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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 343 records · Page 19Linked to original sources
PubMed1985

Enzymatic dissection of the glomerulus.

White rat kidneys were fixed in perfusion, postfixed with 10% glutaraldehyde, and cut into 1-mm slices. The slices were treated with a sequential digestion over 4 days with trypsin, pepsin, and pronase E. This treatment dissolved the glomerular basement membrane and the mesangial matrix. Teasing the slides in buffer released many glomeruli and tubules which were prepared for scanning electron microscopy while attached to gelatine glass cover slips. Four human renal biopsies were similarly treated. The enzymatic removal of the basement membrane permitted viewing of the basilar or capillary slide of loosened podocytes and their processes. The cell body of the podocytes often exhibited a considerable area of contact with the basement membrane. The primary and secondary podocyte processes and foot processes maintained a continuous contact with the basement membrane. Human podocytes, although larger, were similar to the rat. Podocytes from minimal change disease showed severe retraction and flattening of primary and secondary processes and foot processes. Extensive visualization of the basilar surface of the exposed endothelial tubes was possible with this technique. The fenestrated and nonfenestrated portions were revealed including the axial area where the endothelial cells contact the mesangial cells and matrix, which formed an impression on the surface of the endothelium. The mesangial cells and their connecting processes (the mesangial network) were revealed extending from the peripheral lobule to the glomerular hilus where they merged with lacis cells. The mesangial cells exhibited a variety of processes which anchored into the mesangial matrix. At the hilus, these cells assumed a flat, villous, lacy appearance, and these cells encircled the large hilar capillaries. Glomeruli with afferent and efferent arterioles and associated Goormaghtigh (lacis) cells were identified. The transition between mesangial, Goormaghtigh, and smooth muscle cells was observed. These observations provide a unique view of the organization of the rat and human glomerulus and suggest the potential for the use of the present technique in the study of diseased glomeruli.

Animals↗
PubMed1985

Fetal exposure to cimetidine following chronic administration to pregnant sheep.

Our previous short term studies of the placental transfer of cimetidine in the pregnant sheep showed that following infusion of cimetidine to the mother, there was a striking (greater than 25 to 1) maternal to fetal gradient at apparent steady state. The present study examines two possible explanations: 1. That the gradient reflects very low placental permeability to cimetidine, such that in short-term studies a true steady state is not achieved. 2. That the gradient results at least in part from differences in protein binding in maternal and fetal plasma. To determine whether the gradient was due to very low placental permeability to cimetidine, pregnant sheep were infused with cimetidine continuously for 6 days (n=5). The large 25 to 1 cimetidine gradient did not diminish throughout this period, thereby ruling out a non-specific "barrier" effect of the placenta. In vitro protein binding studies of cimetidine in maternal and fetal plasma showed low binding (range = 16 to 46%) and minimal differences between mother and fetus. We conclude that the observed maternal to fetal cimetidine gradient cannot be explained by either low placental permeability, or by differential protein binding of cimetidine in maternal and fetal plasma.

Animals↗
PubMed1984

Modified tissue culture medium for corneal storage I. Investigation of the effect of antibiotics on bacterial contamination.

A series of experiments were performed to determine the effect of modified tissue culture medium (MTCM), temperature, time, and antibiotics on the replication of Staphylococcus epidermidis and Pseudomonas aeruginosa. A known inoculum of the organisms (usually 10(6)/mL) was introduced, and the recovery of viable organisms was compared by different methods of culturing, including techniques of diluting, inactivating, or removing the antibiotic from the system. The invalidity of techniques that failed to remove the antibiotic from the system was substantiated. The newly developed antibiotic removal device was superior to all other culturing techniques. Penicillin G potassium was ineffective in the MTCM system, and gentamicin reagent solution was not uniformly effective against a gentamicin-sensitive strain of P aeruginosa. Placement of the MTCM at room temperature for two hours enhanced the antibacterial activity of gentamicin, although organisms may still be recovered in small numbers.

Anti-Bacterial Agents↗
PubMed1984

Modified tissue culture medium for corneal storage. II. Investigation of the effect of the corneoscleral rim on bacterial contamination.

Our previous experiments showed the effect of time, temperature, and antibiotics on replication of Staphylococcus epidermidis and Pseudomonas aeruginosa introduced into the modified tissue culture medium (MTCM). Penicillin G potassium was ineffective in the MTCM, and gentamicin sulfate was not uniformly effective against a gentamicin-sensitive organism. Placement of the MTCM at room temperature for two hours enhanced the antibacterial activity of gentamicin. Culturing techniques that fail to remove the antibiotic from the system are invalid. Experiments reported herein showed that the addition of the corneoscleral rim (or extraneous protein) prolongs the survival of these same organisms. Organisms can survive in the MTCM despite high concentrations of gentamicin. Maintaining the MTCM at room temperature for two hours after storage at 4 degrees C effectively reduces but may not completely eliminate the recovery of organisms. The antibiotic removal device may be superior to other methods for recovering viable organisms.

Animals↗
PubMed1984

Identification of an anti-monocyte monoclonal antibody that is specific for membrane complement receptor type one (CR1).

A monoclonal antibody (E11) was produced by immunization of mice with intact human cells of monocyte lineage. Despite the finding that E11 did not inhibit rosettes with C3b-coated sheep erythrocytes (EC3b), several lines of evidence indicated that E11 was specific for complement receptor type one (CR1). All monocytes, neutrophils, lymphocytes and erythrocytes that reacted with E11 formed EC3b rosettes. The E11 antigen on these cells was shown to be a molecule of 222 +/- 10 kDa. Treatment of lymphocytes, monocytes, and neutrophils with E11 followed by fluorescein-coupled F(ab')2 anti-mouse-IgG at 37 degrees C in buffer lacking sodium azide, led to capping or apparent endocytosis of the E11 antigen and a diminution in CR1 activity of 88%, 59% and 25%, respectively. This same treatment had no detectable effect on monocyte or neutrophil CR3 activity (EC3bi rosettes). Furthermore, with E11-capped lymphocytes, the residual EC3b rosetting was capped directly over the E11-fluorescence cap, whereas EC3d,g rosetting (CR2 specific) was undiminished and distributed evenly around the circumference of cells containing E11-fluorescence caps. Finally, the binding of E11 to cells was inhibited by the prior treatment of these cells with a well characterized rabbit polyclonal anti-CR1. These data indicated that E11 was specific for a site in CR1 that was distal from the C3b-binding site, so that E11 was unable to block CR1 activity. E11 proved to be useful for identifying CR1 on various cells in tissue sections, and for quantitating CR1 on erythrocytes and neutrophils. Erythrocytes and neutrophils from normal individuals were found to bind an average of 610 and 4.6 X 10(4) 125I-labeled E11 molecules per cell. When E11 was visualized in tissues by immunoperoxidase staining, the cells that apparently contained the greatest amounts of CR1 were dendritic reticulum cells and kidney podocytes. The E11 reactive dentritic reticulum cells were characteristic of both follicular and diffuse follicular center cell tumors. Lymphocytes from patients with chronic lymphocytic leukemia (CLL) characteristically expressed little E11, confirming earlier studies that CLL cells lacked CR1 activity detected by EAC1-3b rosette formation. Because normal B cells have been shown to express CR1 at a very early stage of maturation, the absence of CR1 on CLL cells is discordant with the immature nature of CLL cells defined by immunoglobulin expression.

Animals↗
PubMed1984

Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics.

The pharmacokinetics of a single oral dose (400 mg) of carbamazepine and sodium valproate were compared in peptic ulcer patients before and after four weeks of a therapeutic course of either cimetidine (1 g/day, n = 6 subjects) or ranitidine (300 mg/day, n = 6 subjects). There was a small (up to 20%) but statistically significant decrease in oral clearance of carbamazepine after cimetidine treatment. A similar fall in sodium valproate clearance in five cimetidine-treated patients was accompanied by a significantly prolonged elimination half-life. No such trends were demonstrated during ranitidine treatment. Since both anticonvulsants are partly metabolized by hepatic mixed function oxidases, an inhibition by cimetidine at this level may be responsible for the observed impairment of clearance. Thus a potentially important clinical interaction may occur in patients taking anticonvulsants and cimetidine concurrently.

Carbamazepine↗
PubMed1984

A comparison of cholestyramine and probucol in the treatment of familial hypercholesterolaemia.

Twelve patients with familial hypercholesterolaemia (FH) who had not achieved satisfactory cholesterol levels on dietary advice alone were treated with cholestyramine for 6 months and probucol for 6 months in a randomised cross-over study to compare the relative effectiveness of the two drugs. Over the 6-month period, mean total cholesterol fell by 16.4% on cholestyramine and 12.7% on probucol. Cholestyramine produced a 17.4% fall in low density lipoprotein (LDL) cholesterol, no significant changes in very low density lipoprotein (VLDL) cholesterol or high density lipoprotein (HDL) cholesterol, a 21.4% increase in HDL cholesterol subfraction HDL2 and a 24.1% increase in the HDL/LDL cholesterol ratio. Triglyceride levels rose by 29.6% but remained within the normal range. Probucol produced a 11.7% fall in LDL cholesterol, a 9.9% fall in VLDL cholesterol, a 10% fall in total HDL cholesterol, a 37% fall in HDL cholesterol subfraction HDL2 and no change in the HDL/LDL cholesterol ratio. Triglyceride levels fell by 14%. The mean corrected QT interval increased from 0.418 to 0.434 s (P less than 0.01) on probucol but did not change significantly on cholestyramine (from 0.405 to 0.41 s). The two drugs have different metabolic effects on FH. Cholestyramine has a more marked effect on LDL cholesterol, favourably influences the HDL/LDL cholesterol ratio and is therefore considered to be the drug of choice.

Cholesterol↗
PubMed1984

Pregnancy-specific-beta 1-glycoprotein: effect on lymphocyte proliferation in vitro.

The effects of three different preparations of pregnancy-specific-beta 1-glycoprotein (SP1) were investigated in parallel with progesterone, oestradiol and human chorionic gonadotrophin (hCG) on the proliferative response of lymphocytes in the mixed lymphocyte reaction (MLR), and to the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). A dose-related inhibition of the MLR was obtained with SP1 at 2.5-10 mg/l. SP1 also inhibited the PHA response at 10 mg/l, but had no effect on the PWM response at these concentrations. Progesterone and oestradiol inhibited all systems at 10-20 mg/l while hCG inhibited all systems at 1500-3000 IU/ml. The observations suggest that SP1 selectively inhibits the proliferative responses of T lymphocytes at the concentrations studied.

Chorionic Gonadotropin↗
PubMed1984

Immunoglobulin negative follicle centre cell lymphoma.

Immunoglobulin (Ig) could not be detected on the surface or in the cytoplasm of neoplastic cells from five cases of follicle centre cell lymphoma with centroblastic/centrocytic follicular histology when examined by immunohistology of frozen or wax embedded sections. Examination by fluorescein labelled antibodies of cells in suspensions prepared from the biopsies revealed a monotypic surface Ig positive population in one case and a surface or cytoplasmic Ig kappa:lambda light chain imbalance in a further two cases consistent with neoplastic B cell involvement: in all cases the proportion of cells failing to express Ig or T cell markers ranged from 24 to 75%. The monoclonal antibodies B1 (Pan B cell), FMC4 (HLA class II) and J5 (cALL antigen) stained the majority of cells in suspension with residual cells staining with UCHT1 or OKT11 (T cell monoclonal antibodies). In frozen sections, neoplastic follicular cells did not stain with UCHT1. However, in the one case tested these cells stained with the antibodies B1 and FMC4. In paraffin sections J chain could be demonstrated in the cytoplasm of three out of five cases. Cells from four cases were cultured in vitro for Ig production: two failed to produce Ig and monotypic light chains were the sole Ig product of the remaining two cases. The failure to express Ig by the majority of the neoplastic cells from the cases described in this report is at variance with the follicular histology of these neoplasms. Mechanisms responsible for this failure are discussed with reference to current models of B cell differentiation.

Antibodies, Monoclonal↗
PubMed1984

Spontaneous and Concanavalin A-induced suppressor activity in control and Hodgkin's disease patients.

Indirect evidence suggests that abnormal regulation of B cells exists in Hodgkin's disease (HD) due, perhaps, to the sequestration of regulatory T-lymphocyte subpopulations in the spleen in this condition. Other work implicates the B-cell itself in this abnormality. In this study we have attempted to measure regulatory T-cell function by quantitating spontaneous and Concanavalin A(Con A)-induced suppressor activity in T-enriched spleen cells from control and HD spleens for pokeweed mitogen(PWM)-induced immunoglobulin (Ig) production. Using this polyclonal system, HD patients' spleen T-lymphocytes could not be shown to differ markedly from the control series. Cells capable of spontaneous and mitogen-induced modulation of Ig synthesis were present in both populations and showed a reciprocal relationship implying the activation of the same cell type. In this respect HD and control spleen resembled peripheral blood. A limited parallel investigation of PWM-regulatory activity in cells from spleen and peripheral blood from individual patients was also undertaken. Individual patients showed wide variation in suppression between the two compartments and, therefore, measurements of functional capacity in blood alone may not provide a true estimate of total regulatory capacity in lymphoma patients.

B-Lymphocytes↗
PubMed1984

High carbohydrate-high fibre diets in poorly controlled diabetes.

Fifteen non-insulin-dependent diabetic patients with persistently elevated blood glucoses despite high doses of oral hypoglycaemic agents, were randomly allocated to a high carbohydrate-high fibre diet (HC) or a reinforced low carbohydrate diet (LC). After six weeks the diets were reversed for a similar period. Immediately preceding the study and at the end of each dietary period 24-h biochemical profiles were performed. In the 11 patients who completed the study, fasting and preprandial glucose, percentage glycosylated haemoglobin, VLDL cholesterol and mean 24-h triglycerides were significantly lower on HC than on LC or during the initial profile on their usual diet. There was no significant difference in any of the measurements on LC compared with the usual diet. Previous studies of high carbohydrate-high fibre diets in diabetes have been carried out in relatively well-controlled patients. These data show that poorly controlled non-insulin-dependent patients have an even more striking response.

Aged↗