A total of 32 Wistar rats were given 1, 10, 100 or 1000 mg glove powder (Biosorb®) intraperitoneally for 4, 11, 18 or 25 days. Four control rats received physiological saline. Examination of the abdominal cavity displayed granulomatous inflammation which was clearly dose‐dependent in the experimental animal, but not in the controls. A biphasic time‐sequence of the granulomatous reaction was observed in those rats receiving 100 and 1000 mg Biosorb with a minimum at day 18. The mean size of the granules (8.1 μm) within the inflammatory tissue was almost identical with the size of powder granules found on the external surface of the gloves (8.8 μm). X‐ray microanalysis demonstrated maize‐starch additives of magnesium and aluminium. The study indicates a foreign body reaction to maize‐starch. In addition, immunological factors may play a role later in the development of the disease.
The present study deals with ultrastructural changes of jejunal absorptive epithelium in mucosal biopsy specimens from eleven patients with progressive systemic sclerosis (PSS). Epithelial cells showed cytoplasmic condensations with cholesterol clefts and fat droplets. Intercellular spaces of the epithelium were dilated with deposits of fat droplets, while tight junctions and villi preserved their normal structures. Goblet cells and entero-endocrine cells showed no changes. In the lamina propria, fat droplets were observed as well. Vessels were strongly dilated and in 2 patients contained conglomerates of thrombocytes. Perivascular cell infiltrates consisted of lymphocytes, macrophages and mast cells, while plasma cells were scarcely seen; in 2 patients, plasma cells were abundant. Collagen fibrils, elastic fibres, and nerves showed no definite changes. The findings of epithelial cell degeneration and fat droplet deposits indicate dysfunction of jejunal absorptive epithelial cells in PSS.
Fifty-nine lymph node biopsies from homosexual men with serum antibodies to HTLV-III/LAV were the subject of a detailed histopathological and immunohistochemical study. The histological findings were correlated to the patients clinical status, and the T4/T8 ratios in blood and lymph nodes. Four histological patterns predominated and were defined as follicular hyperplasia (FH), follicular fragmentation (FF), follicular atrophy (FA), and follicular depletion (FD). Immunocytochemical studies indicated that destruction of follicular dendritic cells is related to the initiation of follicular involution from FH to FF, but the possible role of follicular infiltrating T-cells cannot be excluded. Marked individual variations in lymph node angiogenesis increasing during involution were observed, which suggests that the degree of angiogenic host response may predispose for evolution of Kaposi's sarcoma. The majority of the patients with the clinical diagnosis of persistent generalized lymphadenopathy (PGL) were morphologically staged as FH or FF (89%), whereas most of the AIDS patients showed lymph node changes compatible with FA and FD (89%). Patients with AIDS-related complex (ARC) had a wider spectrum of morphological lymph node changes but a majority of cases (62%) were also classified as FA or FD. Clinical follow-up showed progression from PGL to ARC in seven of 21 cases with the FF pattern and only in three of 19 cases with FH, indicating a possible prognostic value in differentiating between FH and FF. Three cases with FD and one with FA progressed to AIDS during the time of observation. T4/T8 ratios in blood and lymph nodes were significantly lower in patients with FD histology compared to patients of the other histological groups. At autopsy, all AIDS cases showed the FD pattern of lymphadenopathy. Autopsy findings in seven patients emphasized the importance of post-mortem studies in clarifying the spectrum of opportunistic diseases, including tumors which afflict the AIDS patients.
Two types of mid-line distortion affecting the primary fissure of the cerebellum in foetal rats were recently described (Conradi 1987a). During the postnatal period, cells of the external granular layer (EGL) in distorted regions differentiated to granule cells, forming a heterotopic granule cell layer replacing the deeper portion of the fissure. Differentiated heterotopic granule cells were seen close to normal EGL. Formation and growth of lobules V and VI, apart from the partial fusion at the mid-line, was not affected by the distortions. The findings support the previous suggestion that foliation is relatively independent of formation of a fissure. A network of capillaries was formed in the heterotopic granule cell layer and was continuous with capillaries in the molecular layer of lobules V and VI. The frequency of capillaries in the heterotopias increased in parallel with an increased activity of oxidative enzymes, simulated that in the internal granule cell layer and was higher than that in the molecular layer. These findings support the suggestion of a correlation between nerve-cell differentiation and capillary growth.
Bronchial biopsies were investigated by light microscopy (LM) and electron microscopy (EM) with the aim to evaluate if EM could contribute to the LM tumour type diagnosis. Fourty-three pairs of biopsies were comparable. A histogenetic typing, especially of light microscopically undifferentiated and unclassifiable carcinomas, was possible by EM. However, when considering the therapeutical possibilities, at present time, LM tumour classification must be regarded as fully sufficient.
Parietal cell density, mucosal height, grade of gastritis and pentagastrin-stimulated acid production were assessed before and three months after parietal cell vagotomy (PCV) in 14 patients with duodenal ulcer. Parietal cell density was found to be unaltered after vagotomy and there was no difference in the parietal cell count in the neck and base of the glands. Both the basal acid production and the pentagastrin-stimulated acid secretion were significantly reduced after PCV. No correlation could be shown between the stimulated acid production and the parietal cell count, either pre- or postoperatively. (r = 0.14 and r = 0.19). Mucosal height and grade of gastritic changes remained unchanged. It is concluded that PCV in duodenal ulcer patients causes no change in parietal cell density assessed at three months post-operatively. Vagotomy causes no mucosal atrophy or gastritic changes within this period.
Fibrous deposits in the perisinusoidal space in the acinar zone 3 are early and prognostically important features of the alcoholic liver lesion. Four connective tissue staining methods: van Gieson's Picro-Fuchsin (VG), Gordon & Sweets' reticulin (GS), Chromotrope Aniline Blue (CAB), and Picro-Sirius (PS) were evaluated concerning their relative sensitivity in the detection of early zone 3 fibrosis. A selected area in 60 liver biopsies with preserved architecture, obtained from chronic alcoholics, were studied. A semiquantitative registration of the degree of fibrosis was made. A comparison between the scores of the various staining methods by means of Pratt's test revealed PS to be significantly the most sensitive method. GS was insignificantly more sensitive than CAB while VG (which in contrast to the other three methods leaves reticulin unstained) was the least sensitive. In five biopsies which only revealed fibrosis in PS, perisinusoidal collagenization was confirmed by transmission electron microscopy. In the histological detection of early zone 3 fibrosis, PS is therefore recommended.
Synaptophysin, an integral membrane glycoprotein of presynaptic vesicles, was tested as an immuno-histochemical marker for childhood neuroblastoma. Synaptophysin immuno-reactivity was found in all neuroblastomas (6/6), but not in the other small round-cell tumors to be considered in its differential diagnosis. Thus, rhabdomyosarcomas (0/5), lymphomas (0/4), or Ewing's sarcomas (0/2) were negative for synaptophysin. The results suggest that synaptophysin is a useful marker for neuroblastoma, and it should belong to the marker panel used for the differential diagnosis of small round-cell tumors of childhood.
The brains and spinal cords from 3 young blue foxes suffering from acute to subacute encephalitozoonosis, were examined by transmission and scanning electron microscopy. Parasitophorous vacuoles (PV) were demonstrated more frequently in vascular smooth muscular cells than in endothelial cells. The present study also indicated that the parasite has great affinity for neurons, including their processes. In addition, PV occurred in macrophages and probably also in intravascular monocytes. PV were readily differentiated from phagosomes by the bleb formations of the limiting membrane. An accumulation of host cell mitochondria near the PV in areas where developmental stages were attached, was a most striking feature. The inflammatory lesions, mainly of the granulomatous type, were almost constantly associated with the presence of released parasites, both in vascular walls and the nervous tissue. Phagocytosed parasites were probably killed by the lysosomal enzymes, although the spores were only slowly degraded.
To determine the prevalence of renal amyloidosis of the AA-type in a defined population, formalin-fixed specimens from the kidneys of all the cases autopsied in 1983 at The General Hospital of Malmö, Sweden, were investigated using immunohistochemical techniques. Amyloid deposits of protein AA were found in 10 of 1,158 investigated cases and the calculated prevalence was 0.86 per cent. The mean age at death of the individuals with the AA-type of amyloidosis was 79 years. Six of the cases with amyloidosis had rheumatoid arthritis. The avidin-biotin-peroxidase complex technique was found to be superior to the immunofluorescence method and a high sensitivity and specificity was achieved when sequence-specific antibodies against a synthetized nonapeptide corresponding to a hydrophilic segment of the polypeptide chain of protein AA were used in the assay. Nine cases with other types of amyloid deposits in the kidneys were also detected. None of these cases showed any AA immunoreactivity but all of them demonstrated Congophilic deposits which were immunohistochemically stained by antibodies against the amyloid P-component. The prevalence of renal amyloidosis comprising all types of amyloid protein deposits was 1.64 per cent.
Antral gastrin-producing cell densities, as well as serum gastrin and gastric acid secretion were obtained prior to parietal cell vagotomy from 60 patients suffering from chronic duodenal ulcer disease. Acid secretion was also measured postoperatively. The patients were followed for five years. The ulcer recurrence rate was 20%. No differences were found in the G-cell densities, fasting serum-gastrin or gastric acid secretion preoperatively between the two groups: recurrence and non-recurrence. The acid secretion was higher postoperatively in patients with recurrent ulcer as compared to those without recurrence of the ulcer, suggesting that incomplete vagotomy is a reasonable explanation of the recurrence, even though post-operative G-cell abnormality cannot definitely be ruled out.
A pathological and histochemical study on the presence of signet-ring cells (SRC) in 108 advanced gastric cancer (AGC) has been evaluated. According to Laurén's classification, 59 were of intestinal (I) and 49 of diffuse (D) type. The amount of SRC seems to be a prognostic parameter in D-carcinoma: the 5-year survival rate was 49% and 22% in cases with 1-24% and 75-100% SRC, respectively. Histochemically, in our series of SRC D-carcinoma the quality of mucin secretion of SRC closely resembled the goblet cells of intestinal metaplasia. The histogenetic origin of D-gastric carcinoma was discussed.
Immunohistochemical estrogen receptor (ER) analysis using a monoclonal ER antibody was performed on a total of 30 specimens from 26 patients with gynecomastia. Twenty-six specimens were ER-positive, 3 were ER-negative, and the analysis failed in one case. Immunohistochemical analysis proved more sensitive than biochemical ER analysis in a group of 20 patients, and in a group of 6 patients, the immunohistochemical analysis correlated well with in vitro hormonal sensitivity of the gynecomastic tissue. Semi-quantified ER content was inversely correlated with patient age. There was no relationship between ER content and either histopathologic features or hormonal status. In conclusion, this study demonstrates that the intracellular ER responsible for estrogenic stimulation is present in most gynecomastic tissue specimens, supporting the general assumption that estrogen can be one of the hormones responsible for the development of gynecomastia.
All cases of biopsy-proven Hodgkin's disease and non-Hodgkin's lymphomas submitted for histological diagnosis in Iceland during 1955-1982 and available for review were typed histologically, using the World Health Organization Classification for cases of Hodgkin's disease and the "International Working Formulation" for cases of non-Hodgkin's lymphoma. A total of 92 cases of Hodgkin's disease were classified with a male-to-female ratio of 1.96. The largest subgroups were those of nodular sclerosis (42%) and mixed cellularity (32%). A prominent peak in the incidence was found in the 21-30 years age group. The incidence and subtypes of Hodgkin's disease in Iceland appears similar to those found in other Western countries. A total of 90 cases of non-Hodgkin's lymphomas were classified with a male-to-female ratio of 1.5. A high incidence of large cell lymphomas was found, especially of the immunoblastic type (35%), while in other respects the distribution of subtypes appeared similar to what has been found in studies from other Western countries. The incidence of non-Hodgkin's lymphomas in Iceland is low during childhood and young adulthood but rises sharply after age 50 and the overall incidence is similar to that found in other European countries.
Sera from 7 patients with primary Sjögren's syndrome and from two control persons were administered intraperitoneally to athymic nude mice transplanted with normal human skin. Seven days after transfer of serum from 5 of the patients, intra-epidermal IgG1 and IgG3 deposits were demonstrated in the skin grafts by immunofluorescence. The deposits closely resembled in vivo deposits found in the skin of these patients. No correlation was found between the presence of epidermal deposits and levels of IgG1 and IgG3 in serum. No IgG deposits were found in skin grafts on animals given control serum, and neither could human IgG be detected in mouse skin adjacent to the grafts. Epidermal deposits of human-IgM, -IgA, -fibrinogen, -C3c and mouse-Ig were not demonstrated in biopsies from grafts or mouse skin. The results support the hypothesis that epidermal in vivo deposits of IgG in patients with primary Sjögren's syndrome are the result of Fc-receptor-mediated binding to epidermal cells.
68% of patients with primary Sjögren's syndrome have previously been found to have intra-epidermal in vivo IgG deposits in clinically unaffected skin. In this investigation, we examined immunohistologically skin biopsies from 5 patients with primary Sjögren's syndrome and from 5 normal controls in order to characterize further the intra-epidermal IgG deposits. Employing direct immunofluorescence and peroxidase-antiperoxidase (PAP) techniques, IgG was localized to epidermal cell surfaces. Double-labelling immunofluorescence experiments showed IgG to be bound to OKT6-positive Langerhans cells, and to some degree also to keratinocytes. Only IgG1, IgG3 and in one patient IgA were deposited, whereas IgG2, IgG4, IgM, IgD, IgE, C1q, C3c, C3d, C4, beta-2 microglobulin, albumin, fibrinogen and C-reactive protein were not found deposited in the intra-epidermal area. The epidermal IgG deposits were reactive with anti-Fc-fragment antibodies and with staphylococcal protein-A. These results are compatible with, although not definitive proofs of, the hypothesis that the in vivo deposited IgG is found in the form of IgG-containing immune complexes.
This study, which is part of a larger immunohistochemical investigation of blood-group antigens in non-neoplastic urothelium and bladder cancer, reports our findings on the expression of an antigen related to the cryptic Thomsen-Friedenreich antigen (beta Gal 1-3 GalNAc) of erythrocytes. De-waxed sections of 19 ureters and of 93 transitional cell tumours, either untreated or pretreated with neuraminidase, were subjected to an indirect immunoperoxidase staining, employing the monoclonal antibody 49H.8. Staining results were compared to Lewis-secretor types, morphology, and in tumours to the clinical course as regards recurrence rate and the development of either stroma invasive recurrence or papillomatosis as well. Ureters not subjected to neuraminidase were unstained, whereas urothelium in 12 of 19 ureters subjected to neuraminidase showed staining. Serial dilution of antibody disclosed quantitative differences related to the Lewis-secretor types. Lea+b- urothelium, i.e., non-secretor urothelium, had the highest end-point titers. Endothelium was unstained. Thirty-six of the 93 tumours showed staining without prior neuraminidase treatment, 31 showed staining after neuraminidase treatment only, while 26 were unstained. Staining correlated with the pathological stage and grade (p less than 0.05), but not with the clinical course (p greater than 0.05). The results do not support previous observations on the prognostic value of Thomsen-Friedenreich antigen determination in superficial bladder cancer.
The number of CD8-positive cells in follicular centres of hyperplastic lymph nodes from 20 Danish and Swedish homosexual men with persistent generalized lymphadenopathy and 43 control patients were enumerated in frozen tissue sections immunostained with monoclonal antibody reactive with the CD8-antigen ("cytotoxic-suppressor" T-cell antigen). All the homosexuals were seropositive for HIV and histology showed changes characteristic of the early stage of HIV lymphadenitis. A significant increase (p much less than 0.001) of CD8-positive cells was demonstrated (mean 1,307 per mm2 follicular centre, SD 639) in HIV-related lymphadenopathy compared with the controls (mean 161 CD8-positive cells per mm2 follicular centre, SD 169). The results of this study show that the immunohistological demonstration of a significant increase of CD8-positive cells in the follicles of hyperplastic lymph nodes is suggestive of HIV-related lymphadenopathy.
In a prospective study, 20 patients with endoscopically proven duodenal ulcers were randomised to be treated with cimetidine 1 g daily or with antacids 350 mmol daily. The duration of treatment was 30 days, but this was extended to three months in 3 patients in the cimetidine group and 4 patients in the antacid group. A morphological study of biopsies taken via a gastroscope from the corpus mucosa showed no change in mucosal height, parietal cell density per unit volume or changes in cellular infiltration after 30 and 90 days treatment in the two groups. Neither H-2 receptor blockers nor antacids alter mucosal height or parietal cell density. Treatment was not found to induce gastritic changes in the mucosa.
The topographical distribution and characteristics of an apocrine epithelial differentiation antigen (AEA) were studied in one endometrial adenocarcinoma cell line (HEC‐1‐B) and two mammary carcinoma cell lines (MCF‐7 and T47‐D), using an antiserum raised against glycoproteins which had been isolated from human milk fat globule membranes. Immunofluorescent staining of HEC‐1‐B and MCF‐7 cells grown in monolayers, or of histological sections of cells grown in fibrin sponges, revealed a strictly polar distribution of the antigen. The antigen was present only in the dorsal‐apical cell membrane. In contrast, T47‐D cells grown under identical conditions displayed a nonpolar membrane distribution of the antigen. Detergent lysates of HEC‐1‐B, MCF‐7 and T47‐D cells, surface‐labeled by the PI(sodiumetaperiodate)‐NaB 3 H 4 method, were immunoprecipitated and analysed by SDS‐PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis). Two closely spaced bands having an apparent MW of 315–290 kD (kilodalton) (HEC‐1‐B), 330–295 kD (MCF‐7) and 320–270 kD (T47‐D). The surface expression of the antigen was found to be hormonally regulated. Cultivation of HEC‐1‐B and MCF‐7 in the presence of prolactin increased the amount of antigen. The T47‐D cells responded only weakly to prolactin, but displayed enhanced antigen expression after treatment by estrogen and/or progesterone, as quantified by 125 I protein A radioimmunoassay. The behaviour of the membrane antigen reported here provides a new and interesting marker for the differentiation and maintenance of polarity in cultured malignant cells of secretory epithelial origin.
