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Biomedical subjects

M Cochran

Publications and source records attributed to M Cochran.

At least 55 records · Page 3Linked to original sources

Phenotypic and functional characterization of normal and malignant terminal B (plasma) cells.

A number of antigens (Ags) are expressed on normal and malignant terminal B (plasma) cells, including plasma-cell, earlier B-cell, and non-B cell-Ags. These Ags, coupled with indirect and dual fluorochrome labelling techniques, permit characterization of normal and malignant in vitro and in vivo terminal B-cell differentiation. The majority (90%) of B cells within spleen bear Bl and lack PCA-1 Ags. As B cells differentiate to pokeweed mitogen in vitro, immunoglobulin (Ig) secretion precedes the appearance of cell surface PCA-1 and plasmacytoid morphology. Dual fluorescence cell sorting permits characterization of in vivo B-cell differentiation: Bl + PCA-1 + cells are more "differentiated" since they are more prevalent in lymph node than spleen, exhibit plasmacytoid morphology and maximal Ig secretion, and no longer respond to triggers of B-cell proliferation; in contrast, Bl + PCA-1-cells are lymphoid in morphology and may respond to triggers of B-cell proliferation as "resting" B cells. Similar studies of myeloma cells demonstrated that they may also include cells expressing plasma-cell, earlier B, and non-B cell Ags. Although they neither proliferated nor secreted Ig in vitro to G/M-CSF, G-CSF, M-CSF, IL-1, IL-1B, IL-2, or IL-4, proliferation without Ig secretion (Stimulation Index greater than or equal to 3.0) was induced to IL-6 in 6 of 10 patients (pts); to IL-3 (2 pts) and to IL-5 (2 pts).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗

SPECT of the peritoneal cavity: method for delineating intraperitoneal fluid distribution.

Seventeen single-photon emission CT (SPECT) studies were performed after intraperitoneal administration of 99mTc-sulfur colloid in patients with a history of colon cancer to assess the extent of intraperitoneal fluid distribution prior to intraperitoneal chemotherapy. Planar gamma images were also obtained in all patients for correlation with the SPECT findings. Four patients had transmission CT scans of the abdomen after intraperitoneal administration of iodinated contrast material. In seven patients, repeat planar and SPECT studies were performed with the original or a different infusion volume to determine if different volumes altered the fluid distribution qualitatively or quantitatively (using a linear profile method). We found that 360 degrees peritoneal SPECT is easily performed after intraperitoneal administration of 99mTc-sulfur colloid. SPECT provides more detailed anatomic information than planar scans do. Spaces of the upper abdomen, such as the lesser sac, were resolved better with SPECT than with planar imaging. SPECT assessment of intraperitoneal fluid distribution also correlated well with transmission CT scans. Quantitative linear-profile radionuclide plots were reproducible at the same volume and showed no major differences in relative intraperitoneal fluid distribution between the 1.5- and 3.0-l infusion volumes, suggesting that the two delivery volumes were equivalent in relative distribution. SPECT appears to be a useful procedure to define the extent and location of intraperitoneally administered fluids. Thus, it may be of value in determining the intraperitoneal distribution of drugs and radiopharmaceuticals used in the treatment of intraabdominal tumors.

Adult↗

Interaction of horse-spleen ferritin with aluminium citrate.

Horse-spleen ferritin was found to bind Al systematically following gel filtration in buffered Al citrate 30 microM, and up to molar ratio 98 when incubated at 37 degrees C with Al citrate, buffered to pH 7.4. Pre-incubation with 3 concentrations of neutral sodium phosphate (0.1, 1.0, 10.0 mM) had no significant effect on binding. Apotransferrin interaction with the Al-ferritin complex to release Fe but not Al. Protein-digestion and EDTA washing procedures showed that the Al was firmly bound to the ferritin, probably to the core. Since ferritin species from different organs are relatively alike, we suggest that in the gut ferritin may scavenge Al followed by its re-excretion into the lumen with the mucosal cells, thus protecting against absorption of the metal.

Aluminum↗

Direct spectrophotometric determination of the two site binding of aluminum to transferrin.

Difference UV spectrophotometry is used to determine the conditional binding constants for aluminum to human transferrin in the presence of HCO3- of initial concentration 18 mM according to a two site model. The values obtained at 37 degrees C and pH 7.4 are: K1 = 3.0 (+/- 0.8) X 10(15) M-2, K2 = 2.9 (+/- 0.7) X 10(15) M-2 for the reactions: Tr + Al3+ + HCO3- = Tr-Al-HCO3 and Tr-Al-HCO3 + Al3+ + HCO3- = Tr-Al2-(HCO3)2 respectively. Possible consequences arising for the transport of aluminum in human serum are discussed.

Aluminum↗

Adenocarcinoma of the alimentary tract: peritoneal distribution scintigraphy.

Effective intraperitoneal (IP) chemotherapy and colloidal radiation therapy depend on contact of the drugs with the entire peritoneal surface. Using technetium-99m sulfur colloid, one can evaluate the completeness of peritoneal fluid distribution. Forty-eight planar IP scans from 26 patients with gastrointestinal malignancies were reviewed and scan findings were correlated with the site of primary tumor, surgical findings, and the location of any residual disease. Of the 26 patients, 22 had undergone resection of the primary lesion prior to scanning. Scans typically demonstrated more activity in the upper and lower portions of the abdomen than in the midabdomen. Diminished uptake in the pelvis, right lower quadrant, and right upper quadrant was generally due to metastases. A tumor mass was identified as responsible in only one of eight patients with diminished or absent left upper quadrant activity. Knowledge of variability in patterns seen on IP scans is essential to rational guidance of IP chemotherapy and radiation therapy.

Adenocarcinoma↗

Differences in density and distribution of surface glycoconjugates between normal and dystrophic mouse Schwann cells detected by statistical analyses of lectin-ferritin binding.

Cultures of Schwann cells and neurons from dorsal root ganglia of normal (C57bl/6J +/+) and dystrophic (C57bl/6J dy2j/dy2j) mice were labeled with wheat germ agglutinin (WGA) and Ricinus communis agglutinin (RCA-I) conjugated to ferritin. Statistical methods were used to compare the regional densities and distribution characteristics of lectin binding in these two types of Schwann cells, which differ in their capacities to ensheath and myelinate axons in vivo and in cultures. Regional variations in lectin binding densities and distributions were observed in both types of Schwann cells. WGA-ferritin was bound at lower densities in dystrophic mouse Schwann cells than in corresponding regions of normal cells. In both normal and dystrophic cells, WGA-ferritin was distributed at greater densities on the free surfaces of Schwann cells than on the substrate-associated surfaces. WGA-ferritin was clustered in all regions of both normal and dystrophic mouse cells. RCA-ferritin densities did not differ significantly between corresponding regions of normal and dystrophic mouse Schwann cells. However, in normal mouse Schwann cells, the density of RCA-ferritin was significantly greater in the thinner, peripheral processes of Schwann cells than in thicker perinuclear regions of the cells. Differences in the degree of RCA-ferritin clustering were also detected between normal and dystrophic Schwann cells. These results indicate that regional differences in the density and distributions of cell surface glycoconjugates occur in Schwann cells of normal and dystrophic mice.

Animals↗

PC12 neurite regeneration and long-term maintenance in the absence of exogenous nerve growth factor in response to contact with Schwann cells.

We have investigated mouse and rat ganglionic Schwann cells as possible sources of neurite outgrowth-promoting factors by co-culturing Schwann cells with nerve growth factor (NGF)-responsive PC12 pheochromocytoma cells primed by pretreatment with NGF. NGF-primed PC12 cells are capable of neurite regeneration when provided with an appropriate neurite promoting factor such as NGF. When primed PC12 cells were co-cultured with Schwann cells in the absence of exogenous NGF, PC12 cells that directly contacted Schwann cells became enlarged and flattened, attaining a neuron-like morphology within one day. When contact with Schwann cells was established, PC12 cells regenerated neurites by the first day of co-culture and these were maintained throughout the experiments (7 weeks). Most PC12 cells cultured in the same collagen-coated dishes with Schwann cells, but not directly in contact with them, failed to regenerate neurites. Instead, they began to proliferate, forming cell clusters. Neurite regeneration by PC12 cells in contact with Schwann cells was not blocked by antibody to NGF. These results demonstrate the presence of a neurite-promoting activity localized to the vicinity of the Schwann cell surface which is capable of eliciting regeneration and long-term maintenance of PC12 neurites in the absence of exogenous NGF. This activity does not appear to be due to NGF.

Animals↗

Schwann cells fail to differentiate when co-cultured in contact with PC12 neurites.

Schwann cells derived from mouse or rat dorsal root ganglia (DRG) were co-cultured with either DRG neurons or nerve growth factor (NGF)-responsive PC12 pheochromocytoma cells for up to 7 weeks. When Schwann cells were grown in the presence of DRG neurites, they displayed normal ensheathing behavior and produced basal laminae and small diameter collagen fibrils within 5-19 days in vitro. However, when Schwann cells were co-cultured in direct contact with PC12 cells and without DRG neurons, they largely failed to ensheath PC12 neurites, and failed to assemble either basal lamina or small diameter collagen fibrils at any point during 7 weeks. Schwann cell proliferation continued in the presence of PC12 neurites, indicating that PC12 cells produced a mitogenic activity for Schwann cells functionally similar to previously described neurite-associated activities. These results demonstrate that Schwann cell contact with PC12 cells does not elicit the final morphogenetic events in Schwann cells (ensheathment, basal lamina formation and collagen fibril assembly) that normally occur when Schwann cells are co-cultured in contact with DRG neurons.

Animals↗

Binding of Al by protein in plasma of patients on maintenance hemodialysis.

Gel filtration of plasma from hemodialysis patients, with use of reagents and apparatus with carefully minimized background Al concentrations, reproducibly showed a single peak for Al, corresponding exactly to the elution position of transferrin. The Al/transferrin molar ratio in adjacent fractions was constant (mean 0.126, SE 0.006) in replicate experiments. In contrast, the association of Al with albumin varied. Using both equilibrium dialysis and gel-filtration techniques, in the presence and absence of calcium or phosphate, we could demonstrate no significant binding of Al by human albumin at Al concentrations of 1 to 12 mumol/L. We saw no Al peak in pooled, concentrated, low-molecular-mass fractions of plasma gel-filtered on Sephadex G-50. Evidently, transferrin is the sole Al-binding protein in plasma of hemodialysis patients.

Aluminum↗

Alternative pathway of bovine complement: concentration of factor B, hemolytic activity and heritability.

Concentrations of bovine factor B (Bbov) were determined by radial immunodiffusion in sera of 46 Holstein cows and heifers aged one to nine years. Mean values were 34.2 +/- 5.3 mg/100 ml. A hemolytic diffusion plate assay in agarose gel in presence of 10 mM EGTA and 5 mM Mg accurately measured concentrations of purified Bbov but gave higher mean values, i.e. 47.8 +/- 10.2 mg/100 ml, for concentrations of Bbov in whole sera. Hemolytic values obtained by the hemolytic diffusion plate assay, however, weakly correlated (r = .4539, p less than 0.01) with the serum concentration of Bbov measured by radial immunodiffusion. It was concluded that the hemolytic diffusion plate assay was not an accurate technique for the quantitative measurement of Bbov but a good assay for quantitation of the total hemolytic activity mediated via activation of the alternative complement pathway. It is suggested that the difference between the values obtained by the two tests for one particular serum is, to some degree, an expression of the ratio of amplification and restriction of the alternative pathway activity. No significant heritability (offspring and one parent) was detected for the hemolytic activity of serum. A heritability of 0.93 at a significance level of p less than 0.1 was determined for the serum concentration of Bbov.

Animals↗

Aluminium interaction with 67Ga uptake by human plasma and transferrin.

To investigate the possible uptake of aluminium by plasma proteins, the Group IIIB element gallium (67Ga) was used as an analogue. Gel filtration confirmed that plasma bound 67Ga in the transferrin region, and this effect could be reproduced using pure transferrin. Approximately 75%, of 67Ga could be displaced by 10 mumol/l aluminium in the buffer. Equilibrium dialysis with samples of plasma, transferrin and albumin (BSA), showed that uptake of 67Ga by plasma or transferrin was systematically inhibited by increasing concentration of aluminium in the range found in dialysis fluid while uptake by albumin was negligible. The results suggest that transferrin plays an important role in aluminium uptake during haemodialysis.

Aluminum↗

Ranitidine disposition in patients with renal impairment.

Ranitidine disposition has been studied in 12 patients with renal impairment following 50 mg given intravenously and 150 mg given by mouth on separate occasions. The clearance of ranitidine from plasma (y) was correlated with creatinine clearance (x): y = 10.47 + 0.289x,r2 = 0.751, but there was no significant correlation of creatinine clearance with distribution volume or bioavailability. The mean (s.e. mean) distribution volume was 1.62 (0.08) 1/kg and the mean bioavailability 0.81 (0.05). These data suggest that in order to obtain similar ranitidine plasma concentrations in anephric patients and patients with normal renal function, the maintenance dose in the anephric patients should be 25-30% of that for patients with normal renal function.

Aged↗

Isotopic bone mineralization rates in maintenance dialysis patients.

The expanding pool model of radiocalcium kinetics has been used in 13 maintenance dialysis patients to measure bone mineralization rate. No difficulties were met in applying the data to the model, and values for the bone mineralization rate ranged from 0.0 to 2.0 mmol/kg Ca++ per day. The bone histology obtained at the time of the study showed a correlation between the degree of secondary hyperparathyroidism and the bone mineralization rate, with low values of the latter occurring in atypical osteomalacia (two patients) or inactive-looking bone (one patient) and raised values in seven patients. The plasma alkaline phosphatase and immunoassayable parathyroid hormone levels each correlated significantly with the bone mineralization rate. These findings suggest that the technique is valid when applied to hemodialysis patients and provides quantitative information about skeletal calcium metabolism in different types of renal bone disease.

Adult↗

Expression of the trembler mouse mutation in organotypic cultures of dorsal root ganglia.

Organotypic dorsal root ganglion (DRG) cultures were established from all the embryos of two trembler (Tr/+) female mice mated to normal (+/+) males to determine if the trembler mutation would be expressed in nerve tissue culture. Dorsal root ganglia from normal mice maintained in our culture system exhibit substantial myelination after 6 weeks of growth. This normal pattern was observed in approximately one half of the cultures in the present series. The remaining half of the explants had marked PNS myelin abnormalities readily detectable at the light microscopic level in living cultures; furthermore, the ultrastructural appearance of these Tr/+ cultures was similar to that of adult trembler sciatic nerve. An analysis of unmyelinated nerve fibers in Tr/+ cultures revealed that the number of neurites resident within each non-myelinating Tr/+ Schwann cell was significantly less than the number observed in +/+ cultures. There are distinctive PNS myelin abnormalities which: (1) develop in DRG cultures established from embryos at risk for the trembler mutation; (2) are highly reliable and readily detectable markers for the trembler genotype; and (3) are similar to the trembler PNS defects detectable in vivo.

Animals↗

Aspects of renal bone disease.

In advanced chronic renal failure hypocalcaemia can be due to a combination of factors. These include decreased delivery of calcium into the plasma and increased renal tubular leakage of calcium. The secondary hyperparathyroidism that follows the hypocalcaemia leads to osteosclerosis, probably by movement of cortical mineral into trabecular bone. In the dialysis population, an atypical and readily identifiable form of osteomalacia sometimes occurs and is probably secondary to a water-borne toxin.

Bone Diseases, Metabolic↗