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C Thomas

Publications and source records attributed to C Thomas.

At least 469 records · Page 26Linked to original sources

Isolation of a Ca2+-dependent actin-fragmenting protein from brain, spinal cord, and cultured neurones.

Extracts of ox spinal cord and chicken brain were fractionated by ion-exchange chromatography and assayed for their ability to reduce the viscosity of muscle F-actin solutions. Two distinct peaks of activity were obtained, one of which was further purified by affinity chromatography on a DNAase-actin Sepharose column. Following molecular exclusion chromatography, the actin component appeared as a complex of 1 molecule of a protein with molecular weight 90,000 and 2 molecules of actin (42,000). This tightly bound complex was resistant to most methods of protein separation, but was resolvable into its component proteins by sodium dodecyl sulphate acrylamide gel electrophoresis. The protein of molecular weight 90,000 could be eluted from such a gel in a fully active form. The activity of the protein from ox spinal cord was closely similar to that of gelsolin, an actin-fragmenting protein originally isolated from rabbit lung macrophages. Like gelsolin, the protein from ox spinal cord produced fragmentation of muscle F-actin filaments at Ca2+ concentrations greater than 10(-7) M, and had a nucleating effect on the polymerisation of muscle actin; the latter was measured most easily by the enhancement of fluorescence of muscle actin conjugated to N-(1-pyrenyl)iodoacetamide. Nucleation was more effective in the presence of Ca2+, but also occurred in its absence, and the same was true of complex formation between the 90,000 protein and muscle G-actin. On the basis of its actin-fragmenting activity, we estimate that the 90,000 molecular weight protein constitutes 0.2% of the protein initially extracted from ox spinal cord. A very similar protein, indistinguishable in its action on actin but containing variable amounts of a protein of molecular weight 85,000 as well as 90,000, was isolated from chicken brain. A similar protein was also detected in pure cultures of sympathetic neurones by enrichment on a DNAase-actin affinity column and by immune blotting and by immunofluorescence. We conclude that a protein similar, if not identical to macrophage gelsolin is present in neurones and that it probably plays a part in the actin-based movements of these cells.

Actins↗

Aldosterone suppression with dopamine infusion in low-renin hypertension.

A dopaminergic mechanism has been proposed to suppress aldosterone secretion. To assess the possibility that a defect in the dopaminergic mechanism might enhance aldosterone secretion in hypertensive patients, we determined basal and adrenocorticotropic hormone (ACTH)-stimulated plasma aldosterone (PA), cortisol, renin activity, and potassium concentrations before and during dopamine receptor stimulation with dopamine infusion and bromocriptine administration and dopamine receptor blockade with metoclopramide. The patient study groups included: (a) seven patients with low-renin hypertension and abnormal aldosterone suppression with sodium loading and presumed bilateral zona glomerulosa hyperplasia (ZGHP); (b) two patients with aldosterone-producing adenoma; (c) five patients with low-renin hypertension but normal aldosterone suppression with sodium loading; and (d) six patients with normal-renin hypertension. Dopamine infusion in patients with ZGHP caused PA to fall (P less than 0.01) into the normal range, but did not block the enhanced (P less than 0.05) aldosterone response to ACTH that is characteristic of these patients. Dopamine infusion in patients with low-renin hypertension but normal aldosterone suppression also suppressed PA (P less than 0.01), whereas it had no effect upon PA in patients with normal-renin hypertension or aldosterone-producing adenoma and did not blunt the PA response to ACTH in either group. Bromocriptine administration had no effect upon basal or ACTH-stimulated PA. Dopamine infusion in patients with ZGHP also enhanced (P less than 0.05) diuresis and natriuresis in comparison with normal-renin patients. Metoclopramide administration increased (P less than 0.01) PA in all patients. Thus, a dopaminergic mechanism appears to be important in the regulation of aldosterone secretion in patients with ZGHP and in other low-renin hypertensives with normal aldosterone suppression with sodium loading. In contrast, this latter group does not exhibit an enhanced aldosterone response to ACTH. Both of these groups differ from normal-renin hypertensives, who have no PA suppression with dopamine infusion.

Adenoma↗

Neuro-ophthalmologic signs in the angiitic form of neurosarcoidosis.

We studied eight patients with CNS sarcoidosis, including two patients with postmortem evidence of sarcoid granulomatous angiitis. Neuro-ophthalmologic findings included perivenular sheathing of retinal veins resembling the dripping of candle wax, vitreous cells, anterior uveitis, optic disk edema or granulomas, and conjunctival granulomas. Perivenous sheathing in the retina and the perivascular meningeal lesions in sarcoid angiitis were identical.

Adult↗

The effect of counselling on physical disability and social recovery after mastectomy.

A controlled trial was conducted to determine if a specialist nurse improved the physical and social recovery of patients after mastectomy and helped them adapt to the breast loss. Seventy five patients were counselled by the nurse who also monitored their progress after discharge while 77 patients received the care normally given by the surgical unit. Twelve to eighteen months after surgery those helped by the nurse showed a greater social recovery, return to work, adaptation to breast loss and satisfaction with their breast prostheses. Eleven percent remained distressed by the mastectomy but most responded well to breast reconstruction. The nurse had little impact on physical disability. The morbidity found in the control group highlights the need to find ways of reducing it. While the appointment of a specialist nurse can achieve this the morbidity would probably also be much reduced if the breast was conserved when possible, reliable staging methods other than axillary clearance were developed and the adverse effects of cytotoxic drugs and radiotherapy were reduced.

Adult↗

Heterogeneity of acute lymphocytic leukemia cell surface markers as detected by monoclonal antibodies.

Monoclonal antibodies 3A1, 4F2, 5E9, OKT3, OKT6, and OKT8 were tested by flow microfluorometry for reactivity with cells from patients with T-cell or null cell acute lymphocytic leukemia (ALL). The 3A1 antibody reacted with a greater percentage of cells from 1 group of patients that could be classified as T-cell leukemia patients as compared to its reaction in the group classifiable as null cell leukemia patients. Reactivity patterns of other monoclonal antibodies with lymphocytes from patients with ALL did not clearly define groups of ALL patients. All cells from individual leukemia patients reacted differently with the seven monoclonal reagents. On the basis of patterns of reactivity, T-cell leukemias could not be classified as malignant clones of cells from the previously described stages of thymus cell maturation. The results demonstrated that the cells undergoing malignant change express a variety of combinations of antigens not found on normal lymphocytes.

Antibodies, Monoclonal↗

16, 16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation.

A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents such as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16, 16-dimethyl PGE2, shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 hr before or 15 min after 137Cs gamma (gamma) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16, 16-dimethyl PGE2 was given before but not after 137Cs gamma irradiation. The maximum degree of 16, 16-dimethyl PGE2-induced radioprotection was seen when the drug was given 1 hr before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 hr or longer. When the time between 16, 16-dimethyl PGE2 and irradiation was kept at 1 hr, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE2 may in part be protected from the lethal effects of ionizing photon radiation.

16,16-Dimethylprostaglandin E2↗

The organization of 10 nm filaments and microtubules in embryonic neurons from spinal ganglia.

The distribution of tubulin and 10 nm filament protein: vimentin and the 70 K neurofilament component, was investigated in cultures of dorsal root ganglion cells by indirect immunofluorescence using antisera specific for these proteins. The neuronal cell bodies and the neurites in these cultures were brightly stained. Fibres stained with both tubulin and 10 nm filament antibodies were visible at branch points, whereas only microtubules extended into growth cones, including those that were in the process of bifurcation. Differences in the arrangement of microtubules and 10 nm filaments were also detected during colcemid-induced neurite retraction. After complete retraction, perinuclear coils of 10 nm filaments were found in the cell bodies whereas only very weak diffuse tubulin staining was visible. When regrowth commenced on removal of colcemid, microtubule organizing centres were visible in the cell bodies and were then rapidly obscured by bright staining which later extended into the neurite stump. Similarly, the 10 nm coils were replaced by fibrous staining which also projected into the growing neurite. These observations suggest that the extension of microtubules and 10 nm filaments is both co-ordinated and sequential, with microtubules having a dynamic role in growth and 10 nm filaments stabilizing the pattern of growth thereafter.

Animals↗

Patho-anatomical demonstration of lymph node metastases in a surgical specimen.

The prognosis of malignant disease is mainly determined by the demonstration or exclusion of lymph node metastases. However, other findings must also be considered, e.g., the number of lymph nodes examined and involved by tumor, differentiation between micro- and macrometastases, intranodal and perinodal growth, and non-neoplastic changes. These findings cannot be established with certainty when conventional examination methods (lamination and palpation) are used. Satisfactory results can only be obtained by employing a clearing technique and by processing the lymph nodes in step sections. For the speedy clearing of adipose tissue two devices have been developed in which hot acetone and xylene act on the tissue. In the transparent adipose tissue the lymph nodes can be easily recognized and accurately correlated topographically. In comparison to the routine method, the number of lymph nodes and nodal metastases detected can be doubled or tripled with this technique and with step sections. In particular, lymph nodes less than 5 mm in size and micrometastases (less than 2 mm) are visualized.

Colonic Neoplasms↗

Vimentin and 70K neurofilament protein co-exist in embryonic neurones from spinal ganglia.

The mesenchymal intermediate filament protein vimentin and the 70K component of neurofilament were detected by two-dimensional gel electrophoresis in cultures of pure sensory and sympathetic neurones derived from chick embryos. The identities of these neuronal intermediate filament proteins were confirmed by comparison of their molecular weights, isoelectric points, and peptide patterns from limited papain digestions with those of the corresponding proteins from fibroblasts and brain, respectively. A specific antibody to vimentin stained filamentous structures and colcemid-induced coils in both neurones and associated satellite cells. In contrast, a specific antibody to the 70K neurofilament protein stained these structures solely in neurones. This neurone-specific staining, as well as its molecular weight and isoelectric point, distinguishes the 70K neurofilament protein from the 68K neurofilament associated protein described by others, which has been claimed to resemble the tubulin assembly protein.

Animals↗

Central nervous system complications of addiction to "T's and Blues".

Thirteen patients displayed neurologic complications of intravenous abuse of "T's and Blues" (pentazocine and tripelennamine). In six, the major presentation was seizures. Three patients had strokes, and three had CNS infections, two fungal and one related to subacute bacterial endocarditis. One patient had hepatic failure and an unusual encephalopathy. Foreign body embolization is common; the materials enter the cerebral circulation because of pulmonary arteriovenous shunts. Emboli may cause seizures, which also occur as a toxic effect of the drugs. Infection is due to unsterile injections. Enzyme elevations and diffuse vasculopathy raise the possibility of immune mechanisms.

Adult↗