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Biomedical subjects

B Harding

Publications and source records attributed to B Harding.

At least 37 records · Page 2Linked to original sources

Diagnostic difficulties in infantile neuroaxonal dystrophy. A clinicopathological study of eight cases.

The clinical features of eight children with infantile neuroaxonal dystrophy are presented. Diagnosis was established by brain biopsy (4 cases), conjunctival biopsy (1 case), and the family history (2 cases), while in one case a presumptive diagnosis was made on the combination of clinical and neurophysiological findings without histopathological confirmation. The pleomorphic clinical picture and variable neurophysiological findings make a firm diagnosis difficult without histopathological confirmation. However, in the appropriate clinical context, serial neurophysiological investigations (ERG, VEP, EEG, ENMG) may suggest the diagnosis after the age of 2 years. Conjunctival biopsy is not invariably helpful, and neuroaxonal spheroïds are not always demonstrated in brain biopsies by conventional techniques. However, they were consistently identified using a non-specific esterase stain and by electron microscopy. This technique is described, and the significance of ultrastructural and neuropathological findings in infantile neuroaxonal dystrophy is discussed.

Axons

Autotransplantation of splenic tissue after splenectomy in rats offers partial protection against intravenous pneumococcal challenge.

Thirty-six splenectomized Sprague-Dawley rats with omental implants of splenic tissue were challenged with intravenous pneumococci. The mortality rate in this group was compared to 31 similarly challenged splenectomized and 28 normosplenic rats. The results showed that while rats with implanted splenic tissue had a better survival rate (p = 0.04) than splenectomized rats, their survival was poorer than that of rats with normal spleens (p = 0.02) (Fischer's exact test).

Animals

Class II histocompatibility antigens on human dendritic cells.

Histocompatibility antigens of the HLA D locus on the surface of human dendritic cells (DC) were visualized in the electron microscope using immunogold labelling. DC from peripheral blood expressed DR that was frequently concentrated at junctions between aggregating DC and lymphocytes or DC and macrophages. Labelling with an antibody to DQ was more diffuse and was not concentrated at points of cell-cell contact. The D locus antibody RFD1 labelled DC in distinct patches that were sometimes located at points of cell contact. Upon labelling DC with antibody to DR and incubating the cells at 37 degrees, some label remained on the cell surface but some was found in deep channels which appeared to be formed between veils at the surface of the cell and became internalized in membrane-bound structures. Under the same conditions, gold bound to DQ molecules remained on the surface of DC. Gold labelling RFD1 also remained mainly on the cell surface but there was occasionally internalization of patches into the cells through depressions in the cell membrane. The changes in distribution of the label on warming the cells suggests that materials bound to different D locus products may be 'processed' differently.

Cell Adhesion

Subacute combined degeneration of the cord, dementia and parkinsonism due to an inborn error of folate metabolism.

A 2-year-old girl with 5,10-methylenetetrahydrofolate reductase deficiency developed subacute combined degeneration of the cord and a leuco-encephalopathy which was confirmed at necropsy. Total folate concentrations in serum, red cells and CSF were markedly reduced whereas vitamin B12 concentrations were normal. In addition the patient had Parkinsonism and reduced concentrations of homovanillic acid, 5-hydroxyindoleacetic acid and total biopterins in cerebrospinal fluid. Folic acid administration was accompanied by fits and acute deterioration in the movement disorder. At necropsy the basal ganglia showed no detectable abnormality.

5,10-Methylenetetrahydrofolate Reductase (FADH2)

The distribution of dendritic cells in the synovial fluids of patients with arthritis.

We have investigated the cellular composition of 108 consecutive samples of synovial fluid from patients with Juvenile Chronic Arthritis (JCA), Rheumatoid Arthritis (RA) and Osteoarthritis (OA). Particular emphasis was placed upon the enumeration of cells with dendritic morphology and the study of their in vitro function. Whilst the cellularity of the synovial fluids varied by a factor of greater than 100 within patient groups, the fluids obtained from patients with inflammatory arthritis (JCA & RA) were more cellular than those from patients with non-inflammatory arthritis (OA). This was also noted with respect to both the number and proportion of dendritic cells. The dendritic cells stimulated allogeneic mixed leucocyte reactions, and enhanced mitogenic responses of peripheral blood lymphocytes when present in numbers as low as 1% of the total mononuclear cells. Syngeneic stimulation of blood lymphocytes by similar numbers of dendritic cells was usually negative. However, occasionally there was a marked syngeneic stimulation, which may be evidence for the presentation of antigen by dendritic cells within the arthritic joint.

Arthritis

Influence of splenectomy and the functional hyposplenism of coeliac disease on platelet count and volume.

Platelet count and volume were measured in 84 splenectomised subjects, 142 patients with coeliac disease and 77 healthy subjects. An inverse, non-linear correlation between platelet count and volume was found in healthy subjects and coeliac patients, but was not present in splenectomised subjects who had higher platelet counts (P = 0.0001) and mean platelet volumes (P = 0.0001) than healthy subjects. Platelet counts correlated with splenic function in patients with coeliac disease and were higher in patients with severe hyposplenism than in normosplenic coeliacs (P = 0.0001). Splenic function did not influence the mean platelet volume (MPV) in coeliac disease but normosplenic coeliacs had higher MPV than normal subjects (P = 0.05). Serum iron and red cell folate were not correlated to MPV in coeliac disease. We conclude that splenic function effects platelet count and volume in non-coeliac subjects and platelet count in coeliac disease. However, other unidentified factor(s) influence the MPV in coeliac disease.

Adolescent

Outcome of anorexia nervosa.

100 females with anorexia nervosa were followed up 4-8 years after first presentation. All but 12 had had refeeding and/or psychotherapy. 48 had a good outcome (weight at least near normal, regular menstruation, largely satisfactory mental state and psychosexual and psychosocial adjustments) but outcome was intermediate in 30, and poor in 20 patients. 2 had died. Poor outcome could be positively associated with clinical data such as longer duration of illness, older age of onset and presentation, lower weight during illness and at presentation, presence of symptoms such as bulimia, vomiting, and anxiety when eating with others, poor childhood social adjustment, and poor parental relationships.

Adaptation, Physiological

Selective decrease in antibody-dependent cell-mediated cytotoxicity in systemic lupus erythematosus and progressive systemic sclerosis.

With the use of two target cells (chicken erythrocytes and Chang cells), the antibody-dependent cell-mediated cytotoxicity (ADCMC) of peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) was studied. Patients with active SLE had a significant reduction in ADCMC against Chang cells whereas cytotoxicity against chicken erythrocytes did not differ significantly from that of a control population. Similarly, a group of PSS patients with positive anti-DNP antibodies demonstrated a selective reduction in ADCMC against Chang cells. These findings support the concept that different effector cells mediate ADCMC against chicken erythrocytes and Chang cells, and indicate that in some patients with SLE and PSS there is a selective reduction or blockade of the ADCMC effector cell active against Chang cells.

Antibody-Dependent Cell Cytotoxicity

Effects of varying the interval between courses of methotrexate on its myelotoxic and anti-leukaemic activities.

The toxicity produced by two courses of methotrexate separated by different intervals has been studied in matched groups of rats. The maximum degree of neutropenia reached when courses were separated by 8 days or more was no greater than that seen after a single course of methotrexate. However, when courses of neutropenia following the second course of methotrexate was directly related to the level of depression of bone marrow cell numbers at the time of the second course. Conversely the anti-leukaemic effects of 2 courses of methotrexate, in terms of time of onset of leukaemia and time of death in rats transplanted with a syngeneic T-cell leukaemia, are shown to be similar when courses of methotrexate are separated by between 2 and 12 days. Thus in this system, chemotherapeutic schedules using methotrexate may be designed on the basis of minimal host toxicity without prejudicing anti-leukaemic effects. These results are discussed in relation to toxicity and anti-leukaemic effects observed during UKALL trials of treatment in acute lymphoblastic leukaemia.

Animals

Myelotoxicity of methotrexate in animals with pyogenic infection.

Rats stimulated into prolonged increased neutrophil production by the induction of a unilateral pyo-hydronephrosis showed consistent profound neutropenia when methotrexate (MTX) was given during the first 2 d of infection. Thereafter greater neutropenia than that observed in non-infected rats was only observed in occasional animals. There was a significant correlation between the degree of neutropenia induced by MTX and the day after MTX upon which this occurred. The main target for myelotoxicity by MTX appears to be the myelocyte. Its precursors seem relatively insensitive.

Agranulocytosis