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Biomedical subjects

H Link

Publications and source records attributed to H Link.

At least 469 records · Page 26Linked to original sources

Direct tissue isoelectric focusing of nervous system and muscle sections for detection of IgG patterns.

Agarose isoelectric focusing (IF) of 5-70 microns sections of frozen autopsy material (direct tissue IF; DTIF) from the central nervous system (CNS) and peripheral nervous system (PNS), and from muscle biopsy, followed by immunofixation with unlabeled or radiolabeled anti-serum against human gamma chains or IgG Fc fragments has been developed for analysis of IgG patterns. The DTIF technique followed by antiserum immunofixation is a promising tool for characterization of proteins in autopsy and biopsy materials from nervous and muscular systems. In multiple sclerosis brains, oligoclonal IgG bands were found which differed regarding number and mobility between the brains, and also between two different regions in single brains. For PNS, IgG patterns were easily detectable. In polymyositis muscle, no difference was found for IgG patterns when compared with normal muscle or serum.

Humans↗

Optic neuritis: oligoclonal bands increase the risk of multiple sclerosis.

In 1974 we examined 30 patients 0.5-14 (mean 5) years after acute unilateral optic neuritis (ON), when no clinical signs of multiple sclerosis (MS) were discernible. 11 of the patients had oligoclonal bands in the cerebrospinal fluid (CSF). Re-examination after an additional 6 years revealed that 9 of the 11 ON patients with oligoclonal bands (but only 1 of the 19 without this CSF abnormality) had developed MS. The occurrence of oligoclonal bands in CSF in a patient with ON is--within the limits of the present observation time--accompanied by a significantly increased risk of the future development of MS. Recurrent ON also occurred significantly more often in those ON patients who later developed MS.

Adolescent↗

Evaluation of anticoagulants in patients with cerebral infarction with slight to moderate neurological deficit.

In a non-randomized controlled study carried out on 238 hospitalized patients with cerebral infarction, anticoagulant treatment (AC) was compared with the natural course in the prevention of transient ischemic attacks (TIA), cerebral infarction, stroke, stroke or death. 137 patients were allocated to AC, mean follow-up 30.5 months, and 101 patients were allocated to the controls (untreated group), mean follow-up 25.2 months. There were no statistically significant differences among the patients in the group who had suffered TIA (AC treated group 10.2%, untreated group 5.9%), cerebral infarction (AC treated group 10.2%, untreated group 11.9%), stroke (AC treated group 14.6%, untreated group 12.9%), stroke or death (AC treated group 22.6%, untreated group 19.8%). Minor bleedings occurred significantly more frequently (P less than 0.01) in the treated group. Severe bleedings occurred in 8 patients in the treated group (5.8%) compared to 1 of the controls (1%). It is concluded from the trial that AC can only seldom be recommended as prophylactic against new strokes in patients with cerebral infarction due to arterial thromboembolism.

Adult↗

Synthesis of the complement factors C3 and C4 within the central nervous system over the course of aseptic meningitis.

The concentrations of complement factors C3 and C4 were quantified by single radial immunodiffusion in unconcentrated cerebrospinal fluid (CSF) and in serum from 38 patients up to 2 months after onset of acute aseptic meningitigs (AM). Elevated absolute concentrations were found in CSF in 26 and 35 patients, respectively, and in serum in 8 and 31, respectively. Elevation of the CSF C3 index, equal to (CSF/serum C3):(CSF/serum albumin), and of the corresponding CSF C4 index were found in 16 and 7 patients, respectively, as evidence of intrathecal synthesis. Only minor differences of the frequencies of elevated CSF C3 and C4 indices were encountered over the course of AM up to 2 months after onset. The occurrence of intrathecal C3 and C4 synthesis in AM is proposed as reflecting activation of hitherto unknown significance within the central nervous system.

Adolescent↗

Latent immunoglobulin G (Gm) allotypes: occurrence in the cerebrospinal fluid in some neuropathological states.

Gm allotypes were detected and quantitated by radioimmunoassay (RIA) in paired serum and CSF samples from patients suffering from various neurological diseases. Of 115 patients with neurological disorders (65 MS and 50 others), seven subjects displayed one or two allotypes in their CSF which were absent in serum. The Gm phenotype in the patient's serum allowed us to infer the genotype without the need of familial data. A comparison of the regression curves obtained in RIA from the unexpected allotype in CSF and the counterpart in a normal serum pool argued for an identity of the Gm antigen carried by both inhibitory molecules. The unexpected allotype(s) in CSF can be considered as the product of a latent Gm gene which may be activated by either immune perturbations due to the disease per se or some particular immune regulations in the central nervous system.

Humans↗

[Phase II study of AMSA in adults with acute therapy-refractory leukemias].

The acridine derivative AMSA, Amsacrine, is a new anticancer drug which was effective in patients with advanced AML and ALL in studies performed in USA. In a multicenter phase II trial we treated 27 patients with acute resistant leukemia with AMSA. All presented progressive disease following several drug combination regimens. Out of the 25 evaluable patients 5 were resistant to primary therapies, 13 were in 2nd relapse, 6 in 3rd, and 1 in 4th relapse. Dosage was 75 mg/m2, iv, day 1-7, all 3-5 weeks. On an average, only 76% of the planned dose per cycle could be given, due to severe leucopenia. From 21 patients with ALL, 1 CR and 3 PR were observed; the 3 patients with ALL presented 1 CR and 1 PR. 1 AUL showed progressive disease. In all patients a marked cell reduction could be observed in the peripheral blood. The general tolerance was good. The most important side-effect was bone-marrow toxicity, 48% (12/25) presented leucopenia less than or equal to 600/mm3, 5 (20%) had fatal septic complications. All 5 early death presented high initial leucocyte counts of greater than or equal to 32.000 mm3 as a common risk factor. In conclusion, AMSA is an effective drug in heavily pretreated patients with AML and ALL.

Adolescent↗

Utility of isoelectric focusing of cerebrospinal fluid and serum on agarose evaluated for neurological patients.

Agarose isoelectric focusing was used to demonstrate oligoclonal bands in cerebrospinal fluid (CSF) and serum from 998 consecutive neurological patients. Compared with agarose electrophoresis, agarose isoelectric focusing was slightly more sensitive, showing more (and more easily discernible) oligoclonal bands. Agarose isoelectric focusing, which has good reproducibility, revealed oligoclonal bands in CSF in 95% of 43 patients with multiple sclerosis, 44% of 39 with aseptic meningoencephalitis, and 14% of 906 with other neurological diseases. Interestingly, oligoclonal bands were found in CSF from 12% of 162 patients with acute cerebral infarction and 23% of 53 with polyneuropathy, and also in 29% of 17 with dementia, while only 4% of 206 patients with headache, vertigo, or psychoneurosis had this CSF abnormality. We recommend this procedure for the routine examination of paired CSF and serum specimens for the presence of oligoclonal bands.

Adult↗

[Bone marrow transplantation in patients with leukemia].

Between October 1979 and March 1982, bone marrow transplantations were performed by the Tübingen Group for BMT on 19 patients with acute leukemia in remission and on one patient with chronic myelocytic leukemia in chronic phase. The conditioning regimen consisted of 2 x 60 mg cyclophosphamide/kg and 10 Gy whole-body irradiation with the linear accelerator. The lung dose was limited by shielding to 8 Gy. In 15 patients, the bone marrow cell suspension of the donor was preincubated with antihuman T-cell globulin (AHTCG) for prophylaxis of graft-versus-host disease (GVHD). All patients showed prompt engraftment of donor cells with good hemopoietic function and complete chimerism. Under reverse isolation in sterile units, no severe bacterial or fungal infections were seen in the phase of bone marrow aplasia. Twelve in twenty patients survived between 25 and 900 days. A severe GVHD was seen only in two patients - one after preincubation with AHTCG. One patient died from relapse of his leukemia, another patient had a testicular relapse which was treated with local radiotherapy. Major problems were seen with chronic GVHD (six patients) and infectious complications, most importantly interstitial pneumonia, in the late post-transplant period.

Acute Disease↗

Demonstration of serum IgG antibodies against myelin during the course of relapsing experimental allergic encephalomyelitis in guinea pigs.

Chronic relapsing allergic encephalomyelitis (r-EAE) was induced in a local strain of guinea pigs. By the use of isoelectric focusing (IF) followed by antigen immunofixation and autoradiography, antibodies directed against central nervous system (CNS) myelin were detected in 21 of 23 sera sampled during the course of r-EAE. Previous absorption of the sera with CNS myelin reduced or abolished antibody activity on autoradiograms. One r-EAE guinea pig developed definite oligoclonal IgG bands in serum while in 7 r-EAE animals faint oligoclonal IgG bands were present. The mobility of oligoclonal IgG bands differed from the mobility of antimyelin antibody bands on autoradiograms. The significance of these findings has not been definitely elucidated but the antimyelin antibodies may possibly be involved in the pathogenesis of the disease while oligoclonal IgG bands may represent an epiphenomenon not pathogenetically related to r-EAE.

Animals↗

Agarose isoelectric focusing of unconcentrated CSF and radioimmunofixation for detection of oligoclonal bands in patients with multiple sclerosis and other neurological diseases.

Agarose isoelectric focusing (AIEF) of concentrated CSF was compared with AIEF of unconcentrated CSF and subsequent immunofixation with radiolabeled antihuman IgG Fc Fragment antiserum and autoradiography for the demonstration of oligoclonal bands in CSF from 287 neurological patients. Oligoclonal bands were demonstrated by AIEF in 98% of 43 patients with multiple sclerosis, 72% of 18 patients with infectious CNS diseases, and 23% of 226 patients with other neurological diseases. The corresponding figures obtained with AIEF of unconcentrated CSF and radioimmunofixation were 98%, 67% and 21%, respectively. In 15 of the patients, oligoclonal bands were demonstrated in CSF and serum by both techniques. They are both useful alternatives for the demonstration of oligoclonal bands in CSF, and the method for unconcentrated CSF can be safely applied when only small CSF volumes are available. The oligoclonal IgG pattern obtained by AIEF was not influenced by concentration of CSF by ultrafiltration and subsequent dilution to the original IgG concentration, nor by storage for 6 months.

Adult↗

Immunoglobulin abnormalities in cerebrospinal fluid and blood in children with febrile seizures.

In a prospective study performed in 1977-1978 (one year), all 90 children (age 6 months to 5 1/2 years, median 21 months) admitted due to febrile seizures were examined for blood brain barrier function and intrathecal immunoglobulin synthesis. The CSF/serum albumin ratio and CSF total protein reflected the blood brain barrier function, while intrathecal immunoglobulin synthesis was presented by determination of the CSF IgG index [CSF/serum IgG ratio]:[CSF/serum albumin ratio] and the corresponding CSF IgA index. CSF IgM concentrations were also determined. CSF and serum taken at admission were available from 64 children, and CSF and serum taken three to four weeks from 28. Intrathecal synthesis of one or more of the immunoglobulins was concluded to occur in 42% of the children at admission and in 25% at the follow-up examination. Normal blood brain barrier function and normal serum immunoglobulin concentrations were found. There were no relations to clinical variables.

Cerebrospinal Fluid Proteins↗

Progressive myoclonus epilepsy is not accompanied by humoral immune response within the central nervous system.

CSF and serum from five patients with progressive myoclonus epilepsy taken on two occasions with about one month's interval were examined for intrathecal humoral immune response. The CSF IgG and IgA index values were normal, and no oligoclonal bands were detectable by agarose electrophoresis or polyacrylamide isoelectric focusing (IEF). Immunofixation of IEF separated IgG with four different viruses as possible antigens, and autoradiography did not reveal any intrathecal antibody production. In contradiction to previous reports, no evidence was obtained for a local humoral immune response in progressive myoclonus epilepsy.

Adult↗

Specificity of immunoglobulins synthesized within the central nervous system in neurosyphilis.

Cerebrospinal fluid from four patients with serologically and clinically verified neurosyphilis contained oligoclonal bands when analysed by isoelectric focusing. By antiserum immunofixation these bands consisted by IgG, and by antigen immunofixation and autoradiography the bands were shown to contain treponemal antibodies. Treponemal antibodies synthesized within the CNS were also detected in polyclonal CSF IgG fractions in two of the patients. In one patient with neurosyphilis followed over 2.5 years, local synthesis of IgM and IgA disappeared within 1 year after treatment, while IgG synthesis persisted. In this patient, besides treponemal antibodies, antibodies against herpes simplex virus were also detected in oligoclonal and polyclonal IgG fractions of CSF. The presence of treponemal antibodies synthesized within the CNS was identified in 2 of 16 controls with negative serological tests for syphilis. This might reflect a previous contact with apathogenic treponemes, and the intrathecal antibody synthesis might be a result of an unspecific activation of memory lymphocytes in CNS.

Adult↗

[Combined chemotherapy and anti-oestrogen administration for metastasising breast carcinoma: randomised study comparing AVC and AVC plus tamoxifen (author's transl)].

In a randomised study two treatment schedules were compared in a total of 84 patients with metastasising carcinoma of the breast. Adriamycin (40 mg/m2 i.v.), vincristin (1 mg/m2 i.v. on day 1), and cyclophosphamide (200 mg/m2 p.o. on days 3--6) (AVC), and tamoxifen (20 mg twice daily) were given to 36 patients, while 48 patients (the control group) received only AVC, without anti-oestrogen. In both groups the AVC treatment cycle was repeated every 3-4 weeks. Remission rate (full or partial) of the AVCT group was 50%, that of the AVC group 54%. Median survival time among the former was 28 months, median duration of remission 18 months. Corresponding results with AVC treatment were 23 and 15 months, respectively. The better results on adding tamoxifen are statistically not significant (P greater than 0.05).

Adult↗

Viral antibody activity of oligoclonal and polyclonal immunoglobulins synthesized within the central nervous system in multiple sclerosis.

Thin-layer polyacrylamide gel isoelectric focusing (PAG IEF), a very high capacity method for separating immunoglobulins (Ig), was performed on cerebrospinal fluid (CSF) and serum. It was followed by antigen immunofixation with measles, mumps, herpes simplex (HSV), and rubella virus antigens and anti-human Ig autoradiography in order to demonstrate viral antibodies in separated Ig zones. Two of 11 control patients and 21 of 25 patients with multiple sclerosis (MS) displayed one or more zones of viral antibodies in the CSF without any counterpart, or with distinctly fainter zones, in the serum. Such reaction patterns were taken to indicate the possibility of intrathecal antibody synthesis. Antibody synthesis to measles was found in one to five zones in 76% of the patients with MS; antibody zones were found to HSV in 36% of the patients, to mumps in 12%, and to rubella in 12%. In 36% of the patients, two or three different antibody specificities (of which one was always measles) were found simultaneously in individual autoradiogram zones. For all viral antibodies detected in the CSF autoradiograms, their counterparts in oligoclonal or polyclonal IgG zones (or both) were demonstrable by PAG IEF of the corresponding CSF. The majority of patients with MS also had one or more oligoclonal CSF IgG zones without known antibody specificity. Antigen immunofixation and autoradiography are mainly qualitative. It is not known whether the viral antibodies present in oligoclonal or polyclonal IgG zones in MS CSF reflect a polyclonal B cell activation, a disease-specific immune reaction, or both.

Adolescent↗