-positive women with normal smears (including four patients infected with HPV 16) were followed for up to 3 years. None developed CIN irrespective of copy number.
Our results show that HPV is present in normal cervices in the absence of CIN. Copy number has no relation to the development of CIN and factors other than the amount of HPV DNA may trigger the neoplastic process.
TL;DR: Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas, so the antibody should prove of value in diagnostic histopathology.
Abstract: Production of a new monoclonal antibody designated NCL-5D3 is described The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material Staining is enhanced by prior treatment of the sections with trypsin Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas Thus the antibody should prove of value in diagnostic histopathology
TL;DR: Findings help identify a high risk group in whom resistance is higher than expected in the absence of classical grade IV changes, and early intra‐cardiac repair is recommended before obstructive intimal fibrosis develops during the second year.
Abstract: Pulmonary vascular structure was analysed using morphometric techniques, and arterial wall abnormalities in lung biopsy specimens taken from 85 cases of ventricular septal defect, aged 3 weeks to 30 years were described. The defect was closed in 53 patients, 12 died at operation and 11 survivors were recatheterized. Structural examination revealed a characteristic pathological picture which appeared to precede classical grade IV pulmonary vascular disease. This predilatation phase was identified by finding pre-acinar obstructive intimal proliferation or fibrosis, associated with only a slight increase in intra-acinar arterial muscularity, in the absence of stigmata of grade IV disease in patients with a pulmonary resistance greater than 6 units m2. Predilatation features occurred in 62 per cent of patients who either died at repair or who had post-operative pulmonary hypertension. These findings help identify a high risk group in whom resistance is higher than expected in the absence of classical grade IV changes. In addition, a marked increase in muscularity without intimal obstruction can also be associated with a pre-operative resistance of more than 6 units m2. The presence of medial hypertrophy only does not ensure either survival or a normal post-operative pulmonary arterial pressure. Early intra-cardiac repair is recommended before obstructive intimal fibrosis develops during the second year.
TL;DR: The results show that a high dose of exclusively short asbestos fibres produces minimal lung injury and fibrosis in spite of long standing macrophage‐fibre interaction in the alveoli.
Abstract: To determine the relationship between the development of pulmonary fibrosis and the size of deposited asbestos, we prepared a pure sample of short crocidolite fibres and instilled 0.5 mg of 0.1 mg to the lungs of mice. Animals were killed up to 20 weeks later with 3H thymidine injected 1 h before death. By bronchoalveolar lavage, there was a rapid transient increase in polymorph neutrophils (PMN) and in glucosaminidase levels; alveolar macrophage (AM) numbers were elevated in the 0.5 mg group for eight weeks. Most fibres were phagocytized by AM, many of which were heavily laden and cleared from the lung over the 20 week period. Some fibres were seen in type 1 epithelial cells, frequently associated with cell injury. From cell kinetic studies, a very brief proliferative response was seen in bronchiolar epithelial and Type 2 alveolar epithelial cells. A greater response was seen in interstitial fibroblasts which showed increased labelling up to two weeks after 0.5 mg asbestos. However no granulomas were seen and very little fibrosis was found by morphology or by biochemistry at any time after 0.5 mg; no fibrosis was seen after instilling 0.1 mg. The results show that a high dose of exclusively short asbestos fibres produces minimal lung injury and fibrosis in spite of long standing macrophage-fibre interaction in the alveoli.