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Biomedical subjects

M E Richardson

Publications and source records attributed to M E Richardson.

At least 19 recordsLinked to original sources
PubMed1992

Thiol manipulation as a means of overcoming drug resistance in a novel cyclophosphamide-induced resistant cell line.

Acquired drug resistance is a major obstacle in the successful treatment of cancer by chemotherapy. To study mechanisms of resistance to alkylating agents, we have derived an in vitro subline of the murine KHT-iv sarcoma, KHT-rcp/iv, that has acquired resistance to cyclophosphamide. Compared to the parental line, KHT-rcp/iv exhibited an approximately 2.8-fold resistance, determined from the ratio of the slopes of the resistant to the parental survival curve. The subline also was found to be cross-resistant to other alkylating agents, as well as to the epipodophyllotoxin, etoposide, a structurally unrelated compound (resistance factor of approximately 2.2). In view of this broad spectrum of cross-resistance observed, we investigated the possibility that glutathione (GSH), an abundant tripeptide implicated in the detoxification of electrophilic species, may be involved. GSH levels were increased two-fold in the resistant line (16.0 +/- 1.0 fmol/cell) as compared to the parent line (8.1 +/- 0.7 fmol/cell). Also, when the GSH content was reduced to that of the parent with the addition of the thiol depletor buthionine sulfoxinine (BSO), the sensitivity of the subline to cyclophosphamide, as well as to the other agents, was enhanced so that it equaled that of the parent cell line. These results imply that enhanced GSH levels may be a major mechanism of resistance in the KHT-rcp/iv cells. Our findings further suggest that thiol manipulation may prove useful in overcoming this type of pleiotropic drug resistance.

Animals↗
PubMed1992

Effect of a hypoxic tumor cell cytotoxic disulfide on the membrane and DNA of tumor cells in culture.

A disulfide, n-butyl 2-imidazolyl disulfide (III-2), recently reported to be more toxic to EMT6 tumor cells under hypoxia has also been shown to be preferentially toxic to KHT/iv cells under hypoxia with an IC90 value 3-fold lower versus that measured in air. The IC90 values for both cell lines were markedly affected when the pHe was decreased. Uptake studies revealed that the disulfide is metabolized at the cell membrane with only one of the metabolites, n-butanethiol, being taken up into the cell. There were no differences in the amount of uptake under oxia or hypoxia. Investigation of potential membrane damage revealed that III-2 was a mixed inhibitor of the enzyme Na+,K(+)-ATPase, from isolated plasma membrane. DNA damage, when examined using plasmid DNA in the absence or presence of glutathione, was absent. Minor single-strand breaks to EMT6 DNA could only be observed following exposure to III-2 at the highest concentrations tested, with no differences observed between treatments in air or under hypoxia.

Animals↗
PubMed1992

Second molar extraction in the treatment of lower premolar crowding.

Thirty-four children with lower premolar crowding were treated by extraction of second molars. Thirteen cases had mechanical lower arch treatment started not less than 6 months after extractions. The remainder had no treatment in the lower arch. The change in premolar crowding was measured, and the reasons why spontaneous alignment occurred in some cases and not in others were examined.

Adolescent↗
PubMed1992

Research note: kinetic and inhibition studies with turkey acrosin.

Acrosin was extracted from turkey spermatozoa and partially purified by chromatofocusing. Enzyme activity was tested over a pH range with three different substrates. In each case, the pH optimum was between pH 8 and 9. When N-alpha-benzoyl-DL-arginine-p-nitroanilide.HCl (BAPNA) was used as a substrate, the Km and Vmax were 1.17 +/- .05 x 10(-3) M and 1.50 +/- .07 x 10(4) mumol/min.milligram, respectively. Turkey acrosin amidase activity was inhibited by aprotinin, ovomucoid, soybean trypsin inhibitor, benzamidine, p-aminobenzamidine, and zinc.

Acrosin↗
PubMed1991

Familial fixed subaortic stenosis.

In this report, we give details of two families in which fixed subaortic stenosis was found in more than one member. It is rare for this entity to show familial incidence.

Adolescent↗
PubMed1990

Residual lower first premolar extraction space.

Residual lower first premolar extraction space was examined in 43 subjects, 16 male and 27 female, 5 years after extraction; 16 subjects were treated mechanically, 27 had no active treatment. Forty per cent of extraction sites had residual spaces averaging 0.62 mm left and 0.71 mm right. Various parameters were measured to try to establish reasons for non-closure of spaces. These included buccal space condition and incisal space condition measured on the pre-extraction models, and alveolar atrophy assessed on final models. The angulation of second premolars and canine to the maxillary plane and molar space were measured on 60 degrees cephalograms. Changes in these three parameters were measured after superimposing a tracing of the pre-extraction film on the final film. Angulation of lower incisors to the maxillary plane was measured on pre-extraction 90 degrees cephalograms, and change in lower incisor angulation and position measured after superimposing a tracing on the final 90 degrees film.

Alveolar Process↗
PubMed1989

Nonrandom chromosomal aberrations are associated with sites of tissue involvement in non-Hodgkin's lymphoma.

In an effort to assess the utility of pretreatment cytogenetics as indicators of sites of involvement by lymphoma, clinical and cytogenetic correlations were performed on 133 consecutive specimens derived from 130 patients with non-Hodgkin's lymphoma. Nonrandom chromosomal aberrations detected at the time of diagnosis were associated with sites of clinical involvement presenting initially or during the progression of the lymphoma. Statistically significant associations included translocation breaks involving the chromosomal region 1p32-36 and bone marrow involvement, chromosome 14 abnormalities including breaks at 14q22-24 and splenic involvement, chromosome 9 abnormalities and pulmonary involvement, and monosomy 11 and bone involvement. A significant correlation was also observed between breaks involving the region 6q22-24, detected during the course of disease, and bone marrow involvement by lymphoma. The relationship of the sites of nonrandom chromosomal breakage reported here to known cellular oncogenes and implications to concepts of tumor evolution and spread are discussed.

Bone Marrow↗
PubMed1989

The effects of prolonged ketamine-xylazine intravenous infusion on arterial blood pH, blood gases, mean arterial blood pressure, heart and respiratory rates, rectal temperature and reflexes in the rabbit.

The prolonged and safe maintenance of general anesthesia in rabbits with commonly used injectable agents is difficult. Protracted, stable anesthesia with short recovery time has been described in humans using continuous intravenous infusion of ketamine with or without sedatives, muscle relaxants and paralytics. This study evaluated the anesthetic plane achieved and respiratory and cardiovascular effects produced with a ketamine-xylazine intravenous infusion in New Zealand White rabbits. Ten female rabbits were anesthetized with intramuscularly administered ketamine hydrochloride (35 mg/kg) and xylazine hydrochloride (5 mg/kg) after the preanesthetic, baseline measurements of arterial blood pO2, pCO2 and pH and heart and respiratory rates were recorded. The above parameters as well as mean arterial blood pressure, righting, palpebral, pedal, and jaw reflexes were monitored ten minutes after the intramuscularly administered dosage and throughout 4 hours of infusion. Results showed moderate hypotension (21.2% deviation from normal, p less than 0.008) and profound hypoxemia (45% deviation from baseline, p less than 0.001) 10 minutes after the intramuscularly administered induction dosage. Then, the 4 hour infusion of ketamine (1 mg/minute) and xylazine (0.1 mg/minute) was started. Hypotension progressed (49.1% deviation from normal, p less than 0.008), but hypoxemia and hypercarbemia gradually improved with no resultant change (p greater than 0.1) in arterial pH. There was no significant change (p greater than 0.1) in respiratory rate but varying qualities of respiration were observed. Both mean arterial pO2 and pCO2 values returned to baseline within 20 minutes after completion of infusion. Heart rate and rectal temperature remained stable during the trial. The righting reflex was abolished in all rabbits throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1988

Turkey acrosin. I. Isolation, purification, and partial characterization.

Acrosin was extracted from turkey spermatozoa by use of urea together with sonication and freezing, and purified approximately 18-fold by sequential use of chromatofocusing and affinity chromatography. The use of chromatofocusing for the initial purification step proved to be superior to preparative isoelectric focusing. Similar to acrosin from many mammalian species, turkey acrosin was found to be a glycoprotein possessing characteristics of serine proteases. Polyacrylamide gel electrophoresis (PAGE) of the enzyme indicated the presence of two isozymes. Sodium-dodecyl sulfate PAGE under reducing conditions revealed three subunits with approximate molecular weights of 11,700, 13,900, and 15,900.

Acrosin↗
PubMed1987

Generalized lymphadenopathy with morphologic features of Castleman's disease in an HIV-positive man.

In recent years the literature has described a highly lethal "multicentric" variant of classic Castleman's disease (CD) with similar hyperplastic angio-follicular morphologic features. A 44-year-old man who was not known to be part of any established high-risk group for the acquired immune deficiency syndrome (AIDS) presented with clinical and laboratory features similar to "multicentric" CD. Serologic testing revealed antibody to the human immunodeficiency virus (HIV) by Western blot analysis. It is suggested that "multicentric" CD may be part of the clinicopathologic spectrum of HIV infection, and there should be a high index of suspicion for HIV in patients presenting with generalized lymphadenopathy and histopathologic features of CD.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Lower third molar space.

Increase in lower third molar space in the five years following complete replacement of the deciduous dentition finds the contributions from ramus resorption and mesial movement of the first molar about equal on average, but highly variable.

Adolescent↗
PubMed1987

Gross and histological characterization of endometrial tissues from SLA miniature pigs with cystic endometrial hyperplasia.

Cystic endometrial hyperplasia (CEH) is a uterine disorder characterized by the formation of large numbers of cysts in the endometrium. The purpose of this study was to examine and characterize cell types in the endometrium associated with the cysts and uterine glands. No apparent histological differences between CEH-involved and normal uterine columnar epithelium were found. Endometrial glands in CEH-involved and normal uteri were lined with simple or ciliated columnar epithelial cells and surrounded by lamellar connective tissue. The cyst epithelium appeared to be stretched obliquely and compressed so that both the cells and nuclei were horizontally oriented relative to the cyst lumen and were surrounded by lamellar connective tissue. Electron microgaphs revealed an abnormally high number of mitochondria in the cystic cells as compared to normal glandular cells. In conclusion, CEH is characterized by the formation of cysts which develop from the uterine glandular tissue. Epithelial cells lining the glands appeared to be distorted, possibly in response to internal pressure from increased volume due to high metabolic activity, and/or no uterine luminal opening.

Animals↗
PubMed1987

Chromosome abnormalities in AIDS-associated lymphadenopathy.

Cytogenetic studies were performed on direct and 24-hour culture preparations of eight lymph node biopsies from seven patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC)-associated lymphadenopathy in whom histological evidence of lymphoma was not detected. Three of these seven had chromosomal abnormalities, including chromosome instability in one and clonal chromosomal abnormalities in two; one of the latter was a t(8;14)(q24;q32). The remaining five showed normal karyotypes. Epstein-Barr virus (EBV) titers were elevated in all three patients that exhibited chromosome abnormalities, two of whom later developed malignant lymphoma. A control group of five patients with reactive lymphadenopathy not associated with AIDS failed to reveal chromosomal aberrations, but elevated EBV titers were present in two. These data are consistent with current views on the role of EBV and chromosome change in the development of lymphoma in immunodeficient states and suggest that karyotypically abnormal AIDS-related lymphadenopathy represents a prelymphomatous proliferation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Intermediate- to high-grade histology of lymphomas carrying t(14;18) is associated with additional nonrandom chromosome changes.

We describe additional nonrandom chromosome abnormalities in 18 cases of intermediate- to high-grade non-Hodgkin's lymphoma (NHL) bearing t(14;18) that were ascertained in a prospective cytogenetic study of all lymphomas seen at Memorial Hospital during the period January 1, 1984, to December 31, 1986. These included seven cases that had histological evidence of transformation from a lower grade and 11 that lacked such evidence. The most common of the additional changes seen in both groups affected chromosomes 6 and 7 and comprised the loss of chromosome 6 or del(6q) and the presence of more than two copies of chromosome 7 or duplication of 7q. Changes affecting these two chromosomes were less frequent in low-grade lymphomas with t(14;18) as well as in lymphomas lacking the translocation. These data suggest that common cytogenetic mechanisms underlie expression of high-grade histologies by lymphomas carrying t(14;18). In addition, they may serve as indicators of transformation when encountered in low-grade lymphomas with t(14;18).

Adult↗
PubMed1987

Cytogenetic and histologic correlations in malignant lymphoma.

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.

Chromosome Aberrations↗
PubMed1986

Late lower arch crowding. The role of facial morphology.

A study of the relationship between dental crowding and facial morphology in 51 individuals studied over the first five years of the permanent dentition, finding some relationships but no strong or consistent pattern.

Adolescent↗