[Choices in the management of epithelial cancer of the skin].
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Biomedical subjects
Publications and source records attributed to V Skoog.
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Peptides of 11 and 15 residue lengths were synthesised according to the sequence of the N-terminal region of the human MC1 melanocyte stimulating hormone receptor. The peptides were conjugated to thyroglobulin and used for preparation of antisera in the rabbit. Each of the conjugates raised antisera which showed high titre and specificity for its respective peptide antigen when evaluated in an ELISA test. Both types of antisera immunostained MC1 receptor expressing COS-7 cells. By contrast, the sera did not stain control COS-7 cells not expressing the MC1 receptor. Moreover, preimmune sera or antiserum preadsorbed with its respective peptide did not stain the MC1 receptor expressing cells. The antisera were used to immunostain sections of normal human skin, as well as samples of cutaneous malignant melanoma tumours obtained from a patient. The cells of the melanoma tumours were very strongly immunostained with the MC1 receptor antisera. By contrast, melanocytes which were present in the normal skin could not be visualised with our antisera.
An experimental study was done in two rabbits to establish whether the early stages of cartilage generation involves stimulation via the platelet-derived growth factor beta receptor (PDGFR-beta). Rib perichondrium was dissected off and transplanted to the knee joint. The perichondrial grafts were removed for microscopic investigation at day 0 and day 6 and kept frozen until analysed by immunohistochemistry and in situ hybridisation for the presence of PDGF beta receptor protein and mRNA, respectively. Samples from day 0 showed sparse cells with a positive immunohistochemical reaction. In samples from day 6 there were signs of perichondrial proliferation and chondroid maturation and a more widespread immunohistochemical staining reaction could be seen mainly on proliferating perichondrial cells, but also on some chondrocytes. In situ hybridisation confirmed the expression of PDGF beta receptor mRNA in the same areas of serial sections. These findings may indicate that PDGF beta receptor activity is part of the early response after autotransplantation of perichondrium.
Reconstruction of cartilage with perichondrium depends on the chondrogenic property of the perichondrial fibrocytes. The present investigation concerns the conditions for the differentiation of fibrocytes into chondrocytes both in vivo and in vitro. For the in vivo studies specimens of rib and auricular perichondrium from adult rabbits were wrapped round silicon rods which were enclosed in dialysis bags. One was placed in the suprapatellar pouch of the knee joint and one was placed intraperitoneally in each rabbit. After two months the bags were extracted, the perichondrium prepared for microscopic examination, and the chondrogenesis evaluated. In vitro the perichondrium was divided into small pieces and incubated with tissue culture medium. The medium was supplemented with fetal calf serum, together with epidermal growth factor, platelet derived growth factor, synovial fluid, or with human serum albumin (control group). After three weeks the explants were prepared for microscopy. Chondrogenesis was judged by the degree of cellular enlargement, capsule formation, deposition of matrix, and activation of the outer fibrocytic layer. In vivo, good cartilage development was found in all specimens placed in the knee joint but, in those placed intraperitoneally, little if any chondrogenesis was seen. In vitro profound differentiation occurred in all cultures supplemented with epidermal growth factor and platelet derived growth factor. An equivalent differentiation was found in perichondrium that had been incubated with synovial fluid. We conclude that the differentiation of perichondrial fibrocytes is initiated in vitro by growth factors. In addition, we have shown that synovial fluid contains factors that promote and enhance the development of cartilage from perichondrium.
ECP (eosinophil cationic protein) and EPX (eosinophil protein X) are two highly basic proteins contained in the granules of human eosinophils. In this study, the effect of ECP and EPX upon lymphocyte proliferation in vitro has been investigated. Peripheral blood mononuclear cells from normal donors were cultured in medium containing ECP or EPX at concentrations from 10(-10) to 10(-7) M. 3H-Thymidine incorporation in PHA-blasts or MLR-blasts was dose-dependently inhibited by both ECP and EPX. The effect was irreversible and was not due to cytotoxic damage. The suppressive effect of EPX may involve suppressor cells. The effect of ECP and EPX on lymphocyte proliferation at relevant in vivo concentrations suggests a regulatory role for the eosinophil in immunological reactions.
Patients with carcinoma of the hepatic duct junction often present the surgeon with a difficult problem. If at all possible radical surgery may be performed either as a resection of the tumour and an anastomosis according to Roux-en-Y or a resection of the left or right hepatic lobe together with the obliterated hepatic duct or ducts. The present series consists of 17 patients treated for cancer of the hepatic duct junction during the period 1965-1974 with a follow-up period of at least five years. The surgical treatment given included a radical procedure in 8 cases, a palliative procedure in 7 cases and in 2 cases surgery of the hepatic ducts was not possible. Radical procedures included 4 patients with a resection of the left hepatic lobe and 4 patients with resection of the left and right hepatic ducts and anastomosis according to Roux. A mean survival time of 22.8 months was reached when a radical operation was attempted with a longest survival time of 8 years. A palliative procedure gave a mean survival time of 2.0 months. These figures indicate that a careful selection of patients for an attempt of radical surgery could be made since removal of the tumour gives a more effective palliation, often a longer survival time and an improvement of quality of life.
A series of 127 patients treated for cancer of the biliary tract during the period 1965-1974 was studied with a follow-up period of at least five years. The mean age was 66 years and the female:male ratio was 3:1. An early diagnosis of biliary tract carcinoma is difficult and the prognosis unfavourable although not hopeless. The surgical treatment given in the present series included a radical approach whenever possible. In the total series 56 patients died within a month, 24 lived for more than one year, 9 longer than three years and 5 longer than five years and 3 are still alive. A mean survival time of 25.6 months was reached when a radical operation was attempted while a palliative procedure gave a mean survival time of 5.5 months. These figures indicated that a careful selection of patients for an attempt of radical surgery should be done since removal of the tumour gives a more effective palliation, often a longer survival time, an improvement of quality of live and in a few patients cure.
In an experimental study the cartilaginous protential of the rabbit ear perichondrium has been compared with that of the rib in vivo and in vitro. Perichondrium was transferred as free autologous grafts to the subcutaneous tissue on the scalp and as loose bodies into the knee joint. The presence of cartilage in the grafts was examined after six weeks. In vitro explants of rabbit perichondrium from the ear and the rib were maintained in an organ culture system. The presence of cartilage was analyzed after one to three weeks. Rabbit perichondrium from the rib appeared to have a greater cartilaginous potential than that from the ear both in vivo and in vitro. Chondrogenesis in perichondrium was demonstrated in vitro.
The morphology and histochemistry of gastroduodenal endocrine tumors from 16 patients were studied. All patients underwent operation, in most cases with a preoperative diagnosis of nonendocrine tumor, ulcer, o polyp(s). The argentaffin reaction was positive in three tumors, and the Hellerström--Hellman argyrophil reaction was positive in four tumors. All tumors reacted positively to the Grimelius argyrophil stain, and 13 were positive with the Sevier--Munger argyrophil stain. Gastrin immunoreactivity was found in eight tumors, and substance-P immunoreactivity in seven tumors. No enteroglucagon, adrenal cortex hormone, or pancreatic polypeptide was observed in any of the tumors. Three patients with Sevier--Munger-positive gastric tumors had concurrent pernicious anemia, and 2 patients with gastrin-immunoreactive tumors had acute or chronic gastroduodenal ulceration. The results indicate that the gastroduodenal endocrine tumor as a rule gives no endocrine symptoms and that the tumor type is an unexpected finding at operation. The tumors may contain gastrin, substance P, somatostatin, and serotonin and tend to be multihormonal.
The presence of serotonin, substance P and enteroglucagon was investigated in 8 argentaffin and argyrophil midgut carcinoid tumours. All tumours were argentaffin and displayed formalin-induced fluorescence indicating a content of serotonin. In addition, all 8 tumours showed substance P immunoreactivity and 7 of them enteroglucagon immunoreactivity. The results indicate that the midgut carcinoid tumours are as a rule multihormonal.
A specific immunofluorescence for enteroglucagon or substance P or for both hormones was demonstrated in nine out of 12 examined rectal carcinoids. One tumor was argentaffin, contained ultrastructurally pleomorphic granules of the entero-chromaffin cell type, and showed immunofluorescence for substance P. The rest were non-argentaffin but were argyrophil with the Grimelius technique and contained round granules. The argyrophil carcinoids were immunoreactive to one or both hormones in eight cases and not fluorescent in three cases. In two of the non-argentaffin carcinoids a small number of argyrophil cells was found with the method of Sevier-Munger.
Nipple discharge, especially the blood-stained type, is regarded as an important symptom in breast disease. In many reports the high incidence of malignancy is stressed and an active surgical approach has often been recommended. In this series of 80 women with nipple discharge the type of secretion and the result of exfoliative cytology were evaluated. Three women had cancer but the nipple discharge was important for the diagnosis in only one case. Six women had papilloma and in all the nipple discharge was essential for the diagnosis. Fibroadenosis and duct ectasia were the most common diagnoses. The blood-stained secretion was due to fibroadenosis in about half of the cases. No cancer was found in 46 women with a serous secretion. When a tumour is present nipple discharge is of little importance for the diagnosis and treatment. In the absence of a tumour and when exfoliative cytology gives no suspicion of cancer and no atypical cells or papillomatous clusters are present, an expectant attitude towards surgery seems satisfactory. With such an approach many surgical biopsies prove unnecessary, but a prerequisite is an organized follow-up.
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