Development and evaluation of an enzyme-linked immunoassay for the prostate: specific antigen utilizing two monoclonal antibodies

Summary PSA is an important tumor-marker for prostatic cancer disease. We developed a sensitive, simple and inexpensive Sandwich ELISA for PSA with two monoclonal antibodies. The precision and reliability of the assay are reflected in the low inter-and intraassay coefficient of variation. PSA was not detectable in sera from normal females (n=50). Sera from males with different serum levels of PSA (normal males, patients with prostate hypertrophy, prostate cancer patients, n=79) and 15 prostate cancer patients treated with Zoladex were measured by our ELISA and by a commercially available RIA. The correlation coefficient between these both testsystems was close to 1 (r=0.97).     

Toxicity of lead acetate to female rabbits after chronic subcutaneous administration. 1. Biochemical and clinical effects

The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10–0.20 g/kg body weight and the high-dose group (15 animals) 0.80–1.20 g/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 g/l after 70 days and in the high-dose group to ca. 900 g/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60–70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stippling of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the highdose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in serveral soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 g lead/l blood no adverse effects were observed that did occur at the high dose level.Part 2, dealing with the histopathology and (electron) microscopy of the kidneys is in preparation     

Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: First steps towards monitoring process activity

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of -endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immuno-regulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation — including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages — often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.     

抗A1试剂血清的研制

目的 :ABO亚型在临床输血中经常造成错定血型及输血反应 ,因而研制抗A1试剂血清是解决ABO亚型鉴定的主要途径。方法 :采用血型血清学特异性抗原抗体吸收实验。结果 :经大量反复实验 ,研制出特异性强 ,效价符合要求的抗A1试剂血清。结论 :抗A1血清是鉴定A亚型的专用试剂血清 ,对临床鉴定ABO亚型及安全输血有实用意义。     

Prevalence and clinical relevance of Blastocystis hominis in diverse patient cohorts

The pathogenicity of Blastocystis hominis is extensively debated in the medical literature. Therefore, we did a prevalence study to investigate the association between the presence of several intestinal parasites and gastrointestinal symptoms in diverse patient cohorts. The study population consisted of 1216 adults, including immunocompromised patients, institutionalized psychiatric or elder subjects, immigrants from developing countries, travellers to developing tropical countries and controls. Several variables for each risk group were considered. Stools specimens, collected in triplicate, were processed by the same technicians. Clinical data about each subject were provided by standardized questionnaires. The presence of gastrointestinal symptoms were related to the presence of any parasite. In addition, on the basis of microbiological results, five subgroups of subjects were evaluated. The results showed a high prevalence of parasites in all the risk groups. Immunocompromised status, recent arrival from developing countries and the presence of behavioural aberrations were significantly related to presence of parasites. B. hominis was the parasite most frequently detected in each studied group. B. hominis showed a significant correlation with gastrointestinal symptoms only when detected in the group including subjects with a severe immunodepression. Immunodepression seems to be a factor of primary importance of the pathogenic role of B. hominis.     

Clinico-immunological profile in juvenile rheumatoid arthritis—an Indian experience

From a Pediatric Rheumatology Clinic 361 children diagnosed as juvenile rheumatoid arthritis (JRA) according to American Rheumatism Association-JRA criteria were studied retrospectively for their clinico-immunological profile. The mean age of onset in systemic, pauciarticular and polyarticular onset, JRA subtypes were 5.2, 6.8 and 7.2 years respectively. There was male preponderance in systemic and pauciarticular JRA. In seropositive polyarticular JRA, girls outnumbered boys. The frequency of occurence of systemic, pauciarticular and polyarticular disease was 87 (24%), 108 (30%) and 166 (46%) respectively. The systemic onset disease was dominated by extra-articular manifestations in terms of fever (100%), rash (57%), hepatomegaly (51%) and lymphadenopathy (25%). The pauci- and polyarticular illnesses were commonly dominated by joint involvement, morning stiffness, and in few patients, by extra-articular manifestations also. The joints were involved symmetrically. Most commonly involved joints in order of decreasing frequency were knee, ankle, wrist and elbow in all the subtypes. Anemia and leucocytosis were observed in majority with higher frequency in systemic onset JRA. The rheumatoid factor (RF) was present in 15% of polyarticular JRA. RF was also present in 7 and 9% of patients with pauciarticular and systemic subtypes respectively. The antinuclear antibody was positive in only 3 out of 66 patients in whom the test was carried out. The demographic profile and trends in clinical features were similar to the studies reported on caucasian population with difference in the actual frequency of various clinical features.     

Acyclovir treatment of relapsing-remitting multiple sclerosis

Acyclovir treatment was used in a randomized, double-blind, placebo-controlled clinical trial with parallel groups to test the hypothesis that herpes virus infections are involved in the pathogenesis of multiple sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or placebo tablets three times daily for 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological examinations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on intent-to-treat data and the primary outcome measure was the exacerbation rate. In the acyclovir group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo group (n = 30) had 94 exacerbations and an annual exacerbation rate of 1.57. Thus, 34% fewer exacerbations were encountered during acyclovir treatment. This difference in exacerbation rate between the treatment groups was not significant (P = 0.083). However, this trend to a lower disease activity in acyclovir-treated patients was supported in subsequent data analysis. If the patients were grouped according to exacerbation frequencies, i.e. into low (0–2), medium (3–5) and high (6–8) rate groups, the difference between acyclovir and placebo treatment was significant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbation rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (n = 19) and placebo (n = 20) patients and acyclovir-treated patients showed a significant reduction of exacerbations (P = 0.024). Otherwise, neurological parameters were essentially unaffected by acyclovir treatment and there were no convincing signs of reduced neurological deterioration in the acyclovir group. This study indicates that acyclovir treatment might inhibit the triggering of MS exacerbations and thus suggests that acyclovir-susceptible viruses might be involved in the pathogenesis of MS. This possibility warrants further investigation.     

Relationship between anterior fontanelle pressure measurements and clinical signs in infantile hydrocephalus

The treatment of choice in progressive hydrocephalus is drainage of cerebrospinal fluid in order to reduce elevated intracranial pressure (ICP). Defining the right moment for surgical intervention, however, in a hydrocephalic infant on the basis of clinical signs alone can be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. In the present study, the relationship between long-term anterior fontanelle pressure (AFP) measurements and clinical signs was investigated in 37 infants with hydrocephalus. The decision as to whether to operate or not was based on clinical signs alone; AFP values were not taken into account. There was an overall difference between the non-operated group and the preoperative measurements in the operated group, and also between the preoperative and the postoperative measurements in the latter, in regard to both AFP measurements and clinical signs. Almost all preoperative AFP values were increased. The direct correlation () between most individual clinical signs and AFP levels, however, was low (=0.15–0.41). The clinical sign tense fontanelle showed the best correlation with the AFP levels (=0.75). Furthermore, using logistic regression analysis, no combination of clinical signs could be found which reliably predicted the AFP. The relationship between the AFP pressure variables and clinical signs was also examined. The pathological A-waves occurred only in the presence of raised (baseline) AFP, a situation in which considerably more frequent B-waves were observed as well. It was concluded that clinical signs of raised ICP in infantile hydrocephalus are not very reliable and AFP monitoring can therefore provide valuable information on intracranial dynamics in patients with dubious neurological manifestations of progressive hydrocephalus.