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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 505 records · Page 28Linked to original sources

Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts.

We have previously demonstrated that DNA of mouse fibroblasts transformed by 3-methylcholanthrene (3-MC) induced foci of transformed cells when applied to monolayer cultures of NIH3T3 cells, which indicates that at least a part of this phenotype is encoded in DNA sequences. However, our conclusions were confined to the effects of DNAs of 3-MC-transformed mouse fibroblasts on recipient NIH3T3 cells, also of mouse fibroblast origin. To elucidate this phenomenon further, we have prepared DNAs from a series of mouse and non-mouse tumour lines of non-fibroblastic origin and investigated whether tumour transforming genes can act across tissue and species barriers to transform NIH3T3 cells. We find that DNAs obtained from human, rabbit and mouse bladder carcinoma lines, a lung carcinoma line and rat neuroblastoma and mouse glioma lines, are able to induce transformation of NIH3T3 cells on transfection.

Animals↗

Rifampin chemoprophylaxis for household contacts of patients with invasive infections due to Haemophilus influenzae type b.

To determine the efficacy of rifampin chemoprophylaxis in eradication of oropharyngeal carriage of Haemophilus influenzae type b, we conducted a multicenter, double-blind, placebo-controlled trial among household contacts of patients hospitalized for invasive HIB infection. Seventy-nine index patients and 400 close contacts were studied; 26.5% of contacts were colonized. The efficacy of rifampin (10 mg/kg/dose, 600 mg/dose maximum, twice daily for two days) in eradicating carriage was 52% and varied with age (75.6% in persons greater than or equal to 5 and 27% in those less than 5 years). Eradication rates in those less than 5 years were not significantly better than for placebo. No resistant isolates were encountered in sensitivity testing. The low efficacy of this rifampin regimen in young children precludes its routine use as a chemoprophylactic agent for family contacts. The occurrence of three cases of invasive HIB infection in individuals outside the defined contact group raises concern regarding the efficacy of any chemoprophylactic regimen.

Clinical Trials as Topic↗

Smoking among new student nurses.

Smoking is very common among nurses. Various explanations have been offered for this but the reasons for it are still unclear. To investigate some aspects of this problem and prepare for a longitudinal study, an intake of students to a large nursing school was surveyed. Information was obtained on their smoking behaviour, social background and preconceptions of nursing.

Adolescent↗

The pathogenesis of experimentally induced Trypanosoma brucei infection in the dog. I. Tissue and organ damage.

Inoculation of dogs with Trypanosoma brucei produced an acute fetal disease similar to that seen following natural infection. The disease was characterised by high levels of parasitaemia, moderately severe anemia, and marked changes in the lymphoid system. Extravascular invasion by large numbers of trypanosomes was widespread throughout the body and was accompanied by severe tissue damage. Tissue invasion by trypanosomes was associated with marked cellular infiltration involving lymphoid cells and plasma cells followed by macrophages and polymorphonuclear leukocytes. Associated with these reactions, severe cellular degeneration and focal necrosis occurred. While these changes were widespread and were found in the majority of tissues examined, consistently severe lesions were found in the heart, eyes and central nervous system. In many organs, lymphatic vessels were distended with fluid, trypanosomes, and a cell population similar to that in the surrounding tissue; fibrin deposition and thrombus formation was sometimes observed within the lymphatic lumens. Thrombosis was also found in the blood vessels of the pampiniform plexus, the venous plexus of the ovary, and branches of the renal vein. A severe necrotizing vasculitis affecting only the coronary vessels was a prominent feature in some animals.

Animals↗

The pathogenesis of experimentally induced Trypanosoma brucei infection in the dog. II. Change in the lymphoid organs.

Marked changes were found in the spleen and lymph nodes of dogs experimentally infected with Trypanosoma brucei. These changes were considered to occur in two phases. First, in animals examined on Days 8 and 16 after inoculation, there was an intense proliferative response; this involved particularly the B-dependent follicular areas and was accompanied by a dramatic increase in the number of plasma cells in the splenic red pulp and medullary cords of the lymph nodes. Although numerous large proliferating lymphoblasts were found in the periarteriolar regions of the spleen and in the peripheral part of the paracortical areas of the lymph nodes, the presence of cells containing Ig in these regions made it difficult to evaluate the degree of involvement of thymus-derived cells. The plasma cell response involved both IgM and IgG, although the increase in IgM-containing cells was most striking. During this initial phase there was focal hemorrhage, deposition of fibrin, necrosis, and infiltration of polymorphonuclear leukocytes in the spleen, these changes being most severe in the peripheral follicular areas. Following the initial proliferative phase and prior to the death of the host during the fourth week of the infection, the spleen and lymph nodes became less reactive, and there was marked disorganization and disruption of their architecture. Compared with characteristics earlier in the infection there was greatly decreased proliferative activity and a reduction in size of the splenic white pulp and lymph node cortices. Germinal centers were reduced in number, size, and activity, had a disorganized appearance, and, by immunofluorescence, showed a reduction of immunoglobulin on the dendritic reticular cells. The lymph node sinuses exhibited a decrease in content of lymphocytes and contained massive numbers of macrophages, including numerous multinucleated giant cells. There was also severe disruption of the reticulum cell network of the sinuses; and accumulations of polymorphonuclear leukocytes, along with extensive deposition of fibrin, were commonly found in the subcapsular sinuses. During this period, foci of erythropoietic cells were present throughout the red pulp of the spleen.

Animals↗

Response of the murine lymphoid system to a chronic infection with Trypanosoma congolense. I. The spleen.

The response within the different cellular compartments of the spleen in mice infected with Trypanosoma congolense was evaluated using histologic and cytologic methods and immunofluorescence to detect intracellular and cell surface immunoglobulin. The isolate of T. congolense used produces a chronic infection in C3H/He mice leading to death 40 to 70 days after inoculation. Previous studies had shown that this infection resulted in a marked immunodepression as judged by a range of in vitro assays of splenic cellular responses. It was found that the splenic cellular changes occurred in two phases. First, coincident with and following the first peak of parasitemia, there was a marked proliferative phase characterized by widespread hyperplasia of the white pulp with the production of large numbers of plasma cells and an expansion of the erythropoietic component of the red pulp. During this period, there was a marked decrease in the intensity of staining for surface Ig on cells of the follicular regions of the white pulp. Following the initial proliferative changes, a more protracted phase ensued during which, although the proliferative activity continued, there was a gradual disorganization of the white pulp with eventual lymphoid depletion. This was accompanied by a progressive expansion of the red pulp due to increased numbers of erythropoietic cells and to a lesser extent granulopoietic cells and macrophages. At the same time, there was a gradual decrease in the number of plasma cells found in the red pulp, although many were still present in the periarteriolar regions. The end result of these changes was an approximately 17-fold increase in total splenic cellularity of which erythropoietic cells contributed more than 50 per cent, and lymphocytes were reduced in absolute numbers to below control levels. A striking feature during both phases of the infection was the lack of discrete germinal centers.

Animals↗

Recovery of substance P in the cat spinal cord after unilateral lumbosacral deafferentation.

Changes in substance P in the cat spinal cord after deafferentation of the hindlimb were investigated using the peroxidase-antiperoxidase technique. Unilateral lumbosacral dorsal root section (L1-S3) is followed by a decrease in dorsal horn (laminae I, II and V) substance P reaction product which is most marked at 10-11 days. There is no observable change in the ventral horn. The 13 or 15 day survivors demonstrate an increase over that seen at 10-11 days, and still greater amounts appear in the dorsal horn of 1 month survivors. After 1 month there is little further observable increase. The location of the returned reaction product resembles that of normals, but differs in its staining characteristics. Substance P containing cell bodies are observed in normal animals and on intact and deafferented sides of experimentals, suggesting that interneurons and propriospinal fibers may be a source of the returning substance P reaction product. The decrease in dorsal horn substance P at short times after rhizotomy followed by an increase at longer times is consistent with axonal sprouting. If so, then the time course of sprouting parallels that of locomotor recovery and supports the hypothesis that the two phenomena are related.

Afferent Pathways↗

Inhibition of proliferation of cloudman S91 melanoma cells by insulin and characterization of some insulin-resistant variants.

Insulin is a potent, reversible inhibitor of proliferation in Cloudman S91 mouse melanoma cells. The inhibition seems to be unique to the Cloudman line since five other cell lines, including the mouse B16 and hamster Greene melanomas, were unaffected by insulin under the same culture conditions. Variants of Cloudman S91 cells were isolated which differed from wild-type (WT) cells in their response to insulin. Most of these variants were resistant to insulin (INSres) and had the same generation time independent of the presence of the hormone. One line (INSdep) was found to require insulin for growth. This line was about 15 times more sensitive to the proliferative effects of insulin than the WT. Revertants of the INSdep line were selected for their ability to proliferate in the absence of insulin. Five out of five such revertants were insulin resistant, suggesting that the INSdep line arose as a results of at least two separate mutations. Both WT and INSdep cells showed enhanced uptake of 14C-alpha-aminoisobutyric acid (AIB) when exposed to insulin. Dose-response curves of the stimulation of AIB uptake in WT and INSdep cells were superimposable. Stimulation of AIB uptake and stimulation of proliferation by insulin were not under coordinate control since AIB uptake was increased equally in the wild-type cells when proliferation was inhibited and in INSdep cells when proliferation was enhanced. Binding of 125I-insulin was used to demonstrate the presence of specific, high affinity insulin receptors on the cells. INSres variants generally had fewer receptors than WT, but in no case did the magnitude of this effect appear to be sufficient to explain the insensitivity to insulin. The INSdep variant showed a greater than two-fold increase in the number of insulin receptors per cell, compared to WT. Revertants of the INSdep line had the same number of receptors as WT. The specificity for both binding and for the effects on proliferation were the same in WT and INSdep cells. Since the effects of insulin on proliferation were opposite in the two lines, we propose at least two distinct sites of insulin action on the cells. Further isolation and analyses of Cloudman lines with unusual responses to insulin should be useful for understanding the molecular basis of action of this hormone.

Aminoisobutyric Acids↗

Naturally occurring neuron death in the optic layers of superior colliculus of the postnatal rat.

Application of light and electron microscopic techniques to the superior colliculus of the normal rat shows that a number of neurons die within the first week after birth. Cells in the earliest recognizable stages of degeneration are characterized by an overall increase in electron density and dilation of the intracellular cisternae, although there are only minimal changes in the chromatin pattern of the nucleus. Synapses are found on these cells. A second type of degenerating cell, with more striking changes in the nucleus, also appears in the tissue but very infrequently. In later stages of degeneration, cells are reduced to a condensed chromatin mass surrounded by disrupted fragments of the rest of the cell. This 'cellular debris' is found within glial cytoplasm. The majority of these debris profiles appear in the first postnatal week and are usually most abundant in the caudal third compared to either the rostral or middle thirds of the colliculus. The results suggest that the mechanisms controlling neuron number in the superior colliculus are operative in the postnatal rat but argue against a simple relationship between the survival of a particular neuron and the total number of optic connections that neuron has received.

Animals↗

On the anatomic relation of choroid plexus to brain: a comparative study.

The size of choroid plexuses and cerebral ventricles relative to brain varies widely among vertebrates. The functional significance of this variability has attracted little attention since Herrick's original proposal that large choroid plexuses might enhance oxygen delivery to the brain and therefore be of adaptive value in the transition of vertebrates from water to air breathing. We compared choroid plexus and brain weight or ventricular and brain volume in 40 species from nine vertebrate groups. Both choroid plexus weight and ventricular volume were unrelated to brain size. Plexus weight ranged from 0 to 5.2% of brain weight and ventricular volume from 0.9 to 132% of brain volume. Amid this diversity the dipnoans, chondrosteans, holosteans, amphibians, and crossopterygian examined in this study are exceptional in uniformly having large plexuses. The adaptive significance of large choroid plexuses may lie in the presence of specific homeostatic mechanisms and their role in the response to the increases in PCO2 that accompany the transition to air breathing.

Animals↗