[Pleuritis in yellow nail syndrome]. / Pleurabefunde beim Yellow-Nail-Syndrom.

A 76-year-old man presented clinically with coughing and shortness of breath and was diagnosed radiologically to have massive pleural effusion as a combined feature of yellow nail syndrome. A lung biopsy was taken and revealed histologically: chronic non-specific inflammation in the pleuropulmonary border, intrapleural edema with eightfold pleural thickening in comparison to normal, angiogenesis in both the nutritive and functional intrapleural blood vessels, no abnormalities of lymphatic vessels with normal topographical distribution as detected by immunohistochemistry for antibody D2-40, granulomatous chronic foreign body reaction as a consequence of pleural effusion therapy by talcum pleurodesis.The histopathological findings of chronic non-specific pleuritis with angiogenesis and increased permeability of blood vessels led to massive intrapleural edema with pleural effusion. Abnormalities of lymphatic vessels could not be confirmed. Considering the features of this disease, they are probably secondary to chronic r infectious or immunological inflammation or paraneoplastic complications with angiogenesis (in about 19%).

Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000.

The present study describes two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000, which are associated with the transformed phenotype of melanocytes. The monoclonal antibodies (MoAb) MUC18 and MUC54, raised against human malignant melanoma, were selected for differential reactivity with normal and neoplastic cells of melanocyte lineage. The antigen defined by MoAb MUC18 is a membrane bound monomeric sialylated glycoprotein with an apparent molecular weight of 113,000. In contrast to the broad reactivity with melanomas, isolated nevus nests were stained in only 1 of 55 nevi investigated. No staining of MoAb MUC18 was observed in a large variety of surgically removed normal and tumor tissues except for smooth muscle cells of the blood vessel wall and hair follicles. MoAb MUC54 immunoprecipitated a cytoplasmic monomeric protein with an apparent molecular weight of 76,000. By immunoperoxidase staining, the antigen was demonstrated on a large number of melanomas and in addition on 1 of 36 nevocellular, 3 of 4 Spitz, and 5 of 14 dysplastic nevi. The Mr 76,000 protein was found in a number of epithelial tissues and various types of neoplasms. Both antibodies presented in this study define structural changes in the antigenic profile of melanocytes occurring during carcinogenesis.

Connective tissue aging in the human hypophysis-gonadal system.

The basic issue in our project was to quantify the age-process in the human hypophysis-gonadal system. Of the many aspects of aging, we estimated, using human autopsy material, the content of desoxyribonucleic acid (DNA), of hydroxyproline, of hexosamines and of uronic acids in the hypophysis, testis, and ovary. The respective organs were weighed and homogenised in acid-buffer solution after which, for each of the parameters, 1.0 ml of homogenate was extracted and processed: DNA-estimation according to modified Dische/Seibert (1929) method; hydroxy-proline according to Stegemann and Stalder (1967); hexosamines and uronic acids according to Gatt and Berman (1966) and Blumenkrantz and Asboe-Hansen (1973) respectively. All values obtained were expressed in micrograms/ml of homogenate. The age investigated ranged from a few days old to 99 years. The DNA-curves for the hypophysis initially showed a decline till about the third decade of life and then remained almost constant with a significant decline up to the senile age. The DNA-curves for the testis and ovary demonstrated a sharp decline initially till the third decade of life, after which the curves remained constant, but showed reduction during higher age. Similar pattern of distribution was also observed for hexosamines, and uronic acids: after the initial decline of uronic acids in the human hypophysis and testis during the first three decades of life and nearly constant values thereafter, hexosamines, together with the uronic acids show minimal decrease in content during the senile period. Contents od hydroxyproline significantly increased in testis, ovary and hypophysis with aging. This biochemically proven age-fibrosis in the human gonads corresponds to the morphologically observed vascular and interstitial sclerosis in the testis and the ovary and may partly help to explain the declined sensitivity of these target organs to hypophyseal stimulation during the aging period.

Topographical analysis of proliferation ([3H]thymidine labelling index and mitotic index) as compared with tumour growth and tumour weight in xenotransplanted melanoma. Changes due to local and systemic application of azelaic acid.

Xenotransplanted human melanoma was investigated by measuring the increase in tumour volume and in final tumour weight (macroscopical parameters) and histomorphological parameters of cell proliferation: Mitotic index (MI) and autoradiographic [3H]thymidine labelling index (LI). A total of 87 tumours, derived from a human melanoma metastasis and a primary nodular melanoma respectively, were analysed by these methods in two series. Topical treatment of the tumours with azelaic acid cream resulted in a statistically significant reduction in the increase in tumour volume and, in the first series, in a clear decrease in final tumour weight and in the MI, as compared with controls. The LI was decreased only in the superficial region of the tumours, i.e. at the site of treatment. Subtumoral injection of azelaic acid (disodium salt solution) was the second route of local therapy. It was followed by a significant reduction in the increase in tumour volume, of final tumour weight (first series) and in the MI. The average LI was clearly smaller than in the controls, especially at the tumour base, which was the site of injection (local effect). Systemic (intravenous) injection of azelaic acid (same concentration of the disodium salt solution) had no negative effect on the increase in tumour volume or final tumour weight, but was followed by a clear reduction of the MI. The average LI of this group was significantly smaller than in the controls as well. This effect was most impressive in the perivascular regions of large and small vessels, which fact can be interpreted as a sort of local effect via the blood stream after systemic application of azelaic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Limb anomalies in the CHARGE association.

We report a male infant with iris coloboma, choanal atresia, postnatal retardation of growth and psychomotor development, genital anomaly, ear anomaly, and anal atresia. In addition, there was cutaneous syndactyly and nail hypoplasia of the second and third fingers on the right and hypoplasia of the left second finger nail. Comparable observations have rarely been reported and possibly represent genetic heterogeneity.

[Histotopochemical quantification of glycosaminoglycans in melanomas and the surrounding epidermis]. / Histotopochemische Quantifizierung von Glykosaminoglykanen in Melanomen und umgebender Epidermis.

15 cases of human malignant melanoma were studied and classified into 5 superficial speading (SSM), 5 nodular melanomas (NM), and 5 melanoma metastasis (Met). The tissue was fixed with formaldehyde and cetylpyridium chloride (CPC). Glycosaminoglycans (GAG) or proteoglycans respectively were characterized by Alcian blue staining following the method of critical electrolyte concentration (CEC) (Scott, Dorling 1965) and by testes hyaluronidase. The staining intensities were quantified by a Leitz MPV photometer microscope in basement membranes (BM) and tumor septa. Tumor septa, which may be looked on as correlates of epithelial BM material, show increased straining intensities as compared to the normal BM (nBM) around the tumor. It is concluded from the sensitivity to testes hyaluronidase and the straining pattern that these are caused by increased straining of GAG of the type of chondroitin sulfates and possibly of dermatan sulfate while unsulfated GAG are rather decreased. The GAG pattern in BM in SSM shows characteristics of tumor septa and of nBM as well. The staining of the tumors shows higher intensities than that of all structures in the normal skin. It is concluded that increasing malignancy is accompanied by increasing changes in GAG which can be quantified by the method used topohistochemically discerning the healthy tissue from malignant structures.

[Age dependence of the early reaction in glycosaminoglycan metabolism of the rat liver on damage following a single dose of thioacetamide]. / Die Altersabhängigkeit der frühen Reaktion im Glycosaminoglycan-Stoffwechsel der Rattenleber auf eine einzeitige Thioacetamidschädigung.

Wistar rats aged 7 or 22 months resp. were treated with 50 mg/kg of thioacetamide (TAA) i.p. The TAA-treated animals as well as control groups of the same ages and containing the same number of animals were injected i.p. with 3H-glucosamine (0.2 microCi/g body weight) 2 hours before sacrifice. Previously to sacrifice, the livers had been perfused in narcosis with NaCl (0.9%). Following degradation of the tissue by pronase, specimen of the substances precipitable by ethanol were digested with chondroitinases, streptomyces-hyaluronidase, keratanase, and nitrite. The quantities of substances were estimated photometrically using Alcian blue; radiometry was performed following precipitation with cetylpyridiniumchloride. In aging animals the amount of dermatan-sulphate (DS) and of the total acidic glycosaminoglycans (a.GAG) is increased as compared to the younger animals, although there ist no age related difference in the incorporation of glucosamine. The incorporation per microgram a.GAG (spec. act.) is decreased. Following TAA the amount of DS is increased in both age groups, whereas the total amount of GAG is increased only in the younger animals. The incorporation per mg dry weight is also increased in all GAG types of both age groups which is also the case with the spec. act. (with the exception of HS in the younger animals). The increase of the incorporation per mg dry weight in DS is significantly lower in the older TAA-animals as compared to the younger ones. HS shows the same tendency, but there is no significance. The age related increase of hydroxyproline parallels that of DS.(ABSTRACT TRUNCATED AT 250 WORDS)

Reaction pattern of xenografted human salivary glands in nude mice. An immunohistological and autoradiographical study.

35 specimens of human parotid gland and 37 of submandibular gland were transplanted into athymic nude mice. At distinct time intervals, from 1 day to 8 months the transplants were collected and examined. The transplanted glands were studied by light microscopy, immunohistology and autoradiography. The following changes were detectable: acute injury to the xenograft and inflammatory reaction (day 1-7), regeneration of the transplant and the beginning of adaptation to the "mouse milieu" (day 8-30), completion of adaptation (day 30 and later). The presence of the following substances was analysed: amylase, lactoferrin, secretory component, tissue polypeptide antigen (TPA). Amylase was only detected in the early transplants. Lactoferrin was seen only in the small duct system. TPA was present during all transplantation periods and was quantitatively correlated with the 3H thymidine labeling index. From our observations we can say that the salivary glands show two different reacting compartments: a large and a small duct system. The histogenesis of the xenografts, and the relationships of the changes observed to human salivary gland diseases were discussed.

[Skin changes in advanced age--biochemical findings corresponding to morphology?]. / Hautveränderungen im hohen Lebensalter--korrespondieren biochemische Befunde zur Morphologie?

The clinically relevant morphological changes of the skin during aging can be summarized by the term "senile atrophy". The changes are a diminished thickness of epidermis with a reduced mitosis rate of epidermal basal cells, shortened and attenuated rete ridges, reduction of epidermal appendages, and a decreased number of fibroblasts and capillaries in the dermis. Corresponding to these morphological findings regarding the cell number in the senile skin (cutis) we found a slight decrease in the DNA concentration of human and rat cutis. The specific DNA activity (3H-thymidine incorporation rate related to DNA concentration) decreased in presenile versus adult animals. The mesenchymal changes in the dermis have been morphologically described by the term "senile elastosis" or "elastoid collagen degeneration", but in fact they correspond to a progressive collagen denaturation with aging. The total collagen concentration, here determined as the hydroxyproline concentration in the human cutis, shows almost constant values from the 3rd until the 9th decade of life in both sexes. This is also true for the skin of two different rat strains. The insoluble collagen fraction shows a relative increase to the disadvantage of the soluble collagen fractions, which can be interpreted as an indicator of a decelerated collagen turnover. In spite of the decelerated turnover, i.e. a prolonged half-life of the collagen metabolism in the skin, the indicators of the collagen neosynthesis (14C-proline incorporation rate, specific hydroxyproline activity, prolyl-hydroxylase activity) are significantly elevated in the cutis of presenile versus adult rats. Any connection of these findings with a possible change in the distribution of collagen types in the senile skin (e.g. pericapillar fibrosis with increase of collagen type I as well as changes in the distribution of type I, III, IV and V) can only be discussed at present. The glycosaminoglycans in the cutis show a minimal increase of the total content of hexosamines and uronic acids with a significant shift in the ratio of the glycosaminoglycan components in favour of dermatan sulfate and keratan sulfate and to the disadvantage of hyaluronic acid and partly also of chondroitin-4-sulfate and -6-sulfate. The neosynthesis of sulfated glycosaminoglycans (indicator method: 35S-sulfate incorporation rate) is only slightly increased whereas the enzyme activities being specific for the glycosaminoglycan catabolism (beta-glucuronidase, beta-N-acetyl-glucosaminidase) are significantly decreased with aging of the skin.(ABSTRACT TRUNCATED AT 400 WORDS)

[Age-related changes in cell content (DNA) and glycosaminoglycan-degrading enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase of connective tissue and parenchymal organs of the rat caused by 6-methylprednisolone (enzyme induction, adaptation, acceleration of maturation and possible modification of aging]. / Altersabhängige Veränderungen des Zellgehaltes (DNA) und der Glykosaminoglykan-abbauenden Enzyme (beta-Glucuronidase, beta-N-Acetylglucosaminidase) bindegewebiger und parenchymatöser Organe der Ratte durch 6-Methylprednisolon (Enzyminduktion, Adaptation, Reifungsbeschleunigung und mögliche Alternsbeeinflussung).

This paper is based on previous investigations, which had shown an evident acceleration of maturation and enzyme induction in several organs, not only in the lung, due to a pre- and postnatal application of prednisolone. Applying the same dosage we now investigated whether there is a similar effect of a short-term application of prednisolone in mesenchymal and parenchymal organs of young adult and presenile rats of the same strain (Chbb: THOM/SPF) analyzing the physiological cell regeneration (DNA concentration) as well as functional parameters of the glycosaminoglycan metabolism (e.g. the lysosomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase). The results show a significant age-dependent decrease of the DNA concentration (lung, spleen, skin, and rib cartilage), a significant age-dependent decrease of the total activity of the beta-glucuronidase (kidney, rib cartilage, and skin) or a significant age-dependent increase of this enzyme activity (spleen and liver) respectively as well as a significant decrease of the beta-N-acetylglucosaminidase activity (skin and rib cartilage) or a significant increase of this enzyme activity (spleen and lung). After application of prednisolone the rats showed a significant reduction of the DNA concentration only in the skin of young adult rats, but no changes in the other organs of the young adult or presenile animals compared to untreated controls. Similar to our findings after postnatal prednisolone application, we found the greatest increases or decreases respectively of the activities of these lysosomal enzymes due to 2- to 3-fold or 4- to 5-fold prednisolone application. Again similar to our previous findings, we found the phenomena of adaptation and rebound effects including the so-called over-compensation in the young adult and especially in the presenile rats but these effects were delayed and weaker in most of the older animals compared to the young adult rats.

[Ultrasound imaging of mesenchymal small intestine tumors in diagnosis of unexplained gastrointestinal hemorrhage]. / Sonographische Darstellung mesenchymaler Dünndarmtumoren in der Diagnostik von unklaren, gastrointestinalen Blutungen.

The presented case reports highlight the value of transabdominal ultrasound as a complementary and non-invasive diagnostic tool in unexplained gastrointestinal bleeding. Seven patients with intermittent melaena and/or chronic anaemia were examined. In all patients, diagnostic procedures like abdominal ultrasound, EGD, colonoscopy and enteroclysis were performed primarily and did not point to a bleeding source. Transabdominal bowel wall ultrasound discovered in all cases a round and smoothly delineated tumour of homogeneous and hypoechoic structure. The diagnosis was confirmed using selective angiography in three cases revealing a roundish hypervascular lesion. Fine-needle aspiration biopsy and re-endoscopy were used in two cases, respectively, to verify the diagnosis. Postoperative histology revealed a benign leiomyoma (n = 3), schwannoma (n = 2), lipoma (n = 1) and angiofibroma (n = 1) with vascular erosions. Transabdominal ultrasound can operate as a complementary imaging technique in case of gastrointestinal haemorrhage, if endoscopic procedures fail to identify the bleeding source in the upper gastrointestinal tract and large bowel.

Wound repair of the oral mucosa. Immunohistological and 3H-thymidine-autoradiographic observations.

The migratory and proliferative capacity of oral epithelium was studied after induction of subepithelial suction blisters in palatal rat mucosa. FITC-coupled lectins and their affinities to epithelial cells at the wound margin were analyzed by immunofluorescence microscopy. Immunocytochemical distribution of 67 K-keratin polypeptides in different epithelial layers were studied using specific antisera against keratin proteins. By means of 3H-thymidine-autoradiography the proliferation of epithelial basal cells and their migration at the wound edge was quantified by evaluation of the labelling index. Double labelling was performed, combining the autoradiographic and the keratin staining technique. It was found that the subepithelial suction blister showed rapid repair (epithelial regeneration after 3-4 days). Peanut Agglutinin (PNA) showed a selective affinity to the basal 2-3 layers of oral rat mucosa. No modifications of lectin affinities were found in epithelial wound repair. PNA-positive keratinocytes were demonstrated in the migratory epithelial tongue. The selective presence of 67 K-keratin (67 K) in the suprabasal epithelial cell layers was interpreted as an indication of the differentiation process in rat oral mucosa. The 3H-thymidine-labelling index of basal cells increased significantly, beginning at the wound edge after 24 h. The peak of the labelling index curve was located in the vicinity of the wound after 96 h. Double labelling technique revealed 67 K-negative and 3H-thymidine-positive basal cells as well as 67 K-positive and 3H-thymidine-negative cells at the migration front. These observations support findings that migrating epithelial cells in oral wound healing derive both from undifferentiated (str. basale) and from differentiated (inferior str. spinosum) cell compartments.

Morphological demonstration and quantification of TSH binding sites in neoplastic and non-neoplastic thyroid tissues. An autoradiographic study using 125I-labelled thyrotropin.

We have developed a morphological method to portray TSH binding sites in intact tissue specimens. Frozen sections were incubated with 125I-labelled TSH so as to localise binding sites by autoradiography. The proof of specificity was substantiated by: the competitive inhibition of 125I-TSH-labelling with cold TSH, the lack of binding in non-target tissues and a lack of binding in TSH target tissues after incubation with 125I-hCG or free 125I. In applying this method to a total of 22 surgical specimens of thyroid, striking differences came to light in respect of the degree to which 125I-TSH binding occurred in the various thyroid disorders. When compared with histologically normal tissue, labelling was generally decreased in toxic adenomas, non-functioning adenomas (cold nodules), and thyroids affected by Graves' disease, whereas non-toxic colloid goitre cases clearly exhibited denser binding. Medullary and anaplastic carcinomas exhibited no specific labelling whilst binding varied in the differentiated carcinomas between no effective binding or a level resembling that found in normal thyroid tissue.

Vascular anastomoses with absorbable suture material: an experimental study.

A synthetic, monofilament, absorbable suture material, polytrimethylene carbonate, was tested to determine its suitability for use in arterial anastomoses. The material studied is a copolymer made of trimethylene carbonate and polyglycolic acid, with a retention time in the tissue of up to six months. In an experimental group of 12 mongrel dogs, using simple end-to-end anastomoses, aortic and femoral patch grafts of bovine heterograft material and iliofemoral bypass implants of 5 mm of expanded polytetrafluoroethylene prostheses were performed and arteriographically and histologically documented. Direct intraindividual comparisons were made with the absorbable (polytrimethylene carbonate) and nonabsorbable (polypropylene, expanded polytetrafluoroethylene suture) materials, a total of 108 anastomoses. No suture material-related complications such as ruptures or suture line aneurysms occurred. Polytrimethylene carbonate sutures led to less inflammation and scar tissue formation than polypropylene sutures. Complete absorption of the suture material by hydrolytic decomposition was followed by an almost complete regeneration in all layers of the vessel wall. Regeneration of the connective tissue structures of the media was noted. Initial associated reactions in the intima eventually disappeared. Both suture materials were equivalent histologically in the early months of the study, but after 10 month follow-up differences were observed, especially in the structure of the media, apart from the fact that polytrimethylene carbonate is absorbed completely after four to seven months.

Intrasplenic hepatocyte transplantation: evaluation of DNA synthesis and proliferation in auxiliary transplanted cells.

The value of isolated hepatocyte transplantation as a temporary support in acute hepatic failure remains controversial regarding the functional capacities of freshly isolated and transplanted hepatocytes. To evaluate the survival rate of intrasplenically transplanted liver cells and their response to a proliferation stimulus like partial hepatectomy, 3H-thymidine incorporation into hepatic and auxiliary transplanted hepatocyte DNA was determined. The survival rate of intrasplenically transplanted hepatocytes was evaluated by analyses of m-albumin-RNA within the splenic tissue and compared to the morphological findings. The histological results show a marked decrease (greater than x 100) of intrasplenically transplanted hepatocytes within 1 week after injection. The amount of surviving cells then remained constant for 3 months without any signs of proliferation. After partial hepatectomy a stimulation of hepatic regeneration was observed in the remaining liver tissue but not in auxiliary transplanted hepatocytes. M-albumin-RNA determination of auxiliary transplanted hepatocytes revealed a decrease of m-albumin-RNA concentration of greater than 100 times within 24 h after transplantation indicating early cell necrosis of the transplanted cells. Since intrasplenically transplanted hepatocytes underwent an early cell necrosis without any evidence for a directly postoperatively inducible cell proliferation, it is concluded that a sufficient metabolic support in acute hepatic failure cannot be taken into consideration.

Melanoma in situ (MIS) adjacent to an invasive nodular melanoma ("SSM/NM") and its metastases--DNA-cytophotometry, mitotic index, and anisokaryosis.

Malignant melanomas of the superficial spreading type usually have an intraepidermal tumour component in their periphery which frequently displays the morphological features of a melanoma in situ (adjacent MIS). It is thus comparable to exclusively epidermal melanomas; melanoma in situ (MIS). Taking 10 superficial melanomas with a nodular component ("SSM/NM") 31 adjacent MIS regions and 36 nodular melanoma components were analysed in serial tissue slides. Planimetric estimation of the nuclear areas was employed as a measure of anisokaryosis. DNA-Feulgen-cytophotometry was applied to obtain an objective variable in judging malignancy in the DNA-histographs (paraffin material). Furthermore we investigated 8 metastases of one of the malignant melanomas applying the methods described. A comparison of the epidermal with the invasive tumour components revealed an increase in the nuclear area which, however, decrease from the superior to the inferior nodular regions and which are further reduced in melanoma metastases. Anisokaryosis is evidently less in metastases compared with all primary melanomas. The nuclear DNA-content increases from the epidermal to the invasive tumour compartments and is lower in the inferior nodular regions when compared with the superior ones. No further significant differences are, however, established in the metastases. The coefficients of variability of the DNA-contents, being a potential indicator of DNA-heterogeneity reflect higher values in the epidermal tumour components compared with the nodular regions, decreasing from the superior to the inferior nodular parts of the tumour. All metastases have smaller values than the respective primary melanoma. In the DNA-histographs 75% of the intraepidermal tumour components have obvious signs of malignancy including tumour cell stem lines in 19% of the cases. 85% of the nodular regions investigated have clear signs of malignancy, 33% of which also have aneuploid stem lines. All metastases have obvious signs of malignancy and tumour cell stem lines in 50% of the cases observed. The following conclusions can be drawn from our findings: DNA-Feulgen-cytophotometry and nuclear planimetry are additional feasible methods for judging the epidermal component of a melanocytic lesion as malignant (adjacent melanoma in situ) on paraffin material. Furthermore these methods give different results in invasive nodular versus epidermal (in situ) melanoma components. Both the DNA-histographs and our immunohistochemical investigations (monoclonal antibody P 3.58) indicate the malignant potential of adjacent MIS.(ABSTRACT TRUNCATED AT 400 WORDS)