Strain differences and the role for HSP47 and HSP70 in adjuvant arthritis in rats.

Because of high sequence homology between microbial and endogenous heat shock proteins (HSP), immunological cross-reactivity to microbial HSP has been suggested as a possible cause of the development of autoimmune diseases, such as rheumatoid arthritis. The present study aimed to determine a potential role of HSP47, a molecular chaperone involved in the synthesis and assembly of collagen molecules, and microbial HSP71 (mHSP71) in adjuvant arthritis (AA) in two rat strains: Dark Agouti (DA), susceptible to AA induction and Albino Oxford (AO), which is resistant to AA induction. Immunization with complete Freund's adjuvant (CFA) induced an increased expression of HSP47 in joints of DA rats, which exhibited severe clinical signs of AA at the time of disease peak, while this protein was not detectable in joints of AO rats. In contrast, no strain differences in HSP72 (rat analogue of mHSP71) expressions in joints were observed. The increased levels of anti-HSP47 antibodies were detected in sera of DA rats during the AA peak, while the immunization with CFA increased levels of anti-mHSP71 antibodies in sera of AO rats. HSP47 and mHSP71 reduced proliferation of draining inguinal lymph node cells (LNC) in resistant AO rat strain, leading to a hypothesis that both HSP participated in AA control. Finally, mHSP71 potentiated the apoptotic response of LNC in susceptible DA rat strain. In conclusion, our findings indicate involvement of HSP47 in the development of AA in the rat, and point out to the regulatory role for both HSP47 and mHSP71.

Perinatal outcome of pregnancies in women aged 40 and over.

Perinatal outcome of pregnancies at forty and over was analyzed starting from the diagnosis of pregnancy to seven days following delivery. Retrospectively, pre-gestational health and reproduction status were dealt with, as well as the course of pregnancy, deliveries, and newborn children (study group). The control group was composed of pregnant women aged 20 to 29, who were identical to study group in terms of parity. Statistical data processing was done by means of chi2-test, and contingency 2 x 2 tables. The difference was significant if p < 0.05. Out of 2,099 diagnosed wanted pregnancies at forty and over, 415 (19.8%) had a miscarriage, in 33 (1.6%) an artificial abortion was performed after determining the fetus karyotype and 1,651 (78.2%) of pregnant women delivered. In 66.2% of pregnancies the fetus karyotype was determined and in 33 (2.5%) fetuses chromosomal abnormalities were found Incidence of deliveries at 40 and over is 1.38%, which is a 35.6-percent increase in the last ten years. Nullipara and pluripara had an increase, and multipara had a decrease. Pre-gestational health and reproduction status in study group is lower than in control group. Complications during pregnancy: threatened abortion, EPH gestosis, placenta praevia, gestational diabetes, late fetal death are more frequent than in control group (p < 0.05). In intrapartal terms, more frequent were induction of delivery, meconium-stained amniotic fluid, fetal distress, operative vaginal deliveries, and Cesarean section (p < 0.05). In neonatal outcome there are more premature infant, there are more VLBW, LBW, SGA, newborn with low Apgar index values, and the total perinatal death is greater than in the control group (p < 0.05). In perinatal terms, (from the diagnosis to the seventh day following delivery) 1,617 children survived (77.0%), meaning that perinatal loss was 482 (23.0%). Authors conclude that pregnancy at 40 and over is a high-risk pregnancy. There is a high risk of pre-gestational and gestational complications, and perinatal loss is high. Therefore, those pregnancies are not desirable from the medical point of view.

Behavior and severity of adjuvant arthritis in four rat strains.

Previous research has suggested that behavioral traits of the histocompatible Lewis and Fischer strains of rats could be related to the difference in their susceptibility to adjuvant arthritis (AA). In the present study, the predictive value of behavioral markers in susceptibility to AA was investigated in nonhistocompatible inbred DA, Lewis, Albino Oxford (AO), and outbred Wistar strain. Behavioral profiles (open filed test and forced swim test) were determined prior to immunization with a single intradermal injection of complete Freund's adjuvant. Animals were daily scored for clinical signs of AA. The occurrence of certain behaviors and clinical indices of AA was significantly associated with strain membership. Discriminant analysis identified strain-related behavioral and illness profiles with very few overlaps among the phenotypes. Discriminant classification significantly exceeded the proportion of cases, which could have been correctly classified on the basis of chance. Open field behavior, in particular, exploration and grooming, differentiated among AA-susceptible and AA-resistant strains. Multiple regression analysis indicated that severity of AA (maximum clinical sign) can be predicted by the latency time and grooming behavior in the open field independently of strain membership. No clear distinction between AA-susceptible and AA-resistant strains was found with respect to forced swim test immobility. It was concluded that (a) strain-related genetic predisposition is important for the expression of certain behavioral traits and for susceptibility to AA and (b) open field behaviors, particularly grooming and latency, predict susceptibility to AA across different rat strains.

Effect of insulin and insulin-like growth factor I on fetal macrosomia in healthy women.

The aim of the study was to determine the values of insulin, insulin-like growth factor I (IGF-I) and glucose in the umbilical cord blood of macrosomic (> or = 4000 g) and control (3,000-3,500 g) infants born to healthy mothers, and to assess their possible correlation with the newborns' birth weight and maternal anthropometric parameters. A series of 207 macrosomic term infants, and 200 control term infants, born to healthy mothers with normal oral glucose tolerance test throughout gestation, were studied. The glucose concentration did not differ between the macrosomic and control group while macrosomic infants had significantly higher values of insulin and IGF-I. Female macrosomic infants had significantly higher levels of insulin and IGF-I than male macrosomic infants. The levels of insulin and IGF-I, but not levels of glucose, differed between the macrosomic and control group according to the maternal weight, height, pregestational body mass index, weight gain during gestation, and maternal birth weight. The maternal anthropometric parameters were significantly greater in the macrosomic infants. Accordingly, macrosomia was concluded to be a multifactorial condition.

Modulation of humoral immune responses in the rat by centrally applied Met-Enk and opioid receptor antagonists: functional interactions of brain OP1, OP2 and OP3 receptors.

We have previously demonstrated that central application of leucine-enkephalin (Leu-Enk) elicits potentiation and suppression of humoral immune responses through OP(1) (delta) and OP(2) (kappa) receptors, respectively. Interestingly, both effects were found to be additionally dependent on OP(3) (mu) receptor function. In the present study, we have further investigated whether opioid receptor interactions underlie the immunomodulatory effects of endogenous opioids as well as exogenously applied methionine-enkephalin (Met-Enk). For that purpose, the plaque-forming cell (PFC) response was determined in rats injected intracerebroventricularly (i.c.v.) with opioid receptor-selective antagonists and Met-Enk. Application of the OP(1) antagonist ICI 174864, but not naltrindole, resulted in suppression of the PFC response. In contrast, i.c.v. injection of the OP(2) selective antagonist nor-binaltorphimine (nor-BNI) significantly potentiated the PFC response. Both effects, presumably mediated by endogenous opioid peptides, were antagonized by the OP(3) receptor antagonist beta-funaltrexamine (beta-FNA) at a dose that was devoid of immunomodulatory activity. The immunopotentiation of the PFC response induced by Met-Enk was reversed by OP(1) receptor antagonists, naltrindole and ICI 174864, but not by beta-FNA or nor-BNI. On the basis of these and previous findings, it may be concluded that central OP(3) receptors are permissive for the central immunomodulatory action of endogenous opioid peptides and Leu-Enk. In contrast, the central immunoenhancing effect of Met-Enk appears to be mediated through OP(3)-independent OP(1) receptors.

Peripheral effects of methionine-enkephalin on inflammatory reactions and behavior in the rat.

Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central nervous system functions. The present study was conducted in order to compare peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met-Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H(2)O(2) production of peritoneal macrophages. Met-Enk-induced immunopotentiation was antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and vertical locomotor activity in the open field that was reversed by i. p. administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk applied i.p. did not affect the number of writhes in the test of analgesia. Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was previously shown to be immunostimulatory, enhanced only basal H(2)O(2) production of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides, i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H(2)O(2) production of peritoneal macrophages under basal and stimulated conditions, respectively. Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was sufficient to modulate immune functions did not influence behavior. It may be concluded that Met-Enk modulated nonspecific immune responses and open field behavior by peripheral mechanisms.

Changes in immunological and neuronal conditions markedly altered antibody response to intracerebroventricularly injected ovalbumin in the rat.

The serum antibody response to ovalbumin (OA) has been investigated following intracerebroventricular (i.c.v.) and intravenous administration of antigen in the rat, under altered neuronal and immunological conditions. I.c.v. administration of antigen was far more potent in eliciting humoral immune response. Central nervous system (CNS) immunization under the conditions of disrupted blood-brain barrier decreased anti-OA antibody production. Peripheral polyclonal stimulation with Bordetella pertussis increased production of specific antibodies to i.c.v. injected antigen, while complete Freund's adjuvant had no effect on the immune response. These results suggest that CNS compartmentalization of antigen may be critical for mounting strong antibody production, and that peripheral polyclonal stimulation of the immune system may markedly contribute to the overall intensity of the immune response.

Immune complexes and complement activation following rupture of intracranial saccular aneurysms.

Circulating immune complexes (CIC) and complement activation (plasma C3d levels) were monitored during a 2-week period in patients with ruptured cerebral aneurysms and also in patients with cerebral hematoma unrelated to saccular aneurysms. Thirteen of 18 aneurysm patients were found to have CIC on admission as compared to three of 21 healthy blood donors (p less than 0.001). The presence of CIC in aneurysm patients was associated with a poor prognosis. Eight of nine patients who developed angiographic vasospasm had CIC on admission compared with one of four without vasospasm. Patients with vasospasm showed a twofold increase in plasma C3d levels at the time when the spasm occurred, whereas no significant changes in the C3d concentration could be demonstrated in aneurysm patients without spasm or in patients with hematoma unrelated to aneurysm rupture. These findings suggest that immunological processes involving complement-activating immune complexes are involved in the pathogenesis of cerebral vasospasm following rupture of saccular aneurysms.

The significance of preoperative radiological examinations in patients treated with Cloward's operation.

During a fifteen-year period 1,106 patients with symptoms and signs of cervical disc disease underwent Cloward's operation. Plain x-rays were performed in 94%, but the severity and extension of degenerative changes had no prognostic value. In 91% of the patients myelography was performed and in recent years mainly metrizamide was used as it was found to be more accurate. The findings on the myelograms were correlated according to age, severity and number of affected disc levels, but were independent of the duration of symptoms. Patients with medullary symptoms were found more often than not to have an anterior indentation into the spinal canal whereas most patients with radicular symptoms had wide cervical root sleeves or lateral compression. The best outcome was found among patients with monosegmental symptoms and signs and one affected disc level on the myelogram underlining that the indication for surgery in cervical disc disease should be based on both clinical and radiological findings.

Dental and skeletal maturity in adoptive children: assessments at arrival and after one year in the admitting country.

Seventy-one adoptive children from Asian countries, mainly Korea, were adopted by Danish parents. Height and weight were measured and dental and skeletal maturity assessed immediately after arrival and one year later. Increase in dental age was in complete concordance with the time interval between the two examinations. With regard to skeletal age, the majority of children showed an increased maturation rate although some of the youngest children seemed to be further retarded in maturation rate during their first year in Denmark. Comparison between two methods for assessing skeletal maturity revealed that the 'catch up' observed for children above one year of age was significantly more pronounced when assessed by the TW-2 method than when applying the G-P method. For the Korean children height and weight measurements increased more than the average values for the Danish population.

Predictive value of radiculography in patients with lumbago-sciatica. A prospective study (Part II).

One hundred patients with symptoms of lumbo-sacral root compression were prospectively and consecutively assigned to operation based alone on clinical findings. A preoperative myelogram was performed in all patients and described without a knowledge of the clinical features. All patients were explored for the clinically and myelographically relevant disc. When the myelogram was normal (16 patients) both lower lumbar interspaces were exposed. In 58 patients a herniated disc was revealed at surgery. Only "myelographic herniation" with indentation of the contrast column was accompanied by a high frequency of disc herniation at surgery (73-87%). In cases with normal myelograms only 5% had a disc herniation. The severity of the myelographic finding was clearly correlated to the frequency of positive surgical findings and good outcomes. The preoperative radiculogram gives a high degree of certainty in the preoperative evaluation whether a surgical lesion is present or not and reveals a precise prediction of the outcome of surgery.

Predictive value of clinical and surgical findings in patients with lumbago-sciatica. A prospective study (Part I).

In a prospective, consecutive study of patients with lumbar back pain and sciatica, various clinical features and surgical findings were evaluated in order to analyse the predictive value regarding (1) level of diseased interspace (2) presence and type of lesion responsible for root compression (3) outcome after surgery. One hundred patients underwent surgery solely on clinical grounds. Fifty-eight had disc herniation. The level of disc herniation was correctly predicted in three quarters of patients with a prolapsed disc. The outcome after surgery was good in 77 patients. Only few clinical features, namely male sex and scoliosis were predictors of a good outcome. Lasegue's sign was indicative of root compression in 90%, but only two-thirds had disc herniation. Conversely one-third had disc herniation in spite of a "negative" test. Lasegue's sign was not superior to other clinical tests in predicting outcome. The most important indicator of a good outcome was the presence of disc herniation at surgery. Patients with disc pathology other than true disc herniation fared equally with patients, who had normal discs disclosed at surgery. Myelography was undertaken in all patients prior to surgery, the results of which are analysed in the following paper. (Espersen et al.: Predictive value of radiculography in patients with lumbago-sciatica. A prospective study (Part II, Acta Neurochirurgica 73 (1984), 213-221.

[Problems in the diagnosis of pheochromocytoma (author's transl)]. / Problematik der Phäochromozytomdiagnose

Reference is made to various possibilities of examination in diagnosis and localisation of pheochromocytoma demonstrated by several cases. The best radiological examination is angiography using Seldinger method, which by means of skilled technique, good contrast media and an optimal treatment with receptor-blocking medicaments will guarantee excellent x-rays for clear tumor localisation without real complications.