The matrilin-3 VWA1 domain modulates interleukin-6 release from primary human chondrocytes.

OBJECTIVE: We previously demonstrated the ability of matrilin-3 to modulate the gene expression profile of primary human chondrocytes (PHCs) toward a state favoring cartilage catabolism. The structure within matrilin-3 responsible for the induction of these catabolic genes is unknown. Here, we investigated the potential of matrilin-3 (MATN3) and truncated matrilin-3 proteins, in both monomeric and oligomeric form, to stimulate interleukin (IL)-6 release in PHCs. METHODS: We expressed full-length matrilin-3 oligomers, matrilin-3 von Willebrand factor A (VWA) domain oligomers, matrilin-3 four epidermal growth factor (EGF) domain oligomers, matrilin-3 monomers without oligomerization domains, matrilin-3 VWA domain monomers, and matrilin-3 4EGF monomers. We then incubated PHCs in the absence or presence of full-length matrilin-3 or one of the truncated matrilin-3 proteins and finally determined the release of IL-6 in cell-culture supernatants. RESULTS: The addition of full-length matrilin-3 oligomers, matrilin-3 VWA domain oligomers, and, less pronounced, matrilin-3 monomers without oligomerization domains, and matrilin-3 4EGF-oligomers to the cell-culture medium led to a significant induction of IL-6 in PHCs. DISCUSSION: Based on recombinant expression of different matrilin-3 domains in both monomeric and oligomeric form, this work demonstrated that the VWA1 domain of matrilin-3 is primarily responsible for the induction of IL-6 release and that the oligomerization of the VWA1 domain markedly promotes its activity.

[Laparoscopic appendectomy from the gynecologic viewpoint. A report of experiences]. / Die laparoskopische Appendektomie aus gynäkologischer Sicht. Ein Erfahrungsbericht.

From November 1992 until the middle of 1997 we had 80 laparoscopic appendectomies in our gynaecological department of the district hospital Parchim. These procedures were done with the Semm 3-sling-technique. Recurrent abdominal pain, ovarial tumor, dysmenorrhoea and the wish of sterilisation were the main indications for laparoscopy. Visible pathological changes of the appendix vermiformis led to the laparoscopic appendectomy. Complications were seen only in three cases in the postoperative period. Conclusions and recommendations are given.

[Disseminated peritoneal leiomyomatosis. A case report]. / Leiomyomatosis peritonealis disseminata. Ein Fallbericht.

Leiomyomatosis peritonealis disseminata (LPD) is a rare benign and mostly asymptomatic disease only occurring in women of reproductive age. Because of the disseminated appearance of multiple subperitoneal nodules malignancy is frequently simulated. A report is given on a case of LPD in a 38 year old woman. Today the cause of LPD is seen in a specific hormonal stimulation of the pluripotent subperitoneal mesenchyma of the müllerian duct in the minor pelvis. An individual disposition is discussed. Radical operation procedures are not indicated because of the good prognosis of this disease. A further application of oral contraceptives or further pregnancies cannot be recommended for such cases of reproductive age.

[Comparison between ketamine, propanidid, and etomidate in general anaesthesia for caesarean section (author's transl)]. / Die Ketaminnarkoseeinleitung bei Sectio caesarea im Vergleich zur Propanidid- oder Etomidateeinleitung.

Propanidid, etomidate, and ketamine were compared for their effects on maternal acid-base balance and circulation as well as on postnatal general condition and acid-base balance of the newborn, on the basis of 44 women in advanced pregnancy to whom caesarean section was applied in general anaesthesia. The probands had not been deliberately selected beforehand. Results obtained from the three above anaesthetics were compared with one another as well as with parameters recorded from spontaneously delivered newborns without any medication. One of the anaesthetics produced sufficiently deep anaesthesia in all patients, and no signs of central depression were recordable from the newborns. The parameters of acid-base balance, following propanidid and etomidate anaesthesia, revealed respiratory acidosis in the newborns immediately after delivery by caesarean section. Their pH values were lower than those recorded in the context of ketamine anaesthesia or spontaneous delivery without any medication. Both values returned to normal within 30 minutes from delivery. The one-minute and five-minute Apgar scores were below those of spontaneous deliveries, at the beginning, but eventually reached normal levels. All the three anaesthetics were found to be suitable for introduction of general anaesthesia for caesarean section on account of high-rate enzymatic degradation and, consequently, absence of foetal depression. Resulting oxygen supply is higher, as compared to spontaneous delivery. Early indication and short-time introduction and delivery, thus possible, have often proved to be important to the newborn's condition.

[Comparative blood coagulation studies in PGF2a- and 15-methyl-PGF2a-induced therapeutic abortion]. / Vergleichende Gerinnungsuntersuchungen bei PGF2a- und 15-Methyl-PGF2a-induzierten therapeutischen Abortus.

In 15 pregnant women of the first trimenon of gravidity an interruption was performed by means of extra-amnial application of PGF2a and in 10 pregnant women by means of i. m. application of 15-methyl-PGF2a. Bleeding time, recalcification time, number of thrombocytes, heat fibrin, and thrombocyte adhesiveness were determined before, during and after treatment. Statistically significant changes could be observed during bleeding time, heat fibrin, and thrombocyte number. The investigations of coagulation, however, did not reveal any considerable impairment of the coagulation system, thus confirming the positive evaluation of prostaglandines used for therapeutic induction of abortion.

PIP: Abortion was performed during the first trimester in 15 pregnant women by means of extraamnial application of PGF2alpha and in 10 pregnant women by means of an intramuscular application of 15-methyl-PGF2alpha. Bleeding time, recalcification time, number of thrombocyte adhesiveness were determined before, during, and after treatment. Statistically significant changes could be observed during bleeding time, heat fibrin, and thrombocyte number. The investigations of coagulation, however, did not reveal any considerable impairment of the coagulation system, thus confirming the positive evaluation of PGs used for therapeutic induction of abortion. (Authors' modified)

Immunochemical investigations on the problem of the pregnancy zone protein. XII. Serum concentrations of pregnancy-associated alpha-2-glycoprotein in diabetic pregnancy.

The concentration in serum of the pregnancy zone protein (PZ), a high molecular pregnancy-associated alpha 2-glycoprotein, increases during pregnancy, when oral contraceptives are taken and under certain pathological conditions. PZ is probably part of a multifactorial immunological defence system which prevents the premature rejection of the fetus and placenta which together may be regarded as an allograft. Normally, the PZ serum concentration begins to rise during the 6th-12th week of pregnancy and reaches its peak at about the 24th week. The mean values then remain stable and afterwards diminish slightly toward the end of the pregnancy. In contrast, the mean values in mothers with insulin-dependent diabetes mellitus continue to rise. Excessively high serum PZ concentrations are significantly more frequent among pregnant diabetic patients, especially where there is also rhesus D antigen incompatibility. No correlation was found between excessively high values and the risk features used for the Priscilla White classification. A few patients with progressive proliferative retinopathy even had unusually low values.

[Experience obtained from intra-uterine foetal transfusion to cope with severe rhesus-caused haemolytic disease of foetus - ten-year report (author's transl)]. / Erfahrungen mit der intrauterinen fetalen Transfusion bei schwerem Rh-bedingtem Morbus haemolyticus fetalis. Ein 10-Jahres-Bericht.

Sixty-three intra-uterine transfusions were applied to 44 foetuses with foetohaemolytic disease, in Rostock, between 1967 and 1976. Patients were selected for treatment by means of stepwise prenatal diagnosis. Details of that selection are described together with the technique of intra-uterine transfusion, with reference being made also to risks and complications. The survival rate of children, following intra-uterine transfusion, accounted for 41 per cent. The survival rate of non-hydropic foetuses was 76 per cent and thus much beyond that of hydropic foetuses of whom only 19 per cent survived. While the incidence of severe foetohaemolytic disease due to blood-group incompatibility is on a declining trend, intra-uterine foetal transfusion should be maintained as a possible therapy for certain cases.

[Postnatal primary therapy of Morbus haemolyticus neonatorum in prematurely born infants, following intra-uterine foetal transfusion (author's transl)]. / Postnatale Primärtherapie Frühgeborener nach intrauteriner fetaler Transfusion bei schwerem Morbus haemolyticus neonatorum.

Intra-uterine foetal transfusion was applied in 63 instances to 44 patients with severe Rh incompatibility in the authors' hospital, between 1967 and 1976. Eighteen of 29 live-born children survived the neonatal period (41 per cent). - Nineteen live-born children with most severe M. h. n. received substitutions of O (d)-erythrocytes, immediately after birth. Ten children with moderate M. h. n. received exchange transfusions in a premature-birth ward not until four hours on average had elapsed from birth. - Comparison between the two groups would provide little consistent information on the effectiveness of such primary therapy, because of difference in severity. - The conclusion drawn by the authors is that the rare cases of severe M. h. n. should be transferred for treatment to a national therapeutic centre where adequate personnel and equipment are available for optimum intra-uterine or early postnatal treatment.

[The effects of Pavulon (pancuronium bromide) on maternal circulation and metabolism as well as on fetal metabolism and postnatal condition at Caesarean section (author's transl)]. / Der Einfluss von Pavulon (Pancuroniumbromid) auf den Kreislauf und Stoffwechselparameter von Mutter und Kind bei Sectio caesarea.

The effects of pancuronium bromide (Pavulon) on maternal circulation and metabolism as well as on fetal metabolism and postnatal conditions were studied in 13 women in late pregnancy (between gestational weeks 33 and 40) requiring Caesarean section in general anaesthesia. A comparison with results of 50 spontaneous deliveries without analgetics was performed. The average dosage of 4 mg did not effect the maternal blood pressure, fetal muscle tonus and cardiorespiratory adaption of the newborn. According to general anaesthesia we found in acid-base status a pH decrease with respiratory acidosis in comparison with spontaneous deliveries without anaesthetics, but pH and pCO2 were normalized 30 min after delivery. On the contrary, the oxygen tension were higher as at delivery as 30 min after delivery by Caesarean section. Although 1 minute Apgar score was lower than after spontaneous delivery the heart rate and frequency of ventilation were normal in every time and in the following minutes Apgar score was 7 to 10, too. An effect of pancuronium bromide to maternal or fetal carbohydrate metabolism could not be found. The less side effects on maternal cardiovascular system and the missing influence in postnatal condition recommand pancuronium bromide as a suitable relaxant in obstetrical anaesthesia, too.

[Serum concentration of the pregnancy-associated alpha2 glycoprotein (alpha2-PAG, protein of the "pregnancy zone", PZ) in malignant gynecologic diseases]. / Die Serumkonzentration des schwangerschaftsassoziierten alpha2-glykoproteins (alpha2-PAG, Protein der "pregnancy zone", PZ) bei malignen gynäkologischen Erkrankungen.

The concentration of pregnancy-associated alpha2-glycoprotein (alpha2-PAG, PZ) was investigated by means of electroimmunodiffusion and single radial immunodiffusion in sera of 30 patients suffering from malignant genital diseases. Results of electroimmunodiffusion indicate that surgical and/or radiological treatment is followed by a significant decrease of PZ serum level. But few months later values have been measured as detected before therapy. There were no significant differences of PZ levels in dependence on localization, histological findings and stage of gynaecological cancer. These findings indicate that periodic determinations of serum PZ do not supply the diagnosis for controlling the course of gynaecological cancer.

[Immunology of pregnancy -- more recent aspects of immunological mother-child relations (author's transl)]. / Schwangerschaftsimmunologie. Neuere Aspekte der immunologischen Mutter-Kind-Beziehungen.

An account is given of some topical aspects relating to immunology of pregnancy, with reference being made to more recent literature. Included are hypothetical considerations on undisturbed embryonic development, the barrier function of the placenta, the ontogenesis of the immune system, immunosuppressive factors of pregnancy serum, the macrophage function of placental cells, pregnancy proteins, and immunological peculiarities of EPH gestosis.

The macrophage electrophoretic mobility (MEM) test for the diagnosis of hydatidiform mole and choriocarcinoma. Preliminary report.

In 1970, Field and Caspary reported that lymphocytes from patients with malignant disease can be stimulated by a basic protein from human brain (human encephalitogenic protein--HEP). The stimulated lymphocytes are capable of releasing the macrophage-slowing factor, which reduces the electrophoretic mobility of guinea-pig macrophages. In general, this effect was not found with lymphocytes from patients without malignant disease. This paper deals with the application of the MEM test using HEP and HCG as antigen in the diagnosis of trophoblastic disease. We have found cellular sensitization against HCG in all patients with gestational trophoblastic tumours and against HEP in patients with hydatidiform moles of the group II or III as well as choriocarcinoma. Patients with malignant tumours of different localization showed a cellular sensitization against HEP, but only some against HCG. In pregnant women no cellular sensitization against HEP as well as HCG was detected. The results of the MEM test using HEP as antigen in patients with gestational trophoblastic tumours are compared with the clinical findings and the histological diagnosis. By means of this combination a more exact evaluation of the biological activity of the trophoblastic disease was obtained.

[Pregnancy proteins]. / Schwangerschaftsproteine.

Proteins, which are elevated in their blood concentration in pregnant women and patients suffering from malignant tumours, are reported because of their growing significance for the clinical practice. At present mainly are the following "pregnancy" proteins of clinical relevance: human chorionic gonadotrophin (HCG), human placental lactogen (HPL), placental heatstable alkaline phosphatase (HAP), pegnancy-associated alpha2-glycoprotein ("pregnancy zone" protein, PZ), socalled pregnancy-specific beta1-glycoprotein (SP1) and alpha1-fetoprotein (AFP). Applications to the clinical practice may be the surveillance of normal pregnancy, the recognition of dangerous conditions for mother and fetus, the inhibition of graft rejection, the induction of abortion, antibodies against pregnancy proteins as abortifacient and antifertilizer as well as the tumour diagnosis including the control of treatment and recognition of recidives.

[Immunochemical investigations on the protein of the "pregnancy zone". XI. Serum concentration of the pregnancy-associated alpha2-glycoprotein (Pregnancy Zone protein) in normal pregnancy (author's transl)]. / Immunchemische Untersuchungen zum Problem der "pregnancy zone". XI. Die Serumkonzentration des schwangerschaftsassoziierten alpha2-Glykoproteins (Protein der "pregnancy zone") in der normalen Schwangerschaft

A quantitative study of the pregnancy zone proteins was made in the sera of 383 healthy pregnant women by means of radial immunodiffusion according to Mancini and co-workers. The serum levels related to a pregnancy serum standard were measured from the 6th to 44th week of pregnancy. The serum concentration of the protein showed a considerable individual variation. The mean concentration began to rise in gestational weeks 8 to 24. Until the week 32 a rather stable average level was reached. Before delivery a slight decrease was observed. Women with over term pregnancies showed particular high mean concentrations. The differences of serum levels were statistically significant until the gestational week 14.

Macrophage electrophoretic mobility (MEM) test in malignant gynaecological diseases.

All patients examined [52] with malignant disease of the female genital tract showed lymphocyte reactions to encephalitogenic factor (EF) of more than 10% as measured by the macrophage electrophoretic mobility (MEM) test and its modification (MOD-MEM). Whilst 13 patients with non-malignant disease of the genital tract and 30 normals showed lymphocyte reaction to EF of less than 6%, 4 patients with nonmalignant gynaecological disease gave values above the 10% limit. The lymphocyte reactions of this latter group of patients were discussed with respect to their previous clinical histories. Some of the malignant cases were carcinoma of the cervix in situ so that the MEM test would appear to be of value in the early diagnosis of cancer. The need for caution in the interpretation of results is discussed as well as further possible applications of the technique.

[Intrauterine extra-amnial administration of prostaglandin F 2 alpha for the induction of abortion in primigravidae and problem cases]. / Intrauterine extraamniale Applikation von Prostaglandin F2alpha zur Abortusinduktion bei Primigravidae und "Problemfällen

With 529 patients (4 groups) abortion was induced through intermittend extraamniotic application of PGF2alpha. In 97,9 per cent, the hourly instillation of PGF2alpha led to the desired success: 25 (4,7 per cent) complete abortions, 416 (78,6 per cent) incomplete abortions, 77 (14,6 per cent) "missed" abortions with opening of the cervix. In groups I to III (primigravidae betw-en the 6th and 12th weeks of pregnancy), in the mean PGF2alpha dosages there were no significant differences between 6,84 and 6,27 mg. The mean abortion time was between 8 hr 32 min and 7 hr 43 min. In group IV ("problem cases" in the first and second trimester of pregnancy), the mean PGF2alpha dosage was 10,68 mg. The mean abortion time 12 hr 04 min. The total complication rate was at 2,2 per cent.

[Induction of labor by prostaglandin F 2 alpha in the treatment of hydatidiform mole]. / Weheninduktion mit Prostaglandin F2alpha zur Behandlung der Blasenmole

Labour was induced by intravenous infusion of prostaglandin F2alpha (PGF2alpha) in 12 patients with hydatidiform mole. After a mean infusion time of 15 h 51 min and a mean dosage of 25,1 mg PGF2alpha, the infusion of 5 to 40 mug PGF2alpha/min led to 1 to 3 cm dilatation of the cervix. In this way, it was possible to perform a mild evacuation of the molar tissue with vacuum curette or fixation forceps and curette. Under continued PG-infusion the uterus was contracted in the time of evacuation of hydatidiform mole. At present the preoperative dilatation of the cervix by means of PG-induced labour and vacuum curettage is the method of choice in the management of hydatidiform mole because of its effectiveness and few undesirable side effects.

On the influence of prostaglandin F2alpha-induced labor at term on the metabolism and coagulation of mother and fetus.

11 pregnancies at term were terminated by dilatation of the uterine cervix, low amniotomy, and by intravenous administration of PGF2alpha. The average infusion time was 3 hours 55 minutes, and the average total dose of PGF2alpha amounted to 2.0 mg. Parameters of acid-base changes, carbohydrate and energic state changes, gas metabolism, and changes in coagulation and fibrinolysis in mother and in fetus were analyzed during labor and after birth. Labor activity and fetal cardiac action were monitored cardiotocographically. Checked against 50 uncomplicated spontaneous deliveries, we found no disadvantageous changes in the parameters investigated.