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Biomedical subjects

T R Miller

Publications and source records attributed to T R Miller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Injury risk among medically identified alcohol and drug abusers.

BACKGROUND: Although nonfatal injury prevalence is higher among substance abusers than in the general population, few studies have estimated the injury risk for clinically recognized substance abusers. The extant studies, moreover, analyze rates of visits for injury treatment rather than rates of injury events. This study estimates the excess risk of medically treated and hospitalized nonoccupational injury for people under age 65 with medically identified substance abuse problems and private health care coverage. METHOD: We conducted a retrospective cohort study by using medical claims data from Medstat Systems, Inc., with a longitudinal database of health care claims for 1.5 million people with health care coverage from 70 large corporations. Claims histories for anyone who had an alcohol-related or drug-related primary or secondary diagnosis during 1987 to 1989 were analyzed. A random sample was selected from the remaining people without a substance abuse diagnosis in their medical records. Injury rates were compared among groups. We used logistic regression to estimate odds of medically treated and hospitalized injury, controlling for demographics. RESULTS: Medically identified substance abusers had an elevated risk of injury in a 3-year period; alcohol and drug abusers had the highest risk (58%), followed by drug-only abusers (49%), alcohol-only abusers (46%), and controls (38%). Alcohol and drug abusers were almost four times as likely to be hospitalized for an injury in a 3-year period when compared with controls. Injury risks were elevated substantially more for female then male substance abusers. CONCLUSIONS: This study greatly improves on available information about the risk of injury for drug and multiple-substance abusers. Medically identified substance abusers, especially adult women, have a higher probability of injury, more hospitalized injuries, and more injury episodes per person injured than nonabusers. More aggressive identification and subsequent treatment of female substance abusers appear warranted.

Adolescent↗
PubMed2001

Financial risk, plan types, and authorizations for managed alcohol treatment services.

OBJECTIVE: To estimate the effects of a managed behavioral healthcare organization's (MBHO's) products/plans and financial risk on levels and amount of care authorized for patients with alcohol-related problems. STUDY DESIGN: Secondary analysis of 1995-1998 MBHO authorization files. PATIENTS: Individuals diagnosed as having an alcohol-related problem without comorbidities. METHODS: Episodes (n = 10,872) were constructed with 60-day clear zones. Multinomial regression equations were used to analyze the proportional distribution of care authorized within episodes at 5 levels: inpatient, residential, partial hospitalization, intensive outpatient, and traditional outpatient. Care equivalency hours were calculated to combine data across outpatient sessions and inpatient days. A linear regression equation analyzed quantity of care within episodes. Product/plan types, financial risk, state of residence, and participation in the MBHO's network were explanatory variables. Age, sex, diagnosis, and episode number were control variables. RESULTS: Most utilization management care hours authorized are inpatient and residential. Relative to other products/plans for managing care, utilization management leads to 50% more authorized hours. More financial risk does not predict fewer care units authorized but shifts hospitalizations toward residential treatment. Increasing age and higher-severity diagnoses predict more overnight care authorizations. Pennsylvania, which mandates minimum levels of care and follows American Society of Addiction Medicine criteria, has significantly more care authorized compared with 8 other states with data. CONCLUSIONS: Other than in utilization management, MBHO financial risk does not predict less care authorization. The MBHO authorizes higher-level care for older adults, for those with more severe diagnoses, and for those with episodes of care beyond the second. Authorization data do not necessarily reflect utilization but can provide a useful, partial view of management strategies.

Adult↗
PubMed2000

Methods for evaluating a mature substance abuse prevention/early intervention program.

The authors describe methods for work in progress to evaluate four workplace prevention and/or early intervention programs designed to change occupational norms and reduce substance abuse at a major U.S. transportation company. The four programs are an employee assistance program, random drug testing, managed behavioral health care, and a peer-led intervention program. An elaborate mixed-methods evaluation combines data collection and analysis techniques from several traditions. A process-improvement evaluation focuses on the peer-led component to describe its evolution, document the implementation process for those interested in replicating it, and provide information for program improvement. An outcome-assessment evaluation examines impacts of the four programs on job performance measures (e.g., absenteeism, turnover, injury, and disability rates) and includes a cost-offset and employer cost-savings analysis. Issues related to using archival data, combining qualitative and quantitative designs, and working in a corporate environment are discussed.

Absenteeism↗
PubMed2000

Phase I/II study of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma: a well-tolerated regimen with activity independent of p53 mutation.

OBJECTIVES: To evaluate the feasibility and activity of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma (TCC) of the urothelium and to relate the activity of this combination to the mutational status of p53. METHODS: In the Phase I portion, paclitaxel 200 mg/m(2) (3-hour infusion), carboplatin dosed to an area under the curve (AUC) of 6 mg/mL. min, and methotrexate 10 mg/m(2), increasing in 10-mg/m(2) increments, were administered on day 1 and every 21 days thereafter with granulocyte colony-stimulating factor (G-CSF) and leucovorin support. Subsequently, a Phase II study was initiated in which the carboplatin dose was lowered to an AUC of 5 to allow treatment without G-CSF. p53 expression was evaluated using immunohistochemistry. RESULTS: Thirty-three patients were accrued. Median age was 66 years. No dose-limiting toxicities were seen in the Phase I portion despite escalation of the methotrexate to 60 mg/m(2). Principal toxicities were myelosuppression and neuropathy. The overall response rate (Phase I and II) was 56% (95% confidence interval 38% to 74%). Median survival was 15.5 months; 88% of patients overexpressed p53 at the primary site. CONCLUSIONS: Paclitaxel, carboplatin, and methotrexate were well tolerated and active in advanced TCC. The high response rate to this regimen despite frequent p53 mutation is consistent with the p53-independent mechanism of paclitaxel. Whether this regimen is superior to methotrexate/vinblastine/doxorubicin/cisplatin, other paclitaxel-based regimens, or to paclitaxel alone will require comparative trials.

Aged↗
PubMed2000

Cost-outcome analysis in injury prevention and control: eighty-four recent estimates for the United States.

OBJECTIVES: The objectives of this study were to review cost-outcome analyses in injury prevention and control and estimate associated benefit-cost ratios and cost per quality-adjusted life-year. DATA SOURCES: Medline and Internet search, bibliographic review, and federal agency contacts identified published and unpublished studies from 1987 to 1998 for the United States. Studies of low quality and analyses of occupational, air, rail, and water transport safety programs were excluded. MEASURES: Selected results were recomputed to increase discount rate, benefit category, and benefit estimate comparability and to update injury incidence rates. RESULTS: More than half of the 84 injury prevention measures reviewed yielded net societal cost savings. Twelve measures had costs that exceeded benefits. Of 33 road safety measures analyzed, 19 yielded net cost savings. Of 34 violence prevention approaches studied, 19 yielded net cost savings, whereas 8 had costs that exceeded benefits. Interventions with the highest benefit-cost ratios included juvenile delinquent therapy programs, fire-safe cigarettes, federal road and traffic safety program funding, lane markers painted on roads, post-mounted reflectors on hazardous curves, safety belts in front seats, safety belt laws with primary enforcement, child safety seats, child bicycle helmets, enforcement of laws against serving alcohol to the intoxicated, substance abuse treatment, brief medical interventions with heavy drinkers, and a comprehensive safe communities program in a low-income neighborhood. Studies of cost-saving measures do not exist for several injury types. CONCLUSIONS: Injury prevention often can reduce medical costs and save lives. Wider implementation of proven measures is warranted.

Accident Prevention↗
PubMed2000

Incidence and costs of 1987-1994 childhood injuries: demographic breakdowns.

OBJECTIVES: Injuries pose a threat to health and well-being and are a major source of medical spending in the United States for children and youth 0 to 21 years of age. This study provides national estimates of the incidence of fatal and nonfatal childhood injuries and comprehensive cost estimates by age, gender, race, family income, metropolitan residence, and place of incident. METHODS: Eight years of National Health Interview Survey data (1987 to 1994) were used to estimate nonfatal injury incidence rates among children and youth 21 years of age and younger. The survey documents all medically attended or temporarily disabling injuries within the 2 weeks before the interview. Injuries were defined as diagnoses 800-995 in the International Classification of Diseases, Ninth Revision, excluding late effects cases. Fatality counts came from 1994 Vital Statistics. Estimates of the costs of injuries (1994 US dollars) included medical spending, lost future work, and lost quality of life. Medical payments included spending on hospital and professional services, rehabilitation, prescriptions, home health care, and medical equipment. Lost future work and lost quality of life consisted of the present value of work that children will be unable to do as adults if they are killed or permanently disabled combined with the pain and suffering that children and their families experience because of the injury. Cost estimates excluded parental income losses from work missed, property damage, legal costs, and insurance claims-adjustment costs related to permanent disability and death. RESULTS: INCIDENCE. A total of 3,073 injury episodes for 3,058 children were obtained from 8 years of National Health Interview Survey data. This represents 20.6 million children in the United States who were injured each year, or approximately 25 per 100 children. This translates to 56,000 nonfatal injury episodes each day that require medical attention or limit children's activity. For fatal injuries, the rate was 38 children per 100,000. The nonfatal injury rate for males (mean: 30; 95% confidence interval [CI]: 29,31) was higher than the rate for females (mean: 20; 95% CI: 19,21); the fatal injury rate for males was more than twice that of females. Injury rates increased with age. Children 0 to 9 years of age had the lowest rate of nonfatal injury. Rates for nonfatal injury among children 0 to 4 years of age were lower (mean: 20; 95% CI: 18,21) than those for the 5 to 9 age group (mean: 22; 95% CI: 20, 23). However, the rate for fatal injuries (21 per 100,000) among the 0 to 4 age group was higher than the 5 to 9 age group (9 per 100,000). Nonfatal injury rates for children 10 years of age and older were higher, with the highest estimated injury rates in late adolescence (15-19 years; mean: 31; 95% CI: 29,33). Nonfatal injuries occurred at higher rates among white children (mean: 27; 95% CI: 26,28) than black children (mean: 19; 95% CI: 17,21) or children from other racial backgrounds (mean: 13; 95% CI: 10,16). The reverse was true for fatal injuries, with higher fatality rates among black children (59 per 100,000). Children in families with incomes under $5,000 had the highest rate of nonfatal injury (mean: 31; 95% CI: 27,35), followed by those in the $35,000 to $49,999 income range (mean: 25; 95% CI: 23,27). The rate of nonfatal injuries in the other income brackets were fairly similar, with those in the highest income bracket having the lowest rate (mean: 14; 95% CI: 13,15). Fatality rates by family income were not available. The nonfatal injury rate in nonmetropolitan areas (mean: 10; 95% CI: 9,11) was higher than in metropolitan areas (mean: 8; 95% CI: 7,8); the same was true for fatal injury rates (33 per 100,000 in nonmetropolitan areas vs 25 in metropolitan areas). Males consistently had higher injury rates than females across all places of injury. Youth 15 years of age and older had higher rates for injuries that occur on the public roads, in recreatio

Adolescent↗
PubMed2000

Suicide acts in 8 states: incidence and case fatality rates by demographics and method.

OBJECTIVES: This study examined incidence rates of medically identified suicide acts (self-inflicted injuries, either fatal or nonfatal) and case fatality rates by age, sex, race, and method used. METHODS: The authors analyzed data on 10,892 suicides and 57,439 attempted suicides among hospital-admitted individuals in 8 states, along with 6219 attempted suicides among individuals released from emergency departments in 2 states. RESULTS: The 8 states experienced a mean of 11 suicides and 119 attempted suicides per 100,000 residents each year. Groups with high suicide rates were men, the elderly, and Whites; groups with high attempted suicide rates were teenagers, young adults, women, and Blacks and Whites aged 25 to 44 years. Blacks aged 15 to 44 years evidenced high attempted suicide rates undocumented in previous studies. Poisoning and firearm were the most common methods used among those attempting suicide and those completing suicide acts, respectively. The most lethal method was firearm. CONCLUSIONS: The characteristics of suicides and attempted suicides differ dramatically. Method used is important in the lethality of the act.

Adolescent↗
PubMed2000

Savings from four transport safety efforts in native America.

This paper presents cost-outcome analyses of four transportation injury prevention efforts in Native American jurisdictions. Pre- and post-intervention data were analyzed to estimate projects' impact on injury reduction. Projects' costs were amortized over the time period covered by the evaluation or over the useful life of physical capital invested. Projects' savings were calculated based on estimated reduction in medical and public program expenses, on estimated decrease in lost productivity, and on estimated quality adjusted life years saved. All four projects yielded positive benefit-cost ratios. The net cost per quality adjusted life years was less than zero for all the projects.

Accidents, Traffic↗
PubMed1999

The medical costs of gunshot injuries in the United States.

CONTEXT: The cost of treating gunshot injuries imposes a financial burden on society. Estimates of such costs are relevant to evaluation of gun violence reduction programs and may help guide reimbursement policies. OBJECTIVES: To develop reliable US estimates of the medical costs of treating gunshot injuries and to present national estimates for the sources of payment for treating these injuries. DESIGN AND SETTING: Cost analysis using E-coded discharge data from hospitals in Maryland for 1994-1995 and New York for 1994 and from emergency departments in South Carolina for 1997. Other sources of data included the National Electronic Injury Surveillance System for 1994 incidence of nonfatal gun injuries, the National Spinal Cord Injury Statistical Center database for 1988-1992 estimates of lifetime medical costs of gun injuries, and the 1994 Vital Statistics census for incidence of fatal gun injuries. MAIN OUTCOME MEASURES: Estimated national acute-care and follow-up treatment costs and payment sources for gunshot injuries. RESULTS: At a mean medical cost per injury of about $17000, the 134445 (95% confidence interval [CI], 109465-159425) gunshot injuries in the United States in 1994 produced $2.3 billion (95% CI, $2.1 billion-$2.5 billion) in lifetime medical costs (in 1994 dollars, using a 3% real discount rate), of which $1.1 billion (49%) was paid by US taxpayers. Gunshot injuries due to assaults accounted for 74% of total costs. CONCLUSIONS: Gunshot injury costs represent a substantial burden to the medical care system. Nearly half this cost is borne by US taxpayers.

Emergency Medical Services↗
PubMed1999

Pharmacological and molecular characterization of ATP-sensitive K+ channels in the TE671 human medulloblastoma cell line.

ATP-sensitive K+ (K(ATP)) channels in the human medulloblastoma TE671 cell line were characterized by membrane potential assays utilizing a potentiometric fluorescent probe, bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC4(3)), and by mRNA analysis. Membrane potential assays showed concentration-dependent and glyburide-sensitive changes in fluorescence upon addition of (-)-cromakalim, pinacidil, diazoxide and P1075. The rank order of potency for these openers was P1075 > (-)-cromakalim approximately = pinacidil > diazoxide. Additionally, glyburide and glipizide inhibited P1075-evoked responses in TE671 cells with half-maximal inhibitory concentrations of 0.22 and 14 microM, respectively. The rank order potencies of both openers and inhibitors were similar to those observed in the rat smooth muscle A-10 cell line. In contrast, in the rat pancreatic insulinoma RIN-m5F cell line, only diazoxide was effective as an opener. Reverse transcription-polymerase chain reaction (RT-PCR) studies detected sulfonylurea receptors SUR2B and SUR1 mRNA in TE671 cells whereas only SUR2B and SUR1 mRNA were, respectively, detected in A-10 and RIN-m5F cells. The inward rectifier Kir6.2 mRNA was detected in all three cell types whereas Kir6.1 was detected only in A-10 cells. Collectively, the molecular and pharmacologic studies suggest that K(ATP) channels endogenously expressed in TE671 medulloblastoma resemble those present in the smooth muscle.

Adenosine Triphosphate↗
PubMed1999

Angiomyolipoma of the liver in fine-needle aspiration biopsies: its distinction from hepatocellular carcinoma.

BACKGROUND: Angiomyolipoma (AML) of the liver is an uncommon benign lesion that may be difficult to distinguish clinically, radiographically, and morphologically from hepatocellular carcinoma (HCC). METHODS: Fine-needle aspiration biopsies (FNAB) of three AMLs of the liver were compared with FNABs from eight cases of HCC. Immunoperoxidase stains for HMB-45, muscle specific actin, and CAM 5.2 were performed on two cell blocks and one resection of AML. RESULTS: All three AMLs yielded cellular aspirates. They were composed of clusters of cells with arborizing transgressing endothelium but no peripherally wrapping endothelium. Smooth muscle cells of AML showed fibrillar cytoplasm and indistinct cytoplasmic borders; HCC showed granular cytoplasm and distinct cytoplasmic borders. Extramedullary hematopoiesis was present only in AML. Mitotic figures were seen only in HCC. Intranuclear inclusions, nucleoli, and large, atypical cells were present in both AML and HCC. Fat was seen in only one case of AML and was scant. Immunoperoxidase stains for HMB-45 and smooth muscle actin were positive in AML and negative in adjacent normal liver. CAM 5.2 stain was negative in AML. CONCLUSIONS: The cytologic features seen on FNABs of AML are distinct from those of HCC. Immunoperoxidase stains can aid in the definitive diagnosis on FNAB. It is important to recognize AML on FNAB to allow conservative clinical management.

Actins↗
PubMed1999

Geographic variation in expenditures for Workers' Compensation hospitalized claims.

OBJECTIVE: Past literature finds considerable variation in the cost of physician care and in the utilization of medical procedures. Variation in the cost of hospitalized care has received little attention. We examine injury costs of hospitalized claims across states. DESIGN: Multivariate regression analysis is used to isolate state variations, while controlling for personal and injury characteristics, and state characteristics. SETTING: Injuries to workers filing Workers' Compensation lost workday claims. PARTICIPANTS: About 35,000 randomly sampled Workers' Compensation claims from 17 states filed between 1979 and 1988. MAIN OUTCOME MEASURE: Medical payments per episode of three injury groups: upper and lower extremity fractures and dislocations, other upper extremity injuries, and back strains and sprains. RESULTS: Statistical analyses reveal considerable variation in expenditures for hospitalized injuries across states, even after controlling for case mix and state characteristics. A substantial portion of the variation is explained by state rate regulations; regulated states have lower costs. CONCLUSIONS: The large variation in costs suggests a potential to affect the costs of hospitalized care. Efforts should be directed at those areas that have higher costs without sufficient input price, quality, or case mix justification.

Arm Injuries↗
PubMed1999

How intoxicated are drivers in the United States? Estimating the extent, risks and costs per kilometer of driving by blood alcohol level.

This study develops and applies an algorithm with international applicability for estimating vehicle kilometers (kms) driven by blood alcohol level (BAL) from police crash report data. In the United States, an estimated one in 120 kms was driven with BAL > or = 0.10% in 1992-1993. The ratio increased to 1 in 7 kms driven on weekend evenings. The estimated cost per vehicle km driven with BAL > or = 0.08% was $3.40 compared to $0.07 per sober km. Males, those age 21-29 and those driving between 22:00 and 04:00 had the greatest percentage of driving with BAL > or = 0.08%. These estimates are computed, in part, from early 1960s data on crash odds by driver BAL and assume crash odds by BAL relative to sober do not vary with driver age and sex. Preliminary investigation indicates that the method provides reliable estimates of alcohol-positive kms from roadside surveys at night, but seems to over-estimate high-BAL kms. Direct field validation is highly desirable.

Accidents, Traffic↗
PubMed1999

Effects of endurance exercise training on left ventricular systolic performance and ventriculoarterial coupling in patients with coronary artery disease.

BACKGROUND: Endurance exercise training can increase left ventricular (LV) ejection fraction during dynamic exercise in coronary artery disease. This adaptation may be mediated by altered cardiac loading conditions rather than an improvement in intrinsic LV systolic function. To minimize these confounding effects, we used isometric handgrip exercise to assess the training-induced changes in LV systolic function and ventriculoarterial coupling. METHODS: Twenty-six patients (52 +/- 2 years of age) trained for 12 months. LV function was assessed with radionuclide ventriculograpy. RESULTS: LV systolic reserve (the change in LV ejection fraction from rest to handgrip exercise) increased from -7.32 +/- 1.2 to -3.4 +/- 1.1 (P =. 033) without acute changes in end-diastolic volume or the effective arterial load. LV end-systolic elastance increased 37% (P =.039) during handgrip exercise. Resting end-diastolic volume increased and the effective arterial load decreased after training. CONCLUSIONS: Data suggest that in coronary artery disease adaptations to exercise training include a lower effective arterial load and an increase in EDV at rest, with an improvement in LV systolic function detectable only during afterload stress.

Arteries↗
PubMed1999

Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma.

Both the association between lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC), and the prognostic significance of lymphocytic infiltrate in patients with thyroid malignancy, remain controversial. We examine the above relationships by retrospectively reviewing our series of patients treated for differentiated nonmedullary thyroid carcinoma at University of California-San Francisco over a 25-yr period (1970-1995). Of the 631 patients with complete data for analysis, 128 patients (20.3%) showed concomitant histologic evidence of LT and 503 patients (79.7%) had no evidence of LT. Prognostic outcome was assessed using Kaplan-Meier survival plots and analysis of risk factors by Cox's proportional-hazard modeling. The cohort with LT revealed a higher frequency of PTC (97.7% vs. 87.3%) and female patients (85.2% vs. 66.8%), a lower frequency of extrathyroidal invasion (7.8% vs. 23.3%) and nodal metastases (25.8% vs. 43.3%), and absence of distant metastases (0% vs. 4.8%), respectively, compared with those without LT. At initial surgery, a significantly greater proportion of patients with LT belonged to lower pathological tumor-node-metastasis stages, compared with those without LT (stage 1, 86.7% vs. 73%; stage 2, 4.7% vs. 8.3%; stage 3, 8.6% vs. 15.3%; and stage 4, 0% vs. 3.4%). Over a mean +/- SE follow-up period of 11.1 +/- 0.4 yr, patients with LT had significantly lower cancer recurrence rate (6.3% vs. 24.1%; P < 0.0001) and cancer mortality rate (0.8% vs. 8.0%; P = 0.001), respectively, compared with those without LT. In summary, our series showed a relatively common occurrence of LT in patients with PTC, and we believed that lymphocytic infiltration developed mainly in response to the tumor itself. We also found a more favorable course of PTC in the presence of LT; this supports the hypothesis that lymphocytic infiltration represents a form of immune reaction to control tumor growth and proliferation.

Adolescent↗
PubMed1999

Fatal nontraffic injuries involving alcohol: A metaanalysis.

STUDY OBJECTIVE: Estimates of alcohol involvement in fatal injuries vary widely. For injuries other than those involving motor vehicles, no national data exist and the quality of regional data is limited. This study synthesizes US medical examiner studies of nontraffic fatalities for the purpose of estimating alcohol involvement by injury mechanism and intent. METHODS: We reviewed 331 medical examiner studies published between 1975 and 1995 that reported nontraffic injury fatalities. These studies were identified from computerized bibliographic databases and by hand searching of reference lists from 26 review publications and the subject indices of 7 prominent journals. A final total of 65 articles (19.6%) met our inclusion criteria for analysis. National data on motor vehicle fatalities were used for comparison. RESULTS: A total of 7,459 unintentional injury deaths, 28,696 homicide cases, and 19,347 suicide cases were aggregated. The aggregate percentage tested for blood alcohol concentration (BAC) was highest among homicide cases (88.2%), followed by unintentional injury deaths (84.0%) and suicide cases (81.7%). The aggregate percentage determined to be intoxicated (BAC, >/=100 mg/dL) was highest among homicide cases (31.5%), followed by unintentional injury deaths (31.0%) and suicide cases (22.7%). Mean and median comparisons produced comparable findings. Fewer than one quarter of the 65 articles reported gender- and age-specific rates. Inconsistent reporting of gender and age-specific rates in fatal nontraffic injuries prevented their analysis by cause of death. Fatally injured motor vehicle drivers, however, demonstrated distinct variation in alcohol involvement by age and gender. CONCLUSION: This metaanalysis is the first systematic attempt to estimate alcohol involvement in fatal nontraffic injuries at the national level. It demonstrates that alcohol is an important factor in many fatal injuries and that its importance varies by cause of injury.

Accidents↗
PubMed1998

Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase.

Guanylyl cyclases (GCs) and adenylyl cyclases (ACs) have fundamental roles in a wide range of cellular processes. Whereas GCs use GTP as a substrate to form cGMP, ACs catalyze the analogous conversion of ATP to cAMP. Previously, a model based on the structure of adenylate cyclase was used to predict the structure of the nucleotide-binding pocket of a membrane guanylyl cyclase, RetGC-1. Based on this model, we replaced specific amino acids in the guanine-binding pocket of GC with their counterparts from AC. A change of two amino acids, E925K together with C995D, is sufficient to completely alter the nucleotide specificity from GTP to ATP. These experiments strongly validate the AC-derived RetGC-1 structural model and functionally confirm the role of these residues in nucleotide discrimination.

Adenylyl Cyclases↗