Search PubMed⌕ Search

Biomedical subjects

R M Hoffman

Publications and source records attributed to R M Hoffman.

At least 19 recordsLinked to original sources

Comparison of self-reported initial treatment with medical records: results from the prostate cancer outcomes study.

Medical records are generally accepted as the most accurate source of information documenting cancer treatments. However, as the health care system becomes more decentralized and more cancer care is delivered in outpatient settings, it is increasingly difficult and expensive to review records from the many surgeons and medical/radiation oncologists who administer cancer therapies in the community setting. Using 1994-1995 data, the authors compared initial treatment for prostate cancer self-reported (from a mailed questionnaire or telephone/in-person interview) by 3,196 US men in the population-based Prostate Cancer Outcomes Study with information obtained from medical records. Agreement between self-reports and medical records varied by type of treatment. Generally, agreement was excellent for more invasive procedures such as prostatectomy or radiation (kappa values > 0.8), with decreasing agreement for hormone shots and pills (kappa values < 0.7). If the medical record abstract is assumed to be the "gold standard," the estimated sensitivity was generally high (>80%) for prostatectomy and radiation but low (68%) for hormone pills, although the estimated specificity was 90% or greater for all treatments. These results can serve as a useful guide to researchers contemplating the use of surveys as an alternative to medical record abstraction to ascertain treatment in studies of patient outcomes.

Adult↗

Methioninase cancer gene therapy with selenomethionine as suicide prodrug substrate.

In this study, we report a novel approach to gene-directed enzyme prodrug therapy for cancer. This gene therapy strategy exploits the toxic pro-oxidant property of methylselenol, which is released from selenomethionine (SeMET) by cancer cells with the adenoviral-delivered methionine alpha,gamma-lyase (MET) gene cloned from Pseudomonas putida. In MET-transduced tumor cells, the cytotoxicity of SeMET is increased up to 1000-fold compared with nontransduced cells. A strong bystander effect occurred because of methylselenol release from MET gene-transduced cells and uptake by surrounding tumor cells. Methylselenol damaged the mitochondria via oxidative stress and caused cytochrome c release into the cytosol, thereby activating the caspase cascade and apoptosis. Adenoviral MET-gene/SeMET treatment also inhibited tumor growth in rodents and significantly prolonged their survival. Recombinant adenovirus-encoding MET gene-SeMET treatment thereby offers a new paradigm for cancer gene therapy.

Adenoviridae↗

Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study.

PURPOSE: To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer. PATIENTS AND METHODS: Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade. RESULTS: More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also were less likely to consider themselves free of prostate cancer after treatment. CONCLUSION: Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions.

Adult↗

Spatial-temporal imaging of bacterial infection and antibiotic response in intact animals.

We describe imaging the luminance of green fluorescent protein (GFP)-expressing bacteria from outside intact infected animals. This simple, nonintrusive technique can show in great detail the spatial-temporal behavior of the infectious process. The bacteria, expressing the GFP, are sufficiently bright as to be clearly visible from outside the infected animal and recorded with simple equipment. Introduced bacteria were observed in several mouse organs including the peritoneal cavity, stomach, small intestine, and colon. Instantaneous real-time images of the infectious process were acquired by using a color charge-coupled device video camera by simply illuminating mice at 490 nm. Most techniques for imaging the interior of intact animals may require the administration of exogenous substrates, anesthesia, or contrasting substances and require very long data collection times. In contrast, the whole-body fluorescence imaging described here is fast and requires no extraneous agents. The progress of Escherichia coli-GFP through the mouse gastrointestinal tract after gavage was followed in real-time by whole-body imaging. Bacteria, seen first in the stomach, migrated into the small intestine and subsequently into the colon, an observation confirmed by intravital direct imaging. An i.p. infection was established by i.p. injection of E. coli-GFP. The development of infection over 6 h and its regression after kanamycin treatment were visualized by whole-body imaging. This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, and the spatial migration of the infectious agents.

Administration, Oral↗

Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice.

This study describes a novel approach to the treatment of brain tumors with the combination of recombinant L-methionine-alpha-deamino-gamma-lyase and chemotherapeutic regimens that are currently used against such tumors. The growth of Daoy, SWB77, and D-54 xenografts in athymic mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of a MET- and choline-free diet and recombinant L-methionine-alpha-deamino-gamma-lyase. The treated tumor-bearing mice were rescued from the toxic effects of MET withdrawal with daily i.p. homocystine. This regimen suppressed plasma MET to levels below 5 microM for several days, with no treatment-related deaths. MET depletion for 10-12 days induced mitotic and cell cycle arrest, apoptotic death, and widespread necrosis in tumors but did not prevent tumor regrowth after cessation of the regimen. However, when a single dose of 35 mg/m(2) of N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), which was otherwise ineffective as a single therapy in any of the tumors tested, was given at the end of the MET depletion regimen, a more than 80-day growth delay was observed for Daoy and D-54, whereas the growth of SWB77 was delayed by 20 days. MET-depleting regimens also trebled the efficacy of temozolomide (TMZ) against SWB77 when TMZ was given to animals as a single dose of 180 mg/m(2) at the end of a 10-day period of MET depletion. The enhanced responses of both Daoy and SWB77 to DNA alkylating agents such as BCNU and TMZ could be attributed to the down-regulation of O(6)-methylguanine-DNA methyltransferase activity. However, the synergy of MET depletion and BCNU observed with D-54 tumors, which do not express measurable O(6)-methylguanine-DNA methyltransferase protein, is probably mediated by a different mechanism. MET depletion specifically sensitizes tumors to alkylating agents and does not significantly lower the toxicity of either BCNU or TMZ for the host. In this regard, the combination approach of MET depletion and genotoxic chemotherapy demonstrates significant promise for clinical evaluation.

Animals↗

Health outcomes after external-beam radiation therapy for clinically localized prostate cancer: results from the Prostate Cancer Outcomes Study.

PURPOSE: Studies reporting effects of radiotherapy for prostate cancer on sexual, bowel, and urinary function have been conducted primarily in referral centers or academic institutions. Effects of external-beam radiotherapy for prostate cancer among a population-based cohort were assessed. PATIENTS AND METHODS: The study population included 497 white, Hispanic, and African-American men with localized prostate cancer from six US cancer registries who were diagnosed between October 1, 1994, and October 31, 1995, and treated initially with external-beam radiotherapy. They were interviewed at regular intervals, and medical records were reviewed. Distributions of responses for bowel-, urinary-, and sexual-related functions at 6, 12, and 24 months after diagnosis and adjusted mean composite change scores for each domain were analyzed. RESULTS: Declines of 28.9% in the sexual function score and 5.4% in the bowel function score occurred by 24 months, whereas at this time, the urinary function score was relatively unchanged. A total of 43% of those who were potent before diagnosis became impotent after 24 months. More than two thirds of the men were satisfied with their treatment and would make the same decision again. CONCLUSION: Sexual function was the most adversely affected quality-of-life domain, with problems continuing to increase between 12 and 24 months. Bowel function problems increased at 6 months, with partial resolution observed by 24 months. Despite the side effects, satisfaction with therapy was high. These results are representative of men in community practice settings and may be of assistance to men and to clinicians when making treatment decisions.

Aged↗

Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid.

Potentiation of the cytotoxic activity of 5-fluorouracil (FUra) by folinic acid (5-HCO-H4folate) is due to elevation of the methylene tetrahydrofolate (CH2-H4folate) level, which increases the stability of the ternary complex of thymidylate synthase (TS), fluorodeoxyuridine monophosphate, and CH2-H4folate that inactivates the TS. Methionine deprivation results in the production of tetrahydrofolate (H4folate) and, subsequently, CH2-H4folate from methyl tetrahydrofolate, as a consequence of the induction of methionine synthesis. We hypothesized that the efficacy of FUra could be augmented by the combination of high-concentration 5-HCO-H4folate and recombinant methioninase (rMETase), a methionine-cleaving enzyme. Studies in vitro were performed with the cell line CCRF-CEM. Cytotoxic synergism of FUra + rMETase and FUra + 5-HCO-H4folate + rMETase was demonstrated with the combination index throughout a broad concentration range of FUra and rMETase. A subcytotoxic concentration of rMETase reduced the IC50 of FUra by a factor of 3.6, and by a factor of 7.5, in the absence and in the presence of 5-HCO-H4folate, respectively. 5-HCO-H4folate increased the intracellular concentrations of CH2-H4folate and H4folate from their baseline levels. Concentrations of folates were not changed by exposure to rMETase. Levels of free TS in cells treated with FUra + 5-HCO-H4folate and with FUra + rMETase were lower than those in cells exposed to FUra alone. The decrease of TS was still more pronounced in cells treated with FUra + 5-HCO-H4folate + rMETase. The synergism described in this study will be a basis for further exploration of combinations of fluoropyrimidines, folates, and rMETase.

Antimetabolites, Antineoplastic↗

Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study.

BACKGROUND: African-Americans have twice the risk of non-Hispanic whites for presenting with advanced-stage prostate cancer. To investigate the reasons for this difference, we evaluated the association between race/ethnicity and advanced-stage prostate cancer, adjusting for demographic, socioeconomic, clinical, and pathologic factors. METHODS: A population-based cohort of 3173 men diagnosed with prostate cancer between October 1, 1994, and October 31, 1995, was analyzed. Medical record abstracts and self-administered survey questionnaires were used to obtain information regarding race/ethnicity, age, marital status, insurance status, educational level, household income, employment status, comorbidity, urinary function, prostate-specific antigen level, tumor grade, and clinical stage. The odds ratio (OR) for advanced-stage prostate cancer was estimated with weighted logistic regression analysis. All P: values were two-sided. RESULTS: Clinically advanced-stage prostate cancers were detected more frequently in African-Americans (12.3%) and Hispanics (10.5%) than in non-Hispanic whites (6.3%). Socioeconomic, clinical, and pathologic factors each accounted for about 15% of the increased relative risk. After adjusting for all covariates, the risk remained statistically significantly increased for African-Americans (OR = 2.26; 95% confidence interval [CI] = 1.43 to 3.58) but not for Hispanics (OR = 1.23; 95% CI = 0.73 to 2.08). CONCLUSION: Traditional socioeconomic, clinical, and pathologic factors accounted for the increased relative risk for presenting with advanced-stage prostate cancer in Hispanic but not in African-American men.

Black or African American↗

Whole-body and intravital optical imaging of angiogenesis in orthotopically implanted tumors.

The development of drugs for the control of tumor angiogenesis requires a simple, accurate, and economical assay for tumor-induced vascularization. We have adapted the orthotopic implantation model to angiogenesis measurement by using human tumors labeled with Aequorea victoria green fluorescent protein for grafting into nude mice. The nonluminous induced capillaries are clearly visible against the very bright tumor fluorescence examined either intravitally or by whole-body luminance in real time. The orthotopic implantation model of human cancer has been well characterized, and fluorescence shadowing replaces the laborious histological techniques for determining blood vessel density. Intravital images of orthotopically implanted human pancreatic tumors clearly show angiogenic capillaries at both primary and metastatic sites. A quantitative time course of angiogenesis was determined for an orthotopically growing human prostate tumor periodically imaged intravitally in a single nude mouse over a 19-day period. Whole-body optical imaging of tumor angiogenesis was demonstrated by injecting fluorescent Lewis lung carcinoma cells into the s.c. site of the footpad of nude mice. The footpad is relatively transparent, with comparatively few resident blood vessels, allowing quantitative imaging of tumor angiogenesis in the intact animal. Capillary density increased linearly over a 10-day period as determined by whole-body imaging. Similarly, the green fluorescent protein-expressing human breast tumor MDA-MB-435 was orthotopically transplanted to the mouse fat pad, where whole-body optical imaging showed that blood vessel density increased linearly over a 20-week period. These powerful and clinically relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological microenvironments.

Animals↗

Efficacy of intra-hepatectomy 5-FU on recurrence and metastasis of human hepatocellular carcinoma in nude mice.

A novel intra-operative chemotherapy nude mouse model for human hepatocellular carcinoma (HCC) has been developed. Intra-peritoneal (i.p.) administration of 5-fluorouracil (5-FU) was begun 2 hr before hepatic resection of HCC and then continued post-operatively for 4 consecutive days. This regime, termed intra-hepatectomy chemotherapy (IHC), significantly prolonged animal survival compared with pre-operative 5-FU, neoadjuvant therapy, 5-FU post-operative adjuvant therapy, surgery alone, 5-FU without surgery, and the untreated control. The median survival of the intra-operative 5-FU-treated group was 127 days compared with 78 days for the neoadjuvantly-treated animals and 53 days for the control group (p<0.006). When all animals with neoadjuvant 5-FU treatment had died, 60% of the animals in the IHC group were still alive (p<0.011). Survival of all other treatment groups, including 5-FU without surgery, surgery alone, and adjuvant post-operative chemotherapy, was not significantly different from the untreated control group. Five animals in the IHC group were free of tumor when sacrificed at day 150 post-surgically. While 100% of animals in the control group had lymph nodes draining the liver involved with metastases, only 20% of animals in the IHC group had lymph node metastases. These data suggested that IHC therapy increased survival by preventing metastases of cancer cells not removed in the liver resection procedure. The results of this study indicate that IHC therapy for resection of HCC should be investigated clinically.

Animals↗

Transduction of liver cells by lentiviral vectors: analysis in living animals by fluorescence imaging.

Viral vectors based on lentiviruses, such as the human immunodeficiency virus, are able to transduce a broad spectrum of nondividing cells in vivo. This ability of lentiviral vectors makes them an attractive vehicle for gene transfer into the liver. In order to determine the requirements for efficient lentiviral gene transfer, we used a fluorescence imaging system, which allows the detection of cells and tissues that express fluorescent reporter genes (e.g., green fluorescence protein) in the living animal. We show that the latest generation of lentiviral vectors efficiently transduces the murine liver. Further analysis demonstrated that neither cell-cycle activation nor division of liver cells is a prerequisite for lentiviral gene transfer in vivo.

Animals↗

Step-down management of gastroesophageal reflux disease.

BACKGROUND & AIMS: As the economic burden of gastroesophageal reflux disease (GERD) is largely weighted to maintenance as opposed to initial therapy, switching from more potent to less expensive medication once symptoms are alleviated (step-down therapy) may prove to be most cost-effective. This study aimed to prospectively evaluate the feasibility of step-down therapy in a cohort of patients with symptoms of uncomplicated GERD. METHODS: Patients whose GERD symptoms were alleviated by proton pump inhibitors (PPIs) were recruited from outpatient general medicine clinics. After baseline demographic and quality of life information were obtained, PPIs were withdrawn from subjects in a stepwise fashion. Primary outcome was recurrence of symptoms during follow-up that required reinstitution of PPIs. Secondary outcomes included changes in quality of life and overall cost of management. Predictors of nonresponse to step-down were assessed. RESULTS: Seventy-one of 73 enrolled subjects completed the study. Forty-one of 71 (58%) were asymptomatic off PPI therapy after 1 year of follow-up. Twenty-four of 71 (34%) required histamine 2-receptor antagonists, 5/71 (7%) prokinetic agents, 1/71 (1%) both, and 11/71 (15%) remained asymptomatic without medication. Quality of life did not significantly change, whereas management costs decreased by 37%. Multivariable analysis revealed younger age and a dominant symptom of heartburn to predict PPI requirement. CONCLUSIONS: Step-down therapy is successful in the majority of patients and can decrease costs without adversely affecting quality of life.

Adult↗

Visualization of GFP-expressing tumors and metastasis in vivo.

We have developed mouse models of metastatic cancer with genetically fluorescent tumors that can be imaged in fresh tissue, in situ, as well as externally. To achieve this capability, we have transduced the green fluorescent protein (GFP) gene, cloned from the bioluminescent jellyfish Aequorea victoria, into a series of human and rodent cancer cell lines that were selected in vitro to stably express GFP in vivo after transplantation to metastatic rodent models. Techniques were also developed for transduction of tumors by GFP in vivo. With this fluorescent tool, we detected and visualized for the first time tumors and metastasis in fresh viable tissue or in situ in host organs down to the single-cell level. GFP tumors on the colon, prostate, breast, brain, liver, lymph nodes, lung, pancreas, bone, and other organs can also be visualized externally, transcutaneously by quantitative whole-body fluorescence optical imaging. Real-time tumor and metastatic growth and angiogenesis and inhibition by representative drugs can be imaged and quantified for rapid antitumor, antimetastatic, and antiangiogenesis drug screening. The GFP-transfected tumor cells enabled a fundamental advance in the visualization of tumor growth and metastasis in real time in vivo.

3T3 Cells↗

CT features of pulmonary alveolar proteinosis.

OBJECTIVE: This investigation describes the CT features of pulmonary alveolar proteinosis in a large group of patients. MATERIALS AND METHODS: A retrospective review of 139 chest CT scans (79 thick-section scans and 60 thin-section scans) from 27 patients with pathologically proven pulmonary alveolar proteinosis was performed. Two independent observers assessed the intraslice patterns and zonal distribution of disease on three CT images of each lung. The observers also graded the percentage of ground-glass opacities, air-space opacities, fibrosis, interlobular opacities, intralobular opacities, and emphysema in each slice. CT scans obtained before and after lavage related to 12 whole-lung lavage treatments on nine patients were evaluated. RESULTS: The dominant intraslice pattern was geographic, but a diffuse pattern was sometimes seen. The most common zonal pattern was uniform; a lower zone predominance was next most frequent. Ground-glass, air-space, and fibrotic opacities had a generally homogeneous craniocaudal distribution, but there was a trend toward more interlobular opacities at the lung bases (p < 0.002). Ground-glass opacities were seen on at least one scan in 100% of the patients. Interlobular opacities (85%), air-space opacities (78%), substantial fibrosis (7%), and intralobular opacities (7%) occurred less frequently. Compared with thick-section images, thin-section images showed more interlobular opacities, but no difference in ground-glass, air-space, or fibrotic disease. The proportion of lung affected by ground-glass and interlobular opacities decreased significantly (p < 0.05) after lavage. CONCLUSION: Pulmonary alveolar proteinosis does not present only with alveolar disease. The CT appearance typically combines different types of opacities with a geographic pattern and a uniform zonal distribution with variation over time.

Adult↗

Hydrolyzable carbohydrates in pasture, hay, and horse feeds: direct assay and seasonal variation.

Carbohydrates may be hydrolyzed or fermented in the digestive tract, and this distinction is important for the evaluation of the diet of herbivores. Both hydrolyzable and fermentable carbohydrates are included in the nonstructural carbohydrate (NSC) fraction as estimated by difference using proximate analysis. Our objectives were to measure hydrolyzable carbohydrates in forages and concentrates, to compare these values with nonstructural carbohydrate, to test for prediction of hydrolyzable carbohydrate concentration in forages from its near-infrared spectrum, and to examine seasonal variation of carbohydrates in pasture. Samples of forages (107) and concentrates (25) were collected, dried, ground, and analyzed for NSC (calculated as 100 - water - CP - fat - ash - NDF), hydrolyzable carbohydrate (CHO-H, direct analysis), and rapidly fermentable carbohydrate (NSC minus CHO-H). Hydrolyzable carbohydrate accounted for 97% or more of the NSC in the concentrates but only 33% in pasture and hay. A two-term polynomial equation fit all the data: CHO-H = 0.154 x NSC + 0.00136 x NSC2, R2 = 0.98, P < 0.0001, n = 132. In 83 pasture samples, CHO-H concentrations were predicted by near-infrared spectra with a calibration R2 of 0.97, a mean of 48 g/kg, and a SE of calibration of 3.5 g/kg DM. In pasture samples collected between September 1995 and November 1996, the coefficient of variation was 31% for both CHO-H and rapidly fermentable carbohydrate (CHO-FR); the largest increments were 31 g/kg of CHO-H from September to October and 41 g/kg of CHO-FR from February to March. The increased risk of certain diseases, such as laminitis and colic, that have been previously associated with an abrupt overload of NSC may be more precisely attributed to CHO-H in grain concentrates, and to CHO-H as well as CHO-FR in pastures.

Animal Feed↗

Disagreement between height/weight classifications of underweight, normal weight, and obesity in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients are classified as underweight, normal weight, or obese by height/weight indices including body mass index (BMI) and the body weight/desired weight (W/DW) ratio. We compared these classifications of degree of obesity in 378 women and 555 men on PD. We used these cut-off values: for underweight, BMI < or = 18.5 and W/DW < or = 0.9; for obesity, BMI > or = 30.0 and W/DW > or = 1.2. The W/DW values were calculated assuming first a small frame, then a medium frame, and finally a large frame for all subjects. Regardless of sex or skeletal frame, BMI correlated highly with W/DW (r value between 0.98 and 0.99); however, the range of BMI values corresponding by linear regression to the normal range of W/DW (0.9-1.2) was narrower than the range of "normal" BMI (18.5-30.0). Consequently, regardless of sex or skeletal frame, smaller fractions of the patient population were classified as underweight or obese by BMI standards than by W/DW standards. The degree of agreement of the classifications of subjects as underweight, normal weight, or obese by BMI and W/DW was evaluated by Cohen's kappa ratio. The kappa ratio varied between 0.47 and 0.58, indicating a reasonable--but not high--degree of agreement beyond chance. The highest kappa ratios were obtained assuming a medium skeletal frame for both women and men. Substantial discrepancies are observed in the classification of PD patients as underweight, normal weight, or obese by BMI and W/DW. Further research is needed to identify the height/weight index that has the strongest association both with clinical outcomes and with other, more precise measurements of body fat content.

Body Constitution↗

Visualizing gene expression by whole-body fluorescence imaging.

Transgene expression in intact animals now can be visualized by noninvasive techniques. However, the instruments and protocols developed so far have been formidable and expensive. We describe here a system for rapidly visualizing transgene expression in major organs of intact live mice that is simple, rapid, and eminently affordable. Green fluorescent protein (GFP) is expressed in the cells of brain, liver, pancreas, prostate, and bone, and its fluorescence is encoded in whole-body optical images. For low-magnification images, animals are illuminated atop a fluorescence light box and directly viewed with a thermoelectrically cooled color charge-coupled device camera. Higher-magnification images are made with the camera focused through an epi-fluorescence dissecting microscope. Both nude and normal mice were labeled by directly injecting 8 x 10(10) plaque-forming units/ml of adenoviral GFP in 20-100 microl PBS and 10% glycerol into either the brain, liver, pancreas, prostate, or bone marrow. Within 5-8 h after adenoviral GFP injection, the fluorescence of the expressed GFP in brain and liver became visible, and whole-body images were recorded at video rates. The GFP fluorescence continued to increase for at least 12 h and remained detectable in liver for up to 4 months. The system's rapidity of image acquisition makes it capable of real-time recording. It requires neither exogenous contrast agents, radioactive substrates, nor long processing times. The method requires only that the expressed gene or promoter be fused or operatively linked to GFP. A comparatively modest investment allows the study of the therapeutic and diagnostic potential of suitably tagged genes in relatively opaque organisms.

Adenoviridae↗