Metabolic consequences of adenosine deaminase deficiency in mice are associated with defects in alveogenesis, pulmonary inflammation, and airway obstruction.

Adenosine deaminase (ADA) is a purine catabolic enzyme that manages levels of the biologically active purines adenosine and 2'-deoxyadenosine in tissues and cells. ADA-deficient mice die at 3 wk of age from severe respiratory distress. This phenotype is progressive and is linked to perturbations in pulmonary purine metabolism. The inflammatory changes found in the lungs of ADA-deficient mice included an accumulation of activated alveolar macrophages and eosinophils. These changes were accompanied by a pronounced enlargement of alveolar spaces and increases in mucus production in the bronchial airways. The alveolar enlargement was found to be due in part to abnormal alveogenesis. Lowering adenosine and 2'-deoxyadenosine levels using ADA enzyme therapy decreased the pulmonary eosinophilia and resolved many of the lung histopathologies. In addition, genetically restoring ADA to the forestomach of otherwise ADA-deficient mice prevented adenine metabolic disturbances as well as lung inflammation and damage. These data suggest that disturbances in purinergic signaling mediate the lung inflammation and damage seen in ADA-deficient mice.

Determination of the pion charge form factor at Q2=1.60 and 2.45 (GeV/c)2.

The 1H(e,e'pi+)n cross section was measured at four-momentum transfers of Q2=1.60 and 2.45 GeV2 at an invariant mass of the photon nucleon system of W=2.22 GeV. The charged pion form factor (F(pi)) was extracted from the data by comparing the separated longitudinal pion electroproduction cross section to a Regge model prediction in which F(pi) is a free parameter. The results indicate that the pion form factor deviates from the charge-radius constrained monopole form at these values of Q2 by one sigma, but is still far from its perturbative quantum chromodynamics prediction.

[Malignant degenerative osteoneoplastic teratoma of the greater omentum (author's transl)]. / Maligne entartetes osteoplastisches Teratom des Omentum majus

A case of teratoma of the greater omentum is reported, which occurred mainly in the form of a highly differentiated osteoma. In the marginal section the tumor showed embryonal structures with signs of degeneration which were found again in metastatic colonization in lymphnodes, pancreas, liver and peritoneum. The malignant component of the neoplasm probably had its origin in the bone marrow of the osteoma.

[Coincidence of liver cirrhosis and gallstones]. / Zur Koinzidenz von Leberzirrhose und Gallensteinen.

In the years 1957-1975 we found out of 13336 autopsies in a medium-sized urban general hospital 912 cases of cirrhosis of the liver. In comparison these persons with sections of non-cirrhotic controls the frequency of gallstones was neither for the total group (33.9%) nor for the males (27.1%) significantly raised. Only in the female subgroup of cirrhotic patients we could demonstrate a significantly increased frequency of gallstones (43.5%) in comparison to the female control group (38.3%). With regards to all kinds of predominantly lithogenous alterations of the gallbladder (concrements, chronic cholecystitis, cholecystectomy) we found for the cirrhotic group and its subgroups a significant positive coincidence of both diseases. The female to male ratio for the frequency of cholelithiasis and for all kinds of lithogenous alterations of the gallbladder was 1.6:1 for the cirrhotic group and the controls.

Histiocytosis X of lungs and kidneys.

Report on a case of histiocytosis X of the lungs and kidneys. The pulmonary changes occured mainly during the fibrotic phase of the illness. In the kidneys, the process had a distinct granulomatous character with direct transition into a scarring final stage. Unusual was the considerable vascularisation of the pulmonary foci. Because of the large amount of plasma cells, particularly in the renal cortex, an allergic-hyperergic pathogenesis of the illness had to be discussed.

[Bilateral tube carcinoma with unusual involvement of the endometrium]. / Beidseitiges Tubenkarzinom mit ungewöhnlichem Endometriumbefall

Report on a case of bilateral, primary carcinoma of the fallopian tube with extensive implantation metastasis of the endommetrium. To judge by the morphological structure of the tumor in the fallopian tubes and in the endometrium, by the nature of the spreading in the mucosa of the uteruscorpus and by the morphology of the intramural fallopian tube sections, the neoplasm is, in differential diagnostic terms, demarcated by a corpus carcinoma of the uterus.

[Malignant fibrous histiocytoma of the larynx]. / Malignes fibröses Histiozytom des Larynx.

Report on two patients with (malignant) fibrous histiocytomas of the larynx. Fibrous histiocytomas of the larynx, malignant or benign are extremely rare. Because of the variety of the tissue the histiological diagnosis of these tumours--especially with regard to the tumour status--can cause great difficulties. Basing on our cases and on the few previous publications on this subject, the biological behaviour and therapy of laryngeal histiocytomas, as well as differential diagnoses of other neoplasms, are discussed. Since the (malignant) fibrous histiocytomas often recur locally, even tumours without unequivocal histological malignancy must be treated by extensive excision.

The effectivity of immunosuppressive therapy on chronic aggressive (active) hepatitis and on chronic nonsuppurative destructive cholangitis (PBC). Morphometric investigations on the portal tracts of the liver.

Morphometric investigations were carried out on liver biopsies of chronic aggressive (active) hepatitis (CAH), type IIa, chronic aggressive (active) hepatitis, type IIb, and on chronic nonsuppurative destructive cholangitis (CNDC) (primary biliary cirrhosis (PBC) in the second and third stages. The goal of the histometric analysis was a comparison of the portal tracts before and after immunosuppressive therapy with azathioprine and corticosteroids as well as with azathioprine alone. The volume and surface measurements of the portal tracts and their components showed that for an evaluation of the effectivity of the immunosuppressive therapy on CAH, along with a division into HBsAg-positive and -negative cases, a histologically determined degree of the severity of the inflammatory activity is extremely significant. The therapeutic effect is significant for all cases of CAH IIb, evident for HBsAg-negative cases of CAH IIa and slight for HBsAg-positive cases of CAH IIa. Immunosuppressive therapy of CNDC has no effect on the characteristic destruction process of the bile ducts and ductule proliferation.

[Pseudoplasmacytoma of the uterine cervix]. / Pseudoplasmozytom der Cervix uteri.

Report on a case of a 21 year old woman with a pseudoplasmocytoma of the cervix of the uterus. A tumour-like proliferation of plasma cells had developed in the area of a glandular ectopia of the cervix mucosa with a secondary erosion, which stretched continuously into the myometrium. The morphological changes were difficult to differentiate diagnostically from an extra-medullary plasmocytoma. After taking into account all histological and clinical data as well as the progression of the disease, the lesion was interpreted to be a well defined tumour-like reactive plasmocytosis of the cervix of the uterus.

[Intraductal (intracystic) papilloma of the male breast]. / Intraduktales (intrazystisches) Papillom der männlichen Brustdrüse.

Report on a case of a 26-year-old man with an intraductal papilloma of the brast developed on a preexisting gynecomastia. Simultaneously the patient is suffering from a tumor of the pituitary gland with signs of acromegaly and pathologically increased serum concentrations of STH and ACTH. The possibility that the pituitary gland tumor has indirectly induced the intraductal papilloma by hormonal stimulation is discussed.

[Malignant clear cell hidradenoma of the external auditory canal]. / Malignes klarzelliges Hidradenom des äusseren Gehörgangs.

A patient with a clear cell (malignant) hidradenoma of the external auditory canal and a detailed review of the literature are presented. Tumours of the ceruminous glands are rare. A sub-classification into distinct histological tumour types is useful with respect to therapy and prognosis. About two-thirds of all these neoplasms are malignant and the frequency of recurrence is very high (50%). Most of the adenomas are not encapsulated. The well differentiated adenocarcinomas (low grade malignancy) of the ceruminous glands can only be distinguished histologically from adenomas by their tendency to invade and infiltrate. Therapy of the ceruminous adenomas is wide excision; the treatment of carcinoma is radical block resection.

[Erysipelothrix endocarditis (author's transl)]. / Erysipelothrix-Endokarditis

Following erysipeloid a 46-year-old man fell ill with septicaemia and endocarditis. Treatment with high doses of antibiotics could not prevent his death. Infection with Erysipelothrix rhusiopathiae in man occurs through a skin lesion and only rarely leads to spreading of the agent in the body presenting as arthritis, meningitis, or endocarditis. Erysipelothrix endocarditis is a severe disease leading to widespread destruction of the involved cardiac valves. The aortic valve is most commonly involved. 16 out of 28 patients with erysipelothrix endocarditis reported in the literature died, eleven of them despite treatment with antibiotics.

[Chronic eosinophilic leukemia with eosinophilic granulomas of the lung (author's transl)]. / Chronische Eosinophilenluekämie mit eosinophilen Granulomen der Lunge

For the first time a report is given on a case of chronic eosinophilic leukemia with occurence of eosinophilic pulmonary granulomas. Even after enucleation of the granulomas eosinophilia remained in the peripheral blood and in the bone marrow, and over a period of 6 years lay at a value of above 50% of the granulocytes. The illness ended with sudden increase in the number of myeloblasts. The autopsy revealed destruction of the bone marrow by myeloblasts, immature and mature eosinophilic granulocytes as well as infiltration of the heart, liver, spleen and kidneys. On the basis of histological, cytological and histochemical examinations of the granulomas, the peripheral blood and the organs after dissection, particularly of the bone marrow, there was good reason to assume common pathogenesis of these changes; it was not however possible to completely exclude an allergically generated cause.

[A case of bleeding angiodysplasia of the colon]. / Ein Fall von blutender Angiodysplasie des Kolons.

Report on a patient with bleeding angiodysplasia of the ascending colon. The clinical course was characteristic for this kind of lesions: long-term, chronic, recurrent intestinal hemorrhages with a gradual increase of anemia. Diagnosis was complicated by lack of success in finding the source of the hemorrhage and by evidence of various pathological findings. Histologically, there were vessel variations typical for angiodysplasia and, furthermore, cholesterol emboli of the submucosal colic arteries. The latter's pathogenetic role as trigger for the hemorrhage is discussed.

[A tapeworm infection with fatal outcome (author's transl)]. / Eine tödlich verlaufene Bandwurmerkrankung (Taenia saginata).

Parasitoses of the intestinal tract are rare in Europe. Their diagnosis is difficult since the general symptoms are frequently only little pronounced or completely lacking. On the other hand, the course of the disease may be fatal. Such cases from the literature and our own observations are intended to call to memory the differential diagnosis of intestinal parasitosis.

Vascular tumors in the region of the breast.

Three vascular tumors in the breast region with different degrees of differentiation are presented. The first neoplasm is a haemangiosarcoma (of the vascular neoplasms, these tumors are the type which occur most frequently in the breast). Haemangiosarcomas show an infiltrative growth of atypical blood capillaries, frequently with formation of highly cellular and solid capillary sprouts. Ultrastructurally, the tumor cells are characterized as endothelial, also in the region of the capillary sprouts. The second tumor (an angiosarcoma in Stewart-Treves-syndrome, STS) is characterized by an intensive endothelial proliferation. Solid spindle-celled regions are also found in which the tumor cells correspond to undifferentiated mesenchymal cells, but other cells possessing properties of smooth muscle cells and pericytes may be found. The third tumor corresponds light and electron microscopically to a haemangiopericytoma of the soft tissue. The pericytic character of the tumor cells is most clearly seen in the immediate vicinity of the vessels. With increasing distance from the capillaries, the tumor cells take on the characteristics of fibroblasts. The tumors reflect the diversity of the angioplastic differentiation potential of the mesenchyme.

Morphometric investigations on the portal tracts of the liver, the differentiation of variable progression in chronic persistent hepatitis.

Morphometric investigations were carried out on the portal tracts of the liver in different forms of chronic hepatitis. The investigation groups each contained 25 liver biopsies, which were subdivided into cases with normal liver, a subsiding acute virus hepatitis, three different forms of chronic persistent hepatitis (CPH) and chronic aggressive hepatitis type IIa (CAH IIa). Determinations of the volume and surface of the portal tracts and their components enabled three forms of COH (type Ia, Ib, Ic) to be characterised. Preliminary clinical and semiquantitative histological investigations were correlated with a significant difference in the histological characteristics and prognosis. HBsAg-positive and HBsAg-negative cases showed no significant morphologically detectable differences in all grups investigated. Morphometry is suitable for investigation of pathological changes in liver tissue, especially the portal tracts.

Semiquantitative and morphometric investigations on the histopathology of chronic hepatitis non-A, non-B.

Ninety-five cases (202 liver biopsies) with chronic hepatitis Non-A, Non-B (NANB) were investigated histologically. The alterations were analysed semiquantitatively. The histological indices (e. g. volume of the portal tracts, number of acidophilic bodies) of various case groups of chronic hepatitis NANB were determined morphometrically and the results were checked for internal statistical significance and for correlations with comparison groups of chronic hepatitis B. The large number of acidophilic bodies and sinusoidal cells are the sole characteristic histological sign of hepatitis NANB which enable its differential diagnosis, especially from hepatitis B. The chronic post-transfusion hepatitis NANB has a relatively good prognosis and in 80% of the cases shows the course of a chronic persistent hepatitis (CPH). In sporadic hepatitis NANB a chronic aggressive hepatitis (CAH) is present in 60%. The frequency of cirrhosis based on an already chronic stage is 12.6%. An indication for immunosuppressive therapy of sporadic chronic aggressive hepatitis NANB can only be established individually after a sufficiently long observation of the biochemical and histological alterations.

Adenosine-mediated mast cell degranulation in adenosine deaminase-deficient mice.

Adenosine is a signaling nucleoside that has been suggested to play a role in asthma in part through its ability to influence mediator release from mast cells. Adenosine levels are elevated in the lungs of asthmatics, further implicating this molecule in the regulation of lung inflammation and suggesting that animal models exhibiting endogenous increases in adenosine will be useful for the analysis of adenosine function. Adenosine deaminase (ADA) is a purine catabolic enzyme responsible for regulating the levels of adenosine in tissues and cells. ADA-deficient mice develop lung inflammation and damage reminiscent of that seen in asthma in association with elevated adenosine levels. In the current study, we investigated the status of mast cells in ADA-deficient lungs. ADA-deficient mice exhibited extensive lung mast cell degranulation concurrent with elevated adenosine levels. ADA enzyme therapy prevented the accumulation of lung adenosine as well as mast cell degranulation, suggesting that this process was dependent on elevated lung adenosine levels. Consistent with this, treatment of ADA-deficient mice with broad spectrum adenosine receptor antagonists attenuated degranulation by 30 to 40%, supporting the involvement of adenosine receptor signaling. Moreover, these studies demonstrate the ability of endogenously generated adenosine to influence lung mast cell degranulation in a receptor-mediated manner and establish ADA-deficient mice as a model system to investigate the specific adenosine receptor responses involved in the degranulation of lung mast cells.