Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis

BACKGROUND: It is suggested that the highly cation-charged fraction of the IgG and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast, immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column-low invasive selective immunoadsorbent apheresis therapy (SDSC-IAT) has been applied to lupus nephritis with favorable results. However, elimination using pathogenic IgG by SDSC-IAT has never been investigated. METHOD: Two patients with diffuse proliferative lupus nephritis were treated using SDSC-IAT concomitant with immunosuppressive therapy. The eluates from the SDSC, and the patients' serum obtained before and just after SDSC-IAT were subjected to an IgG charge analysis using isoelectric focusing and immunoblotting, and also to laser nephelometry assay, which is used for measuring IgG subclass concentration. Indirect immunofluorescence staining was performed to detect IgG subclass deposition in the glomerulus. RESULTS: Both of the patients had an immediate decrease in anti-double-strand DNA antibody and in the circulating immune complex with a following clinical improvement. Repeated biopsies demonstrated improvement of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG of the SDSC eluates consisted of highly cation charged (isoelectric points: 9-10) fractions. In addition, IgG3 was specifically removed from the patients' serum using an SDSC among the IgG subclasses. The subclass of deposited IgG in the glomeruli showed IgG3 predominance. CONCLUSION: SDSC-IAT specifically removed the highly cation charged fractions of IgG and IgG3 from the patients' serum and the elimination of these fractions may have resulted in clinical improvement.     

Effects of hydrocortisone and adrenaline on natural killer cell activity

We have studied the effects of hydrocortisone and adrenalineon natural killer (NK) cell activity and on the distributionof circulating lymphocyte sub-populations in 30 patients undergoingelective partial laminectomy under general anaesthesia. Thepatients were allocated to receive adrenaline (group 1, n =11), hydrocortisone and adrenaline (group 2, n = 11) or neitherhydrocortisone nor adrenaline (group 3, n = 8). Group 1 andgroup 2 patients received local adrenaline infiltration duringoperation to reduce bleeding. The mean dose of adrenaline administeredwas 2.1 (SD 0.2) µg kg^–1 Group 2 received hydrocortisone10 mg kg^–1 i.v. after premedication. In groups 1 and 2,adrenaline produced an instantaneous increase in NK cell activityaccompanied by a selective increase in circulating NK cells.The measurements returned to pre-infiltration levels within120 min of administration of adrenaline. The effect of adrenalinein causing increased NK cell activity was not blocked by pre-administrationof hydrocortisone. There was a significant decrease in the ratioof T helper/inducer cells (CD4) to T-suppressor/ cytotoxic cells(CD8) in all patients after induction of anaesthesia. In groups1 and 3, the CD4/CD8 cell ratio did not change significantlyduring operation. However, compared with groups 1 and 3, group2 showed a significantly reduced CD4/CD8 cell ratio during operation.Therefore, these results suggest that even in cases of suchsevere stress that the immune response was depressed by increasedserum cortisol concentrations, adrenaline-induced NK cell activityenhancement was preserved.     

Pharmacological Properties of β-Amyrin Palmitate,a Novel Centrally Acting Compound,Isolated from Lobelia inflata Leaves

Abstract— Effects of β-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, β-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg^?1). β-Amyrin palmitate (5, 10 and 20 mg kg^?1) or mianserin (5, 10 and 20 mg kg^?1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg^?1) increased locomotor activity and potentiated methamphet-amine-induced hyperactivity. β-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg^?1) and imipramine (10 and 20 mg kg^?1) antagonized the reserpine-induced effect. Unlike imipramine, β-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. β-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg^?1) decreased it in a dose-dependent manner. A potentiating effect of β-amyrin palmitate (5, 10 and 20 mg kg^?1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg^?1) but weaker than that of mianserin (2·5, 5 and 10 mg kg^?1). These results suggest that β-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action. We suggest that β-amyrin palmitate has antidepressant activity with a mianserin-like profile of action.     

Diagnosis of Small Pancreatic Carcinoma

A retrospective analysis was performed to evaluate the clinicalsymptoms and abnormal test findings in small pancreatic carcinoma.Five hundred and thirty-six cases of pancreatic carcinoma withthe histology of duct cell carcinoma were collected from 14medical centers in Japan. In 440 of the cases, tumor size wasmeasured at the time of laparotomy or from the resected specimen.Three hundred and seventy-seven patients (86%) had a carcinomalarger than 3.0 cm; only 30% of these were resectable. Sixty-threepatients (14%) had a carcinoma of 3.0 cm or less, with resectabilityof 97%. Detecting a tumor of "3 cm or less" with a high probabilityof resectability is the objective of early diagnosis with theresulting possibility of a cure. In most cases these small carcinomaswere found easily when obstructive jaundice was present (73%).However, the estimated occurrence of obstructive jaundice associatedwith carcinomas of 3 cm or less was only 10% among the totalcases of pancreatic carcinoma studied. Therefore, it is necessaryfor early diagnosis to detect carcinomas of 3 cm or less presentingwithout jaundice. The symptoms of small carcinoma without jaundiceare weight loss, anorexia, upper abdominal pain, back pain anda palpable abdominal mass. Among the various available examinations,endoscopic retrograde cholangiopancreatography, computerizedtomography and ultrasonography were valuable in diagnosing thesesmall carcinomas.     

Coronary risk factors in school children in relation to their family history of coronary heart disease and hyperlipidemia

A school-based study was implemented to assess the family history of coronary heart disease (CHD) and hyperlipidemia (HL) in relation to serum lipoprotein and apolipoprotein levels. One hundred and twenty-five elementary school students (aged9–10 years) and 297 junior high school students (aged12–13 years) participated. Family history was evaluated by the following scoring method: positive family history in a parent. 2 points: in a grandparent. 1 point: and onset of CHD before age 60, 1 additional point. Family history of HL was positive in 8.2% of elementary school students, and 4.2% in junior high school students. Family history of CHD was positive in 11.5% of elementary students, and 11.0% in junior students. Family history score (FHS) for HL was related to serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol, apolipoprotein A-T, apolipoprotein B (apoB) and lipoprotein (a) in elementary students, and to TC, LDLC, triglyceride and apoB in junior students. There was no relationship between FHS for CHD and serum lipoprotein or apolipoprotein levels in any student. The children with a positive FH of HL already demonstrated an atherogenic lipid profile while those with FH of CHD did not. which was probably because lipid profiles in children are more genetically mediated by a FH of HL than of CHD.     

A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders

A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) has been established to estimate serum thrombopoietin (TPO) concentrations in healthy volunteers and patients with haemopoietic disorders. The ELISA uses a mouse monoclonal antibody (Ab) as the capture Ab and a biotinylated rabbit polyclonal Ab as the detector. The ELISA was reproducible, highly sensitive and specific for human TPO. The coefficients of intra- and inter-assay variation were from 3.0% to 4.9% and from 5.9% to 6.1%, respectively. The quantitative limit of the ELISA was 0.09 fmol/ml in serum. The quantitative limit was lower than the normal level. The dose–response curves of serum samples from healthy volunteers and patients with haemopoietic disorders were parallel to the standard curves. The ELISA did not cross-react with a variety of blood components and cytokines to produce false-positive results.
The serum TPO concentrations from 29 normal males and 21 females were 0.79 ± 0.35 and 0.70 ± 0.26 fmol/ml, respectively. Serum TPO levels in patients with aplastic anaemia (AA), acute lymphocytic leukaemia (ALL) and essential thrombocythaemia (ET) were measured using the ELISA. The serum TPO levels in the patients with ET ( n  = 6, 2.80 ± 1.55 fmol/ml) were higher than the normal level. The patients with AA ( n  = 7, 18.53 ± 12.37 fmol/ml) and ALL ( n  = 5, 10.36 ± 5.57 fmol/ml) had significantly higher serum TPO levels than normal individuals. These results indicate that the ELISA specific to TPO should prove useful in measuring the TPO concentration in serum samples.     

Assessment of body composition measured by bioelectrical impedance in children

Bioelectorical impedance methods have been found to be a valid and reliable way of estimating per cent body fat (%BF) in adults. We applied them to healthy children and compared them with conventional anthropometry methods. One thousand two hundred and sixteen children participated in this study. Impedance and skinfold thickness were measured, and %BF was estimated using these values. Bodyweight and height were measured, and per cent obesity (%OB) and body mass index (BMI) were obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6 ± 4.0% in the junior male group, 14.2±2.8% in the junior female group, 7.9±4.7% in the senior male group and 16.1 ±2.9% in the senior female group. The % BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi correlated strongly with variables from conventional methods. It was concluded that it is a reliable way of assessing lipid storage in children.     

An α-adrenoceptor-mediated mechanism of hypoactivity induced by β-amyrin palmitate

Abstract— Inhibitory effects of β-amyrin palmitate in locomotor activity of mice were studied by combining this compound with α-adrenergic agonists or antagonists and a dopaminergic agonist. β-Amyrin palmitate (2·5, 5·0 and 10·0 mg kg^?1, i.p.) decreased locomotor activity of mice in a dose-dependent manner. It enhanced hypoactivity of mice treated with clonidine (0·025 mg kg^?1, i.p.) and antagonized hyperactivity produced by phenylephrine (40 μg, i.c.v.). The inhibitory action of β-amyrin palmitate was not affected by yohimbine (1·5 mg kg^?1, i.p.), but was potentiated by prazosin (0·75 mg kg^?1, i.p.). When combined with a dopaminergic agonist, apomorphine (2·0 mg kg^?1, i.p.), β-amyrin palmitate (5·0 and 10·0 mg kg^?1, i.p.) did not affect locomotor stimulation produced by apomorphine. These results suggest that β-amyrin palmitate might inhibit α₁-adrenoceptors.