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Biomedical subjects

R Milo

Publications and source records attributed to R Milo.

At least 19 recordsLinked to original sources
PubMed1995

Interferon beta-1b reduces interferon gamma-induced antigen-presenting capacity of human glial and B cells.

Interferon (IFN) beta-1b has been shown to alter the course of multiple sclerosis and to inhibit MHC class II expression, but its effect on antigen presentation has not been examined in a functional assay (Neurology 43 (1993) 655-661). The effect of IFN beta-1b on alloantigen presentation by human antigen-presenting cells (APC) including human fetal astrocytes (HFA) and microglia was examined. The effect of IFN beta-1b on the ability of B cells to present tetanus toxoid (TT) to TT-specific T cell lines was also examined. APC were pre-treated with IFN gamma (100 units/ml), IFN beta-1b (10-2000 units/ml), or a combination of IFN gamma and IFN beta-1b for 3 days and washed thoroughly prior to culture with allogeneic peripheral blood lymphocytes (PBL) for a period of 6 days. Lymphocyte proliferation was then measured by tritiated thymidine uptake. Treatment of the APC with IFN beta-1b resulted in a reduction in the IFN gamma-enhanced alloantigen-induced T cell responses. This reduction ranged between 50 and 70%, was associated with a 30-50% reduction in HLA class II (DR) and 35-40% reduction in ICAM-1 expression on the HFA used as APC. IFN beta-1b pretreatment of B cells reduced their constitutive and IFN gamma enhanced capacity to present TT to TT-specific T cell lines by 50-80%. This was associated with a 30 +/- 11% mean reduction in class II (DR) expression and approximately 50 +/- 1% reduction in ICAM-1 expression in IFN beta-1b + IFN gamma-treated B cells compared to IFN gamma-treated B cells (mean of three experiments).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Additive effects of copolymer-1 and interferon beta-1b on the immune response to myelin basic protein.

Copolymer-1 (Cop-1) inhibits the T cell response to myelin basic protein (MBP), suppresses experimental autoimmune encephalomyelitis in many animal species, and was recently shown to be effective in the treatment of multiple sclerosis (MS). Interferon beta-1b (IFN-beta), an immune modulator with no antigenic specificity, is already approved for treatment of relapsing-remitting MS. We investigated the combined effect of these two agents on the cellular immune response to MBP. Antigen-specific Th1-like cell lines were generated from two healthy individuals with different MHC phenotypes. Cop-1 inhibited the proliferation of all MBP-specific lines but had no suppressive effect on tuberculin (PPD) or tetanus toxoid (TT)-specific T cell lines from either donor, while IFN-beta non-specifically reduced proliferation of all T cell lines. When combined in vitro, Cop-1 and IFN-beta had additive suppressive effects on proliferation of MBP-specific T cell lines, with 70-100% inhibition depending on the concentration of antigen. Synthesis of the pro-inflammatory cytokines interleukin-2 and IFN-gamma by MBP-specific lines was also inhibited additively (up to 100%). When antigen-presenting cells (APC) were pretreated with Cop-1, IFN-beta or both, T cell proliferation was inhibited in the same additive pattern, even though the inhibitors were not present in culture, indicating that they acted primarily through modulation of APC function. Additive effects were not found with PPD- or TT-specific cell lines. Pretreatment of APC with IFN-beta resulted in dose-dependent reduction in HLA-DR and HLA-DQ expression, which paralleled inhibition of T cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗
PubMed1993

Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein.

Although T cell responses to the quantitatively major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP), are likely to be of importance in the course of multiple sclerosis (MS), cell-mediated autoimmune responses to other myelin antigens, in particular quantitatively minor myelin antigens, such as myelin-associated glycoprotein (MAG) and the central nervous system-specific myelin oligodendrocyte glycoprotein (MOG), could also play a prevalent role in disease initiation or progression. Highly purified myelin antigens were used in this study to assess cell-mediated immune response to MOG in MS patients, in the context of the reactivity to other myelin antigens, MBP, PLP, and MAG. The greatest incidence of proliferative response by MS peripheral blood lymphocytes was to MOG, as 12 of 24 patients tested reacted and, of these, 8 reacted to MOG exclusively. In contrast, only 1 control individual of 16 tested reacted positively to MOG. The incidence of responses to MBP, PLP, and MAG did not differ greatly between MS patients and control individuals. A predominant T cell reactivity to MOG in MS suggests an important role for cell-mediated immune response to this antigen in the pathogenesis of MS.

Adolescent↗
PubMed1992

Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein.

Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has been shown to be effective in suppression of experimental allergic encephalomyelitis and has been proposed as a candidate drug for multiple sclerosis. Cop 1 is immunologically cross reactive with myelin basic protein (BP) and was shown to inhibit murine BP-specific T-cell lines of various H-2 restrictions. In the present study these findings were extended to include human T-cell lines. Cop 1 competitively inhibited the proliferative responses and interleukin 2 secretion of six BP-specific T-cell lines and 13 clones with several DR restrictions and epitope specificities. Conversely, BP inhibited--albeit to a lesser extent--the response of all the Cop 1-specific T-cell lines and clones, irrespective of their DR restrictions. Another random copolymer of tyrosine, glutamic acid, and alanine, denoted TGA, had no effect on these lines. Neither Cop 1 nor BP inhibited the response of lines and clones specific for purified protein derivative. Cop 1 and BP exerted their cross-inhibitory effects only in the presence of antigen-presenting cells. These results suggest that Cop 1 can compete with BP for the binding to human major histocompatibility complex molecules. In view of recent studies implicating BP reactivity in multiple sclerosis, these findings suggest a possible mechanism for the beneficial effect of Cop 1 in this disease.

Antigen-Presenting Cells↗
PubMed1991

"Prokinetic" treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride.

The effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome (IBS) were evaluated in a randomized, double-blind, placebo-controlled study. Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d.; this dosage could be changed if necessary. The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 (p less than 0.05) during weeks 8-12 of treatment, and the number of days with stools of normal consistency increased to 3.5 and 1.9 (p less than 0.05), respectively. At week 12, the reduction in severity and frequency scores for abdominal pain was significantly greater (p less than or equal to 0.05) in the cisapride group (60 and 61%) than in the placebo group (40 and 32%), as it was for abdominal distension (p less than 0.05). Cisapride tended to be better than placebo in diminishing flatulence. In 71% versus 39% of the patients the overall rating for the response to treatment was good or excellent at week 12. Cisapride was well tolerated. These results suggest that the drug will be useful for the management of constipation-predominant IBS.

Abdominal Pain↗
PubMed1991

Tiapride as treatment for certain patients with idiopathic torsion dystonia.

Five female patients with idiopathic torsion dystonia (ITD) responded to treatment with tiapride, a selective D-2 dopamine antagonist. Previous treatments with various drugs, including anticholinergics, were ineffective. It is suggested that the previously reported genetic subgroups of ITD respond to different drug regimens. The autosomal dominant group responded to anticholinergics, while the autosomal recessive group responded best to a selective D-2 dopamine antagonist.

Adult↗
PubMed1989

Acute intermittent porphyria in pregnancy.

A 27-year-old, previously healthy normotensive woman was admitted for hyperemesis gravidarum and treated with intravenous fluids and metoclopramide. Thereafter, a neuropsychiatric syndrome developed, with acute asymmetrical axonal motor-sensory polyneuropathy and marked anxiety, depression, irritability, and memory and concentration difficulties. Raised porphyrin precursors were found in the patient's urine, but not in her feces. Although the association of acute porphyria and pregnancy is rare, the pregnancy itself, combined with a state of starvation, and the administration of metoclopramide, could have precipitated the acute attack in this case. Thiamine deficiency, Guillain-Barré syndrome, and an obstetric complication producing closely related symptoms were excluded. The drug was stopped and the patient was treated with a high-carbohydrate diet and physiotherapy. A normal infant was delivered spontaneously at term.

Acute Disease↗
PubMed1988

CSF fistula and tension pneumatocele 22 years after head injury.

An unusual case of CSF fistula and tension pneumatocele developing in a patient 22 years after a severe craniocerebral injury is reported. The patient had been asymptomatic during this long interval, but immediately after a minor head trauma massive rhinorrhea and diffuse pneumocephalus occurred. This was followed by the development of bifrontal tension pneumatocele with intracranial hypertension and neurological deterioration. The patient recovered after closure of the CSF fistula. The pathophysiological mechanism of this rare condition and the pertinent treatment are discussed.

Brain Concussion↗
PubMed1987

Delayed epidural hematoma. A review.

Since the CT has become the main diagnostic tool in head trauma, more cases of DEDH have become confirmed and published although some have been classified among other entities and under different criteria. This review tries to describe the characteristics of DEDH based on the cases previously published, as well as on three of our own cases. The entity is mainly radiological i.e. appearance of an epidural hematoma in a CT scan following up a previous one which has not shown this pathology. Although not specific, we have found some common features among the cases published. The patients are usually young people. The cause of many injuries is either a fall injury or involvement of a pedestrian in a road accident. Skull fracture under which the DEDH develops is the rule. DEDH is not found in the usual location of the classic epidural hematoma (the temporal fossa). Some of the patients developed DEDH after an earlier neurosurgical operation for evacuation of another traumatic mass lesion for urgent decompression. Others developed DEDH after medical treatment aimed at restoring normal blood pressure or reducing increased ICP. This main group of patients had other associated lesions, mainly intracranial. The others (including our case no. 1) were considered to have a skull fracture associated only with concussion of the brain, as the clinical picture changed or persistent headache developed, another CT scan was indicated and DEDH was then found. This group constitutes those patients in whom the prognosis is expected to be good or excellent. Keeping in mind the necessity for repeated CT scans in this group (we think the number will increase in the future), other patients will benefit from the awareness of the clinician of the importance of this diagnostic tool. CT scan is efficient, accurate and can be repeated at short intervals. It enables a correct diagnosis to be made in nearly 100% of cases of head trauma. Although this liberal use of CT may increase the number of negative scans, it will also increase the number of DEDH's diagnosable at an earlier stage.

Adult↗
PubMed1980

Use of the peripheral dopamine antagonist, domperidone, in the management of gastro-intestinal symptoms in patients with irritable bowel syndrome.

An evaluation was carried out of the effect of domperidone on gastro-intestinal symptoms in patients with irritable bowel syndrome. Ninety-eight patients were included; 32 in an open pilot study and 66 in a double-blind placebo-controlled study. Domperidone was taken at a dosage of 10 mg tablets 4-times daily. At the end of the 4-week treatment, symptoms had disappeared or were at least markedly improved in about 80% of the domperidone-treated patients. Significant superiority of domperidone to the placebo was observed for the symptom clusters 'post-prandial flatulence', 'abdominal pain' and 'abnormal bowel habit'. No side-effects were reported.

Abdomen↗
PubMed1976

Congenital enzymopenic methaemoglobinaemia. Clinical and biochemical study of a family with three homozygotes.

Three brothers with congenital recessive methaemoglobinaemia without mental retardation were found to be homozygous for NADH diaphorase deficiency. Twelve family members were heterozygous. One of the probands had marked digital clubbing, an unusual feature in this disease. In the probands, the red-cell NADH diaphorase was very low and unstable, whereas in the leucocytes this enzyme was present at a normal level. Isoelectric focusing of haemoglobin in the three probands showed that the alpha-chain was preferentially oxidized spontaneously. This confirms the greater oxidizability of this chain, as already described on isolated chains.

Adolescent↗