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M Riggs

Publications and source records attributed to M Riggs.

At least 19 recordsLinked to original sources
PubMed1994

Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases.

To study alternative splicing and tissue-specific expression of the mammalian genes encoding type-IV cAMP-specific phosphodiesterases, which are homologs of the dnc learning and memory gene of Drosophila melanogaster, we cloned seven cDNAs from four rat loci (PDE1, PDE2, PDE3 and PDE4) homologous to dnc. The deduced amino-acid sequences of the proteins encoded by the rat loci were shown to have a 1:1 correspondence with those encoded by the four human dnc homologs. The proteins encoded by at least one cDNA from each of the four rat loci contained novel N-terminal upstream conserved regions (UCR1 and UCR2), described previously in proteins encoded by the human dnc homologs and by dnc. cDNAs from three of the rat loci (PDE2, PDE3 and PDE4) had a structure consistent with alternative splicing of the 5' coding regions of their respective mRNAs. UCR1, and in one case a portion of UCR2, were absent in one of the alternatively spliced transcripts from these three loci. RNase protection analysis showed that the rat PDE3 and PDE4 loci were each expressed at relatively constant levels in multiple regions of the brain, while PDE2 transcripts were more abundant in temporal cortex and brainstem. One of the alternatively spliced mRNAs from the PDE4 locus was relatively more abundant in temporal cortex and cerebellum. One alternatively spliced transcript from the PDE3 locus was expressed more abundantly in parietal cortex. Both of the alternatively spliced transcripts from the human DPDE4 locus (the homolog of rat PDE4) were expressed in temporal cortex.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Incidence, racial differences, and prognostic significance of prostate carcinomas diagnosed with obstructive symptoms.

BACKGROUND: It is unknown how often prostate carcinomas are diagnosed as a result of urinary obstructive symptoms or whether prostate carcinomas diagnosed because of obstructive symptoms have a favorable or unfavorable prognosis. It is also unknown whether racial differences in obstructive symptoms could help explain why black men with prostate carcinoma are diagnosed with more advanced stages and grades of prostate carcinoma than are white men with prostate carcinoma. METHOD: At a single Veterans Administration Medical Center, 478 consecutive cases of prostate carcinoma diagnosed between 1973 and 1985 were identified. The incidence of obstructive symptoms at diagnosis, racial differences in obstructive symptoms, and the survival of patients with and without obstructive symptoms, stratified by stage and grade, were determined. In addition, racial differences in the frequency of surgical intervention required to relieve the obstructive symptoms were determined. RESULTS: All patients diagnosed with Stage A prostate carcinoma and most (82%) patients diagnosed with Stage C prostate carcinoma had obstructive symptoms. Those diagnosed with Stage B and Stage D prostate carcinomas had with similar frequencies (53% and 55%, respectively) of obstructive symptoms. Survival, stratified by stage and grade, was similar for men with and without obstructive symptoms. The incidences of obstructive symptoms and the frequency of surgical intervention to relieve the obstructive symptoms, stage for stage, were similar for white and black men. CONCLUSION: Survival, stratified by stage and grade, is not affected adversely by obstructive symptoms. Neither racial differences in the incidence of obstructive symptoms nor the frequency with which obstructive symptoms require surgical correction explain why black men with CAP consistently are diagnosed more frequently with Stage D prostate carcinoma and less frequently with Stage A CAP than white men with CAP.

Adult↗
PubMed1994

Long-term survival of stage A prostate carcinoma, atypical hyperplasia/adenosis and BPH.

Between 1972 and 1986, 134 patients with stage A carcinoma of the prostate (CAP) were diagnosed at a single Veterans Administration medical centre and followed annually by the hospital tumour registry. Seventy-four were classified as stage A1, defined as non-palpable, well-differentiated CAP, regardless of amount, found unexpectedly on transurethral resection of the prostate (TURP). Twenty-eight were classified as stage A2, defined as non-palpable, moderately or poorly differentiated CAP, regardless of amount, found unexpectedly on TURP. The remaining 32 were reclassified as atypical hyperplasia/adenosis (AH/A) rather than CAP. The survival of each group was compared with the survival of a control group from the same medical centre who had TURPs showing histologically proven benign prostatic hyperplasia (BPH). Survival and tumour progression were similar for patients with stage A1 CAP, AH/A and BPH. Furthermore, patients with stage A1 CAP, with or without therapy, had similar survivals as patients with BPH in each age group (under 65, 65-74 and over 74 years). Stage A2 CAP was associated with a significantly worse survival and more tumour progression. Within stage A1 CAP and stage A2 CAP the percentage of chips with CAP or the amount of CAP removed did not affect survival.

Adult↗
PubMed1993

Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase-deficient Saccharomyces cerevisiae.

We have established a highly sensitive functional screen for the isolation of cDNAs encoding cAMP phosphodiesterases (PDEs) by complementation of defects in a Saccharomyces cerevisiae strain lacking both endogenous cAMP PDE genes, PDE1 and PDE2. Three groups of cDNAs corresponding to three distinct human genes encoding cAMP-specific PDEs were isolated from a human glioblastoma cDNA library using this functional screen. Two of these genes are closely related to the Drosophila dunce cAMP-specific PDE. The third gene, which we named HCP1, encoded a novel cAMP-specific PDE. HCP1 has an amino acid sequence related to the sequences of the catalytic domains of all cyclic nucleotide PDEs. HCP1 is a high affinity cAMP-specific PDE (Km = 0.2 microM) that does not share other properties of the cAMP-specific PDE family, i.e. extensive sequence homology to the Drosophila dunce cAMP PDE and sensitivity to rolipram and R020-1724. The PDE activity of HCP1 is not sensitive to cGMP or other inhibitors of the cGMP-inhibitable PDEs, such as milrinone. The biochemical and pharmacological properties of HCP1 suggest that it is a member of a previously undiscovered cyclic nucleotide PDE family. Northern blot analysis indicates that high levels of HCP1 mRNA are present in human skeletal muscle.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs.

We have isolated cDNAs for four human genes (DPDE1 through DPDE4) closely related to the dnc learning and memory locus of Drosophila melanogaster. The deduced amino acid sequences of the Drosophila and human proteins have considerable homology, extending beyond the putative catalytic region to include two novel, highly conserved, upstream conserved regions (UCR1 and UCR2). The upstream conserved regions are located in the amino-terminal regions of the proteins and appear to be unique to these genes. Polymerase chain reaction analysis suggested that these genes encoded the only homologs of dnc in the human genome. Three of the four genes were expressed in Saccharomyces cerevisiae and shown to encode cyclic AMP-specific phosphodiesterases. The products of the expressed genes displayed the pattern of sensitivity to inhibitors expected for members of the type IV, cyclic AMP-specific class of phosphodiesterases. Each of the four genes demonstrated a distinctive pattern of expression in RNA from human cell lines.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

SNC1, a yeast homolog of the synaptic vesicle-associated membrane protein/synaptobrevin gene family: genetic interactions with the RAS and CAP genes.

SNC1, a gene from the yeast Saccharomyces cerevisiae, encodes a homolog of vertebrate synaptic vesicle-associated membrane proteins (VAMPs) or synaptobrevins. SNC1 was isolated by its ability to suppress the loss of CAP function in S. cerevisiae strains possessing an activated allele of RAS2. CAP is a component of the RAS-responsive S. cerevisiae adenylyl cyclase complex. The N-terminal domain of CAP is required for full cellular responsiveness to activated RAS proteins. The C-terminal domain of CAP is required for normal cellular morphology and responsiveness to nutrient extremes. Multicopy plasmids expressing SNC1 suppress only the loss of the C-terminal functions of CAP and only in the presence of activated RAS2.

Amino Acid Sequence↗
PubMed1992

Genetic and biochemical analysis of the adenylyl cyclase-associated protein, cap, in Schizosaccharomyces pombe.

We have identified, cloned, and studied a gene, cap, encoding a protein that is associated with adenylyl cyclase in the fission yeast Schizosaccharomyces pombe. This protein shares significant sequence homology with the adenylyl cyclase-associated CAP protein in the yeast Saccharomyces cerevisiae. CAP is a bifunctional protein; the N-terminal domain appears to be involved in cellular responsiveness to RAS, whereas loss of the C-terminal portion is associated with morphological and nutritional defects. S. pombe cap can suppress phenotypes associated with deletion of the C-terminal CAP domain in S. cerevisiae but does not suppress phenotypes associated with deletion of the N-terminal domain. Analysis of cap disruptants also mapped the function of cap to two domains. The functional loss of the C-terminal region of S. pombe cap results in abnormal cellular morphology, slow growth, and failure to grow at 37 degrees C. Increases in mating and sporulation were observed when the entire gene was disrupted. Overproduction of both cap and adenylyl cyclase results in highly elongated large cells that are sterile and have measurably higher levels of adenylyl cyclase activity. Our results indicate that cap is required for the proper function of S. pombe adenylyl cyclase but that the C-terminal domain of cap has other functions that are shared with the C-terminal domain of S. cerevisiae CAP.

Adaptor Proteins, Signal Transducing↗
PubMed1992

A gene encoding a protein with seven zinc finger domains acts on the sexual differentiation pathways of Schizosaccharomyces pombe.

Byr3 was selected as a multicopy suppressor of the sporulation defects of diploid Schizosaccharomyces pombe cells that lack ras1. Like cells mutant at byr1 and byr2, two genes that encode putative protein kinases and that in multiple copies are also suppressors of the sporulation defects of ras1 null diploid cells, cells mutant at byr3 are viable but defective in conjugation. Nucleic acid sequence indicates byr3 has the capacity to encode a protein with seven zinc finger binding domains, similar in structure to the cellular nucleic acid binding protein (CNBP), a human protein that was identified on the basis of its ability to bind DNA. Expression of CNBP in yeast can partially suppress conjugation defects of cells lacking byr3.

Amino Acid Sequence↗
PubMed1991

Prostate-specific antigen levels from completely sectioned, clinically benign, whole prostates.

Clinically benign whole, untrimmed prostates and pelvic lymph nodes were obtained from 105 patients at autopsy. All 105 patients had premortem serum from which prostate-specific antigen (PSA) levels were obtained. Sixty-eight did not have carcinoma of the prostate (CAP), 28 had CAP less than 1 ml and 9 had CAP larger than 1 ml. Eleven untrimmed prostates weighed 80 g or more and eight had elevated PSA levels (more than 4.0 ng/ml): five of eight without CAP, two of two with CAP less than 1 ml, and one of one with CAP larger than 1 ml. Ninety-four whole untrimmed prostates weighed less than 80 g and 20 had elevated PSA levels: ten of 60 without CAP, two of 26 with CAP less than 1 ml, and eight of eight with CAP larger than 1 ml. This study suggests that PSA levels from patients with untrimmed prostates weighing 80 g or more (equivalent to a 60-g trimmed prostate) are usually elevated regardless whether CAP is present. However, CAP less than 1 ml, in untrimmed prostates less than 80 g, usually does not elevate PSA levels whereas CAP larger than 1 ml usually does (P less than 0.0001). The likelihood that elevated PSA levels, from patients with untrimmed prostates less than 80 g, are due to CAP larger than 1 ml increases as the PSA level increases.

Adult↗
PubMed1991

Expression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae.

Saccharomyces cerevisiae strains expressing the activated RAS2Val19 gene or lacking both cAMP phosphodiesterase genes, PDE1 and PDE2, have impaired growth control and display an acute sensitivity to heat shock. We have isolated two classes of mammalian cDNAs from yeast expression libraries that suppress the heat shock-sensitive phenotype of RAS2Val19 strain. Members of the first class of cDNAs also suppress the heat shock-sensitive phenotype of pde1- pde2- strains and encode cAMP phosphodiesterases. Members of the second class fail to suppress the phenotype of pde1- pde2- strains and therefore are candidate cDNAs encoding proteins that interact with RAS proteins. We report the nucleotide sequence of three members of this class. Two of these cDNAs share considerable sequence similarity, but none are clearly similar to previously isolated genes.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

sar1, a gene from Schizosaccharomyces pombe encoding a protein that regulates ras1.

Proper ras1 function is required for normal sexual function in the yeast Schizosaccharomyces pombe. We have found a gene in S. pombe, sar1, that encodes a product capable of regulating ras1 function. sar1 is a member of an expanding family of RAS GTPase-activating proteins (GAPs) that includes mammalian GAP, the yeast Saccharomyces cerevisiae IRA proteins, and the product of the human neurofibromatosis locus, NF1 sar1, like these other proteins, can complement the loss of IRA function in S. cerevisiae. Computer analysis shows that the highest degree of sequence conservation is restricted to a very small number of diagnostic residues represented by the motif Phe-Leu-Arg-X-X-X-Pro-Ala-X-X-X-Pro. We find no evidence that sar1 is required for the effector function of ras1.

Amino Acid Sequence↗
PubMed1991

Inpatient cardiopulmonary resuscitation: is survival prediction possible?

We retrospectively reviewed 443 patients who had cardiopulmonary resuscitation (CPR). The focus of the study was to discover what preexisting factors should be assessed to determine the probability of survival. There were 88 successes out of 340 cases (25.9%). The absence of a previous myocardial infarction (MI), shock, partial pressure of oxygen (PaO2) less than 60 mm Hg, blood urea nitrogen (BUN) level greater than 20 mg/dL, pneumonia, pulmonary edema, and oliguria were found to predict a successful outcome. Logistic regression was used to predict percentage of successes in the various groups of patients with various clinical characteristics. The observed and predicted numbers of successes were in close agreement in most cases. We also constructed a classification function to predict whether an individual subject would survive the event for which CPR was required. Sixty-seven of the 88 observed successes would have been predicted, for an estimated sensitivity of 76%, and 164 of the 252 failures would have been predicted, for an estimated specificity of 65%. A large percentage (24%) of cases in which the patient actually survived CPR would have been predicted to be failures. We conclude that preexisting factors before a cardiopulmonary arrest do not accurately predict survival after CPR.

Aged↗
PubMed1991

byr2, a Schizosaccharomyces pombe gene encoding a protein kinase capable of partial suppression of the ras1 mutant phenotype.

Schizosaccharomyces pombe contains a single gene, ras1, which is a homolog of the mammalian RAS genes. ras1 is required for conjugation, sporulation, and normal cell shape. ras1 has been previously identified as ste5. We report here a gene we call byr2 that can encode a predicted protein kinase and can partially suppress defects in ras1 mutants. ras1 mutant strains expressing high levels of byr2 can sporulate competently but are still defective in conjugation and abnormally round. byr2 mutants are viable and have normal shape but are absolutely defective in conjugation and sporulation. byr2 is probably identical to ste8. In many respects, byr2 resembles the byr1 gene, another suppressor of the ras1 mutation, which has been identified previously as ste1. Our data indicate that if ras1, byr2, and byr1 act along the same pathway, then the site of action for byr2 is between the sites for ras1 and byr1.

Amino Acid Sequence↗
PubMed1991

Colorectal cancer: current trends in initial clinical manifestations.

Colorectal carcinoma (CRC) is a common cause of cancer morbidity and mortality in the United States. There continues to be controversy regarding the effectiveness and feasibility of various screening programs for CRC. To determine how cases of CRC are currently detected, we reviewed a series of 246 consecutive patients with well-documented pathologic staging and clinical presentation. Patients with low stage CRC (0 or A) had smaller tumors, were less likely to be anemic at presentation, and were more likely to have tumors located in the left side of the colon than patients with tumors at stage B or higher. Thirty-two of the 246 tumors were detected in asymptomatic patients through screening. These tumors were more likely to be of a lower stage than those in patients with active gastrointestinal symptoms. In our experience active screening programs detect a relatively small number of CRCs. A majority (66%) of CRCs are still detected from symptoms referable to the gastrointestinal tract.

Aged↗
PubMed1990

Mast cell tumors in three ferrets.

Pruritic open skin lesions (5 mm diameter) on the thorax, neck, or head of 3 ferrets were diagnosed as mast cell tumors. Diagnosis of the tumors was based on histologic examination of biopsy specimens. Histologic diagnosis was necessary because the lesions had been treated as mycotic or bacterial ulcers and did not respond to conventional treatment. Excised mast cell tumors did not recur, and malignant behavior of the tumors was not observed.

Animals↗
PubMed1990

Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group.

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.

AIDS-Related Complex↗
PubMed1990

Characterization of ROS1 cDNA from a human glioblastoma cell line.

We have isolated and characterized a human ROS1 cDNA from the glioblastoma cell line SW-1088. The cDNA, 8.3 kilobases long, has the potential to encode a transmembrane tyrosine-specific protein kinase with a predicted molecular mass of 259 kDa. The putative extracellular domain of ROS1 is homologous to the extracellular domain of the sevenless gene product from Drosophila. No comparable similarities in the extracellular domains were found between ROS1 and other receptor-type tyrosine kinases. Together, ROS1 and sevenless gene products define a distinct subclass of transmembrane tyrosine kinases.

Amino Acid Sequence↗