Biomedical subjects

M Riggs

Publications and source records attributed to M Riggs.

At least 19 recordsLinked to original sources

PubMed2005

High-resolution ROMA CGH and FISH analysis of aneuploid and diploid breast tumors.

Combining representational oligonucleotide microarray analysis (ROMA) of tumor DNA with fluorescence in situ hybridization (FISH) of individual tumor cells provides the opportunity to detect and validate a wide range of amplifications, deletions, and rearrangements directly in frozen tumor samples. We have used these combined techniques to examine 101 aneuploid and diploid breast tumors for which long-term follow-up and detailed clinical information were available. We have determined that ROMA provides accurate and sensitive detection of duplications, amplifications, and deletions and yields defined boundaries for these events with a resolution of <50 kbp in most cases. We find that diploid tumors exhibit fewer rearrangements on average than aneuploids, but rearrangements occur at the same locations in both types. Diploid tumors reflect at least three consistent patterns of rearrangement. The reproducibility and frequency of these events, especially in very early stage tumors, provide insight into the earliest chromosomal events in breast cancer. We have also identified correlations between certain sets of rearrangement events and clinically relevant parameters such as long-term survival. These correlations may enable novel prognostic indicators for breast and other cancers as more samples are analyzed.

Aneuploidy↗

PubMed2002

Frozen section diagnosis of metastatic prostate adenocarcinoma in pelvic lymphadenectomy compared with nomogram prediction of metastasis.

OBJECTIVES: To compare the sensitivity and negative predictive values of frozen section analysis of pelvic lymphadenectomy in patients undergoing radical retropubic prostatectomy for prostate adenocarcinoma with the predictive power of published nomograms for metastasis to lymph nodes. METHODS: A retrospective review was performed on all patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for prostate adenocarcinoma between 1991 and early 1997. The sensitivity and negative predictive values were computed comparing frozen section analysis, and patients were grouped by risk stratification. Comparison was made using the McNemar text. RESULTS: The sensitivity for detecting lymph node metastasis on frozen section analysis for all risk groups was 33% (9 of 27). The sensitivity for identifying patients at high risk of having nodal metastasis by published nomograms alone was 67% (18 of 27) (P = 0.04). The overall negative predictive value for frozen section analysis was 96.5% (503 of 521). The negative predictive value for uninvolved lymph nodes, using low and intermediate-risk groups stratified by published nomograms, was 97.9% (436 of 445). CONCLUSIONS: Frozen section analysis of pelvic lymph nodes to detect metastatic prostate adenocarcinoma is less sensitive in determining which patients will have lymph nodes involved by metastatic adenocarcinoma than using risk stratification by published nomograms. The negative predictive value of frozen section analysis in all risk groups was very high, up to 97.9%.

Adenocarcinoma↗

PubMed2001

A computerized reminder strategy is effective for annual influenza immunization of children with asthma or reactive airway disease.

BACKGROUND: Influenza virus infection frequently triggers asthma exacerbation and hospitalization. Annual influenza immunization is recommended for children with chronic conditions, including those with asthma or reactive airway disease (RAD); however, <10% receive it each year. METHODS: In September, 1997, we instituted a computerized staged reminder strategy for annual influenza immunization of children with asthma/RAD at the Scott and White Pediatric Clinic in Temple. A reminder letter, followed six weeks later by an autodial recall telephone message, was sent to the parent/guardian of children with asthma/RAD using the Shared Medical Systems to identify children with asthma/RAD and the Integrated Client Encounter System to record immunizations. The effect of this computerized reminder system on the influenza immunization rate of a cohort of 925 Scott and White Pediatric Clinic children with asthma/RAD was examined for the 1996 to 1997 and 1997 to 1998 influenza seasons, before and after intervention. RESULTS: A significant increase in influenza immunization rate from 5.4% to 32.1% occurred in all age groups, regardless of the insurance status. The medically attended acute respiratory illness rate per 100 subjects was significantly higher in vaccinated than in unvaccinated children for each of the two influenza epidemics and in the period between the two epidemics. CONCLUSION: A computerized reminder letter followed by an autodial recall telephone message is effective in increasing the influenza immunization rate of children with asthma/RAD. Children with significantly higher respiratory morbidity during and in between two influenza epidemics were more likely to be immunized after receiving written and telephone autodial reminders.

Adolescent↗

PubMed2001

Effect of HER2/neu expression on survival in non-small-cell lung cancer.

Major prognostic factors for early-stage non-small-cell lung cancer (NSCLC) are tumor size and nodal status. It has been suggested that HER2/neu overexpression may be related to poor prognosis in NSCLC. We evaluated the significance of HER2/neu overexpression on survival in patients with NSCLC. Data were collected on 239 patients treated surgically for stage I/II NSCLC between 1987 and 1996. None of the patients received adjuvant chemotherapy or radiation. Formalin-fixed, paraffin-embedded tumor tissue samples were stained with p185/HER2 receptor antibody. Results were reported as positive (2+, 3+) or negative (0, 1+) (Group A). A separate analysis considered only 3+ as positive (Group B). HER2/neu overexpression was seen in 18% in Group A (43 of 239) and 6% in Group B (15 of 239). HER2/neu overexpression was highest in bronchoalveolar cell carcinoma and adenocarcinoma. More stage I tumors were positive than stage II in both groups, but this was significant only in Group A (21% vs. 7%, P = 0.02). No difference was seen with age, gender, or grade for either group. In Group A, the relapse rate was 55% for HER2/neu-overexpressing tumors and 31% for HER2/neu-negative tumors (P = 0.003). Median time to relapse in patients with HER2/neu-positive tumors was 2.9 years; it was not reached in patients with HER2/neu-negative tumors. Median survival of patients with HER2/neu-positive tumors was 3.6 years compared to 5 years in patients with HER2/neu-negative tumors (P = 0.66). In Group B, the relapse rate was 60% for HER2/neu-overexpressing tumors and 33% for negative tumors (P = 0.036). Median time to relapse was 3.4 years in HER2/neu positive and had not been reached in negative tumors. There was no difference in 5-year survival rates for both groups (47% for HER2/neu positive and 50% for negative, P = 0.66).

Journal Article↗

PubMed1996

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates.

Clinically benign, whole untrimmed prostates were obtained from 104 patients at autopsy, completely sectioned, and examined microscopically. The histological and gross findings of the prostate were correlated with premortem prostatic acid phosphatase levels (PAP, enzymatic method, ACA, Dupont Co.) to determine how often carcinoma of the prostate (CAP) affected PAP levels and to identify other findings within the prostate associated with elevated PAP levels. Sixty (58%) prostates did not have CAP, 34 (33%) had CAP smaller than 1 ml in volume, and 10 (10%) had CAP larger than 1 ml in volume. PAP levels were elevated (greater than 1 U/L) in 8 of 60 (13%) prostates without CAP, in 2 of the 34 (6%) prostates with CAP smaller than 1 ml, and in 1 of the 10 (10%) prostates with CAP larger than 1 ml. These differences were not statistically significant. Likewise, a statistically significant correlation between PAP levels and patient age, patient race, severe inflammation, of high grade prostatic intraepithelial neoplasia (PIN) was not found. However, there was a statistically significant correlation between PAP levels and prostate weight (p < 0.0001). This study suggest that PAP cannot distinguish between patients with clinically undetected CAP and patients without CAP. Furthermore, elevated PAP levels are often not due to metastatic CAP and additional evidence should be present, even in patients with known CAP, before an elevated PAP level is considered to be conclusive evidence of metastatic CAP.

Acid Phosphatase↗

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↗