Serum-induced chronic pancreatitis

Summary Clinical research into patients with idiopathic chronic pancreatitis points to a possible immunopathogenetic process in a number of cases.In order to examine the behaviour between the exocrine pancreas under the influence of anti-rat-pancreas immune serum produced in rabbits, a 1.00 ml immune serum is administered once a week over a maximum 26 week period into Wistar-rats by intraperitoneal injection. By electrone-microscopy a much reduced production of enzymes apparently takes place, though to differing extent. There is also destruction of the basal membrane of acinocytes; the production of interstitial oedema, the new formation of collagen fibres and the proliferation of connective tissue cells. Under a conventional light microscope the first changes become noticeable after 8-12 weeks of study. These take the form of localised cell decay, deterioration and lysis of acinocytes; and an increasing non-specific inflammation. There is also the new formation of connective tissue. After 20–26 weeks the exocrine pancreas is characterised by reduction of parenchyma, acino-ductal metaplasia, chronic inflammatory infiltrates of differing density, fibrous and irregular calibres of the smaller and larger ducts.The findings are almost identical to the structural changes of chronic idiopathic pancreatitis in human beings. The results support the view of an immuno-pathologic aetiology for human chronic idiopathic pancreatitis.Supported by Deutsche Forschungsgemeinschaft     

The Resistance of Certain Tissues to Invasion: Penetrability of Explanted Tissues by Vascularized Mesenchyme

If puppy tissues are explanted onto the chick chorioallantoic membrane, those tissues which normally have a blood supply are rapidly invaded by vascularized mesenchyme of host origin. Hyaline cartilage, a tissue virtually devoid of blood vessels, is impenetrable by proliferating mesenchyme of the host, while calcified cartilage, which normally is vascularized, is penetrable. The stroma of the cornea, another normally avascular tissue, is readily penetrable, but Descemet's membrane forms a barrier to invasion by host tissues. The experimental system used permits the design of experiments in which the study of factors responsible for the resistance of tissues such as cartilage to invasion can be undertaken.     

Effects of the calcium ionophore A23187 on pancreatic acinar cell membrane potentials and amylase release.

1. The effects of the Ca2+-ionophore A23187 and the non-metabolizable cholinergic agonist bethanechol on acinar cell membrane potentials and amylase release from the superfused mouse pancreas were studied. 2. In the presence of extracellular Ca2+ (2.56 mM), A23187 (10(-5)M) and bethanechol (3 X 10(-5)M) caused an equal increase in the release of amylase. Both stimulants depolarized theacinar cells, A23187 by 6-0 mV and bethanechol by 12-3 mV. 3. When Ca2+ and Mg2+ were removed from the superfusate, the ability of A23187 to increase the rate of amylase release was virtually abolished, while the effect of bethanechol remained unaltered. Similarly, in the absence of these divalent cations, A23187 did not cause depolarization of the acinar cells, while depolarization in response to bethanechol was largely normal. Consequently it is unlikely that cholinergic agonists initiate secretion by activating a Ca2+-ionophore-like mechanism in the cell membrane. 4. When the concentration of Ca2+ in the medium was raised to 10 mM was the only extracellular divalent cation present, the depolarization in response to A23187 was increased to 11-8 mV. When Mg2+ in a concentration of 10 mM was the only extracellular divalent cation, the depolarization was only 2-1 mV. 5. The Ca2+ dependent, A23187-induced depolarization was abolished in the absence of Na+ (Tris substitution). Addition of Na+ to the superfusate caused an immediate depolarization. 6. It is concluded that the Ca2+ dependent depolarization of pancreatic acinar cells induced by A23187 is not directly due to an increased divalent cation conductance. Our findings are consistent with the view that the depolarization is due to an increased influx of Na+ resulting from a Ca2+ mediated increase in Na+ permeability.     

Fatal familial cholestatic syndrome in Greenland Eskimo children

Summary We report the first detailed study of hepatic morphlogy in 28 biopsies from 16 Greenland Eskimo children with fatal familial cholestatic syndrome. The changes were categorized as early, intermediate and late. In the early stage, until 5 months of age, changes were restricted to zone 3, consisting of cholestasis and rosette formation without fibrosis. In the intermediate stage, from 5 to 14 months, cholestasis persisted and rosette formation increased, both with further extension into zone 2. Perisinusoidal fibrosis developed, first in zone 3 and later in zone 1. The late stage, from 17 to 60 months, showed a further increase in cholestasis and rosette formation, and fibrosis of zones 3 and 1 in nearly all biopsies. Portal to portal and portal to central fibrosis was evident with resulting cirrhosis in 2 of 7 patients. The morphological features can be summarized as pure cholestasis with prominent rosette formation followed by zone 3 fibrosis, zone 1 fibrosis, and, cirrhosis. Other characteristics are the virtual absence of inflammation and the lack of anatomical abnormalities such as paucity of bile ducts. The changes and their progression resemble those of Byler disease. Clinical and biochemical features are also largely similar, except for the presence of thrombocytosis in many of the Eskimo patients.     

Pattern and persistence of the epitope-specific IgM response against human cytomegalovirus in renal transplant patients.

The humoral immune response against human cytomegalovirus (HCMV) was evaluated in immunocompromised patients by Western blotting (WB) based on recombinant viral envelope (gB and gH) and tegument (pp150 and pp65) proteins. Three groups of patients were investigated: (a) 74 renal transplant recipients; (b) 24 hemodialysis patients, both groups without clinical evidence of viral infections; and (c) 19 renal transplant patients with manifest HCMV infections. The results obtained suggest that (i) the WB is considerably more sensitive, recognizing the HCMV-specific IgM response rather than the enzyme-linked immunosorbent assays. An IgM response was detected in one-third of all clinically asymptomatic renal patients. (ii) The virus-specific IgM response is primarily directed against the pp150 epitope. (iii) In patients with clinically manifest HCMV disease, additional IgM reactivities are most frequently directed against the glycoprotein B epitope. (iv) The severity of HCMV infections correlates with the extent of the IgM antibody response, i.e. with the number of specific epitopes involved. (v) After transplantation, IgM reactivity and its epitope-specific pattern persist for years.     

Prevalence of human T-Cell lymphotropie virus infections in Germany

The extent of human T-cell lymphotropic retorvirus HTLV-I and HTLV-II infections in the general population in central Europe has not been investigated fully. Two hundred forty-eight thousand blood donors from southern Germany were examined serologically for antibodies to the human lymphotropic retroviruses HTLV-I and HTLV-II: 0.021% were confirmed postive and 0.056% were “indeterminate”. A limited number of seropositives and “indeterminate” samples were analyzed by polymerase chain reaction (PCR): the seropositives were confirmed as positive and 43% of the “indeterminate” samples were PCR-positive. The range of 0.021% HTLV-positives in 248,000 donors, i.e. about two in 10,000 individuals, mirrors closely the published data for the United States. © 1994 Wiley-Liss, Inc.     

Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes,diagnosis, and care

Arthrogryposis or AMC, arthrogryposis multiplex congenita, is defined as multiple congenital joint contractures in more than two joints and in different body areas. The common cause of all AMC is lack of movement in utero, which in turn can have different causes, one of which is CNS involvement. Intellectual disability/CNS involvement is found in approximately 25% of all AMC. AMC with CNS involvement includes a large number of genetic syndromes. So far, more than 400 genes have been identified as linked to AMC, with and without CNS involvement. A number of neonatally lethal syndromes and syndromes resulting in severe disability due to CNS malfunction belong to this group of syndromes. There are several X‐linked disorders with AMC, which are primarily related to intellectual disability. A number of neuromuscular disorders may include AMC and CNS/brain involvement. Careful clinical evaluation by a geneticist and a pediatrician/pediatric neurologist is the first step in making a specific diagnosis. Further investigations may include MRI of the brain and spinal cord, electroencephalogram, blood chemistry for muscle enzymes, other organ investigations (ophtalmology, cardiology, gastrointestinal, and genitourinary systems). Nerve conduction studies, electromyogram, and muscle pathology may be of help when there is associated peripheral nervous system involvement. But most importantly, genetic investigations with targeted or rather whole exome or genome sequencing should be performed. A correct diagnosis is important in planning adequate treatment, in genetic counselling and also for future understanding of pathogenic mechanisms and possible new treatments. A multidiciplinary team is needed both in investigation and treatment.     

The osmotic behaviour of toad skin epithelium (Bufo viridis)

The effect of saline adaptation on the intracellular Na, K, Cl, P concentrations and dry weight content of the toad skin epithelium (Bufo viridis) was studied using the technique of electron microprobe analysis. The measurements were performed on isolated abdominal skins either directly after dissection or after additional incubation in Ussing-type chambers.Adaptations of the toads to increasing NaCl concentrations for 7 days resulted in increased blood plasma osmolarity and a parallel increase in the cellular electrolyte, P and dry weight concentrations of the epithelium, the K increase representing the most significant fraction of the intracellular osmolarity increase. No evidence was obtained to show that the nucleus and cytoplasm reacted differently from each other and all living epithelial cell types basically showed the same response.Incubation of the isolated skins under control conditions showed a drastic inhibition of the transepithelial Na transport after adaptation to high salinities. In spite of the large variations in the transport rate almost identical intracellular electrolyte concentrations were observed. In tap water adapted toads the average cellular concentrations were 8.8 mmole/kg wet weight for Na, 109.6 for K, 41.5 for Cl, and 135.3 for P, respectively. Incubation of the skin with Ringer's solution of different osmolarities demonstrated that the epithelial cells are in osmotic equilibrium with the inner bathing solution. The results are consistent with the view that the osmotic adaptation is mainly accomplished by the movement of water.This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Stiftung Volkswagenwerk     

Elektronenmikroskopische Untersuchungen am embryonalen Mycetom der Kleinzikade Euscelis plebejus Fall. (Homoptera,Cicadina)

Zusammenfassung Die a-Symbionten von Euscelis plebejus treten während der Embryonalentwicklung ihres Wirts in zwei morphologischen Typen auf, die als Infektionsstadium und als vegetative Form beschrieben werden. Die Infektionsstadien teilen sich durch septenartiges Einwachsen der Symbiontenmembranen. Infektionsstadien von Zikadensymbionten waren bisher nur während der Ovarialinfektion aus den Mycetomen weiblicher Imagines bekannt. Die a-Infektionsformen sind gekennzeichnet durch ihr elektronendichtes Cytoplasma, eine ungleichmäßige Verteilung der Ribosomen mit einer ribosomenfreien Randzone und durch Membrankörper. Das Cytoplasma der vegetativen Symbionten erscheint elektronendurch lässiger. Die Ribosomen liegen homogen in der Cytoplasmagrundsubstanz verteilt.Die a-Symbionten liegen vom Zeitpunkt der Eiablage bis zum Eindringen in die a₁-Mycetocyten als Infektionsstadien vor. Nach der Aufnahme in die a₁-Mycetocyten nehmen sie das Aussehen vegetativer Formen an. Im transitorischen Mycetom erscheinen erneut Infektionsstadien während der Übersiedelung in die zweikernigen a₂-Mycetocyten.Jeder Symbiont wird von zwei eigenen Membranen umgeben. Beim Eindringen von Ooplasma in den Symbiontenball wird jeder Symbiont von einer Wirtsmembran umhüllt, die er bis zur Infektion der Wirtszelle behält. In den Mycetocyten umgibt eine offensichtlich vom Wirtscytoplasma erneut gebildete Hüllmembran die vegetativen Symbionten. In den vegetativen a-Symbionten tritt häufig ein mikrofibrillärer kristallartiger Einschlußkörper auf. — Kernäquivalentstrukturen waren in keinem Symbiontenstadium cytologisch mit Sicherheit nachzuweisen.

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Electron microscopic studies on the embryonic mycetome of the leafhopper Euscelis plebejus fall. (Homoptera, cicadina)

Summary During the embryonic development of their host the a-symbiotes of the leafhopper Euscelis plebejus appear in two different morphological types: infective form and vegetative form. The infective forms are able to multiply by ingrowth of their membranes. Until now infective forms of leafhopper symbiotes were only known from the ovarial infection by adult female mycetomes. The infective form of the a-symbiote is characterized by its electron dense cytoplasm, an asymmetric distribution of the ribosomes, a ribosome-free border, and by membraneous bodies. The cytoplasm of the vegetative form is less electron dense and the ribosomes are scattered throughout the cytoplasm.From the time of oviposition until they enter the a₁-mycetocytes, the a-symbiotes are found as the infective form. After entering the a₁-mycetocytes they take on the appearance of the vegetative form. In the transitory mycetome the infective forms appear again during the transition into the binucleate a₂-mycetocytes.Each symbiote is surrounded by two unit membranes of its own. As the ooplasm penetrates the symbiote mass, each symbiote is also surrounded by a host membrane, which remains until the infection of the host cells. In the mycetocytes the vegetative symbiotes have a new membrane around them, which is obviously developed from the cytoplasm of the host cell. In the vegetative a-symbiotes there is frequently a paracrystalline inclusion. — It was impossible to demonstrate nucleoid structure with certainty in any symbiote form.

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Abkürzungen a a-Symbionten - a_i a-Infektionsstadien - a_v vegetative a-Symbionten - a-Mc a-Mycetocyt - a-Z a-Zelle - eK elektronendichter Körper - ER endoplasmat. Retikulum - M₁ innere Symbiontenmembran - M₂ äußere Symbiontenmembran - M₃ Hüllmembran - Mf Mikrofibrillen - Mi Mitochondrien - Mk Membrankörper - Mt Mikrotubuli - Nu Zellkern - Py Kernpyknosen - Ri Ribosomen - Sb Symbiontenball - Sm Symbiontenmembranen - t t-Symbionten - t_v vegetative t-Symbionten - t-Mc t-Mycetocyt - t-Z t-Zelle - Zm Zellmembran Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.Herrn Prof. Dr. K. Sander danke ich für stete Förderung meiner Arbeit und Frau A. Kaufmann für die Einführung in die elektronenmikroskopische Technik.