Search PubMed⌕ Search

Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 541 records · Page 30Linked to original sources

Three distinct distributions of F-actin occur during the divisions of polar surface caps to produce pole cells in Drosophila embryos.

The F-actin distribution was studied during pole cell formation in Drosophila embryos using the phalloidin derivative rhodaminyl-lysine-phallotoxin. Nuclei were also stained with 4'-6 diamidine-2-phenylindole dihydrochloride to correlate the pattern seen with the nuclear cycle. The precursors of the pole cells, the polar surface caps, were found to have an F-actin-rich cortex distinct from that of the rest of the embryo surface and an interior cytoplasm that was less intensely stained but brighter than the cytoplasm deeper in the embryo. They were found to divide once without forming true cells and then a second time when cells formed as a result of a meridional and a basal cleavage. Three distinct distributions of the cortical F-actin have been identified during these cleavages. It is concluded that the first division, which cleaves the polar caps but does not separate them from the embryo, involves very different processes from those that lead to the formation of the pole cells. A contractile-ring type of F-actin organization may not be present during the first cleavage but is suggested to occur during the second.

Actins↗

Prevention of edema formation in the perfused lung preparation by oxygen radical scavengers.

Oxygen-derived free radicals have been implicated as mediators of pulmonary microvascular injury. In the present study we addressed the question of the role of radicals formed in the lung parenchyma in development of pulmonary edema. Rat lungs were perfused with cell-free solutions with and without addition of colloid. Edema formation was measured as dry-wet weight ratios. Edema developed following 30 min perfusion with all perfusates except nonoxygenated Dextran-Tyrode. Addition of free radical scavengers, superoxide dismutase and catalase, reduced the edema formation with the various oxygenated perfusates. We conclude that in the isolated lung perfused with oxygenated solutions oxygen-derived radicals are formed that mediate increased permeability.

Animals↗

Cytoplasmic immunoglobulin content in multiple myeloma.

Bone marrow cells of 82 patients with multiple myeloma were subjected to flow cytometric analysis of DNA and cytoplasmic immunoglobulin (CIg) content using propidium iodide and direct immunofluorescence assays. Except for two patients with nonsecretory myeloma, there was conformity in the immunoglobulin type derived from immunoelectrophoresis and plasma cell CIg staining. One patient with nonsecretory myeloma exhibited monotypic CIg staining, while the second showed no reaction. In eight patients with IgG lambda myeloma, the same tumor cells contained both lambda and kappa light chains, suggesting the productive rearrangement of both light chain genes. 14 patients with previously unrecognized plasma cells of low RNA content, all of whom were resistant to chemotherapy, were identified by CIg staining. By revealing previously unrecognized plasma cells with low RNA content, CIg analysis identified more patients with treatment-refractory myeloma.

Bone Marrow Cells↗

Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer.

Risk factors for local-regional recurrence of breast cancer were analyzed in a retrospective review of 117 patients treated with adjuvant CMF (Cytoxan [Mead Johnson & Co, Evansville, Ind], methotrexate, 5-fluorouracil) after radical or modified radical mastectomy at the Vincent T. Lombardi Comprehensive Cancer Center (Washington, DC). The median follow-up time was 50 months after mastectomy. The median time to recurrence was 23 months. The actuarial local-regional failure rate was 19% at five years. Risk of local failure correlated with size of primary (27% for T3 v 15% for T1) and axillary node status (36% for four or more positive nodes v 9% for three or fewer positive nodes). These findings suggest a rationale for the addition of postoperative radiation therapy in high-risk patients treated with adjuvant chemotherapy.

Actuarial Analysis↗

Demyelinating encephalopathy in Lyme disease.

A 38-year-old man from southeastern Connecticut developed a diffuse encephalopathy with partial complex seizures, followed weeks later by arthritis, cryoglobulinemia, and increased serum IgM. CT showed confluent low-density lesions in the deep cerebral white matter consistent with demyelination. Neither the encephalopathy nor the CT abnormalities improved. Lyme disease was diagnosed serologically 4 years later.

Adult↗

Adult, foetal and transformed fibroblasts display different migratory phenotypes on collagen gels: evidence for an isoformic transition during foetal development.

Data are presented indicating that the migration of fibroblasts into three-dimensional collagen gels is affected by cell density. We have defined a 'cell density migration index' (CDMI) to express this behavioural response in quantitative terms. The results of a survey of 77 different cell types indicate that the CDMI values expressed by normal adult skin fibroblasts and transformed cell lines fall into two distinct, non-overlapping groups. Measurement of the CDMI therefore provides an additional means of distinguishing between normal and transformed cells and may be used in conjunction with other commonly recognized criteria (e.g. anchorage-independent growth) to assess expression of a transformed phenotype in vitro. It is of interest to note that the CDMI values expressed by foetal cells define a group lying intermediate between normal and transformed cells. Both uncloned and cloned foetal cells have been observed to undergo a stable transition to expression of CDMI values characteristic of adult cells when followed throughout the duration of their in vitro lifespan. In addition to providing a novel means of distinguishing between normal adult and foetal cells, our results suggest that foetal fibroblasts undergo an 'isoformic' transition at some point in their developmental history, which is manifest in vitro by the expression of an adult CDMI.

Adult↗

Prognostic implications of tumor cell DNA and RNA content in multiple myeloma.

Flow cytometric studies of bone marrow DNA and RNA content were conducted in 71 previously untreated patients with multiple myeloma. There was a progressive increase in response rate with rising plasma cell RNA content. The DNA-derived ploidy level also affected chemotherapy sensitivity: only one of 11 patients with either hypodiploidy or biclonal DNA stemlines responded. DNA-RNA-defined marrow plasmacytosis was the only tumor mass-related variable adversely affecting remission induction. Survival was longer in patients with low tumor burden and favorable DNA features. The availability of objective and quantitative pretreatment variables associated with both initial response and survival should permit a risk-based selection of patients for novel treatment approaches.

Bone Marrow↗

Anterior thigh pain or tenderness. A diagnostically useful manifestation of bacteremia.

In four patients with putative infectious process, anterior, bilateral proximal thigh pain and tenderness unaccompanied by generalized myalgias developed. This unusual manifestation, observed in these and other patients, was associated with demonstrable bacteremia. Aside from tenderness, no local abnormalities were found and the pain and tenderness disappeared after appropriate therapy. Creatine kinase levels, measured in three of the four patients, were elevated in only one. This manifestation is useful clinically as it strongly suggests bacteremia; attention to this finding can be lifesaving.

Abdomen↗

The role of high dose corticosteroids (HDC) in pulmonary capillary-alveolar membrane integrity.

Disturbed microvascular integrity is an initial event in the development of respiratory insufficiency following trauma and shock. Increased permeability in the pulmonary microvessels has been demonstrated in both experimental animals and in man. High dose corticosteroids have been used to prevent the development of the permeability lesion and to reduce it once it has occurred. Data from experimental animals are indicative of a positive effect of HDC and in patients with adult respiratory distress syndrome leakage of macromolecules over the capillary alveolar membrane was reduced significantly. Using the lung lymph fistula preparation in sheep we have demonstrated that the pulmonary microvascular sieving capacity was reduced (as indicated by a reduced osmotic reflection coefficient) following the operative trauma and manipulation of lungs necessary for cannulation of the lymphatics. We studied the effects of HDC (methyl-prednisolone 30 mg/kg) given preoperatively in 7 operated sheep and compared to 3 nonoperated controls. Permeability surface area product (PS) and osmotic reflection coefficient (sigma) for total protein were calculated by iterative curve fitting using the non-linear flux equation and data were compared to sigma achieved at maximal lymph flow following increased left atrial pressure. After surgery there were no differences between the two groups in baseline observations. In the experimental group lymph to plasma ratio for total protein (L/P) at maximal lymph flow was 0.46 +/- 0.09 corresponding to a sigma of 0.54. Maximal lymph flow was attained at microvascular pressure (Pmv) 38 +/- 2 mmHg. Calculated sigma was 0.61 +/- 0.03 and PS 0.09 +/- 0.01. Corresponding values in the control group were 0.69 +/- 0.003 and 0.1 +/- 0.0003 respectively. L/P at maximal lymph flow was 0.39 +/- 0.04 at Pmv = 35 +/- 6 mmHg in the control group. In this experiment HDC did not prevent the increase in pulmonary microvascular permeability as demonstrated after operative trauma by a decrease in the osmotic reflection coefficient for total protein. Data from patients indicate however, that HDC may have a beneficial effect on the integrity of the alveolar capillary membrane. Further studies are needed to elucidate these problems.

Animals↗

Significance of 801 monoclonal proteins detected during 7 years of screening in a district general hospital.

This study describes the biochemical follow-up of 801 patients in whom a monoclonal protein had been detected, by screening protein electrophoresis, during a 7-year period. A further blood sample was obtained from 61% of the group and information was available on an additional 32%. Follow-up times ranged from 2 months to almost 8 years. The level of monoclonal protein was measured and any increase related to the level at detection, presence of reduced polyclonal immunoglobulins (RPI), and Bence Jones Protein (BJP). Seventeen (2.1%) monoclonal proteins had disappeared and 428 (88%) demonstrated no significant change in level. Only 26 (3.2%) patients showed a significant increase. This suggests that the majority of monoclonal proteins detected on screening electrophoresis are benign. The presence of BJP is still considered to be the most significant biochemical prognostic criterion. In contrast, finding RPI seems to be least useful. A monoclonal protein level greater than 19 g/l is usually associated with an immunocyte related disease as is an increase in the level of more than 6 g/l. Therefore, assessment of the benign or malignant nature of monoclonal proteins using biochemical prognostic criteria at detection alone is not sufficient. It is recommended that the minimum follow-up should involve review at 3 months and then at yearly intervals.

Aged↗

Positive direct antiglobulin tests and immune hemolytic anemia in patients receiving procainamide.

To characterize the autoimmune phenomena in patients receiving procainamide, we studied the prevalence of positive direct antiglobulin (Coombs') tests and immune hemolytic anemia in 100 such patients and compared them with 100 age-matched and sex-matched controls. There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05). The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia. In contrast, positive direct antiglobulin tests in control patients were due to the presence of complement components. Red-cell autoantibody production secondary to procainamide was not correlated with a higher-than-expected frequency of antinuclear antibodies or the clinical syndrome of drug-induced lupus erythematosus. In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia. In two of the three cases, the anemia resolved after the medication was discontinued and did not require steroid therapy. We conclude that procainamide often results in the production of red-cell autoimmune phenomena.

Aged↗

Rapid calcium mobilization by vasopressin and prostaglandin F2 alpha is independent of sodium influx in quiescent 3T3 cells.

Vasopressin (VP) rapidly increased 45Ca2+ efflux. A VP antagonist prevented VP from mobilizing Ca2+ and stimulating DNA synthesis. Prostaglandin F2 alpha (PGF2 alpha) also stimulated rapid 45Ca2+ release. The effectiveness of different prostaglandins corresponded to their effectiveness as mitogens. The removal of external Na+ or Ca2+ had no effect on VP-or PGF2 alpha-induced 45Ca2+ release. The present results indicate that the mobilization of intracellular Ca2+ by these hormones is independent of Na+ or Ca2+ influx and that Ca2+ mobilization is important for growth stimulation.

Angiotensin II↗