Rodney Howell | University of Miami (original) (raw)

Papers by Rodney Howell

American family physician, 1995

Pediatrics, 2011

BACKGROUND: Although newborn screening for critical congenital heart disease (CCHD) was recommend... more BACKGROUND: Although newborn screening for critical congenital heart disease (CCHD) was recommended by the US Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and Children to promote early detection, it was deemed by the Secretary of the HHS as not ready for adoption pending an implementation plan from HHS agencies. OBJECTIVE: To develop strategies for the implementation of safe, effective, and efficient screening. METHODS: A work group was convened with members selected by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children, the American Academy of Pediatrics, the American College of Cardiology Foundation, and the American Heart Association. RESULTS: On the basis of published and unpublished data, the work group made recommendations for a standardized approach to screening and diagnostic follow-up. Key issues for future research and evaluation were identified. CONCLUSIONS: The work-group members found...

Journal of Venomous Animals and Toxins including Tropical Diseases, 2012

This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high le... more This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high level of acetylcholinesterase (AChE) activity. The enzyme showed optimum activity at alkaline pH (8.5) and 45°C. Krait venom AChE was inhibited by substrate. Inhibition was significantly reduced by using a high ionic strength buffer; low ionic strength buffer (10 mM PO 4 pH 7.5) inhibited the enzyme by 1. 5mM AcSCh, while high ionic strength buffer (62 mM PO 4 pH 7.5) inhibited it by 1 mM AcSCh. Venom acetylcholinesterase was also found to be thermally stable at 45°C; it only lost 5% of its activity after incubation at 45°C for 40 minutes. The Michaelis-Menten constant (Km) for acetylthiocholine iodide hydrolysis was found to be 0.068 mM. Krait venom acetylcholinesterase was also inhibited by ZnCl 2 , CdCl 2 , and HgCl 2 in a concentrationdependent manner. Due to the elevated levels of AChE with high catalytic activity and because it is more stable than any other sources, Bungarus sindanus venom is highly valuable for biochemical studies of this enzyme.

Journal of Clinical Investigation, 1962

Genetics in Medicine, 1999

Objective-To summarise a conference convened to examine how cystic fibrosis screening might appro... more Objective-To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. Methods-Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. Results-Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost eVectively by identifying racial/ethnic groups at suYcient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. Conclusions-Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis.

American journal of human genetics, 1981

We have defined a new autosomal recessive disorder in patients stemming from a small community in... more We have defined a new autosomal recessive disorder in patients stemming from a small community in northern Mexico. Diagnosable at birth, its major symptoms include brittle hair, mental retardation, and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy. Hair cystine content is reduced while the copper/zinc ratio in hair is increased.

Pediatrics, 1963

Studies on two siblings with histidinemia have shown that the enzymatic defect in this metabolic ... more Studies on two siblings with histidinemia have shown that the enzymatic defect in this metabolic disease is the absence of histidase. As a consequence, blood levels of histidine are greatly elevated, and histidine and imidazolepyruvic acid are excreted in the urine. Imidazolepyruvic acid in the urine of these patients gives a green color with ferric chloride, and the disease may be confused with phenylketonuria. Patients with histidinemia lack urocanic acid in the skin and sweat. Both siblings with histidinemia have speech defects but normal intelligence. The possible relationship between the defect in speech and the metabolic disease has been discussed. The mode of inheritance of this disease is not clearly established, but it may be a Mendelian recessive.

The Western journal of medicine, 1975

International Journal of Neonatal Screening

One of the most dramatic discoveries in metabolic disease research was that of Ashbørn Følling, w... more One of the most dramatic discoveries in metabolic disease research was that of Ashbørn Følling, who in 1934, published his research outlining unusual biochemical findings in a set of siblings with severe developmental delay [...]

International Journal of Neonatal Screening

Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked disease and is the most comm... more Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked disease and is the most common pediatric-onset form of muscular dystrophy, affecting approximately 1:5000 live male births. DNA testing for mutations in the dystrophin gene confirms the diagnosis of this disorder. This study involves assessment of screening newborns for DMD using an immunoassay for muscle-type (MM) creatine kinase (CK) isoform—the GSP Neonatal CK-MM kit. Comparisons were made with CK activity determination by fluorescence measurement. In addition, the study evaluated the effect of gestational age, age of infant at time of sampling and how stable the CK-MM was over time. This assay discriminates well between normal, unaffected and Duchenne affected populations and is suitable for Duchenne newborn screening.

Annual Review of Genomics and Human Genetics

Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by gen... more Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by genetic disorders that could be treated if diagnosed in infancy, launched my six-decade career. This autobiographical article reflects on my childhood, early research, and professional experiences in pediatric genetics. My laboratory research focused on inborn errors of metabolism, including the glycogen storage diseases. My effort to organize newborn screening through the recommended uniform screening panel shaped and standardized newborn screening nationwide. Looking ahead, the expansion of whole-genome and whole-exome sequencing into newborn screening raises ethical and policy issues regarding informed consent procedures and the storage and use of residual blood spots.

Journal of Cellular and Comparative Physiology, Sep 30, 1965

... GORDON M. TOMKINS, LEONARD D. GARREN, R. RODNEY HOWELL,* AND BEVERLY PETERKOFSKY National Ins... more ... GORDON M. TOMKINS, LEONARD D. GARREN, R. RODNEY HOWELL,* AND BEVERLY PETERKOFSKY National Institutes of Health, National Institute of Arthritis and ... By contrast, the bulk of the mRNA is stable for much longer times in liver (Villa-Trevino et al., '64; Revel and ...

Seminars in Perinatology, Apr 1, 2010

Federal advisory committees (or commissions, councils, or task forces) are created either by cong... more Federal advisory committees (or commissions, councils, or task forces) are created either by congressional action or a federal department to bring together a variety of viewpoints on specific policy issues. The committees or advisory bodies are generally directed to advise various bodies within the government, either by congressional mandate, government decree, or executive order. The committees are often created to aid the government in subject matters with difficult issues. In the Department of Health and Human Services (HHS), current advisory committees range from advising the Secretary, Department of Health and Human Services, on immunization practices, to organ donation, blood safety, to issues related to newborn and child screening. This article describes the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. Its history offers insight into connection of the development of policy guidelines and the creation of legislation to implement that policy. Its current activities have affected and will continue to affect not only state newborn screening programs but also the policy and practice of screening children for heritable disorders. Semin Perinatol 34:121-124 Published by Elsevier Inc.

The New England Journal of Medicine, 1991

Molecular genetics and metabolism

Mental retardation and developmental disabilities research reviews, 2006

American journal of diseases of children (1960), 1980

A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated ... more A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated with tyrosinemia that was not corrected by the administration of ascorbic acid at 50 mg/day but that subsequently responded to ascorbic acid at 500 mg/day. Cerebrospinal fluid analysis for neurotransmitter metabolites showed elevated concentrations of homovanillic acid and 5-hydroxyindoleacetic acid when the child was symptomatic and normal concentrations after successful ascrobic acid therapy. These observations suggest that a high level of tyrosine in serum can affect the metabolism in the brain of dopamine and serotonin.

The Journal of biological chemistry, Jan 10, 1967

Ribosomes in rat liver are present either free or attached to endoplasmic reticulum and in both s... more Ribosomes in rat liver are present either free or attached to endoplasmic reticulum and in both states exist largely as polyribosomal aggregates. The present communication presents a quantitative study of the distribution of ribosomes between these two states and examines a number of properties of these two groups of ribosomes. It is shown that the base composition and the rate of synthesis of the ribosomal ribonucleic acid of free and membrane-bound ribosomes are the same, and these tindings, along with the results of previous studies of other properties, are consistent with the possibility that there are no intrinsic differences between the ribosomes found in these two states. Since certain conditions are known to produce alterations in the distribution of free and membrane-bound ribosomes which are rapid with respect to the turnover time of ribosomal RNA, it is further suggested that a given ribosome can exist in either state according to the needs of the cell. Although the administration of hydrocortisone in uivo induces acute rises in the levels of certain specific liver enzymes within a few hours, it has no marked effect upon the ratio of free to membrane-bound ribosomes during this period. The ribosomal aggregates obtained by the methods used here are shown to be sufficiently pure to permit the use of ultraviolet absorption as a direct measure of their concentration without applying a correction for ferritin absorption. Homogenization and zone centrifugation do not produce significant artifacts in the determination of the proportions of free and membrane-bound ribosomes. In a previous communication it was shown that the great majority of ribosomes in rat liver are attached to large membranous structures (1). Data were presented which showed that ribosomes in all fractions of liver homogenates are active in protein synthesis in tivo and in vitro, and it was further shown

Hybridoma, 1985

A sensitive and specific immunological assay for detection of human lysosomal alpha-glucosidase w... more A sensitive and specific immunological assay for detection of human lysosomal alpha-glucosidase was developed using a mouse monoclonal antibody incorporated into a biotin-avidin amplified ELISA. The immunoassay was more than 60 times more sensitive than the currently used enzymatic assay for alpha-glucosidase activity using a fluorimetric substrate. This methodology provides an alternative approach with increased sensitivity for screening individuals for alpha-glucosidase deficiency.

American family physician, 1995

Pediatrics, 2011

BACKGROUND: Although newborn screening for critical congenital heart disease (CCHD) was recommend... more BACKGROUND: Although newborn screening for critical congenital heart disease (CCHD) was recommended by the US Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and Children to promote early detection, it was deemed by the Secretary of the HHS as not ready for adoption pending an implementation plan from HHS agencies. OBJECTIVE: To develop strategies for the implementation of safe, effective, and efficient screening. METHODS: A work group was convened with members selected by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children, the American Academy of Pediatrics, the American College of Cardiology Foundation, and the American Heart Association. RESULTS: On the basis of published and unpublished data, the work group made recommendations for a standardized approach to screening and diagnostic follow-up. Key issues for future research and evaluation were identified. CONCLUSIONS: The work-group members found...

Journal of Venomous Animals and Toxins including Tropical Diseases, 2012

This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high le... more This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high level of acetylcholinesterase (AChE) activity. The enzyme showed optimum activity at alkaline pH (8.5) and 45°C. Krait venom AChE was inhibited by substrate. Inhibition was significantly reduced by using a high ionic strength buffer; low ionic strength buffer (10 mM PO 4 pH 7.5) inhibited the enzyme by 1. 5mM AcSCh, while high ionic strength buffer (62 mM PO 4 pH 7.5) inhibited it by 1 mM AcSCh. Venom acetylcholinesterase was also found to be thermally stable at 45°C; it only lost 5% of its activity after incubation at 45°C for 40 minutes. The Michaelis-Menten constant (Km) for acetylthiocholine iodide hydrolysis was found to be 0.068 mM. Krait venom acetylcholinesterase was also inhibited by ZnCl 2 , CdCl 2 , and HgCl 2 in a concentrationdependent manner. Due to the elevated levels of AChE with high catalytic activity and because it is more stable than any other sources, Bungarus sindanus venom is highly valuable for biochemical studies of this enzyme.

Journal of Clinical Investigation, 1962

Genetics in Medicine, 1999

Objective-To summarise a conference convened to examine how cystic fibrosis screening might appro... more Objective-To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. Methods-Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. Results-Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost eVectively by identifying racial/ethnic groups at suYcient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. Conclusions-Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis.

American journal of human genetics, 1981

We have defined a new autosomal recessive disorder in patients stemming from a small community in... more We have defined a new autosomal recessive disorder in patients stemming from a small community in northern Mexico. Diagnosable at birth, its major symptoms include brittle hair, mental retardation, and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy. Hair cystine content is reduced while the copper/zinc ratio in hair is increased.

Pediatrics, 1963

Studies on two siblings with histidinemia have shown that the enzymatic defect in this metabolic ... more Studies on two siblings with histidinemia have shown that the enzymatic defect in this metabolic disease is the absence of histidase. As a consequence, blood levels of histidine are greatly elevated, and histidine and imidazolepyruvic acid are excreted in the urine. Imidazolepyruvic acid in the urine of these patients gives a green color with ferric chloride, and the disease may be confused with phenylketonuria. Patients with histidinemia lack urocanic acid in the skin and sweat. Both siblings with histidinemia have speech defects but normal intelligence. The possible relationship between the defect in speech and the metabolic disease has been discussed. The mode of inheritance of this disease is not clearly established, but it may be a Mendelian recessive.

The Western journal of medicine, 1975

International Journal of Neonatal Screening

One of the most dramatic discoveries in metabolic disease research was that of Ashbørn Følling, w... more One of the most dramatic discoveries in metabolic disease research was that of Ashbørn Følling, who in 1934, published his research outlining unusual biochemical findings in a set of siblings with severe developmental delay [...]

International Journal of Neonatal Screening

Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked disease and is the most comm... more Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked disease and is the most common pediatric-onset form of muscular dystrophy, affecting approximately 1:5000 live male births. DNA testing for mutations in the dystrophin gene confirms the diagnosis of this disorder. This study involves assessment of screening newborns for DMD using an immunoassay for muscle-type (MM) creatine kinase (CK) isoform—the GSP Neonatal CK-MM kit. Comparisons were made with CK activity determination by fluorescence measurement. In addition, the study evaluated the effect of gestational age, age of infant at time of sampling and how stable the CK-MM was over time. This assay discriminates well between normal, unaffected and Duchenne affected populations and is suitable for Duchenne newborn screening.

Annual Review of Genomics and Human Genetics

Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by gen... more Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by genetic disorders that could be treated if diagnosed in infancy, launched my six-decade career. This autobiographical article reflects on my childhood, early research, and professional experiences in pediatric genetics. My laboratory research focused on inborn errors of metabolism, including the glycogen storage diseases. My effort to organize newborn screening through the recommended uniform screening panel shaped and standardized newborn screening nationwide. Looking ahead, the expansion of whole-genome and whole-exome sequencing into newborn screening raises ethical and policy issues regarding informed consent procedures and the storage and use of residual blood spots.

Journal of Cellular and Comparative Physiology, Sep 30, 1965

... GORDON M. TOMKINS, LEONARD D. GARREN, R. RODNEY HOWELL,* AND BEVERLY PETERKOFSKY National Ins... more ... GORDON M. TOMKINS, LEONARD D. GARREN, R. RODNEY HOWELL,* AND BEVERLY PETERKOFSKY National Institutes of Health, National Institute of Arthritis and ... By contrast, the bulk of the mRNA is stable for much longer times in liver (Villa-Trevino et al., '64; Revel and ...

Seminars in Perinatology, Apr 1, 2010

Federal advisory committees (or commissions, councils, or task forces) are created either by cong... more Federal advisory committees (or commissions, councils, or task forces) are created either by congressional action or a federal department to bring together a variety of viewpoints on specific policy issues. The committees or advisory bodies are generally directed to advise various bodies within the government, either by congressional mandate, government decree, or executive order. The committees are often created to aid the government in subject matters with difficult issues. In the Department of Health and Human Services (HHS), current advisory committees range from advising the Secretary, Department of Health and Human Services, on immunization practices, to organ donation, blood safety, to issues related to newborn and child screening. This article describes the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. Its history offers insight into connection of the development of policy guidelines and the creation of legislation to implement that policy. Its current activities have affected and will continue to affect not only state newborn screening programs but also the policy and practice of screening children for heritable disorders. Semin Perinatol 34:121-124 Published by Elsevier Inc.

The New England Journal of Medicine, 1991

Molecular genetics and metabolism

Mental retardation and developmental disabilities research reviews, 2006

American journal of diseases of children (1960), 1980

A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated ... more A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated with tyrosinemia that was not corrected by the administration of ascorbic acid at 50 mg/day but that subsequently responded to ascorbic acid at 500 mg/day. Cerebrospinal fluid analysis for neurotransmitter metabolites showed elevated concentrations of homovanillic acid and 5-hydroxyindoleacetic acid when the child was symptomatic and normal concentrations after successful ascrobic acid therapy. These observations suggest that a high level of tyrosine in serum can affect the metabolism in the brain of dopamine and serotonin.

The Journal of biological chemistry, Jan 10, 1967

Ribosomes in rat liver are present either free or attached to endoplasmic reticulum and in both s... more Ribosomes in rat liver are present either free or attached to endoplasmic reticulum and in both states exist largely as polyribosomal aggregates. The present communication presents a quantitative study of the distribution of ribosomes between these two states and examines a number of properties of these two groups of ribosomes. It is shown that the base composition and the rate of synthesis of the ribosomal ribonucleic acid of free and membrane-bound ribosomes are the same, and these tindings, along with the results of previous studies of other properties, are consistent with the possibility that there are no intrinsic differences between the ribosomes found in these two states. Since certain conditions are known to produce alterations in the distribution of free and membrane-bound ribosomes which are rapid with respect to the turnover time of ribosomal RNA, it is further suggested that a given ribosome can exist in either state according to the needs of the cell. Although the administration of hydrocortisone in uivo induces acute rises in the levels of certain specific liver enzymes within a few hours, it has no marked effect upon the ratio of free to membrane-bound ribosomes during this period. The ribosomal aggregates obtained by the methods used here are shown to be sufficiently pure to permit the use of ultraviolet absorption as a direct measure of their concentration without applying a correction for ferritin absorption. Homogenization and zone centrifugation do not produce significant artifacts in the determination of the proportions of free and membrane-bound ribosomes. In a previous communication it was shown that the great majority of ribosomes in rat liver are attached to large membranous structures (1). Data were presented which showed that ribosomes in all fractions of liver homogenates are active in protein synthesis in tivo and in vitro, and it was further shown

Hybridoma, 1985

A sensitive and specific immunological assay for detection of human lysosomal alpha-glucosidase w... more A sensitive and specific immunological assay for detection of human lysosomal alpha-glucosidase was developed using a mouse monoclonal antibody incorporated into a biotin-avidin amplified ELISA. The immunoassay was more than 60 times more sensitive than the currently used enzymatic assay for alpha-glucosidase activity using a fluorimetric substrate. This methodology provides an alternative approach with increased sensitivity for screening individuals for alpha-glucosidase deficiency.