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The prevention of exudative epidermitis could be confirmed in experimental investigations with gnotobiotic piglets when the skin first was colonized with avirulent strains of Staphylococcus (Staph.) hyicus and subsequently exposed to virulent strains of Staph. hyicus. However, locally restricted cutaneous lesions in the area of application corresponding to exudative epidermitis were seen in five of nine piglets. Using the strain Staph. sciuri the spread of virulent Staph. hyicus could not be suppressed. Such infected two piglets developed generalized exudative epidermitis. In another experiment with four piglets it could be shown, that the relative protective mechanism correlating to bacterial interference on the one hand can be influenced by the virulence of causative organisms. On the other hand it even can be abolished when skin lesions are involved. For that reason probably the utilization of bacterial interference in prevention of exudative epidermitis under field conditions is considerably limited.

A set of rat-human and rat-rat chimeric mAb has been created, all possessing V regions identical in their specificity for the mouse CD8 Ag. In vitro all antibodies were able to block cell-mediated lysis but varied greatly in their capacity to utilize rabbit complement. We examined the ability of these chimeric antibodies to deplete in vivo and established a clear hierarchy. Of the human IgG subclasses, only IgG1, 2, and 3 could fix complement in vitro, yet all (IgG1-4) were remarkably potent at depleting CD8+ PBL in vivo. In contrast, human IgA2 and IgE were ineffective at clearing CD8+ PBL. The vector system used to create these antibodies together with the small doses of antibodies required to deplete in vivo make this a simple and rapid system for testing the effects of different antibody isotypes and mutants. We have shown that a mutant of human IgG1, which is incapable of fixing complement, depletes perfectly well in vivo, whereas an aglycosyl IgG1 mutant is rendered inactive. Our model provides a unique opportunity to study effector functions and motifs that are used by mAb in vivo and will help in the design of improved antibodies for human therapy.

The eradication and control of swine dysentery in breeding or farrow-to-finish herds require comprehensive knowledge about the epidemiology, pathogenesis and immunology of this typical multifactorial disease. Based upon this background information, the characteristics of chemotherapy, immunoprophylaxis and other necessary concomitant measures are described. The objectives of the eradication and control schemes should be the production of Treponema-free weaner pigs and a long-term prevention of reinfections.

Islet allografts are particularly vulnerable to rejection, and current immunosuppressive agents are deleterious to their function. They are, however, highly suitable for 'immunomodulation', i.e., the removal or inactivation of passenger leukocytes to reduce their immunogenicity. For this purpose we have used 3 rat anti-dog monoclonal antibodies (Mabs) which are synergistic for leukocytolysis in the presence of autologous dog serum. Spleen cells or purified islets treated with these Mabs together with autologous serum were tested in mixed leukocyte and islet co-culture assays. The stimulatory properties of the Mab-pretreated splenocytes or islets were markedly reduced; moreover, the Mab cytolytic activity was shown to be confined to the leukocyte target cells and did not affect islet secretory function upon glucose stimulation. We conclude that this method of modifying the immunogenicity of dog islets could lead to successful islet grafting in vivo, allowing the reduction of conventional immunosuppression. Successful in vivo studies in this model, which are currently in progress, could have implications for clinical islet transplantation.

Protectin (CD59) is a recently discovered 18-20 kDa glycoprotein that effectively inhibits lysis by the membrane attack complex of the homologous complement system. This glycoprotein is widely distributed on the membranes of human blood cells (erythrocytes and leukocytes). By using immunofluorescence microscopy, protectin was observed in vascular endothelia throughout the body and in extravascular tissues. Cells expressing protectin were also found in ductal epithelia of pancreatic, biliary, and salivary systems, bronchi, and kidney collecting ducts. Furthermore, protectin was expressed in the epidermis and in the syncytiotrophoblast of placenta. The expression of protectin in endothelia, in various epithelial cells, and in placenta presumably protects autologous tissues and the fetoplacental unit from complement-mediated damage.

Comparative examinations of renal function using inulin- and endogenous creatinine-clearance tests in 5 pigs showed nearly identical values of glomerular filtration rate (GFR). Based on this relation 79 healthy pigs, weighting 2 kg to 230 kg were investigated using the creatinine-clearance test for determination of normal values of GFR and urine flow rate (Vu) as well as renal excretion (E), renal clearance (Clr) and fractional excretion (FE) of urea, sodium, potassium, calcium, phosphorus, glucose and lactate. The renal excretion of creatinine (E-Creat) was closely correlated with the body weight. Therefore it is possible to use the body weight for estimation of E-Creat and to calculate GFR and Vu using plasma and urine concentrations of creatinine independent of a timed volumetric urine collection. Subsequently E, Clr and FE of electrolytes or other endogenous substances can be evaluated. Finally the practicability of this procedure for detection of disturbed glomerular filtration or tubular reabsorption was demonstrated in piglets suffering from colidiarrhoea and/or transmissible gastroenteritis.

In an investigation over five months the adrenal toxic effect of the quinoxaline derivate olaquindox in pigs of different ages (10 and 16 weeks) after accidental feeding of a 15-fold overdosage of olaquindox is demonstrated. The substance induced clinical and hematological changes comparable with Addison's disease. A reduced gain of body weight was observed, predominant hematological findings were a hyperkalemia and a hyponatremia, which reversed to normal values after 17 weeks in the younger group and after 14 weeks in the older group. Whereas five weeks after the first intake of the feed, degenerative changes of the zona arcuata were most prominent, a destructive fibrosis and a reduction of the adrenal cortex were more marked 12 and 13 weeks later. Due to the loss of aldosterone the electrolyte imbalances led to degenerative changes in the skeletal muscles and in the myocardium. Pigs of younger age were more affected than elder ones. Subcapsular cells with basophilic nuclei resembling normal cells of the zona arcuata appear 18 to 22 weeks after the first overdosage of olaquindox and are suggestive in combination with normal electrolyte values of a regeneration of the zona arcuata.

The use of non-proteases for the selective removal of protecting groups from peptides and glycopeptides is described. The N-terminal deprotection of peptides can be achieved by the hydrolysis of the phenylacetyl (PhAc) amide blocking group catalyzed by penicillin G acylase. On the other hand, the lipase-mediated hydrolysis of n-heptyl (Hep) and 2-bromoethyl esters allows for the liberation of the C-terminal carboxy group. The selective C-terminal deprotection can be applied advantageously for the construction of acid- and base-sensitive polyfunctional O-glycopeptides. In all cases the enzymatic reactions are completely selective and proceed under mildest conditions (pH 7-8, r.t. to 37 degrees C) without damaging the various other functionalities present in the complex substrates.

Endogenous creatinine clearance was determined in 5 healthy female pigs of different body weight simultaneously to the clearance of inulin. The average creatinine clearance (3.74 +/- 0.57 mg/min/kg) has been found to be 7% higher than inulin clearance indicating some tubular secretion of creatinine. However, since this difference was not significant, the endogenous creatinine clearance is a practicable method for the measurement of glomerular filtration rate in swine. Data of creatinine concentration in plasma and of creatinine excretion showed close relationships to the body weight. It is discussed, whether the glomerular filtration rate can be predicted from the creatinine concentration in plasma and creatinine excretion, which might be estimated from the body weight without quantitative urine collection.

Human cells are relatively resistant to lysis by the homologous complement system. Here we describe the mechanism of action of a recently discovered and widely distributed 18,000-20,000 molecular weight (MW) membrane glycoprotein (CD59), which appears to act as a major protective element against complement-mediated lysis (hence called protectin). When incorporated into heterologous erythrocyte membranes, protectin efficiently prevented cell lysis by human serum. Neutralization with antibody of the naturally occurring protectin on human erythrocytes or on nucleated K562 cells increased their susceptibility to lysis by homologous complement. During complement activation, protectin became incorporated into the membrane attack complex (MAC). By interacting with newly exposed regions in the C5b-8 complex and in aggregating C9 it limited the number of C9 molecules associating with the C5b-8 complex to a C8:C9 ratio of 1:1.5 instead of a normal average of 1:3.5. The results demonstrate directly that protectin is a powerful inhibitor of complement cytolysis and acts by inhibiting the C5b-8 catalysed insertion of C9 into the lipid bilayer.

If unmodified monoclonal antibodies are to be used for effective therapy, careful attention must be paid to isotype and specificity. The optimum istoypes of rodent and human antibodies for interaction with human effector mechanisms have been defined using matched sets of antibodies. Some antigens are much better targets than others and the CAMPATH-1 antigen (CDw52) is a particularly good example. A rat IgG2b CAMPATH-1 antibody proved to be rather effective for depleting human lymphocytes in vivo but therapy could be limited by anti-globulin responses. A reshaped human antibody with the same specificity was constructed by genetic engineering. This has been used in the treatment of two patients with lymphoma with the clearance of large numbers of tumour cells from blood, marrow, spleen and lymph nodes. We believe that this antibody will be a potent immunosuppressant as well as being useful as a component of therapy for lymphoid malignancies.

After a short review about etiology, epidemiology, clinical symptoms, diagnosis and therapy of leptospirosis the course and therapy of an acute leptospirosis outbreak in a breeding herd with nearly 240 sows is described. The microscopic agglutination test (MAT) served for diagnosis and was most reliable for estimation the actually stage of infection when used twice with an interval of several weeks. As causative agent serovar L. pomona was identified, whereby cross-reactions were seen to serovars L. grippotyphosa, L. bratislava and L. copenhageni. Therapy of all animals with Terramycin/LA (Pfizer) at three times with intervals of five days and doses of 20 mg oxytetracycline/kg b.w. distinctly reduced the incidence of abortion and stillborn or mummified pigs. Local irritations, relative to the intramuscular administration of oxytetracycline, mostly were low-graded and temporary. For the next months acute infections could not be registered. Probably due to infections from leptospires-reservoirs, maintained by numerous existing mice and puddles on the pasture-ground, leptospirosis occurred again six months later. Only another antibiotic therapy of the whole herd and simultaneous eradication of rodents as well as closing the pasture led to a long-termed control of leptospirosis in this herd.

Despite excellent long-term results of bone marrow transplantation (BMT) in acquired severe aplastic anemia (SAA), graft-versus-host disease (GVHD) continues to remain a major concern. Approximately 30–40% patients experience chronic GVHD resulting in long-term complications and impaired quality of life. At St. George’s Hospital, we investigated the role of anti-CD52 monoclonal antibodies (MoAb) in transplant protocols for SAA. The CD52 antigen is expressed widely on virtually all lymphocytes including T and B-cells, NK cells, dendritic cells, eosinophils and macrophages but is absent from erythrocytes, platelets and marrow progenitors. Between Aug 1989 and Nov 2003, 33 patients at our centre with acquired SAA underwent BMT from HLA-identical sibling donors using cyclophosphamide (CY) 50 mg/kg x 4 (days −5 to −2) and anti-CD52 MoAb 0.75–1 mg/KgBW as conditioning. Prior to 1999, rat derived anti-CD52 MoAb (Campath-1G) was used. We switched to humanized version of anti-CD52 MoAb (Alemtuzumab) when it became available in 1999. Median age at BMT was 17 yrs (range 4–46). Prior to BMT, 58% were heavily transfused (>50 transfusions) and 42% had previously failed anti-thymocyte globulin (ATG) based immunosuppressive therapy. Unmanipulated bone marrow was used as source of stem cells in all except one. GVHD prophylaxis was with cyclosporine (CSA) alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to CSA. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 (24%) patients (primary,4; secondary, 4). Graft failure was non-significantly higher in heavily transfused patients and those receiving CSA and anti-CD52 MoAb as GVHD prophylaxis. Of those failing grafts, 4 survived long-term (complete autologous recovery, 2; autotransplant from previous stored marrow, 1; second allograft, 1). Acute grade II-IV GVHD and chronic GVHD was seen in 13% and 4%, respectively. None developed extensive chronic GVHD. Of the 19 recipients positive for cytomegalovirus (CMV), reactivation was seen in 5(26%) with in 100 days. No cases of late CMV reactivation were observed. Six patients died of complications related to BMT at a median of 248 days (range 47–414). With a median follow-up of 59 months, the 5-year survival was 81% (95% C.I. 68–96). There was a non-significant trend towards improved survival in patients transplanted after 1995 (93% vs. 74%). The performance status of all survivors is 100% except one who developed avascular necrosis of hip. We conclude that the conditioning regimen containing CY and anti-CD52 MoAb is well tolerated and efficacious for acquired SAA using HLA-matched sibling donors. The long-term survival with this conditioning appears to be equivalent to current standard conditioning for acquired AA (CY and ATG) and the impact on acute and chronic GVHD is particularly notable. Based on the results of our study we are further investigating the role of Alemtuzumab in the transplant protocols for AA using CSA alone as GVHD prophylaxis.

The local magnetic behavior of isolated Fe and Ni ions has been determined in ZnS and other semiconducting compounds via the hyperfine interaction at the nucleus. It is concluded that in ZnS Fe ions are observed in the 1+ state while Ni is found in two states, the 1+ state, observed as a magnetic component, and, less abundant, the 2+ state in a nonmagnetic configuration. In InP and other semiconducting compounds, Ni is typically found in a nonmagnetic state.

Applied to the two-state version of a quality control model introduced byRoss [1971], we derive upper and lower bounds for the minimal expected total discounted cost, give regions for nonoptimality for each of the three actions (produce, inspect, revise), and construct nearly optimal decision rules easy to realize.

Zn1-xMnxSe (0.016

A system is subject to a sequence of randomly occurring shocks. Each shock causes a random amount of damage which accumulates additively. Any of the shocks might cause the system to fail. The shock process is in some sense related to an environmental process in order to describe randomly varying external factors of an economical and/or technical nature as well as internal factors of a statistical nature. A discrete time formulation of the problem is given. Sufficient conditions are found for optimality of a generalized control-limit rule with respect to the total cost criterion: Whenever the accumulated damage s is not less than a specified critical number t(i), depending on the environmental state i, replace the system by a new one; otherwise do not replace it. Moreover, bounds are given for these critical numbers.

Monotone upper and lower bounds are found for the lifetime distribution of a company, the first two moments of the lifetime, different probabilities of ruin, and the expected dividend payments during the lifetime. The results are applied to the problem of maximizing the expected dividend payments subject to an acceptable minimal expected life.

Upper and lower bounds are given to the solutionV of a renewal equation by applying a well-known monotonicity argument. The results are applied to the renewal function of an ordinary renewal process.

Upper and lower bounds are derived for the distribution of the run length N of both the one-sided and two-sided CUSUM schemes. Based upon a sequence of iterates Pr(N > 0), Pr(N > 1), …, bounds are constructed such that (m n −) i Pr(N > n) ≤ Pr(N > n + i) ≤ (m n +) i Pr(N > n) holds for all n, i = 1, 2,…, with constants 0 ≤ m n −; ≤ m n + ≤ 1 suitably chosen. The bounds converge monotonically in the sense that (m n −) i+1Pr(N > n) ≤ (m n+1 −) i Pr(N > n + 1), (m n +) i+1Pr(N > n) ≥ (m n+1 +) i Pr(N > n + 1), and, under some mild and natural conditions, . As a by-product, bounds are presented for the percentage points of the distribution function of N, for the average run length of the inspection scheme, for the standard deviation of N, and finally, for the probability mass function of N. Some numerical results are displayed to demonstrate the effkiency of the method.

The IR emission and the corresponding low energy excitation spectra of the wide band gap semimagnetic semiconductors Zn1−xMnxTe, Cd1−xMnxTe, Zn1−xMnxSe, Cd1−xMnxSe, Zn1−xMnxS, and Cd1−xMnxS are critically discussed in the light of the models proposed until now. The similar shape of these spectra and the comparison with the spectra due to Mn in tetrahedral coordination lead to the conclusion that the longwave emission and excitation bands of these substances can tentatively be interpreted as due to cubically coordinated Mn2+ ions on interstitial sites or in octahedrally coordinated MnTe, MnSe, and MnS cluster. The crystal field parameters B, C, and Dq of these Mn2+ ions (Td or Oh symmetry) are determined on the basis of the experimental data. Die IR-Emission und die entsprechenden niederenergetischen Anregungsspektren der semimagnetischen Halbleiter mit groser Bandlucke Zn1−xMnxTe, Cd1−xMnxTe, Zn1−xMnxSe, Cd1−xMnxSe, Zn1−xMnxS und Cd1−xMnxS werden im Licht der bisher vorgeschlagenen Modelle kritisch diskutiert. Die Ahnlichkeit dieser Spektren untereinander und der Vergleich mit den bekannten Spektren der substitutional eingebauten Mn2+-Ionen fuhren zur Schlusfolgerung, das die langwelligen Emissions- und Anregungsbanden dieser Substanzen versuchsweise durch die Existenz von Mn2+- Ionen in kubischer Koordination auf Zwischengitterplatzen oder durch oktaedrisch koordinierte MnTe-, MnSe- und MnS-Cluster erklart werden konnen. Die Kristallfeldparameter B, C und Dq entsprechend koordinierter Mn2+-Ionen (Td oder Oh-Symmetrie) werden mit Hilfe der experimenttellen Daten bestimmt.

A pig grower ration containing olaquindox at a concentration of 778 mg/kg was accidentally fed to 10 respectively 16 weeks old weaner pigs. The subsequent intoxication was characterized by poor growth and long-term disturbances of renal function and electrolyte metabolism. A deficiency of aldosterone, produced by a selective degeneration of the arcuate zone of the adrenal cortex, is probably the cause of the hyponatremia, hyperkalemia and hemoconcentration observed. Simultaneously plasma levels of urea and creatinine were elevated five- to eightfold. Due to hyperkalemia episodes with collapse, paralysis and severe electrocardiographic changes occurred several times. Two pigs died in the course of such attacks. Individuals, which transiently showed distinct clinical symptoms of intoxication, did not show any signs of disease 15 or 18 weeks later. Therefore it may be assumed, that the lesions of the adrenals, heart and skeletal muscle caused by olaquindox intoxication are reversible in some cases.

Zusammenfassung Der dreiphasige Direktumrichter wird als Stellglied bei der Regelung von Drehfeldmaschinen verwendet, wenn hinreichend niedrige Frequenzen verlangt werden. Dies ist bei Synchronmotoren zum Antrieb von neuartigen Rohrmuhlen und bei doppeltgespeisten Schleifringlaufermotoren in elastischen Netzkupplungsumformern und Stosleistungsumformern der Fall. Fur derartige Drehstromantriebe werden entkoppelte Zweigrosen-Regelsysteme eingesetzt. Ihre Struktur und die erreichten Betriebsergebnisse werden beschrieben.

We consider a discrete review, single product, dynamic inventory model, in which the demand process is related to an environmental process. Sufficient conditions are found for the optimality of a $(z,Z)$-order-policy: whenever the environmental process is in state $i \in I$, order up to $Z(i)$, if the stock is less than $z(i)$, and do not order, otherwise. Moreover, bounds are given for the critical numbers $z(i)$, $Z(i)$, of an optimal $(z,Z)$-order-policy.