In vivo effects of recombinant human interleukin 2 on antitumor and antiviral natural immunity in induced or natural murine immunodeficiency states.

We have examined the ability of in vivo treatment of mice with recombinant interleukin 2 (rIL-2) to affect natural immunity measured against tumor (YAC-1) or virally infected (herpes simplex type 1) target cells. rIL-2 treatment leads to significant increases in natural killer/lymphocyte-activated killer (NK/LAK) function and spleen cells recovered. This effect is dose dependent and strain related. The latter parameter correlated with the pretreatment NK activity level of the strain. The rIL-2 induced NK/LAK augmentation is also kinetically restricted as treatment must have occurred within 48-72 h of assay to be effective. The rIL-2 therapy effectively enhances both antitumor and antiviral NK/LAK activity and results in a noticeable increase in asialo-GM1-positive cells in the spleens of treated mice as well as a significant increase in IL-2 receptor expression as monitored by either cytometry or radioligand binding. In vivo treatment of mice with an antibody directed to the ASGM1 determinant effectively reduces the rIL-2 augmentation of both antitumor and antiviral activity even though this treatment does not affect the pretreatment level of antiviral activity. Various natural and induced immunodeficiency states (immunotherapy, irradiation, immunosuppressive drugs, cytoreductive drugs) have been examined for the ability of in vivo treatment with rIL-2 to enhance NK/LAK activity. In vivo rIL-2 administration is differentially effective in enhancing NK/LAK activity in these situations. Notably, in these induced immunodeficiency states, although NK/LAK activity is commonly enhanced, the number of spleen cells recovered often is only marginally affected. Thus, as expected, a limiting aspect in this use of a natural immunomodulator is the number of potentially responsive cells present in the immunodeficiency condition. In addition, correlations between rIL-2 effect, several of the immunodeficiency states, and vascular leak syndrome are briefly discussed.

Priming of immune responses to hepatitis B surface antigen with minimal DNA expression constructs modified with a nuclear localization signal peptide.

Nuclear localization signal (NLS) peptides conjugated to DNA increase transfection efficiency in vitro. We tested in mice whether conjugation of NLS peptides to DNA vaccines enhances their immunogenicity after intramuscular injection or gene gun mediated intradermal delivery. We constructed the plasmid pMOK-HBsAY that contains a transcription unit encoding hepatitis B surface antigen (HBsAg) and bacterial sequences for amplification of plasmid DNA. From this plasmid we derived the minimal expression construct pMOK-HBsAY-MIDGE, a covalently closed linear DNA that contains only the HBsAg transcription unit. Both constructs stimulated similar (predominantly IgG1) antibody response to HBsAg after gene gun immunization. In contrast, pMOK-HBsAY plasmid DNA was more efficient than pMOK-HBsAY-MIDGE DNA in priming predominantly IgG2a antibody responses to HBsAg after intramuscular injection. Both constructs efficiently primed cytotoxic T lymphocyte responses after intramuscular immunization. When a NLS peptide was coupled to the pMOK-HBsAY-MIDGE DNA, HBsAg transfection efficiency in vitro and priming of antibody responses to HBsAg after intramuscular (but not gene gun mediated) injection was enhanced 10- to 15-fold. These data show: (a) MIDGE constructs can be used as DNA vaccines indicating that bacterial sequences are not essential cofactors; and (b) in intramuscular (but not gene gun mediated) delivery the immunogenicity of a MIDGE-based vaccine is enhanced by coupling NLS peptides to the vector DNA.

Neuroendocrine regulation of in vivo cytokine production and effects: I. In vivo regulatory networks involving the neuroendocrine system, interleukin-1 and tumor necrosis factor-alpha.

We have investigated the in vivo regulatory network involving the neuroendocrine system, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF). Adrenalectomy or hypophysectomy shifted the sensitivity curve to lipopolysaccharide (LPS)-induced lethal shock as well as TNF- and IL-1-induced deaths. Serum levels of IL-1 or TNF were altered in adrenalectomized or hypophysectomized mice following in vivo stimulation with LPS when compared to appropriate sham-operated control mice. Exogenous administration of either IL-1 or TNF could induce increases in serum corticosterone in sham-operated mice. Finally, treatment of adrenalectomized mice with corticosterone or dexamethasone could inhibit the induction of serum IL-1 and TNF and modified the pattern of these cytokine-induced deaths. Dexamethasone was more effective in these conditions than the natural glucocorticoid, corticosterone. Taken together, these data provide in vivo evidence for a feedback system involving the neuroendocrine axis (hypothalamus, pituitary and adrenal glands) leading to corticosterone production and subsequent regulation and/or modulation of IL-1 or TNF levels or activity.

[Retro-aortic renal veins - a possible cause of left-sided varicocoeles (author's transl)]. / Retroaortale Nierenvenen - eine mögliche Ursache der linksseitigen Varikozele.

Retro-aortic renal veins have been found as a possible cause of left-sided varicocoeles in a series of 137 selective retrograde phlebograms of the left testicular vein.

[Follow-up angiography after palliative renal artery occlusion with the GAW-(Gianturco-Anderson-Wallace)-spiral (author's transl)]. / Kontrollangiographische Befunde nach palliativer Nierenarterienokklusion mit der GAW-(Gianturco, Anderson-Wallace-)Spirale.

Follow-up angiograms were carried out in six patients after palliative renal artery embolisation for hypernephromas using a GAW-spiral. The following conclusions were reached: it is possible to obtain complete occlusion of the renal artery with cessation of haematuria, reduction in tumour size and in the extent of the pathological vessels. It is necessary, however, to place the spiral accurately in the vessel to be occluded and to embolise all major arteries supplying the tumour. Even when the renal artery has been completely occluded, tumour growth results in the development of varying extent. In order to reduce this collateral circulation, vessels to the tumour periphery should be embolised with a suitable substance before spiral occlusion is carried out.

[Osteoid osteoma. (Plain films, angiography and scintigraphy in fifty patients) (author's transl)]. / Das Osteoid-Osteom. (Nativröntgenologische, angiographische und szintigraphische Untersuchungen bei 50 patienten).

The radiological diagnosis and differential diagnosis of osteoid osteomas was considered in relation to a series of 50 histologically verified cases. In twenty, angiography had been performed and scintigraphy was carried out seven times. Various problems in the diagnosis of osteoid osteomas in relation to their localisation within bone (cortical, medullary, sub-periosteal, subarticular) and within the skeleton (near the hip, in the hand or foot, in the spine and in flat bones) are discussed.

[The mechanism of contrast filling of the liver following lymphography (author's transl)]. / Zum Mechanismus der Kontrastmitteldarstellung der Leber nach Lymphographie

Contrast filling of the liver after lymphography is described in one patient. The authors agree with the literature which indicates the significance of lymphatic blocks and caval obstruction. A splenoportogram was demonstrated during the performance of a cavogram and in this way direct contrast filling of the liver is demonstrated for the first time.

[A clinical-radiological investigation concerning the accuracy of diatrizoate (Gastrografin) in the demonstration of anastomosis dehiscence and perforation of the gastro-intestinal tract (author's transl)]. / Klinisch-radiologische Untersuchung über die Treffsicherheit des Diatrizoat-(Gastrografin-) Testes zum Nachweis von Anastomosendehiszenzen und Perforationen des Gastrointestinaltraktes

A Gastrografin test is described for diagnosing perforations and dehiscence of anastomoses in the gastro-intestinal tract by carrying out a simple urine analysis. False positive and false negative results can be avoided by obtaining radiographs of urine samples under standard conditions. The accuracy of the method was checked in 97 patients by comparing the results of the urine analysis with radiographic examinations and with the clinical course. From this, it appears that the test is reliable, simple and capable of being used anywhere. The test is therefore recommended a) where there is a lack of radiographic facilities, b) for immobile patients, c) where there is clinical suspicion of a perforation or dehiscence of an anastomosis in the absence of radiographic findings and d) in individual cases where the radiographic changes are positive.

[Methods of diagnosis and treatment of idiopathic varicocele in Germany, Austria and Switzerland (author's transl)]. / Methoden der Diagnostik und Therapie bei idiopathischer Varikozele im deutschsprachigen Raum.

Replies from 115 urological departments, which were part of a general inquiry within Germany, Austria and Switzerland, were evaluated. 37% of all departments perform a varicocelectomy already after the 6th year of age, 68% after 10 years of age. A preoperative phlebography is performed regularly only by 8%, but the phlebography prior to recurrent surgery is carried out by 72%. The most frequent operative method is the Bernardi technique in 39%, the method of Palomo, ligation superior to the internal inguinal ring and lumbal ligation of the spermatic vein are used equally often. The additional dissection of accompanying veins at the level of internal inguinal ring was reported only by 24%. A postoperative inspection with palpation control is regularly performed by 85%, with semen analysis in 58%. No department reported, postoperative results with sperm analysis for more than one year.

A new method of transfemoral testicular vein obliteration for varicocele using a balloon catheter.

Selective obliteration of the testicular vein as a treatment for varicocele is described in 51 patients. Twenty-five patients had a history of infertility. A coaxial catheter-balloon catheter system was used. The procedure was done on an outpatient basis. The complications and success rates are comparable to postoperative results. Four of the 25 patients whose primary indication for the procedure was infertility have fathered children.

[Catheter embolization of inoperable kidney neoplasms with the GAW-spiral]. / Katheterembolisation des inoperablen Nierentumors mit der GAW-Spirale.

On the basis of 4 cases with inoperable hypernephroma the possibilities of the transfemoral catheter embolisation with the GAW-spiral are discussed. Simplicity of the technique and advantages in comparison to the material embolisation methods are discussed. The case in question was in 2 patients a primary embolisation, in 2 patients a secondary one with recanalised material embolisation. Up to now the patients were controlled over 3 months after the vascular occlusion. A recanalisation could not be observed, rather by total occlusion a tendency to the formation of collateral circulations.

[The problem of angiographic diagnosis of giant cell tumors (author's transl)]. / Zur Problematik der angiographischen Dignitätsbeurteilung beim Riesenzelltumor.

The value of angiography in the diagnosis of giant cell tumors of the bone was investigated in 12 patients listed in the Viennese bone tumor register. It could be shown that angiographic criteria of malignancy can frequently be found in grade II cell tumors. Therefore angiography does not seem to be helpful in differentiation and prediction of benign and malignant course of giant cell tumors.

[Partial cirrhosis of the kidney after radiotherapy of a colon carcinoma. Case record (author's transl)]. / Partielle Schrumpfnieren nach Bestrahlung eines Kolonkarzinoms. Fallbericht.

The radiological symptoms of excretion urography and angiography of a partial radiogenic cirrhosis of the kidney is discussed on the basis of a case of operated colon carcinoma with subsequent curative radiotherapy because of malignant infiltrations into the adjacent adipose tissue. Furthermore, a relationship between radiological morphology and pathophysiology of the chronic radionephritis is established.

[Late results of the Noble operation. Clinical and radiological follow-up examination]. / Spätergebnisse der Nobleschen Operation. Klinische und radiologische Nachuntersuchung

The results of 58 Noble operations performed during the period between 1964 and 1973 are reported. A partial operation was carried out in 9 cases. In 4 cases there were fatal complications due to technical errors such as too long a terminal ilial loop and direct suture to the intestine. Two cases of late ileus were observed after 2 and 6 months respectively following a partial plication. Follow-up examination at an average of 4 years after Noble operation showed that 26 patients were free of complaint. The Noble operation is best suited for cases with chronic recurrent adhesion ileus when a permanent folding of the small intestine is necessary. For other indications, the newer alternative procedures. (Childs and Phillips and Reiffersceid and Phillip's small intestine splinting) should be used.

Long-term results after sclerotherapy of the spermatic vein in patients with varicocele.

Ninety-seven patients received transfemoral sclerotherapy of the spermatic vein for varicocele. After observation for 2 to 5 years, follow-up was available in 69 patients (71.2%), in 11 of whom the procedure failed (16.0%). Complications during angiography (N = 12, 12.4%) or sclerotherapy (N = 31, 32.0%) did not require hospital treatment. At least one parameter of the spermiogram was improved in 25 of 32 patients (78.1%). Forty-four of 69 patients (63.8%) treated because of a childless marriage, and whose wives were not known to be infertile, had a pregnancy rate of 47.7%. Thi method may be considered equal to surgical procedures in achieving venous occlusion; furthermore it is simple and can be used on an outpatient basis without anesthesia.

The progression of the inflammation in established collagen-induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities.

Alterations in the progression of the inflammatory disease in mice with established collagen-induced arthritis (CIA) by in vivo treatments with either anti-T cell antibodies or an immunosuppressive drug, whose main targets of action are T cells, were studied. It was demonstrated that the in vivo administration of either monoclonal anti-L3T4, anti-Ly-2 or the combination of anti-L3T4 and anti-Ly-2 failed to modify the inflammatory disease after the arthritis had been initiated. Nevertheless, the progression of disease was decreased by treatments with rabbit anti-mouse lymphocyte sera (ALS) in mice with established CIA. While there was a substantial reduction in the proliferative responses to the T cell mitogen concanavalin A (Con A) in these ALS-treated mice, proliferation to a B cell mitogen, lipopolysaccharide, was unaffected. Furthermore, treatments with anti-Thy-1.2 monoclonal antibody (mAb) by itself did not alter the progression of the ongoing inflammatory disease, but combined treatments with both anti-Thy-1.2 and anti-L3T4 mAb prevented the further advancement of the arthritic disease. Although mice receiving either anti-Thy-1.2 alone or both anti-Thy-1.2 and anti-L3T4 exhibited complete absence of Thy-1+ cells within their inguinal lymph nodes, the proliferative responses to Con A by LN cells from mice treated with the combination of anti-Thy-1.2 and anti-L3T4 were drastically reduced compared to the responses of either the anti-Thy-1.2 or anti-L3T4-treated groups. Finally, daily treatments with cyclosporin A, an immunosuppressive drug which preferentially acts on T cells, were also effective in modifying the clinical course of the arthritic disease in mice with established CIA. These results suggest that immunocompetent cells which express the Thy-1 surface marker, most likely Thy-1+ T cells, may play a role in maintaining and perpetuating the inflammatory disease of established CIA.