Biomedical subjects

B S Morse

Publications and source records attributed to B S Morse.

At least 19 recordsLinked to original sources

PubMed1999

Evaluation of fibrin sealants in cutaneous wound closure.

Human fibrin sealant (HFS) and bovine fibrin sealant (BFS) were delivered as preformulated fibrinogen-thrombin mixtures that are light activated. These formulations were evaluated in the healing of incised cutaneous wounds in beagle dogs. Four groups were differentiated by sealant type and study duration with group: BFS for 10 days, HFS for 10 days, BFS for 30 days, and HFS for 30 days. Healing was evaluated by noting incidences of open wounds, laser Doppler perfusion imaging (LDPI), planimetry, breaking strength, and histopathology. In the absence of tension, both sealants tended to hold wound edges together; however, HFS tended to be better than its controls and BFS. Both sealants augmented suture closure, necessitating fewer sutures for wound closure. At 5 and 30 days BFS wounds had more perfusion than HFS wounds, indicating more inflammation. At 10 and 30 days BFS wounds had larger scar areas than their controls, while scar areas of HFS wounds were smaller than either BFS wounds or controls. Breaking strengths indicated that HFS wounds were stronger than their controls and BFS wounds. Histologically, mild to moderate chronic-active inflammation was observed in wounds receiving either sealant, and this persisted longer in BFS wounds. Overall, HFS had positive qualities, thus showing potential for functional and cosmetic wound closure.

Animals↗

PubMed1997

P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity.

The MDR1 P-glycoprotein (Pgp), a member of the ATP-binding cassette family of transporters, is a transmembrane ATPase efflux pump for various lipophilic compounds, including many anti-cancer drugs. mAb UIC2, reactive with the extracellular moiety of Pgp, inhibits Pgp-mediated efflux. UIC2 reactivity with Pgp was increased by the addition of several Pgp-transported compounds or ATP-depleting agents, and by mutational inactivation of both nucleotide-binding domains (NBDs) of Pgp. UIC2 binding to Pgp mutated in both NBDs was unaffected in the presence of Pgp transport substrates or in ATP-depleted cells, whereas the reactivities of the wild-type Pgp and Pgps mutated in a single NBD were increased by these treatments to the level of the double mutant. These results indicate the existence of different Pgp conformations associated with different stages of transport-associated ATP hydrolysis and suggest trapping in a transient conformation as a mechanism for antibody-mediated inhibition of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Altered drug-stimulated ATPase activity in mutants of the human multidrug resistance protein.

The characteristics of P-glycoprotein (MDR1), an ATP-dependent drug extrusion pump responsible for the multidrug resistance of human cancer, were investigated in an in vitro expression system. The wild-type and several mutants of the human MDR1 cDNA were engineered into recombinant baculoviruses and the mutant proteins were expressed in Sf9 insect cells. In isolated cell membrane preparations of the virus-infected cells the MDR1-dependent drug-stimulated ATPase activity, and 8-azido-ATP binding to the MDR1 protein were studied. We found that when lysines 433 and/or 1076 were replaced by methionines in the ATP-binding domains, all these mutations abolished drug-stimulated ATPase activity independent of the MgATP concentrations applied. Photoaffinity labeling with 8-azido-ATP showed that the double lysine mutant had a decreased ATP-binding affinity. In the MDR1 mutant containing a Gly185 to Val replacement we found no significant alteration in the maximum activity of the MDR1-ATPase or in its activation by verapamil and vinblastine, and this mutation did not modify the MgATP affinity or the 8-azido-ATP binding of the transporter either. However, the Gly185 to Val mutation significantly increased the stimulation of the MDR1-ATPase by colchicine and etoposide, while slightly decreasing its stimulation by vincristine. These shifts closely correspond to the effects of this mutation on the drug-resistance profile, as observed in tumor cells. These data indicate that the Sf9-baculovirus expression system for MDR1 provides an efficient tool for examining structure-function relationships and molecular characteristics of this clinically important enzyme.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Linking object boundaries at scale: a common mechanism for size and shape judgments.

The area over which boundary information contributes to the determination of the center of an extended object was inferred from results of a bisection task. The object to be bisected was a rectangle with two long sinusoidally modulated sides, i.e. a wiggly rectangle. The spatial frequency and amplitude of the edge modulation were varied. Two object widths were tested. The modulation of the perceived center approximately equaled that of the edges at very low edge modulation frequencies and decreased in amplitude with increasing edge modulation frequency. The edge modulation had a greater modulating effect on the perceived center for the narrower object than for the wider object. This scaling with object width didn't follow perfect zoom invariance but was precisely matched by the scaling of the bisection threshold with width, strongly supporting the idea that the same mechanism determines both the location of the perceived center for these stimuli and its variance. We propose that this mechanism is the linking of object boundaries at a scale determined by the object width.

Form Perception↗

PubMed1989

A rapid method for estimating mean platelet survival time.

Platelet survival studies were performed in 27 consecutive subjects, and mean platelet life span was derived by computerized calculations of radioactivity in blood samples obtained daily for 9-11 days. These computer derived estimates were then correlated with the raw whole blood radioactivity data obtained for the first 3 days of each study. Data from the 48-hr point correlates with the computer estimates so that platelet survival data can now be reported in 2 days with 93% precision of the long method and without visual curve fitting. Thus, one may take a "quick look" at the probable platelet lifespan, under steady state conditions, in order to evaluate therapy while avoiding problems of patient compliance.

Blood Platelets↗

PubMed1989

Actuarial analysis of a uniform and reliable preservation method for viable heart valve allografts.

CryoLife has developed a method for cryopreserving allograft heart valves for transplantation. Since 1984, 6,907 valves have been processed and 4,216 transplanted. Documentation was available on 2,647 transplants, 11 of which were removed for structural deterioration and 13, for nonstructural deterioration. At the end of 35 months, actuarial survival was 99.17% and the estimated freedom from reoperation, 97.16%. There have been no reports of thromboembolism or valve-related death.

Actuarial Analysis↗

PubMed1987

Chromium-51 dosimetry of lymphocytes labeled incidentally during nuclear medicine procedures.

Conventional dosimetry based on MIRD procedure fails to consider the localized energy deposition from the radionuclides decaying by the emission of Auger electrons. The cellular dosimetry of human peripheral blood lymphocytes labeled with 51 Cr, an Auger electron emitter, was calculated. Conventional dosimetric calculations reveal a dose of 0.024-0.17 rad/h/tube. In contrast the lymphocyte dose ranged from 0.053-0.339 rad/h with projected cumulative values of 51-324 rad for surviving lymphocytes.

Chromium Radioisotopes↗

PubMed1986

Strategies of hemopoietic stress adaptation within the medullary cavity.

Gravimetric determination of total bone water space was used as an index of available bone marrow space in mice following various specific stressors, i.e., splenectomy, hypoxia, bone fracture, and estrone-induced osteosclerosis. Data was corrected for bone weight and was reported as specific bone marrow volume (total bone water space/mg dry bone X 100). A direct relationship was observed between specific bone marrow volume and medullary hemopoietic activity induced by stress. Absolute and/or relative marrow space increased following splenectomy, hypoxia, and fracture. Osteosclerotic animals shift most hemopoietic activity from marrow to spleen, and splenectomized osteosclerotic animals become anemic. Both intact and splenectomized hypoxic animals develop increased specific bone marrow volume and successfully compensate for hypoxia with enhanced erythropoiesis. Animals sustaining a fracture callus increase both specific bone marrow volume and hemopoietic activity at the callus without an increase in hemopoietic demand. Increased specific bone marrow volume extends the marrow bone interface, where primitive stem cells accumulate, while expanding marrow stromal space, where stem cells lodge, proliferate and differentiate. Therefore, it would appear that availability of competent marrow space may play an integral part in passively permitting hematopoiesis and in determining hemopoietic reserve capacity. Stem cell migration increases during intensified hemopoietic demand, which also may be related to available marrow space. Mice have a low medullary hemopoietic reserve capacity; subsequently, when available medullary hematopoietic stroma becomes occupied, stem cells are more likely to migrate from the marrow to extra-medullary sites where they mature before entering the circulating pool.

Adaptation, Physiological↗

PubMed1984

Platelet-associated IgG in hepatitis and cirrhosis.

Increasing evidence is accumulating which indicates that immunological abnormalities contribute to the development of liver disease and its signs and symptoms. Platelet-associated IgG (PAIgG) levels were quantified in 42 patients with biopsy-proven liver disease of various etiologies to determine the relationship of thrombocytopenia to immunologic abnormalities in these disorders. Five of six nonthrombocytopenic patients with acute viral hepatitis B had elevated PAIgG. Six of ten patients with chronic active hepatitis had elevated PAIgG and thrombocytopenia. In contrast, only one of six patients with chronic persistent hepatitis had elevated PAIgG. Nine of ten patients with alcoholic hepatitis had elevated PAIgG; seven of the nine were thrombocytopenic. Seven of ten alcoholic patients with cirrhosis had elevated PAIgG; six of seven were thrombocytopenic. Thus the increase in PAIgG may be present without thrombocytopenia in acute liver injury, while patients with chronic persistent hepatitis do not usually exhibit this abnormality. Severe chronic active liver disease is accompanied by thrombocytopenia and an increase in PAIgG levels.

Biopsy↗

PubMed1984

Homologous recombination between plasmids in mammalian cells can be enhanced by treatment of input DNA.

We have used the eukaryotic-prokaryotic shuttle vector pSV2Neo to demonstrate that cultured mammalian somatic cells have the enzymatic machinery to mediate homologous recombination and that the frequency of this recombination can be enhanced by pretreatment of the input DNA. Two nonoverlapping deletion mutants of pSV2Neo were constructed, each affecting the bacterial aminoglycoside 3'-phosphorylase gene (the neo gene), which confers resistance to aminoglycoside antibiotics on bacteria and resistance to the antibiotic G418 on mammalian cells. Mammalian cells transfected with either deletion plasmid alone yield no G418 -resistant colonies. Cells cotransfected with both deletion plasmids yield G418 -resistant colonies with high frequency. We show that these resistant colonies result from recombination involving homologous crossing-over or gene conversion between the deletion plasmids by rescuing from the resistant cells both types of reciprocal recombinant, full-length plasmids, and doubly deleted plasmids. Cutting one of the input plasmids to generate a double-stranded gap in the neo gene considerably enhances the frequency of homologous recombination within the gene. This suggests that targeting exogenous DNA to specific sites in mammalian chromosomes could be facilitated by suitable pretreatment of the DNA.

Animals↗

PubMed1984

Insulin-induced reactivation of an inactive herpes simplex thymidine kinase gene.

A line of mouse cells transformed with ultraviolet-irradiated herpes simplex virus type 1 and containing a methylated and inactive viral thymidine kinase (TK) gene was treated with insulin in an attempt to induce expression of the inactive gene. Insulin was found to be capable of inducing the inactive TK gene in these cells. The induction of the TK+ phenotype was dose dependent (from 1-100 micrograms of insulin per ml), and the TK activity induced was shown to be of viral origin. Analysis of the methylation pattern of the viral TK gene by using the methylation-sensitive restriction endonucleases Sma I, Hpa II, and Hha I revealed that the active viral TK gene in the parental transformed cells was hypomethylated, whereas the inactive TK gene in the uninduced TK- cells was methylated. The active TK gene in three insulin-induced TK+ lines also was methylated, but the methylation patterns in the insulin-induced lines all were different from the uninduced TK- line. These data suggest that extensive hypomethylation of the inactive TK gene is not required for insulin induction. Four other transformed lines containing an inactive viral TK gene were tested for insulin inducibility, but insulin was unable to induce expression of the TK gene in any of the other lines. Thus, insulin inducibility does not seem to be a function of the viral TK gene itself. These results suggest that insulin inducibility of the viral TK gene may be a reflection of the region of the host genome into which the TK gene was integrated.

Animals↗

PubMed1984

Circulating immune complexes and platelet IgG in various diseases.

Correlation between platelet associated IgG (PAIgG), platelet count, and plasma polyethylene glycol (PEG) precipitable IgG immune complex (IC) like material was tested in normal subjects and patients with immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE) and various types of liver disease. Elevated IC were observed in 27% and 22% of ITP and recovered ITP, respectively. A significant inverse correlation between platelet count and PAIgG was demonstrable in the ITP group. A significant direct correlation between platelet count and IC was found only in SLE patients. Impaired reticuloendothelial cell (RE) Fc receptor function in SLE patients is suggested as a possible explanation for the data. If receptor function was normal in SLE patients, lower IC levels and lower platelet counts would have been expected.

Antigen-Antibody Complex↗

PubMed1983

Platelet-associated IgM levels in thrombocytopenia.

Platelet-associated IgG (PAIgG) and IgM (PAIgM) levels were quantitated in patients with thrombocytopenias of various etiologies. 32 of 34 patients with immune thrombocytopenia had elevated PAIgG, 8 of the 34 patients had elevated PAIgM levels. Only 1 patient suffering from immune thrombocytopenia had elevated PAIgM with normal PAIgG levels. Elevated PAIgM was most often associated with elevated PAIgG except for the following: 2 patients with lymphoproliferative disorders, 1 patient with heparin-induced thrombocytopenia, 1 patient with pernicious anemia, and 2 patients with Waldenström's macroglobulinemia. PAIgM determinations may prove to be a useful adjunct for evaluating patients with thrombocytopenia, particularly those in whom the PAIgG is not elevated.

Blood Platelets↗

PubMed1983

Platelet associated IgG in uremia.

Platelet-associated IgG (PAIgG) levels, a useful adjunct for the evaluation of patients with immunologic mediated thrombocytopenia, were obtained in 36 patients with end stage renal disease undergoing maintenance hemodialysis. Twenty-five of the 36 had elevated PAIgG. Nine of the 36 were thrombocytopenic and only 3 of the 9 had elevated PAIgG. Fifteen patients in the group admitted to recent substance abuse. All but one had elevated PAIgG and only one patient was thrombocytopenic. In contrast to patients with idiopathic immune thrombocytopenic purpura (ITP), a direct relationship was not found between PAIgG and total platelet protein (TPP) in the uremic group. It can be concluded that PAIgG values in patients with uremia are difficult to interpret since elevated PAIgG values are found in the majority of uremic patients with normal platelets counts.

Blood Platelets↗

PubMed1982

A rapid quantitation of platelet-associated IgG by nephelometry.

Platelet-associated IgG (PAIgG) was measured by a simple rapid nephelometric technique using washed solubilized platelets and commercially available, prestandardized reagents. Normal subjects with normal platelet counts had PAIgG levels of 2.1-6.7 fg/platelet. Subjects with idiopathic immune thrombocytopenic purpura (ITP) had levels of 7.2-43.3 fg/platelet. Ninety percent of ITP patients had values exceeding 2 SD units of the mean of normal subjects. Elevated values were also found in 17% of patients with recovered ITP, patients with SLE with and without thrombocytopenia, patients with thrombocytopenia occurring during septicemia, and patients with IGg myeloma. Results can be obtained within several hours of receipt of blood specimen, and are similar to the reports that used more complex techniques.

Blood Platelets↗

PubMed1981

Quantitation of platelet-associated IgG by radial immunodiffusion.

Platelet-associated IgG (PAIgG) was measured by a simple radial immunodiffusion technique using washed solubilized platelets and commercially available immunoplates. Subjects with normal platelet counts had PAIgG levels of 1.5--7.0 fg/platelet. Subjects with idiopathic immune thrombocytopenic purpura (ITP) had levels ranging from 5.7 to 70.5 fg/platelet. All patients with recurrent ITP and 85% of patients with acute ITP had elevated PAIgg. Elevated PAIgG was also found in 17% of patients with recovered ITP, 40% of patients with SLE and thrombocytopenia, 57% of patients with thrombocytopenia occurring during the course of septicemia, and 100% of patients with IgG myeloma in whom the serum IgG level was clearly elevated, regardless of the platelet count. The results are similar to reports that used more complex techniques.

Blood Platelets↗

PubMed1980

Mechanism of arsenic-induced inhibition of erythropoiesis in mice.

Anemia accompanies arsenic intoxication in man. The present studies were undertaken to clarify further the effects of arsenic on erythropoiesis. A dose-related inhibition of red cell 59 Fe incorporation and reticulocyte response was observed in normal mice treated with a single injection of arsenic. Arsenite was approximately two times as inhibitory as arsenate. The effects of arsenic on erythropoietin-induced erythroid differentation revealed a significant inhibitory effect on young, proliferating marrow nucleated erythroid precursor cells. More mature, nonproliferating nucleated erythr oid cells were resistant to the toxic action of arsenic. A dose-related inhibitory effect of arsenic on DNA synthesis was observed in fetal liver nucleated erythroid cells incubated with 3 H thymidine. Ineffective erythropoiesis as well as the megaloblastic morphology accompanying aberrant DNA synthesis -- manifestations of arsenic toxicity in man -- were not evident in the present studies.

Animals↗

PubMed1977

Trauma as a stimulus to marrow regeneration in the osteosclerotic mouse.

Hemopoietic regeneration was studied in the tibia of mice rendered osteosclerotic by estrone injections. Trauma induced by fracture and periosteal damage was followed by a local hemopoietic response in both normal and osteosclerotic mice. Endosteal damage induced by drilling an artificial cavity in the osteosclerotic tibia was not followed by local hemopoietic regeneration, whereas in normal tibias similarly treated incomplete hemopoietic regeneration was observed. These studies indicate that trauma induced by fracture and periosteal damage is followed by a fairly uniform local hemopoietic regenerative response regardless of whether or not marrow is present in the traumatized bone. Creation of a simulated marrow cavity by drilling through osteosclerotic bone is an insufficient stimulus for hemopoietic regeneration in the mouse. New bone tissue was found to occupy the drilled shaft. This suggests that failure to regenerate hemopoietic tissue may be a consequence of insufficient bone resorption. A differential effect of trauma on endosteal and periosteal tissue is therefore postulated.

Animals↗