Search PubMed⌕ Search

Biomedical subjects

J Greer

Publications and source records attributed to J Greer.

At least 19 recordsLinked to original sources
PubMed1992

Extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma.

BACKGROUND: Many regimens are used for cutaneous T-cell lymphoma (CTCL), but with advanced disease response rates and patient survival are not adequate with any current therapy. Recently extracorporeal photochemotherapy (ECP) was proposed as an alternative therapy. OBJECTIVE: Our purpose is to present the results of ECP in patients with CTCL refractory to other treatments. METHODS: Patients with CTCL received ECP at 3- to 5-week intervals for at least 6 months. All patients except one were in stage T2 (patch/plaque) or higher. Eight patients had extracutaneous disease involving lymph nodes (six patients), bone marrow (five), or Sézary cells (six). The interval between initial symptoms and diagnosis was 5.9 +/- 1.9 years (mean +/- standard error of the mean) and the interval between diagnosis and ECP was 2.2 +/- 0.4 years. RESULTS: A complete response (disappearance of all lesions) was obtained in five patients (25%) and a partial response (disappearance of at least 50% of lesions) in six patients (30%). Four patients (20%) showed stabilization of their disease and five progressed (25%). The only variable that predicted responders versus nonresponders was the number of ECP sessions (p < 0.05 by multivariate logistic regression). In contrast, no separate beneficial effect of adjunctive chemotherapy (p > 0.5) or electron beam therapy (p > 0.1) was found. CONCLUSION: Long-term ECP may be an effective alternative treatment for CTCL refractory to other therapies and is likely to be even more useful when combined with other modalities.

Adult↗
PubMed1992

High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol.

PURPOSE: A phase II trial was undertaken to assess the feasibility, toxicity, and efficacy of high-dose carboplatin and etoposide with autologous bone marrow transplantation in patients with relapsed or refractory germ cell tumors. PATIENTS AND METHODS: Forty patients with recurrent germ cell cancer received carboplatin 500 mg/m2 and etoposide 400 mg/m2 given at 7, 5, and 3 days before marrow infusion. Autologous marrow infusion (day 0) was accomplished using one half of the bone marrow harvested before chemotherapy. Patients who achieved a complete or partial response with the first cycle of treatment received a second identical cycle of chemotherapy followed by infusion of the remaining cryopreserved bone marrow. RESULTS: Objective responses were obtained in 17 of the 38 patients (45%) assessable for response, including eight partial and nine complete remissions. Five of these patients remain in continuous complete remission with minimal follow-up of 1 year. Toxicity encountered was primarily hematologic, and five patients (13%) died of treatment-related complications. Significant toxicities often seen with high-dose cisplatin (ototoxicity, neurotoxicity, and renal toxicity) were manageable in this regimen of high-dose carboplatin. CONCLUSIONS: This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer.

Adolescent↗
PubMed1991

Temporal replacement of donor erythrocytes and leukocytes in nonanemic W44J/W44J and severely anemic W/Wv mice.

The dominant white spotting, W, locus in the mouse encodes Kit, a receptor molecule with cytosolic tyrosine kinase activity. Mutations in Kit deplete hematopoietic cells by an as yet unknown mechanism, but one that presumably affects the early progenitors of all cell lineages. To examine cell lineage-specific changes caused by different W mutations, we injected genetically marked normal marrow cells into mutant mice and monitored repopulation kinetics. In the present report, we compare repopulation of the various peripheral blood cells in nonanemic W44J/W44J and severely anemic W/Wv mice administered increasing increments of donor cells. At all doses of cells tested, donor erythrocyte repopulation precedes leukocyte repopulation regardless of the recipient phenotype. There is, in fact, little difference in the rate or extent of nonerythroid repopulation in W44J/W44J mice injected with between 6 x 10(6) and 2 x 10(7) donor cells. The fact that donor cells rapidly replace erythrocytes, even in the nonanemic W44J/W44J host, while other cell lineages become donor type more slowly provides further evidence that mutations at the W locus are especially damaging to erythrocyte progenitors. We suggest that host nonerythroid hematopoietic cells compete with normal cells, probably at the level of early progenitors rather than at the level of the totipotent hematopoietic stem cell. The fact that successively higher doses of donor cells do not markedly alter nonerythroid repopulation kinetics implies that it may be possible to maximize autologous therapeutic marrow transplantation.

Anemia, Macrocytic↗
PubMed1991

Mutations affecting the activity of urokinase-type plasminogen activator.

Mutagenesis throughout the single-chain urokinase-type plasminogen activator (scu-PA) cDNA molecule, followed by expression of the mutant genes and secretion of the resulting mutant proteins from yeast, has been used to determine the amino acid residues important for activity of scu-PA molecules. Twelve out of 13 colonies secreting variant scu-PA molecules with decreased ability to form a zone of fibrinolysis had mutant genes with a single codon alteration in the serine protease encoding domain (B-chain). Many of these changes are of highly conserved residues in the serine proteases and are consequently of considerable interest. A model three-dimensional structure of the protease domain of urokinase was used to explain the basis for the effects of these down mutations. The model showed that the strongest down mutations result from either interference of the mutated side chain with substrate binding at the active site or the introduction of bulky or charged groups at structurally sensitive internal positions in the molecule. Attempts to find second site revertants of five down mutants, altered either at the plasmin activation site or near the serine at the active site, only resulted in same-site revertants, with the original or closely related amino acids restored.

Base Sequence↗
PubMed1991

Comparative modeling of proteins in the design of novel renin inhibitors.

Renin, the first enzyme in the renin-angiotensin system, is critically important for the maintenance of blood pressure, and, therefore, as a target for antihypertensive therapy. The three-dimensional structure of renin would be an invaluable aid in understanding the functional properties of renin as well as in the design of novel, potent inhibitors. Three-dimensional models of renin have been developed by a number of different groups based on comparative homology modeling from the other known aspartic proteinase structures. These models have been used widely in the drug design process to suggest targets for synthesis and to rationalize the structure-activity relationships of compounds. This review describes the different published renin models and compares them to the extent possible. Applications of these model renin and renin-inhibitor complex structures to biological function and inhibitor design are summarized.

Amino Acid Sequence↗
PubMed1991

Improved amplification of cytomegalovirus DNA from urine after purification of DNA with glass beads.

Cytomegalovirus can be detected in a variety of specimens including leukocytes, urine, saliva, feces, and various tissues by polymerase chain reaction (PCR) amplification of viral DNA. Although methods for amplification are fairly standard, sample preparation is not well characterized, especially for tissue. Typically, preparation of samples for PCR amplification ranges from simple boiling to phenol/chloroform extraction and quantification before testing. Several reports have described inhibition of the PCR in some samples types. Here we show that reliable detection of cytomegalovirus DNA in urine is obtained only after some degree of DNA purification, presumably because of PCR inhibition by a yet unidentified component present in a few of the urine samples tested. Glass, in the form of fine beads, was used to adsorb DNA such that protein and other substances could be selectively eluted before the recovery of DNA for PCR amplification. Urine samples prepared by this method did not show inhibition, and results correlated well with those by tissue culture for detection of cytomegalovirus.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Comparative modeling methods: application to the family of the mammalian serine proteases.

Comparative modeling methods are described that can be used to construct a three-dimensional model structure of a new protein from knowledge of its sequence and of the experimental structures and sequences of other members of its homology family. The methods are illustrated with the mammalian serine protease family, for which seven experimental structures have been reported in the literature, and the sequences for over 35 different protein members of the family are available. The strategy for modeling these proteins is presented, and criteria are developed for determining and assigning the reliability of the modeled structure. Criteria are described that are specially designed to help detect cases in which it is likely that the local structure diverges significantly from the usual conformation of the family.

Algorithms↗
PubMed1990

Placental glutathione-S-transferase-pi mRNA is abundantly expressed in human skin.

Four overlapping cDNA clones were isolated from a lambda gt11 human placenta cDNA library using purified human IgG antibody, from a patient with bullous pemphigoid. The sequence was homologous to human placenta glutathione-S-transferase-pi (GST-pi). Using the placenta clone, epidermal cDNA clones were isolated from a human keratinocyte library. Expression of GST-pi mRNA in human skin, cultured keratinocytes and fibroblasts, and disorders of squamous hyperplasia was demonstrated by Northern blotting and in situ hybridization. Human epidermal and placental cDNA clones hybridized to the same genomic DNA fragments. Hybridization of placental cDNA to interspecific somatic cell hybrids showed retention of chromosome 11, confirming the assignment of GST 3 to the long arm of chromosome 11 by molecular means. Anti-GST-pi antibody did not give a basement membrane zone pattern, although some normal and BP sera contained antibodies to GST-pi. Human skin expresses glutathione-S-transferase-pi, which belongs to an enzyme family important for detoxification and carcinogenesis.

Amino Acid Sequence↗
PubMed1990

Recent trends in cadaveric renal transplantation.

1. Cadaveric transplantation increased steadily from 1981 through 1986 and then leveled off. The gap between patients awaiting transplant and cadaveric transplants performed increased rapidly after 1986. 2. There has been a trend in the age distribution of cadaveric transplant recipients toward transplantation of older patients. The number of cadaveric transplants to patients 50 and over continued to increase after 1986, while the number to patients under 50 declined. The proportion of transplants to patients 60 and over has shown a particularly dramatic increase. 3. The rate of transplantation is highest in the pediatric age group and declines with age. The rate of transplantation increased in all age groups until 1986 and then declined in all age groups except the 50 and over group. The magnitude of the decline is greatest in the younger age groups. 4. Among all dialysis patients, males have a higher rate of transplantation than females, and Whites have a higher rate than Blacks. These differences in rates increase with increasing recipient age. There are moderate trends toward decreased differences by sex and increased differences by race. 5. Repeat transplants make up about 15% of all cadaveric transplants in 1988, with higher proportions of repeat transplants in the younger age groups. The transplantation rates for repeat transplants has been declining relative to that for first transplants when the relevant pool of dialysis patients is used. For the 50 and over age group, the repeat transplant rate was 3.6 times as high as the first transplant rate in 1988. 6. Compared to the general population, cadaver transplant donors are younger, less often female, and less often Black. There has been a trend toward older donors and toward a smaller difference by sex. 7. There has been a trend toward fewer nephrectomies and splenectomies prior to transplantation. 8. There are no clear time trends in sharing of organs among transplant centers and only a slight increase in the proportion of transplants with 0 HLA-antigen mismatches.

Age Factors↗
PubMed1989

Clear cell adenocarcinoma of the ovary: a clinical analysis and comparison with serous carcinoma.

Forty-four patients with clear cell adenocarcinoma of the ovary diagnosed between 1944 and 1981 were compared with a matched cohort of 55 patients with the most common epithelial malignant lesion, serous adenocarcinoma, in terms of their presentation and clinical course. None were lost to follow-up. Median follow-up was 9 years. Fifty percent of clear cell patients presented in Stage I versus 31% of serous patients. Patients with clear cell carcinoma presented more often with pelvic masses (84% vs 65%) and had larger (diameter greater than 10 cm) primary tumors (73% vs 29%). Forty-nine percent of clear cell patients were nulligravid compared with 24% of serous patients and endometriosis was strikingly more common in clear cell patients (58% vs 12%). When compared stage for stage, clear cell tumors were uniformly associated with poorer 5-year survival rates with an overall rate of 34%. In patients with recurrent disease, lymph node involvement was much more common in patients with clear cell carcinoma (40% vs 7%). Parenchymal organ involvement was also more common in the clear cell group (40% vs 13%). Ovarian clear cell adenocarcinoma has distinctly different clinical behavior compared to serous carcinoma and should be regarded as an aggressive epithelial histologic type.

Actuarial Analysis↗
PubMed1989

Active reduced-size hexapeptide analogues of luteinizing hormone-releasing hormone.

A series of reduced-size hexapeptide analogues of LH-RH were synthesized that contain the residues corresponding to amino acid positions 4-9 and are linked to various carboxylic acids in place of residue 3. These compounds were tested in vitro in the rat pituitary receptor binding and LH release assays. A wide range of binding affinities was obtained up to and exceeding that of LH-RH. Both agonists and antagonists were obtained. From the SAR studies, it appears that a very precise size, length, and shape of the substituent at position 3 is required to achieve agonist activity, whereas the structural requirements for antagonist activity appear to be much less stringent. Depending on the nature of the substituent at positions 6 and 4, the biological response switches from antagonist to agonist or vice versa. The results suggest that conformational changes at position 6 or 4 feed back to the substituent at position 3, which induces the change from agonist to antagonist. The most potent compounds in the series were tested in vivo and found to be active.

Animals↗
PubMed1978

Macromolecular shape and surface maps by solvent exclusion.

A quantitative function equivalent to the "molecular" surface proposed by F. M. Richards [(1977) Annu. Rev. Biophys. Bioeng. 6, 151--176] is defined by the closest approach of solvent spheres to a macromolecule. The function can be used to visualize surface topography, polarity, and charge either as a three-dimensional net or by mapping onto a plane; to calculate surface areas; and to demarcate complementary sites in contacts between subunits. Applications to shape-specific recognition in protein structure and aggregation are discussed.

Methemoglobin↗