Search PubMed⌕ Search

Biomedical subjects

C Morris

Publications and source records attributed to C Morris.

At least 145 records · Page 8Linked to original sources
PubMed1994

Bone marrow transplantation in Fanconi anemia using matched sibling donors.

Eighteen patients with Fanconi anemia (FA) with evidence of bone marrow (BM) aplasia underwent allogenic BM transplants (BMT) from matched sibling donors (MSD). Median age at BMT was 7.6 years. Conditioning consisted of low-dose cyclophosphamide (CY; 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI; 400 cGy). Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A and prednisone. In addition antithymocyte globulin (ATG) was administered in the pretransplant period to promote engraftment and in the posttransplant period for additional GVHD prophylaxis. Engraftment occurred rapidly (median, 12 days for an absolute neutrophil count > or = 0.5 x 10(9)/L; median, 22 days for platelet count > or = 50 x 10(9)/L). Seventeen patients have sustained engraftment and are transfusion-independent, with Lansky scores of 100% at median follow-up of 27 months. One patient developed graft failure 4 months after initial engraftment and required a second BM infusion. None of the patients developed acute GVHD; 3 patients (16%) developed chronic GVHD. BMT is a feasible option for FA patients having an MSD and should be performed at a young age and early in the course of the disease, before the development of complications. We believe the addition of ATG to the transplant regimen of low-dose CY, TAI, and cyclosporin was responsible for improvement in the survival of FA patients undergoing BMT. The regimen was well tolerated and was associated with a low incidence of complications including GVHD.

Abdomen↗
PubMed1994

Prediction of atherosclerotic cardiovascular death in men using a prognostic score.

Treadmill and clinical data were gathered prospectively on consecutive patients who underwent exercise testing for evaluation for coronary artery disease in a 1,200 bed Veterans Affairs Medical Center. From 3,609 men referred for exercise testing from 1984 to 1990, 3,134 patients remained after excluding those with significant valvular heart disease and those with prior coronary artery bypass surgery. Of these, 588 were selected for clinical reasons to undergo cardiac catheterization within 3 months of evaluation leaving 2,546 who were not selected. Over 3 years, there were 158 cardiovascular deaths, 99 nonfatal myocardial infarcts and 183 patients who underwent coronary artery bypass surgery. In the total population, the Cox proportional-hazards model demonstrated the following characteristics to be statistically significant independent predictors of time until cardiovascular death: a history of congestive heart failure and/or taking digoxin, exercise-induced ST depression, the change in systolic blood pressure during exercise, and exercise capacity in METs. Using the Cox model coefficients to weight the variables, a simple score (the Veterans Affairs Prognostic Score) was constructed based on these items. Average annual cardiovascular mortality was plotted against the score enabling its estimation for any given patient. In the subgroup selected for cardiac catheterization (n = 588), the mean score was greater, consistent with a poorer prognosis, compared with the total population; 53% (n = 312) had a score < -2 associated with an annual mortality < 2%. Thus, in over half of the patients selected for catheterization, the catheterization was unnecessary if performed to lessen their chance of cardiovascular death, since no intervention could improve their prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Distribution of neuronal nicotinic receptor subunits in human brain.

Neuronal nicotinic acetylcholine receptors (nAchRs) are multimeric proteins constituted of two different subunits, alpha and beta, with different subtypes arrangement and different pharmacological and functional properties. nAchRs mediate neurotransmission in many central and peripheral synapses and appear to be affected in human degenerative disorders. We have studied the distribution of nAchR in human brain, particularly in the hippocampus and thalamus, by binding of 3H-nicotine and 3H-cytisine and by in situ hybridization with human alpha 3 and beta 2 nAchR subunits of mRNA. An alpha 3 probe shows a strong hybridization signal in the thalamus, while a beta 2 probe has a good signal at the level of the enthorinal cortex, hippocampus and in caudate and putamen. The alpha 3 and beta 2 mRNA localization is different from that described in other species. 3H-nicotine and 3H-cytisine binding were very similar in terms of anatomical distribution and comparable to the binding described in other animal species. The binding of the two ligands was distributed over the areas labeled by the alpha 3 and beta 2 probes and did not completely overlap with either of the subunits.

Alkaloids↗
PubMed1994

Quantification of cellular proliferation in acne using the monoclonal antibody Ki-67.

The mechanism by which ductal hypercornification occurs in acne is uncertain. We investigated proliferation in normal and acne follicles and in the interfollicular epidermis using the monoclonal antibody Ki-67, which reacts with a nuclear antigen expressed by cells in the G1, S, M, and G2 phases of the cell cycle. Cryostat sections of biopsies from the interscapular region from acne patients and from normal volunteers were stained with Ki-67 antibody and counterstained with 2% methyl green. The number of Ki-67-positive nuclei in the basal layer were counted and expressed as a percentage of the total number of basal nuclei in the ductal or interfollicular epithelia. The data was expressed as mean percent +/- SD. In normal follicles from acne-affected sites 17.40% +/- 1.86% (n = 8) of the nuclei were Ki-67 positive. This was significantly higher (p < 0.01) than follicles from an area of skin unaffected by acne (11.01% +/- 6.16%, n = 8). In the follicular epithelia of non-inflamed lesions, the percentage of Ki-67 positive nuclei was 23.44% +/- 8.36% (n = 15). It was impossible to count the nuclei of follicular epithelium of inflamed lesions because little of this remained intact. In normal interfollicular epidermis, Ki-67-positive nuclei represented 5.33% +/- 3.36% (n = 8) of the total. This value was not significantly different from the value obtained for interfollicular epidermis near non-inflamed lesions (10.46% +/- 4.45%, n = 15). However, the number of Ki-67-positive nuclei in the interfollicular epidermis near inflamed lesions was significantly higher than either of these two values: 25.26% +/- 6.83%, n = 13, p < 0.05. Our results with Ki-67 confirm that ductal hyperproliferation occurs in acne and shows that normal follicles from acne skin may be "acne-prone."

Acne Vulgaris↗
PubMed1994

Immunohistochemical study of desmosomes in acne vulgaris.

Desmosomes contribute towards adhesion between adjacent keratinocytes. In acne vulgaris, increased intercellular adhesion is thought to contribute to the retention of keratinocytes within the follicular lumen during comedogenesis. Therefore, the distribution of different desmosomal components was investigated in normal and acne subjects. Biopsies were cryostat-sectioned (6 microns), and stained with antibodies to different desmosomal components: desmoplakin 1/2, desmoglein 1, desmocollin 3a/3b, and a late desmosomal antigen, G36-19. Desmoplakin 1/2, desmoglein 1 and desmocollin 3a/3b shared a similar distribution in follicles from control skin, from acne-affected skin, and in non-inflamed lesions. All three proteins were expressed around the periphery of keratinocytes of all the intrafollicular epidermis, except the basal lamina and the upper stratum corneum. In inflamed lesions, the expression of desmoglein 1 and desmocollin 3a/3b was diminished; in 12.5%, staining for these two proteins was completely abolished, and in 81.25% of the lesions investigated the staining was patchy. The antibody G36-19 bound to an antigen in the upper granular layer in the infundibular epidermis. No differences were noted in the staining pattern of the follicular epithelia of controls, non-inflamed, and inflamed lesions. This study, using monoclonal antibodies, did not identify any changes in the desmosomal components which might explain the increased adhesion between follicular keratinocytes during comedogenesis.

Acne Vulgaris↗
PubMed1994

Investigation of the expression of the extracellular matrix glycoproteins tenascin and fibronectin during acne vulgaris.

Tenascin and fibronectin are extracellular matrix glycoproteins which can interact with cells and alter their capacity to adhere, migrate and proliferate. In contrast with fibronectin, tenascin has a restricted distribution in normal skin, but is induced during epidermal proliferation, and in wound healing. Because acne involves hyperproliferation of ductal keratinocytes, and rupture of the duct may occur during inflammation, the distribution of tenascin and fibronectin was investigated in acne lesions, and also in acne keloids. Biopsies obtained from patients attending the acne clinics were cryostat-sectioned and stained with tenascin antiserum. The extent of tenascin staining in the dermis around the pilosebaceous unit was measured. Tenascin was continually expressed around normal control pilosebaceous ducts; it was maximal around the acroinfundibulum, extending 20.83 +/- 9.32 microns (n = 14) into the dermis, compared with staining around the infrainfundibulum (11.88 +/- 3.70 microns, n = 14). This was not significantly different from staining around normal pilosebaceous ducts obtained from acne patients. In non-inflamed lesions tenascin staining increased significantly around the infrainfundibulum to 76.88 +/- 29.97 microns (n = 12), compared with this region in the normal follicles. The staining around the acroinfundibulum did not change significantly. Around inflamed lesions the whole of the dermis was positive for tenascin. No changes were detected in the staining pattern for fibronectin, which stained the whole dermis in all the sections tested. The keloid samples stained strongly for both extracellular matrix glycoproteins. Thus, increased tenascin expression appears to be associated with the development of acne lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗
PubMed1994

Characterization of human antibody responses to four corners hantavirus infections among patients with hantavirus pulmonary syndrome.

Hantavirus pulmonary syndrome (HPS) is a human disease caused by a newly identified hantavirus, which we will refer to as Four Corners virus (FCV). FCV is related most closely to Puumala virus (PUU) and to Prospect Hill virus (PHV). Twenty-five acute HPS serum samples were tested for immunoglobulin G (IgG) and IgM antibody reactivities to FCV-encoded recombinant proteins in Western blot (immunoblot) assays. All HPS serum samples contained both IgG and IgM antibodies to the FCV nucleocapsid (N) protein. FCV N antibodies cross-reacted with PUU N and PHV N proteins. A dominant FCV N epitope was mapped to the segment between amino acids 17 and 59 (QLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLG). All HPS serum samples contained IgG antibodies to the FCV glycoprotein-1 (G1) protein, and 21 of 25 serum samples contained FCV G1 IgM antibodies. The FCV G1 antibodies did not cross-react with PUU G1 and PHV G1 proteins. The FCV G1 type-specific antibody reactivity mapped to a segment between amino acids 59 and 89 (LKIESSCNFDLHVPATTTQKYNQVDWTKKSS). One hundred twenty-eight control serum samples were tested for IgG reactivities to the FCV N and G1 proteins. Nine (7.0%) contained FCV N reactivities, 3 (2.3%) contained FCV G1 reactivities, and one (0.8%) contained both FCV N and FCV G1 reactivities. The epitopes recognized by antibodies present in control serum samples were different from the epitopes recognized by HPS antibodies, suggesting that the control antibody reactivities were unrelated to FCV infections. These reagents constitute a type-specific assay for FCV antibodies.

Adolescent↗
PubMed1993

Predicting hospital charge and length of stay for congenital heart disease surgery.

Three hundred twenty-two consecutive operations between December 1985 and December 1989 for 10 types of low-risk congenital cardiac malformations were reviewed to determine the hospital charge and postoperative length of stay. Multiple regression analysis of variance was used to predict the influence of the primary diagnosis and various preoperative parameters. The average hospital charge was $27,262 +/- $20,644 and the postoperative length of stay was 9.3 +/- 8.3 days. Age at operation alone did not influence the dependent variables. The diagnosis of atrial septal defect (p = 0.002) or coarctation of the aorta (p = 0.002) decreased the mean charge, whereas the 8 other primary diagnoses did not significantly influence the mean charge. Other preoperative factors found to be predictive of increased hospital charge were: the date of operation (p < 0.001), cyanosis (p = 0.008), previous thoracic surgery (p = 0.02), failure to thrive (p < 0.001), associated major extra cardiac anomalies (p < 0.001), oxygen requirement (p = 0.02), and distance > 100 miles from home to hospital (p = 0.05). A primary diagnosis of atrial septal defect decreased the mean postoperative length of stay by 3.1 days (p < 0.001). Other preoperative conditions increased the mean postoperative length of stay: major extracardiac malformation (p < 0.001), failure to thrive (p < 0.001), and oxygen requirement (p = 0.003). Charge and length of stay equations were generated which may assist in the prediction of resource utilization in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗
PubMed1993

Localization of a gamma-glutamyl-transferase-related gene family on chromosome 22.

A gene family encompassing a minimum of four genes or pseudogenes for gamma-glutamyl transferase (GGT; EC 2.3.2.2) is present on chromosome 22q11. We have previously isolated a cDNA related to GGT but clearly not belonging to its gene family. The chromosomal location of this related gene, GGTLA1, has been determined by both isotopic and fluorescence in situ hybridization to metaphase cells and by Southern blot analysis of somatic cell hybrid DNAs. We show that GGTLA1 is part of a distinct gene family, which has at least four members (GGTLA1, GGTLA2, GGTLA3, GGTLA4). At least two loci are located on chromosome 22 within band q11 and proximal to the chronic myelogenous leukemia (CML) breakpoint in BCR (breakpoint cluster region gene). At least one other member is located more distally between the breakpoints found in Ewings sarcoma and CML. Some of the GGT and GGTLA family members are located on NotI restriction enzyme fragments of a similar size. Combined results indicate that a segment of human chromosome 22q11 has undergone large-scale amplification events relatively recently in evolution.

Blotting, Southern↗
PubMed1993

Dose-response relationships for furosemide ototoxicity in rat.

Furosemide is an ototoxic loop diuretic which is highly bound to serum albumin. Previous studies have shown that rats deficient in albumin are more susceptible to furosemide ototoxicity than are rats with normal serum albumin concentrations. The present study was designed to compare the dose-response relationships for furosemide ototoxicity in rats with normal serum albumin concentration to rats without albumin in their serum. Young adult rats 50-80 days of age from each group were anesthetized with Rompun, and the endocochlear potential (EP) and compound action potential (CAP) thresholds were measured before and after furosemide injection. Afer a stable EP and CAP threshold were measured, each animal was injected with a single dose of furosemide through a cannula in the jugular vein. Rats with normal serum albumin had very little change in the EP or CAP threshold until the dose of furosemide was 40 mg/kg or greater. The dose-response curves for EP reduction and CAP threshold elevation then rose steeply to reach a maximum at 50 mg/kg. Albumin-deficient rats were much more sensitive to the effects of furosemide. The dose-response curves for both EP and CAP were shifted to the left. The doses resulting in half-maximal effects in the albumin-deficient rats were about half that found in the normal rats. These findings support the hypothesis that the access of furosemide to its site of ototoxic action in the cochlea depends on the quantity of unbound furosemide in the serum.

Action Potentials↗
PubMed1993

Isolation of NotI sites from chromosome 22q11.

Chromosome 22q11 contains a large number of interesting loci, including genes associated with cancer and developmental defects. The region is also the site of the lambda immunoglobulin variable and constant regions and the BCR, gamma-glutamyl transpeptidase, and GGT-like activity multigene families. Because of the complexities associated with mapping highly related gene families, we have examined the utility of mapping large areas of DNA using a defined approach. A total of 21 complete NotI sites from band q11 were cloned and ordered into six noncontiguous clusters of sites using a combination of somatic cell hybrid panels, NotI jumping and linking libraries, and fluorescence in situ hybridization. The largest cluster spanned an estimated 2 Mb of NotI fragments, the smallest 115 kb. Approximately 3.5 Mb of band q11 could be examined for rearrangements in NotI restriction enzyme fragments. A number of conserved sequences, two genes, and a minimum of two families of related sequences were identified adjacent to NotI sites.

Animals↗
PubMed1993

Geographic variation of procedure utilization. A hierarchical model approach.

In this study, an abbreviated introduction to hierarchical statistical models for quantifying and explaining variations in the utilization of medical care is presented. The illustrative example was derived from an analysis of interstate variation in coronary angiography utilization for Medicare patients with a recent acute myocardial infarction. The hierarchical model distinguished within-from between-states variation: the former was modeled via a separate logistic regression for each state, with age and sex as the independent variables, while the latter was modeled via a multivariate normal distribution for the coefficients of the state-specific logistic models. Alternative computation approaches were compared and model fit was assessed. Estimates of the distribution of state rates of angiography for an average patient and for age-by-sex strata were obtained. The results showed substantial interstate variation in angiography utilization, but only moderate interstate variation in the effects of age and sex on the decision to perform angiography. This analytic approach allows substantially more detailed results than those by standardization, and accounts for sample size differences between units of aggregation. The next major step in the analysis would be to derive smoothed estimates of the individual state logistic models by pooling data across states. The analysis can also be extended to incorporate other patient characteristics, such as race and comorbidity, and state characteristics, such as geographic location and availability of the procedure.

Aged↗
PubMed1993

Haemopoietic stem/progenitor cell transplant in Fanconi anaemia using HLA-matched sibling umbilical cord blood cells.

There have only been a few reports documenting the use of umbilical cord blood as a source of stem cells for haemopoietic reconstitution. We report our experience with a child with Fanconi anaemia (FA) who underwent a stem cell transplant using umbilical cord blood cells from his HLA matched sibling. Although the engraftment was somewhat slow, it was complete and comparable to other transplants performed in FA patients using HLA matched sibling marrow. There was no graft-versus-host disease. The post-transplant period was uncomplicated and, at a follow-up of 36 months, this child is well with normal blood counts and immune function.

Child, Preschool↗
PubMed1993

Ph-positive leukemia: a transgenic mouse model.

The presence of the BCR/ABL chimeric gene is the hallmark of defined types of human leukemia. To increase our knowledge of the oncogenic processes and to develop a model for this type of leukemia we generated a BCR/ABL (P190) transgenic mouse line. Over 95% of mice of this line die of leukemia or leukemia/lymphoma within 35-200 days of age. Karyotypically visible genetic alterations were absent from the early stages of BCR/ABL generated leukemia. A high frequency of aneuploidy was found in advanced leukemia indicating a primary and pivotal role for BCR/ABL in leukemogenesis. Moreover, the data suggest that BCR/ABL has a destabilizing effect on the regulation of the cell cycle. BCR/ABL expression was also found in tissues other than hematopoietic cells. However, this did not result in the development of solid tumors, strongly suggesting that the oncogenicity of BCR/ABL is limited to the hematopoietic lineage.

Animals↗