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Exophytic tumors of the urinary bladder were examined by means of transmission electron microscopy for the presence of neural tissue because, as yet, there has been hardly any discussion of a neuronal component in the biology of neoplasms. In the stroma and rarely in the epithelium of bladder tumors, fine nerve strands were found to be irregularly distributed. These strands comprised one to a maximum of five axons containing predominantly colocalized clear and dense-core vesicles. Immunohistochemistry revealed some nerve-like structures showing vasoactive intestinal neuropeptide (VIP) reactivity. This response and the combination of vesicle types indicate that parasympathetic cholinergic neurons contribute to the innervation of the tumors. Thus, a morphological basis for neuronal influence on the behavior of such tumors has been demonstrated.

Abstract. It is generally assumed that tumours are not innervated. However, following an accidental observation of a nerve fibre within an adenoma of the ciliary body epithelium of the eye, we have further examined two such tumours. One pigmented and one non-pigmented adenoma of the ciliary body epithelium (APCE and ANCE, respectively) that had been surgically removed from two human eyes were processed for ultrastructural evaluation and systematically screened and analysed for the occurrence of nerve tissue under a transmission electron microscope. The adenomas were composed of epithelial tumour cell strands and interposed vascularised connective tissue. Both tumours contained a small number of fine unmyelinated nerve fibres containing clear and dense core vesicles. In both adenomas, the nerve fibres were located in the tumour periphery close to blood vessels and tumour cells. In the APCE, they were also seen in more central areas. Since nerves always have a function, this finding, if confirmed in other neoplasms, may influence our understanding of such innervated tumours.

Abstract:  An 8-year-old girl had a painless circumscribed nodule in the right parotid gland for 4 weeks. A tumour (1.3 cm diameter) within the salivary gland parenchyma showed small cystic spaces with horn-like material macroscopically. The tumour tissue contained solid squamous cell formations and cystic spaces limited by multilayered squamous epithelium and covered by layers of ortho- and parakeratotic cells. The cystic spaces contained keratotic lamellae. In some areas pin-like epithelial proliferations were seen. All epithelial cells were characterized by uniform nuclei, and no atypical mitoses were seen. Keratinizated masses with partial calcification were occasionally located in the interstitial tissue and replaced by multinucleated giant cells. The tumour was classified as a choristoma and resembled a trichoadenoma. The ectodermally derived oral and salivary gland epithelium may be the source of skin-like or adnexal tumours.

A histopathological study was carried out on 27 patients with chronic inflammatory liver disease and clinical and/or biochemical evidence of cholestasis who had either mitochondrial antibodies against mitochondrial antigen fractions of 1.19 density (“PBC antigen”; 14 cases) or of 1.13 density (“CAH-PBC mixed-type antigen”; 13 cases). For comparison, the liver biopsies of 17 patients with chronic-aggressive hepatitis (CAH) and antinuclear and/or anti-smooth muscle antibodies but without cholestasis and mitochondrial antibodies, were evaluated. The 14 patients with mitochondrial antibodies against the PBC antigen showed the typical histological features of primary biliary cirrhosis (PBC). The 13 patients with mitochondrial antibodies against the CAH-PBC mixed-type antigen had heterogenous liver alterations. In 11 cases highly active CAH and/or active postnecrotic cirrhosis (AC) were found both with augmented ductular proliferation. Some of these cases showed distinct criteria of PBC as early bile duct lesions or absence of regular bile ducts. The liver histology of one case corresponded to classical PBC; another case to chronic persistent hepatitis. The CAH-patients without cholestasis and mitochondrial antibodies only occasionally showed bile duct proliferation. In conclusion, a high correlation was found between mitochondrial antibodies against the CAH-PBC mixed-type antigen and highly active CAH or early AC with augmented ductular proliferation. This represents an overlapping of CAH and PBC. In contrast, the cases with antibodies reacting to the PBC antigen showed the slowly progressive liver changes of typical PBC.

Summary The influence of the autonomous nervous system on the ultrastructure of the parotidean acini and the terminal neuraxon was tested on 70 Wistar rats under the following experimental conditions: sympathetic stimulation (Aludrin 2 mgm/100 gm of body weight daily), parasympathetic stimulation (Pilocarpine 0.2 mgm) sympathicolysis (Guanaclin 5 mgm), parasympathicolysis (Scopolamine 0.2 mgm) and sympathico-parasympathicolysis (Guanaclin 5 mgm and Scopolamine 0.2 mgm). The following aspects were of primary importance to the comparative analysis: changes in the secretory cycle and cell organelles; a comparison between the acinar structure and changes in the neuraxons; the relationships of the findings to human sialadenosis. In addition, morphometric measurements of the diameters of the acini were carried out in all test groups.

30 parotid biopsies of patients with sialadenosis-a symmetrical, painless, non-inflammatory, recurrent parotid swelling-were studied by electron microscopy. The patients suffered from different diseases, such as diabetes mellitus, liver diseases, hypertension and other affections. Parotid biopsies from 25 patients with slight parotitis or with oral cancer were used as controls. Morphometric studies reveal that the parotid swelling is caused by an enlargement of acinar cells. In controls the average diameters of the acinar cells are 30 to 40 µ. In sialadenosis the diameters are enlarged to 50 to 70 µ, in some cases to a maximum of 100 µ.

Dysgenetic (bilateral) polycystic parotid glands present a rare pathological picture which has not yet been described in detail. In the Salivary Glands Register (Institute of Pathology, University of Hamburg) 360 non-tumourous cysts were registered (from a total of 5739 cases of disturbances of the salivary glands for the years 1965–1979). Among them there were 2 cases of polycystic parotid glands. The analysis of the observations in these cases led to the following conclusions concerning polycystic parotid glands:1.The disease may be unilateral or bilateral. The cysts, which are not uniform in size, are bounded by duct epithelia exhibiting various sorts of differentiation (striated duct and intercalated duct epithelium, primitive epithelial buds) and containing secretion products, spheroliths and microliths. Regressive focal epithelial alterations with desquamation occur. The remains of the glandular parenchyma can be found among the cysts.2.The cystic change is due to a developmental malformation of the duct system, in particular a disturbance of ramification and canalization. Evidence for this conclusion can be found in the spur-like septation of the cysts and the hourglasslike indentations.3.Polycystic parotid glands can be compared with cystic malformations of the pancreas (cystic pancreas) or the lung (cystic lung).4.This disease must be distinguished from congenital sialectasias of the parotid glands, from cysts of the salivary ducts and from lymphoepithelial cysts. The criteria for differential diagnosis are presented.

Langerhans cells in oral mucosa and epidermis have been identified using antibodies to intermediate filament proteins in conjunction with antibodies to T6 and HLA-DR antigens. Langerhans cells, lymphocytes and melanocytes are positive when tested with antibodies to vimentin, and negative with antibodies to prekeratin. Langerhans cells are also positive with antibodies directed against HLA-DR and T6 antigens. In contrast keratinocytes are positive for prekeratin and negative for vimentin, HLA-DR and T6. These methods provide a useful tool for the identification of Langerhans cells at the level of the light microscope, and have been used to show changes in the number and arrangement of these cells in squamous cell carcinomas of skin and oral mucosa, and in inflammatory conditions.

Embryonal tumors are a neoplastic proliferation of cells of organ rudiments. Morphologically, these tumors are similar to the developmental stages of these organ rudiments. Embryonal tumors of the salivary glands have not been previously described. In the salivary gland register, reviewing the years 1965–1982 (n=8043), we diagnosed 2,878 tumors of the salivary glands, of these 73 were tumors in children. One case was a malignant epithelial tumor in a 12-year-old boy, which showed the criteria of an embryonal carcinoma in light- and electron microscopy. The tumor revealed solid undifferentiated areas, epidermoid structures with keratinization and acinic structures. Immunhistochemically, the better differentiated epidermoid cells reacted positively with anti-CEA and anti-keratin, the acinic cells were positive with anti-amylase. The ultrastructure was characterized by primitive ductular epithelial cells and acinic cells with their typical morphological features. The embryonal carcinoma has to be distinguished from undifferentiated carcinomas of the salivary glands, which consist of primitive ductular structures only. The failure to detect other tumor markers (lactoferrin, tissue polypeptide antigen) indicates that poorly and well differentiated areas can exist simultaneously in embryonal carcinomas.

Distribution and redistribution of intra- and pericellular calcium was investigated in the parotid gland of rats under secretory stimulation and hypercalcaemia. The effects of hypercalcaemia and secretory stimulation and of the combination of both were compared. Calcium content was determined by atomic absorption spectrometry. Calcium distribution within the tissue was demonstrated by light microscopical (GBHA) staining and electron microscopical (pyroantimonate method) cytochemistry in combination with X-ray microanalysis. Typical calcium depot sites were the basal and cellular membranes, the calcium buffer organelles (i.e. mitochondria) the secretory granules and the acinar lumina. After stimulation (by isoprenalin) a decrease of calcium-enriched secretory granules and a depletion of intracellular calcium buffer organelles occurred. During hypercalcaemia (induced by dihydrotachysterol), a calcium overloading of the cell membrane and intracellular buffer organelles without calcification was observed. Combined stimulation and hypercalcaemia induced an excessive calcium overloading of all intra-and extracellular calcium depots with excessive calcium release into the acinar lumina resulting in calcium phosphate aggregates and stone formation. Secretory stimulation and simultaneous hypercalcaemia exert potentiating effects on intracellular and intraluminal calcification proposing an importance for pathogenesis of human sialolithiasis.

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.

Six cases of adenoid cystic carcinoma of salivary glands have been examined with antibodies specific for either keratin or vimentin. Tumor cells in all six cases showed coexpression of keratin and vimentin.

Specimens of the human parotid gland were studied by immuno-electron microscopy for the presence of amylase. Both the protein A-gold technique and the biotin-avidin-gold technique were used on the same specimens. Different fixations were tried. Amylase was detected in the zymogen granules in high amounts. This enzyme could even be seen in glutaraldehyde fixed and routinely embedded material. The subcellular localization of this enzyme opens a new field of functional morphological studies and studies in special tumours including acinic cell carcinomas.

Antibodies to different intermediate-sized filament proteins can distinguish cells and tissues of epithelial, mesenchymal, muscle, astrocytic and neural origin. Antibodies to prekeratin, vimentin and desmin have been used to distinguish cells of epithelial, mesenchymal and muscle origin in the normal human parotid gland, and in addition to study some common tumors of this gland. Prekeratin-positive and vimentin-positive cells are found among the tumor cells in the pleomorphic adenomas. In contrast the tumor cells of the mucoepidermoid tumors and squamous cell carcinomas are prekeratin-positive but vimentin-negative.

The presence of CEA in parotid gland tumours was studied by immunohistochemical methods. 52 cases were analysed. 7 of 8 adenocarcinomas, 3 of 5 cystadenocarcinomas, 3 of 4 adenoid cystic carcinomas and all 3 salivary duct carcinomas were positive for CEA. 5 of 8 squamous cell carcinomas and 9 of 21 carcinomas in a pleomorphic adenoma were also positive for CEA.

Lactoferriin and lysozyme, parts of the non-specific defense system, were studied in normal and diseased parotid glands, using the immunohistochemical PAP-method. 31 normal and inflamed glands were investigated. The presence of lactoferrin and lysozyme was demonstrated in the acinar cells and some duct cells. The amount of these substances was increased in obstructive parotitis. The 52 carcinomas showed a distinct distribution pattern for lactoferrin (positive cases: adenocarcinomas 5 of 8; cystadenocarcinomas: 3 of 5; adenoid cystic carcinomas 2 of 4; salivary duct carcinomas 2 of 3). Some of the carcinomas in pleomorphic adenomas were positive for lactoferrin. Squamous cell carcinomas and anaplastic carcinomas were constantly negative.

Summary 52 salivary adenocarcinomas of the years 1965–1980 from the files of the Salivary Gland Registry, Institute of Pathology, University of Hamburg, were evaluated retrospectively with regard to clinical follow up and cytochemically assessed nuclear DNA content. The age distribution showed a peak from the 6th to 8th decade (range 3 to 87 years). The m:f ratio was 1:1.36, the mean age was 59.3 years. Over 80% of the tumours were located in the major salivary glands. The clinical course was characterized by metastases present at initial diagnosis (16 cases), subsequent development of metastases (9 cases), local recurrence (15 cases) or death from tumour (10 cases) and was related to differentiation, grade 3 tumours showing the worse clinical courses. In 37 cases, nuclear DNA content was determined by a single scanning cytophotometry device. 28 cases were diploid, 9 were atypical. The clinical course was significantly related to the histogram type, atypical tumours showing a dismal prognosis.

Summary: Parotid and submandibular glands of miniature pigs were exposed to 36 Gy X-irradiation given as 66 Gy in 3 weeks. Half of the animals received orciprenaline and carbachol before each dose. The effects were analysed 6 months later by light and electron microscopy. Ultrastructural examination showed less change in the pretreated glands. Semi-quantitative light microscopic data confirmed the significance of the differences. Acinar cells of both glands were significantly more numerous (P<0.01) and the cells were better preserved (P<0.01) in the pretreated group. The effect was more pronounced in the parotid gland, which appeared almost normal. Intercalated ducts of the parotid glands (P<0.01) and striated ducts of the submandibular glands (P<0.05) showed less change in pretreated animals. The findings confirm the radioprotective effect of pharmacologically induced degranulation of acinar cells. The biological effects of the radiation schedule (cumulative radiation effect value 18.76) as well as the dosage of orciprenaline and carbachol are within the normal range of medical treatment. Similar results may be expected from future studies in man.

16 human parotid glands from the 10th to 40th week of pregnancy were studied by light and electron microscopy. Three developmental stages of the gland can be distinguished by analogy with findings in animals: 1. The first stage concerns the primordium and the subsequent development of the gland until the end of the 3rd embryonal month. In this stage the gland consists of bilaminar, dichotomously ramified duct proliferations. The lumenal aspect of the ducts are limited by ciliated embryonal epithelial cells. Myoepithelial cells are arranged between the epithelial cells and the basement membrane at the periphery of the duct proliferations. 2. In the second stage further differentiation of the gland occurs, by arrangement in to lobules. Within the gland lobules, functional units originate in dichotomous ramification and canalisation. At the end of the second stage differentiation of the excretory ducts takes place. Myoepithelial cells are observed only in the terminal duct system. From the 30th week of pregnancy endoplasmic rectiulum and a supranuclear Golgi apparatus is established in the cells of the acini. 3. In the third stage further structural maturation begins. In the 35th week of pregnancy the first secretory granules are formed in acinic cells. Up to the 40th week of pregnancy further differentiation of these cells and intercalated ducts occurs. Differentiation of striated ducts has not been observed prenatally. Myoepithelial cells exist in the terminal duct system and in the acini. Based on these observations, comparative studies of the ultrastructural cytodifferentiation of salivary gland tumours seems to be possible.

The WHO classification of salivary gland tumours distinguishes three types of monomorphic adenomas (cystadenolymphoma, onkocytoma and ‘other types’). In the material of the salivary gland register (1965–1978), 362 monomorphic adenomas were investigated (252 cystadenolymphomas, 5 onkocytomas and 105 cases of ‘other types’). In the tumour group of ‘other types’ the ‘salivary duct adenoma’ represented the most frequent type (79 of 105 cases=75%). The following determinations were made for the definition and differential diagnosis of the salivary duct adenoma:1.The salivary duct adenoma was localized predominantly in the parotid gland (57 cases=72%), in the other cases (22 cases=28%) in the minor salivary glands (especially upper lip, cheek and palate). The age peak is in the seventh decade, the female sex predominates with 65%.2.In the histologic architecture trabecular, tubular and cystic duct formations can be distinguished which are limited by a PAS-positive basement membranelike substance at the outside. There is no mucoid or chondroid stroma such as is found in pleomorphic adenomas.3.The cytologic structure is characterized by basal reserve cells (basal cells) at the outside and by variably differentiated duct epithelias at the inner side with secret production into the duct lumen. Within the trabecular lumenless formations so-called transformation cells are found.4.The histologic and cytologic differentiation is comparable with the embryonal stages of the salivary duct system as well as with mature parts of salivary ducts. Tubular and cystic structures represent higher stages of maturation and are found more frequently than trabecular formations which correspond to the early stages of the salivary duct's embryogenesis.5.The term ‘salivary duct adenoma’ comprises all monomorphic adenomas with ductlike structures and replaces the many synonyms previously used (‘trabecular, tubular, canalicular adenomas; cystadenomas’). Rare types of adenoma which were especially described in the minor salivary glands (‘papillary cystadenoma; sialadenoma papilliferum, intraductal papilloma’) are also included under the term ‘salivary duct adenoma’.6.The basal cell adenoma is subclassified as a special variant of the salivary duct adenoma. The term ‘basal cell adenoma’ is only used for adenomas which possess the characteristic structure of basal cells and have a distinctly limited stroma. We found 19 basal cell adenomas (=18%) in the group of monomorphic adenomas of ‘other types’.7.In differential diagnosis, the salivary duct adenoma must be distinguished from the stroma-poor pleomorphic adenoma and from other rare monomorphic adenomas (sebaceous lymphadenoma, clear-cell adenoma, mucous-producing adenoma, etc.).

Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.

In 21 patients who had undergone total pancreatectomy for pancreatic head carcinoma, the uninvolved pancreas was examined with regard to the type, incidence and regional distribution of duct epithelial proliferation. The results were compared with those in 37 operative specimens from patients with chronic pancreatitis, in 46 normal pancreases from autopsies and with findings in experimental pancreatic carcinogenesis.

Cystadenolymphomas (CAL) of the parotid gland are variable in their epithelial differentiation and the ratio of the epithelial tumor component to lymphoid stroma. Two hundred and seventy five cases of CAL from the files of the Salivary Glands Register of the Institute of Pathology, University of Hamburg (1965–1979) were analysed. Their pathogenesis from parenchyma included in regional lymph nodes is discussed. The following Subclassification was established.1.Depending on to the ratio of epithelial tumor component to lymphoid stroma, three subtypes were distinguished. Subtype 1, “typical CAL” with an epithelial tumor component of 50%, amounted to 77% of all cases of CAL studied. Oncocytic differentiation and focal metaplasia to goblet cells or squamous epithelium was also found. 13.5% of CAL were classified as subtype 2, “stroma-poor CAL” with an epithelial tumor component of 70 to 80%). The tumor structure was similar to that of an oncocytoma in places. Two per cent of the CAL were in subtype 3, “stroma-rich CAL” with an epithelial tumor component of only 20 to 30%. Subtype 3 was found solely in men. The average age at presentation (61 years) was slightly lower than that of all the cases studied (65 years).2.In 7.5% of the cases large areas of squamous cell metaplasia and regressive changes was found within a CAL. These cases were classified as subtype 4 (“metaplastic CAL”). The average age was 67 years. The case histories showed that 20% of these metaplastic CAL had previously been irradiated.3.Bilateral CAL was found in 7.5% of the cases. In 4% multifocal CAL occurred in the parotid gland unilaterally. Recurrences were observed in 2% of all CAL.4.Carcinoma in CAL is rare (we found two cases in our own material). In 50% of all cases reported radiotherapy was mentioned in the case histories.5.Malignant tumors coincident with CAL were recorded in 3% of the cases.6.The lymphoid stroma showed reaction patterns similar to those of the regional lymph nodes. These included granulomatous changes (foreign body granuloma with cholesterol deposits, tuberculosis) and tumor metastases. In the neighborhood of oncocytic tumor epithelium focal accumulations of plasma cells forming IgA and IgG were found.

Immune sera against total keratin and keratin polypeptide subunits were induced in guinea pigs, using the different bands of SDS polyacrylamide gel electrophoresis of fibrous proteins of stratum corneum, derived from normal human epidermis.

IgA-containing plasma cells in the periductal gland tissue are part of the special secretory immune system of the salivary glands. The reaction of Ig-containing plasma cells (localization, frequency, specific Ig-content) was analyzed by the indirect immunoperoxidase method in chronic recurrent parotitis (9 cases), chronic myoepithelial parotitis (benign lymphoepithelial lesion, Sjögren's syndrome; 8 cases), and malignant lymphoma associated with chronic myoepithelial parotitis (11 cases). The following results were obtained:1.In chronic recurrent parotitis, parallel to the increase in IgA in the salivary secretion, a marked multiplication of IgA-containing plasma cells was found in the inflammatory infiltrate and the remaining non-inflamed periductal parenchyma of the parotid gland. In the marginal zone of inflammation, a slight increase of IgG-containing plasma cells was also observed.2.In chronic myoepithelial parotitis, the total plasma cellular infiltration was slightly less distinct than in chronic recurrent parotitis. The most remarkable increase in Ig-containing plasma cells developed in the marginal zones — away from the myoepithelial cellular islands — as well as in the area of ductular proliferations, and was characterized by a strong increase of IgG-containing plasma cells. At the same time, a slight increase of IgM-containing plasma cells was observed. No plasma cells were found in the myoepithelial cellular islands.3.In the malignant lymphomas associated with myoepithelial parotitis, which were mainly highly differentiated lymphomas (immunocytomas, centrocytic-centroblastic lymphomas) and rarely poorly differentiated immunoblastic lymphomas, there was a distinct decrease of IgG-containing plasma cells when compared with the numbers in this group without lymphoma.

Myoepithelial and luminal cells of human exocrine glands can be positively identified with two different monoclonal antibodies. Myoepithelial cells including those of the salivary gland, mammary gland and sweat gland are positively identified by an antibody CKB1. This antibody does not stain luminal cells, but stains the basal cell layer of certain human stratified epithelia and a few basal cells in simple epithelia. Thus myoepithelial cells and basal cells have certain common features. Luminal cells can be positively stained with the CK5 monoclonal keratin antibody specific for keratin polypeptide 18; this antibody does not stain myoepithelial cells. Of interest is that CKB1 also appears to stain basal and suprabasal cells in certain hyperplastic conditions.

The distribution of various tissue antigens was studied in mucoepidermoid carcinomas (n=74) and acinic cell carcinomas (n=38) by means of immunocytochemistry. Mucoepidermoid carcinomas were generally positive for cytokeratin and showed double expression for cytokeratin and vimentin in 31.1% and triple expression for cytokeratin, vimentin and GFAP in 24.1%. CEA was studied using new monoclonal antibodies which distinguish between epitopes that are present on CEA alone and those which are present on nonspecific cross reacting antigens as well. The monospecific CEA antibody was completely negative in mucoepidermoid carcinomas, while nonspecific cross reacting antigens (NCAs) were positive in mucoepidermoid carcinomas to a varying degree. Alpha 1-antichymotrypsin, a marker formerly thought to be specific for tissues for histiocytic origin, was positive in 85.1% of mucoepidermoid carcinomas. Twenty three percent of mucoepidermoid carcinomas showed focal infiltration by S-100 positive dendritic stromal cells, tumour cell being negative. Leu-M 1 antigen was positive in 58.1% of mucoepidermoid carcinomas. Acinic cell carcinomas were generally positive for cytokeratin and in single cases showed double expression for cytokeratin and vimentin and triple expression for cytokeratin, vimentin and GFAP. Monospecific CEA antibody positivity could be demonstrated in 24.2% of acinic cell carcinoma, while nonspecific cross reacting antigens (NCAs) were positive in acinic cell carcinomas to a varying degree. Alpha 1-antichymotrypsin was positive in 97.4% of acinic cell carcinomas. 2.5% of acinic cell carcinomas showed focal infiltration by S-100 positive dendritic stromal cells, 2.5% of acinic cell carcinomas were positive for S-100 protein with no dendritic stromal cells present. Leu-M 1 antigen was positive in 86.8% of acinic cell carcinomas. For S-100 protein and Leu-M 1, no correlation with the clinical course, as reported previously for other tumours, could be observed.

Abstract:  Long-term treatment with proton pump inhibitors in patients with Helicobacter pylori gastritis can lead to atrophic changes in the corpus mucosa. What is still unclear, however, is whether this atrophy can regress in response to Helicobacter pylori eradication. We report on a male patient with Helicobacter pylori gastritis receiving long-term treatment (4 years) with omeprazole for gastro-oesophageal reflux disease, who developed autoaggressive gastritis with progressive atrophy, hypochlorhydria, hypergastrinaemia and nodular ECL-cell hyperplasia. To determine whether these changes might be induced to regress, Helicobacter pylori eradication therapy was administered. Ten months after Helicobacter pylori eradication autoaggressive lymphocytic infiltrates were no longer detectable, and the glands in the corpus mucosa had normalised despite continued treatment with omeprazole – a finding that was confirmed at two further follow-up surveys performed at 6-month intervals. This case report shows that atrophy of the corpus mucosa developing under long-term treatment with a proton pump inhibitor can be cured by eradicating Helicobacter pylori.

Unter der Arbeitshypothese, daß dem sog. Mantelgewebe der Mamma eine besondere Reaktionsbreite und Jugendlichkeit innewohnen könnte, wurden die menschlichen Brustdrüsen bei leukämischen Erkrankungen einer systematischen Untersuchung unterzogen.

Die orthologischen Veränderungen des qualitativen Inselzellbildes im Altersablauf sowie seine Abweichungen bei zahlreichen Krankheits-gruppen wurden an 269 menschlichen Pankreas aller Altersstufen mittels der modifiziertenBensley-Terbrüggenschen Färbemethode nachgeprüft und mit den bisherigen Untersuchungsergebnissen kritisch verglichen. Dabei ergaben sich folgende Befunde hinsichtlich der Orthologie der A-B-Relation im menschlichen Inselapparat:a)Bei Frühgeburten mens VI–VIII fand sich ein Mittelwert der A-B-Relation von 1:0,9, bei Frühgeburten mens IX von 1:1,2, bei Frühgeburten, die länger als 2 Monate am Leben geblieben waren, ein Mittelwert von 1:1,3.b)Bei Säuglingen betrug die A-B-Relation zunächst etwa 1:1,2 und stieg am Ende des 1. Lebensjahres auf 1:2. Eine Abhängigkeit des qualitativen Inselzellbildes von den Blutzuckerschwankungen der Neugeborenenperiode konnte nicht festgestellt werden.c)Im Kindesalter blieb der Mittelwert relativ konstant bei 1:2 und ließ keine Abhängigkeit von den Streckungsphasen erkennen.d)Das qualitative Inselzellbild der Erwachsenen zeigte größere Schwankungen (1:1,3–4,6) bei einem Durchschnittswert von 1:3,5. Geschlechtsunterschiede bestanden nicht. Bemerkenswert ist ein bisher nicht genügend berücksichtigter Abfall der A-B-Relation im höheren Alter bis auf Werte von 1:2.

Bei der Vielgestaltigkeit des klinischen und morphologischen Erscheinungsbildes der Cytomegalie und der Schwierigkeit einer differentialdiagnostischen Abgrenzung gegenüber Toxoplasmose, Erythroblastose, Lues und anderen fetalen und kindlichen Infektionskrankheiten wurde an Hand einer systematischen Untersuchung von 250 Kindersektionen (Frühgeburten Mens VI/IX sowie Säuglinge und Kleinkinder bis zu 2 Lebensjahren) der Frage nachgegangen, welche diagnostische und pathogenetische Bedeutung die Häufigkeit der Syntropie von Cytomegalie und anderweitigen Organveränderungen besitzt. Die Untersuchung brachte folgendes Ergebnis:1.Von 250 kindlichen Sektionsfällen wiesen 33 (= 10%) eine Cytomegalie auf mit Lokalisation in der Parotis (30mal), Glandula submandibularis (15mal), Glandula sublingualis (2mal), dem Pankreas (2mal), der Lunge (3mal), Leber (1mal), Niere (9mal) und Schilddrüse (2mal). In den übrigen untersuchten Organen konnten keine cytomegalen Zellveränderungen gefunden werden.2.Der Untersuchung der bei der üblichen Sektionstechnik meist nicht herauspräparierten Parotis kommt infolge des häufigen Vorkommens der Cytomegalie an dieser Stelle (100% im eigenen Untersuchungsgut) eine große Bedeutung für die Diagnostik der Cytomegalie zu.3.Aus der Häufigkeit der Syntropie von plasmacellulärer interstitieller Pneumonie (mit Pneumocystis Carinii) und Cytomegalie (in 80% der 33 eigenen Cytomegaliefälle, dagegen nur in 5% der 217 Kontrollfälle ohne Cytomegalie) ergibt sich ein wichtiges pathognomonisches Hinweiszeichen für das Vorliegen einer Cytomegalie bei bestehender interstitieller Pneumonie, ohne daß die Beziehungen der Pathogenese beider Krankheiten vorerst zu klären sind.4.Desgleichen kann das morphologische Bild der Erythroblastose (persistierende Blutzellherde, Hyperplasie von Leber und Milz, Ikterus) nach Ausschluß einer Rh- und ABO-Unverträglichkeit ein wertvolles pathognomonisches Hinweiszeichen für eine bestehende Cytomegalie sein (in 17 von 33 eigenen Cytomegaliefällen).5.Bei generalisierter Cytomegalie findet sich zuweilen eine nekrotisierende und verkalkende Encephalitis mit Hydrocephalus und Porencephalie (mitunter auch mit Einschlußkörperbildung), die differential-diagnostisch von der Toxoplasmose durch die negativen serologischen Reaktionen und den fehlenden Erregernachweis abgegrenzt werden kann.6.Den übrigen Organveränderungen (interstitielle Entzündung der parenchymatösen Organe u. a.) kommt nur ein sehr begrenzter pathognomonischer Wert zu, zum Teil handelt es sich um eine zufällige Syntropie ohne jede diagnostische Bedeutung.7.Die typischen cytomegalen Zellveränderungen sind auf Grund ihrer besonderen morphologischen Struktur krankheitsspezifisch, während ihre Virusspezifität beim Menschen noch nicht sicher bewiesen ist.

A study was made of the calciphylactic reaction in the salivary gland of the white rat under varying experimental conditions, using a total of 80 female animals. Dihydrotachysterol was applied orally (1–2 mg) to accelerate calcium metabolism. Salivary gland activity was conditioned by treatment with serotonin (3 mg, twice daily, s.c.) or Aludrin (20–25 mg daily, i.p.) or potassium iodide (10 mg, once or twice daily, i.p.). Other animals received chrome chloride (10 mg, i.v.) as a calcifying agent.

Ratten erhielten am ersten Versuchstag als sensibilisierende Substanz („sensitizer“) 3–5mg Dihydrotachysterin in öliger Lösung (A. T. 10®) mit der Schlucksonde, am zweiten Versuchstag Alloxan als 5% ige wäßrige Lösung intraperitoneal. In allen Versuchsgruppen mit Einwirkung von Dihydrotachysterin und Alloxan kam es zur Ausbildung eines typischen Alloxan-Diabetes. Eine Inselverkalkung trat jedoch nur dann auf, wenn die Tiere nach der Sensibilisierung in der kritischen Zeitperiode bis zur Alloxaneinwirkung gehungert hatten. Histochemisch ging die Insel Verkalkung mit einer Anreicherung saurer Mucopolysaccharide, einer verstärkten Aktivität der sauren und alkalischen Phosphatase sowie einem Aktivitätsverlust der Succinodehydrogenase in den Inseln einher. Für die Auslösung einer Inselcalciphylaxie spielt der Funktionszustand der Inselzelle und die Zeitperiode zwischen Sensibilisierung und Intoxikation eine Rolle. Die Mucopolysaccharid-Calcium-Komplexe entstehen durch eine Kettenreaktion unter Mitwirkung enzymatischer Faktoren, besonders der Phosphatasen.

We compared the ultrastructure of human parathyroids from three control subjects, three patients with secondary hyperparathyroidism, and three parathyroid adenomas. As characteristic features of normal human parathyroids we found complex lipid bodies and numerous individual lipid vacuoles. Various types of electron dense granules could be differentiated; a possible line of development (prosecretory granules, secretory granules, lysosomal crinophagy, lipid vacuoles) is suggested.

An über 900 Sektionsfällen wurde eine vergleichende pathohistologische Untersuchung der großen Kopfspeicheldrüsen (Parotis, Submandibularis, Sublingualis) und Tränendrüsen im Hinblick auf die Frage vorgenommen, ob es eine charakteristische gewebliche Reaktionsform in dieser Drüsenregion beim Rheumatismus gibt. Unter den nach einem einheitlichen Befundschema beurteilten Beobachtungen fanden sich 6 Fälle, die ein Gewebsbild besonderer Eigenart mit folgender Befundtrias boten: starke interstitielle lymphoide Zellinfiltration, deutliche Gerüstsklerose und Parenchymalteration (Atrophie der Endstücke, Gangdyschylie, myoepitheliale Inseln). Es handelte sich dabei um Krankheiten des rheumatischen Formenkreises, die teilweise auch die klinischen Symptome eines Sjögren-Syndroms gezeigt hatten. Die Gewebsveränderungen wurden zunächst nach der qualitativen Spezifität der Einzelmerkmale analysiert und dabei festgestellt, daß den myoepithelialen Inseln besondere diagnostische Beweiskraft zukommt.

Untersucht wurde die Parotis, Submandibularis und Sublingualis von 43 jungen weißen Ratten und 20 weißen Mäusen, die tägliche intraperitoneale Injektionen von 0,5 mg Äthionin pro g Körpergewicht (Ratten durchschnittlich 650 mg Äthionin, Mäuse 240 mg Äthionin) erhalten hatten. Einige Ratten bekamen zusätzlich Pilocarpininjektionen. Die stärksten Veränderungen fanden sich bei weiblichen Ratten in der 2. Versuchswoche.

Morphological and ultrastructural changes in the salivary glands were investigated after treatment with daily intraperitoneal injections of ethionine (0.2 mg/g body weight) for 10 days in female Wistar rats. Initial changes are the vacuolization of the rough endoplasmic rediculum. Later the membrane-bound ribosomes disappear, partial damage of endoplasmic membranes develops, osmiophilic cytoplasmic condensations appear, the Golgi apparatus becomes vesiculated, enzyme granules vanish and the nuclei change. The morphological alterations induced by ethionine occurred much earlier in the parotid gland than in the submandibular gland. In addition, cristalloid particles appeared in mucoid vaculoes of submandibular gland after eight days treatment with ethionine. The morphological findings after ethionine treatment represent metabolic impairment of secretory and enzymatic metabolism in the salivary glands.

The frequency, intensity and localization of lime incrustations in the annulus fibrosus and the left valvular apparatus are studied in 491 human hearts of all age groups and the disposition by age and sex is recorded. An experimental calcinosis of the cardiac frame was induced in 149 female albino rats by using the model of calciphylaxis. One mg dihydrotachysterine was given orally on the first day of the study. In addition, the single groups of the study received ferrous dextran (10 mg i.v.) or metallic salts (2 mg cobalt chloride or 100–150 mg magnesium chloride or 10 mg manganous chloride or 10 mg zinc acetate daily i.p.) throughout a period up to 17 days. The following results were obtained:1.In human hearts, lime incrustations are found in the aortic annulus in 40%, in the aortic valve and in the mitral annulus in 22% and in the mitral valve in 8%. The earliest lime incrustations in the mitral and the aortic annulus are recorded in men aged 30, in the aortic valve in men aged 40 and in the mitral valve in men aged 50. In men over 60, calcification of the aortic valve is noted in 50% of the examined cases, in men over 80, in 80–100%. On the other hand, the calcification rate of the mitral annulus and the aortic valve was 30–40% and of the mitral valve about 15% in men over 70. Lime incrustations in the mitral annulus develop significantly earlier and more intense in women than in men. With regard to the more intense calcifications the mitral annulus of women is calcified four times more commonly than that of men, the mitral valve nearly three times.2.In rats, analogous calcifications can be produced in the annulus fibrosus as well as in the aortic and mitral valves. The calcifications of the mitral annulus are considerably reduced by zinc acetate and manganous chloride. The initial changes during the course of the calciphylactic reaction are an enlargement of the fibroblasts, a swelling of the collagenous fibres, a decomposition of elastic fibres and an increase of acid mucopolysaccharides. From the 4th day of the study an incrustation of lime salts is seen with the highest rate on the 9th. day.

The carcinoma of the ducts of the salivary glands, according to light- and electronmicroscopic analyses of 8 cases, corresponds to an epithelial-myoepithelial carcinoma of the intercalated ducts. The intercalated duct carcinoma is a rare and special type of salivary gland carcinoma (it represents about 0.5% of all epithelial tumors of the salivary gland; its highest incidence is in the 7th decade; it occurs more frequently in women). The tumors consist of two cell types, with organoid structures. There are on the one hand dark cells with few organelles forming the inner layer of the tubules (similar to the intercalated ducts), and on the other clear cells rich in organelles and glycogen that form the outer layer with myoepithelial differentiation (myofilaments, endoplasmatic reticulum, pinocytosis vesicles, glycogen- and lipofuscin granulas).

The ultrastructure of myoepithelial sialadenitis (“benign lymphoepithelial lesion”, Sjögren's syndrome, Mikulicz's disease, autoimmune sialadenopathy) was investigated in 4 cases (6 parotid biopsy specimens). The study showed that the islands of myoepithelial cells are derived from the intercalated ducts. In addition to myoepithelium the islands include epithelium belonging to these ducts and inflammatory cells (lymphocytes, plasma cells, mast cells, reticulum cells). In their initial stage the islands are characterized by (1) intercalatedduct epithelial cells arranged around (2) the remains of the duct lumen; (3) myoepithelial cells situated more peripherally and (4) basement membrane limiting the complex externally. Later there is destruction of the duct epithelium, proliferation of the myoepithelium and infiltration by lymphocytes and histiocytes. In the final stage extensive hyaline transformation occurs. Besides myofilaments the myoepithelial cells produce basement-membrane-like substances that are extruded into the interstitium. Myoepithelial sialadenitis is regarded as an immunologically induced inflammatory reaction.

In 24 Wistar-rats the right Stenon duct was tied off and the gland tissue studied by light- and electron microscopy at different time intervals after duct ligation (6 hours to a maximum of 6 months). The left parotid gland was used for comparsion. The earliest and most pronounced structural changes were found at the highly differentiated acini of the gland (fragmentation and vesicular transformation of the endoplasmatic reticulum, focal cytoplasm necroses, osmiophilic inclusions, mucoid transformations of the secretory granula).

Long-term treatment of hypertension with the adrenergic blocking agent Guanacline has the side effect of severe pain in the parotid gland which starts on chewing. To gain some insight into this clinical symptom five parotid-gland biopsies were taken from hypertensive patients after treatment with Guanacline and investigated by light and electron microscopy. Biopsies from patients without hypertension and not treated with Guanacline were studied as controls.

Eleven biopsies of the parotid gland were studied by electron microscopy after guanacline medication and in untreated patents. The sympathetic nervous system predominates in the innervation of the normal human parotid gland. Ultrastructurally no terminal axon was observed to penetrate the basal membran reaching the myoepithelial cell or acinar cell. The smallest distance between the terminal axon and effector cell is 1 000–1 500 Å. After immersion fixation with potassium permanganate two kinds of synaptic vesicles were demonstrable: granular (adrenergic) and agranular (cholinergic) vesicles, both of which had a diameter of about 500 Å.

The effect of Guanacline on the autonomic innervation of the parotid gland of rats was studied in 70 female Wistar rats by means of electron microscopy and a cytocytochemical method (demonstration of catecholamine fluorescence after Falck). Guanacline was given intraperitoneally in a daily dose of 50 mg/kg or. 100 mg/kg body weight. To study the possible influence of hypertony on the changes in the autonomic nervous system, observations were also made on rats with hypertony with and without administration of Guanacline for comparison. In addition, the ganglion cervicale superior was studied by the same methods. The model of the ultrastructural alterations is characterized by the following signs: destruction of the granular vesicles in the terminal axons, degeneration of the mitochondria and appearance of lysosome-like bodies both in the axons and in the cytoplasm of the Schwann cells; appearance of osmiophilic bodies in the cytoplasm of the ganglion cells with destruction of the ganglion cells (70% after 6 weeks of the experiment), and lymphocytic infiltration. The depletion of biogenic amines in the sympathetic nerve fibers is parallelled by the destruction of the granular vesicles. The changes result only from the administration of Guanacline, and are not seen in rats with hypertony if Guanacline is not administered. Guanacline is thought to cause direct cytotoxic damage to the autonomic innervation of the parotid gland. The cytotoxic effect occurs at the site f resorption of substances. The changes in the parenchyma gland represent a secondary effect on the receptor tissue.