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Biomedical subjects

J V Wells

Publications and source records attributed to J V Wells.

At least 19 recordsLinked to original sources

There is substantial nuclear and cellular disintegration before detectable phosphatidylserine exposure during the camptothecin-induced apoptosis of HL-60 cells.

BACKGROUND: An early sign of apoptosis in many cells is the appearance of phosphatidylserine (PS) on the outside of the plasma membrane, whilst the cells still retain the ability to exclude DNA-binding molecules such as propidium iodide and 7-aminoactinomycin D (7-AAD). The protein annexin V binds preferentially to PS and has often been used to monitor the early phase of apoptosis. There have been some conflicting results concerning whether annexin V binds to camptothecin (CAM)-treated HL-60 cells, a commonly used model for apoptosis. We investigated the effects of culturing HL-60 cells for up to 8 h with a range of CAM concentrations. METHODS: We used flow cytometry to measure cellular light scatter, annexin V-FITC binding, and 7-AAD uptake, and DNA content after fixation and permeabilization. We also used microscopy to examine the morphology of cells (both unsorted and sorted according to their light scatter) after cytocentrifugation. RESULTS: We found that CAM caused the rapid appearance of low light scatter apoptotic bodies. Even among cells with "normal" light scatter, there was widespread DNA cleavage and nuclear fragmentation by 3 h. The percentage of apoptotic bodies peaked at about 4 h and it was only afterward that annexin V binding could be detected to both intact cells and to apoptotic bodies. When they first appeared, the intact annexin V+ cells had S-phase DNA content. CONCLUSIONS: During CAM-induced apoptosis of HL-60 cells, the external exposure of PS can either precede or follow DNA cleavage, which suggests that PS exposure is not always an indicator of early apoptosis.

Annexin A5↗

Detection of anti-ovarian antibodies by indirect immunofluorescence in patients with premature ovarian failure.

The sera of 30 patients with premature ovarian failure (POF) and a control group of 19 menopausal women were screened for anti-ovarian and other tissue antibodies. Anti-ovarian antibodies were detected by indirect immunofluorescence using monkey ovary substrates from two different commercial sources. Serum anti-ovarian antibodies were detected in only one of the patients with POF. This test does not appear to be reliable for the detection of serum anti-ovarian antibodies, and the clinical usefulness of screening patients with POF for anti-ovarian antibodies is questionable.

Adrenal Glands↗

Immunoglobulin abnormalities in renal transplant recipients.

Five renal transplant recipients were observed to have recurrent infections in association with low serum immunoglobulin levels. They have benefited from parenteral gamma globulin therapy. Following this observation, 110 renal transplant recipients were assessed; 46% had abnormal serum immunoglobulins with 4 patients identified as having monoclonal gammopathies, 8 polyclonal gammopathies, and 39 low levels of 1 or more immunoglobulins. Those with abnormal serum immunoglobulins had been immunosuppressed longer, but maintenance immunosuppression dosage was not different from those with normal immunoglobulins. Respiratory tract infection and skin cancer were more frequent in those with low immunoglobulin levels.

Adolescent↗

Drugs as allergens: detection and combining site specificities of IgE antibodies to sulfamethoxazole.

An immunoassay was developed for the detection of sulfamethoxazole reactive IgE antibodies in the sera of patients who experienced life threatening anaphylactic reactions following the ingestion of co-trimoxazole (trimethoprim and sulfamethoxazole). Patients who had significant levels of sulfamethoxazole reactive IgE antibodies in their sera did not have IgE antibodies that reacted with trimethoprim-Sepharose. Inhibition experiments with a number of sulfonamides to determine the fine structural specificities of the sulfamethoxazole reactive IgE antibodies in three patients revealed that sulfamethoxazole and, depending on the serum, sulfamerazine and sulfamethizole, were the most potent inhibitors of IgE binding, whereas the parent sulfonamide, sulfanilamide, was a very poor inhibitor. From a detailed examination of structure-activity relationships, we concluded that the 5-methyl-3-isoxazolyl group on the sulfamethoxazole molecule was the allergenic determinant for all three patients with the 5-methyl group being particularly important for IgE antibody recognition. The assays for the detection of IgE antibodies to sulfamethoxazole and trimethoprim should prove useful for the diagnosis of immediate hypersensitivity to co-trimoxazole and perhaps for monitoring drug therapy in AIDS patients where a high incidence of adverse reactions to co-trimoxazole has been reported.

Adult↗

Epidemic cholera in Mali: high mortality and multiple routes of transmission in a famine area.

During the 1984 cholera epidemic in Mali, 1793 cases and 406 deaths were reported, a death-to-case ratio of 23%. In four affected villages, the mean clinical attack rate was 1.5 and 29% of affected persons died. In 66% of cases the illness began more than 48 h after the village outbreak began, when supplies from outside the village were potentially available. Deaths occurred because patients failed to seek care or received only limited rehydration therapy when they did. Case-control studies identified two routes of transmission: drinking water from one well in a village outside the drought area, and eating left-over millet gruel in a drought-affected village. Drought-related scarcity of curdled milk may permit millet gruel to be a vehicle for cholera. Cholera mortality in the Sahel could be greatly reduced by rapid intervention in affected villages, wide distribution of effective rehydration materials, and educating the population to seek treatment quickly.

Adolescent↗

Multiple myeloma with renal failure. A case for intensive treatment.

A series of nine consecutive patients with multiple myeloma and renal failure is presented. All patients were treated with urinary alkalinisation with sodium bicarbonate and/or acetazolamide, diuresis with saline, mannitol and/or furosemide, pulse melphalan and prednisone and, where indicated, allopurinol and aluminium hydroxide. A substantial and sustained improvement in renal function has been achieved in all nine patients. Of five patients with a urea more than 25 mmol/L at presentation, the median survival to date is 64 weeks. Of these patients only one has died --not from renal failure but pneumonia, eighteen months after presentation. The others are alive and well. The results confirm the effectiveness of these measures in both improving renal function and prolonging survival, and suggest a more optimistic prognosis for patients with multiple myeloma and renal failure.

Adult↗

Cell-bound immunoglobulin on peripheral blood mononuclear cells of patients with myeloma.

Four patients who had myeloma were examined for monoclonal lymphocytes in the peripheral blood using anti-idiotype antibodies. All the patients had received treatment and two were in apparent complete remission. In no case was there any evidence of peripheral blood mononuclear cells (PBMC) with endogenous surface idiotypic determinants, even in patients with active disease. It was found, however, that substantial cytophilic IgG may remain bound to Fc receptors on PBMC even after extensive incubation and washing at 37 degrees C.

Adult↗

A prospective study of serum complement (C3 and C4) levels in normal human pregnancy: effect of the development of pregnancy-associated hypertension.

Serum levels of complement components (C3 and C4) were measured serially in 173 initially normotensive pregnant women and the results compared with those obtained in 32 nonpregnant women of similar ages. There was significant elevation of serum levels of both C3 and C4 during gestation. Pregnancy-associated hypertension developed in the third trimester in 26 pregnant women but they had the-same degree of elevation of serum C3 and C4 levels as did the 147 pregnant women who remained normotensive throughout their pregnancy. Measurements of serum C3 and C4 levels and therefore of no value in predicting the development of pregnancy-associated hypertension.

Adolescent↗

Childhood pemphigus initially seen as eosinophilic spongiosis.

The condition of a 3-year-old boy with an intermittent, generalized, bullous eruption was initially diagnosed as (and treated as) bullous impetigo. After a relapse, two skin biopsies were performed. Each biopsy specimen showed the changes of eosinophilic spongiosis. A third biopsy specimen was also examined by direct immunofluorescence microscopy. The specimen showed deposition of IgG in the intercellular region of the epidermis. The patient's serum contained intercellular antibodies in a dilution of 1:160, confirming the diagnosis of pemphigus. A biopsy should be performed in the case of a child with a persistent or recurring bullous eruption; immunofluorescence microscopy of the biopsy is essential.

Child, Preschool↗

Selective IgA deficiency in Australian blood donors.

Selective serum IgA deficiency (defined as a serum IgA level less than 50 mg/l) was detected in 14 of 6,191 Australian blood donors screened by double diffusion analysis of serum specimens in agarose. This prevalence rate of 0.23% (1 in 442) is the same as that found in blood donors in Sweden but is higher than rates found in blood donors in France (0.05%), Norway (0.08%), USA (0.15%). England (0.19%) and Finland (0.20%). Antibodies to human IgA were detected in the serum of three of 11 blood donors with selective IgA deficiency (27%). There was no evidence in the present study of blood transfusion reactions from these anti-IgA antibodies when they were transfused into recipients.

Adolescent↗

Adverse reactions to human plasma proteins.

Adverse reactions to human plasma proteins range from mild urticaria to fatal anaphylaxis and may occur with virtually any blood product. The most common clinical settings appear to be whole blood transfusion in subjects with no previous history of reactions, or the infusion of fresh frozen plasma or injection of human immune serum globulin (HISG) to patients with known immunodeficiency. The immunological processes involved and the management of reactions are discussed.

Antibodies, Anti-Idiotypic↗