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Biomedical subjects

J A Martin

Publications and source records attributed to J A Martin.

At least 73 records · Page 4Linked to original sources

News & notes: paper digestion by the cellulolytic ruminal bacterium Fibrobacter succinogenes.

The objective of this study was to evaluate the ability of the predominant cellulolytic ruminal bacterium Fibrobacter succinogenes S85 to digest filter paper, office paper, newspaper, and magazine paper. When F. succinogenes S85 was incubated with all four paper sources, little digestion of any paper occurred between 0 and 48 h. However, digestion of filter paper increased from 12% at 48 h to 80% at 120 h. No significant digestion of office paper, newspaper, or magazine paper occurred between 48 and 120 h. These results suggest that F. succinogenes S85 is unable to digest office paper, newspaper, or magazine paper.

Animals↗

Annual summary of vital statistics-1997.

Many positive trends in the health of Americans continued into 1997. In 1997, the preliminary birth rate declined slightly to 14.6 births per 1000 population, and the fertility rate, births per 1000 women 15 to 44 years of age, was unchanged from the previous year (65.3). These indicators suggest that the downward trend in births observed since the early 1990s may have abated. Fertility rates for white, black, and Native American women were essentially unchanged between 1996 and 1997. Fertility among Hispanic women declined 2% in 1997 to 103.1, the lowest level reported since national data for this group have been available. For the sixth consecutive year, birth rates dropped for teens. Birth rates for women 30 years or older continued to increase. The proportion of births to unmarried women (32.4%) was unchanged in 1997. The trend toward earlier utilization of prenatal care continued for 1997; 82.5% of women began prenatal care in the first trimester. There was no change in the percentage with late (third trimester) or no care in 1997. The cesarean delivery rate rose slightly to 20.8% in 1997, a reversal of the downward trend observed since 1989. The percentage of low birth weight (LBW) infants rose again in 1997 to 7.5%. The percentage of very low birth weight was up only slightly to 1.41%. Among births to white mothers, LBW increased for the fifth consecutive year, to 6.5%, whereas the rate for black mothers remained unchanged at 13%. Much, but not all, of the rise in LBW for white mothers during the 1990s can be attributed to an increase in multiple births. In 1996, the multiple birth rate rose again by 5%, and the higher-order multiple birth rate climbed by 20%. Infant mortality reached an all time low level of 7.1 deaths per 1000 births, based on preliminary 1997 data. Both neonatal and postneonatal mortality rates declined. In 1996, 64% of all infant deaths occurred to the 7.4% of infants born at LBW. Infant mortality rates continue to be more than two times greater for black than for white infants. Among all the states in 1996, Maine, Massachusetts, and New Hampshire had the lowest infant mortality rates. Despite declines in infant mortality, the United States continues to rank poorly in international comparisons of infant mortality. Expectation of life at birth reached a new high in 1997 of 76.5 years for all gender and race groups combined. Age-adjusted death rates declined in 1997 for diseases of the heart, accidents and adverse affects (unintentional injuries), homicide, suicide, malignant neoplasms, cerebrovascular disease, chronic liver disease and cirrhosis, and diabetes. In 1997, mortality due to HIV infection declined by 47%. Death rates for children from all major causes declined again in 1997. Motor vehicle traffic injuries and firearm injuries were the two major causes of traumatic death. A large proportion of childhood deaths continue to occur as a result of preventable injuries.

Adolescent↗

The design, synthesis and properties of highly potent and selective inhibitors of herpes simplex virus types 1 and 2 thymidine kinase.

The rational design and synthesis of nucleotide analogues as inhibitors of herpes simplex virus (HSV) thymidine kinase is described. Starting from thymidine, product analogues which included phosphates, phosphonates, sulphonates, sulphonamides and carboxamides were prepared. The carboxamide series showed good structure-activity relationships and afforded a lead structure which inhibited the HSV-2 enzyme in the low micromolar range. Replacing the 5-methyl group in thymidine by ethyl enhanced the potency of the lead structure 10-fold. Further optimization of the carboxamide moiety afforded inhibitors active in the sub-nanomolar range and finally the introduction of a 2'-beta-fluoro substituent improved the potency a further twofold. The low water solubility of the most potent inhibitor was overcome by conversion to the 3'-valyl ester, which had good oral bioavailability and showed activity by the oral route in murine models of infection.

Animals↗

Births and deaths: United States, 1996.

OBJECTIVES: This report presents preliminary data on births and deaths in the United States from the National Center for Health Statistics for 1996. U.S. data are shown by age, race, and Hispanic origin. National and State data on births by marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include life expectancy, leading causes of death, and infant mortality. METHODS: This report, the third in a new statistical series, presents preliminary data for 1996 on births and deaths based on a substantial sample of vital records. The records are weighted to independent control counts of births, infant deaths, and total deaths received in State vital statistics offices during calendar year 1996. RESULTS: According to preliminary data for 1996, the birth rate for teenagers dropped 4 percent in 1996 to 54.7 births per 1,000 women aged 15-19 years. The teen birth rate has declined 12 percent since 1991 (62.1), with larger reductions for young teenagers 15-17 years and for black teenagers. Birth rates for women aged 20-34 years increased 1-2 percent, while rates for women aged 35-44 years rose 3 percent. The number and percent of births to unmarried women increased about 1 percent, while the birth rate for unmarried women declined 1 percent. The rate of prenatal care utilization improved and the cesarean delivery rate declined. The overall low birthweight rate increased to 7.4 percent. The 1996 preliminary infant mortality rate reached a record low of 7.2 infant deaths per 1,000 live births with all-time lows for white and black infants. Life expectancy reached a record high of 76.1 years with all-time highs for white and black males and black females. The largest declines in age-adjusted death rates among the leading causes of death were for Human immunodeficiency virus (HIV) (26 percent) and Homicide (11 percent), which dropped from the 12th to the 14th leading cause of death.

Adolescent↗

"De novo" duplication Xq23-->Xq26 of paternal origin in a girl with a mildly affected phenotype.

We report a de novo dup(X)(q23-->q26) in a 3-year-old girl with growth retardation, developmental delay, and minor anomalies. X-inactivation in lymphocytes by BRDU labeling showed the abnormal X was late replicating. The androgen receptor assay (HAR) demonstrated a skewed methylation (88.8%) of the paternal allele and a 11.2% methylation of the maternal allele. These data, which suggest the duplication was paternally inherited, are the first parental-origin identification of a duplication Xq. The mild phenotype of the patient may be related to the size and region of the duplication, the low percentage of a dup(X) active detected by the HAR assay, or a combination of these mechanisms.

Alleles↗

Age-related decline in chondrocyte response to insulin-like growth factor-I: the role of growth factor binding proteins.

The synthetic activity of chondrocytes in articular cartilage declines with age, possibly as a result of decreased sensitivity to anabolic growth factors such as insulin-like growth factor-I. The sensitivity of these cells to insulin-like growth factor-I is regulated, in part, by the synthesis of insulin-like growth factor-I binding proteins. We hypothesized that, as cartilage ages, an increase in the expression of these binding proteins suppresses the synthetic response of chondrocytes to insulin-like growth factor-I. To test this hypothesis, we measured proteoglycan synthesis (incorporation of [35S]sulfate per cell) in alginate cultures of chondrocytes from the articular cartilage of 1, 3, 12, and 24-month-old rats. A dose-response to insulin-like growth factor-I was determined for cells from each age group; incorporation of [35S]sulfate per cell declined with age, regardless of the dose. The sharpest decline was found between cells from the 1 and 3-month-old groups. Using the Western ligand blot technique, we then compared the expression of insulin-like growth factor-I binding protein in chondrocytes from the 1 and 3-month-old rats and found that it was increased in the cells from the older animals. Recombinant insulin-like growth factor-3, when added to the cell cultures of the 1-month-old rats, inhibited incorporation of [35S]sulfate and blocked responses to insulin-like growth factor-I. These findings suggest that the age-related decline in the synthetic response of chondrocytes to insulin-like growth factor-I results, at least in part, from increased expression of insulin-like growth factor binding protein.

Aging↗

Objective structured assessment of technical skill (OSATS) for surgical residents.

BACKGROUND: The technical skill of surgical trainees is not well assessed. This study aimed (1) to compare the reliability of three scoring systems, (2) to compare live and bench formats and (3) to assess construct validity of a test of operative skill. METHODS: Parallel examinations of operative skill, one using live animals and one using simulations, were developed. Performance was graded using operation-specific checklists, detailed global rating forms and pass/fail judgements. Twenty surgical residents each took both formats. RESULTS: Disattenuated correlations between live and bench scores were high (0.69-0.72). Mean interrater reliability across stations ranged from 0.64 to 0.72. Internal consistency was moderate to high (alpha: 0.61-0.74) for the live format using the checklist and for live and bench formats using global ratings. Global ratings discriminated between resident levels for both formats (bench: F(2,17) = 4.45, P < 0.05; live: F(2,17) = 3.55, P < 0.05), checklists did not. CONCLUSION: This preliminary study suggests that the Objective Structured Assessment of Technical Skill can reliably and validly assess surgical skills. Global ratings are a better method of assessment than task-specific checklists. Bench model simulation gives equivalent results to use of live animals for this test format.

Clinical Competence↗

De novo der(X)t(X;10)(q26;q21) with features of distal trisomy 10q: case report of paternal origin identified by late replication with BrdU and the human androgen receptor assay (HAR).

We describe an 11 year old girl with a de novo unbalanced t(X;10) that resulted in a deletion of Xq26-->Xqter and a trisomy of 10q21-->10qter. Her clinical features were of distal trisomy 10q, but she lacked the cardiovascular and renal malformations observed in duplications of 10q24-->10qter and had only moderate mental retardation. X inactivation was assessed on peripheral blood lymphocytes by late replication with BrdU (LR) and the human androgen receptor assay (HAR). By LR the der(X) was inactive without spreading to 10q21-->10qter in all cells. The HAR assay showed skewed methylation of the paternal allele (90%). The correlation of HAR and LR suggests that the der(X) was paternally inherited and is consistent with data from other de novo balanced and unbalanced X;autosome translocations detected in females. This is the first report of parental origin of a de novo trisomy 10q.

Abnormalities, Multiple↗

Annual summary of vital statistics--1996.

Several recent trends in the vital statistics of the United States continued in 1996, including an increase in life expectancy and declines in infant mortality, births to teenage mothers, age-adjusted death rates, and death rates for children and adolescents. In 1996, there were an estimated 3 914 953 births in the United States. The preliminary birth rate remained unchanged at 14.8 births per 1000 population, and the fertility rate, births per 1000 women 15 to 44 years of age, was essentially the same at 65.7. Fertility rates rose slightly for most racial and ethnic groups except black women, for whom the rate hit a historic low of 70.8. Overall, fertility remains particularly high for Hispanic women, although there is considerable variation within this heterogenous group. For the fifth consecutive year, birth rates dropped for teenagers. Birth rates for women >/=30 years of age continued to increase. The birth rate for unmarried women declined 1% in 1996 to 44.6 births per 1000 unmarried women, continuing the decline noted in 1995 for the first time in 2 decades. The percentage of women who began prenatal care in the first trimester rose in 1996 to 81.8%, whereas the percentage with late (third trimester) or no care dropped to 4.1%. The rise in timely prenatal care was greatest for black and Hispanic women. The percentage of low birth weight (LBW) infants reached 7.4% in 1996, its highest level since 1975. The very low birth weight rate remained unchanged at 1.4%. The rise in LBW occurred primarily among white women, whereas the LBW rate for black women dropped to 13.0%, the lowest rate reported since 1987. The rise among white women is only partially a result of increases in multiple births, because LBW rates have also risen among white singleton births. The multiple birth ratio rose again in 1996 by 2%, as it has since 1980. The rise was particularly large for higher-order multiple births. Infant mortality reached an all time low level of 7.2 deaths per 1000 births, based on preliminary 1996 data. Neonatal and postneonatal rates declined, as did rates for both black and white infants. National birth weight specific mortality rates are reported here for the first time. In 1995, 63% of infant deaths occurred to the 7.3% of the population that was born LBW. The four leading cause of infant death were congenital anomalies, disorders relating to short gestation and unspecified birth weight, sudden infant death syndrome, and respiratory distress syndrome, accounting for more than half of infant deaths in 1996. Despite the declines in infant mortality, the United States continues to rank poorly in international comparisons of infant mortality. Expectation of life at birth reached a new high in 1996 of 76.1 years for all gender and race groups combined. Age-adjusted mortality rates declined in 1996 for diseases of the heart, malignant neoplasms, cerebrovascular diseases, accidents and adverse effects, chronic liver disease and cirrhosis, and suicide. They rose, as in the past several years, for chronic obstructive pulmonary diseases, diabetes mellitus, and pneumonia and influenza. For the first time since human immunodeficiency virus infection was created as a special cause-of-death category in 1987, death rates for human immunodeficiency virus infection declined from 15.6 in 1995 to 11.6 in 1996. The homicide rate also declined, as it has since 1991. Death rates for children between 1 and 19 years of age declined in 1996, with an estimated 29 183 deaths to children. Unintentional injury mortality has dropped by approximately 50% among children and adolescents since 1979, although it remains the leading cause of death for all age groups of children from 1 to 19 years. Homicide was the fourth leading cause of death for children 1 to 4 and 5 to 9 years of age, the third leading cause for children 10 to 14, and the second leading cause for 15 to 19 year olds.

Adolescent↗

Triplet births: trends and outcomes, 1971-94.

OBJECTIVES: This report describes changes in the number and ratio of live births in triplet and other higher order multiple deliveries from 1971 to 1994 by maternal race, age, education, and marital status. The report also examines the birth outcomes of triplets compared with singletons, including overall gestation specific, and birthweight specific infant mortality rates. METHODS: Birth data are obtained from the U.S. certificates of live birth. Mortality data were obtained from the Linked Birth and Infant Death Data Sets for the 1983-91 birth cohorts. Most analyses are based on triplet and other higher-order multiple births (quadruplet and quintuplet and greater births) in the aggregate. (Triplet births comprise about 92 percent of all higher order multiple births.) Triplet and other higher order birth ratios for most variables are computed by combining data for years 1982-84 and 1992-94, and for infant mortality by combining birth cohorts for years 1987-91. FINDINGS: Between 1971 and 1994 the number and ratio of triplet births quadrupled, rising from 1,034 to 4,594, and from 29.1 to 116.2 per 100,000 live births. Most of the increase was among births to white mothers, particularly among married and more educated mothers. Only about one-third of the increase in triplet birthing among white mothers between 1989 and 1994 could be attributed to changes in the maternal age distribution. Massachusetts reported the highest triplet birth ratio (215.9), more than twice the U.S. ratio (105.5). Other States with comparatively high ratios were New Hampshire, New Jersey, and Iowa. Nine of 10 triplets were born preterm compared with 1 of 10 singletons. The average triplet weighed 1,698 grams at birth, one-half that of the average singleton (3,358 grams). Triplets were about 12 times more likely to die during the first year of life as singletons, but had a survival advantage over singletons at lower gestations and birthweights.

Adult↗

Three-dimensional structure of the alpha-conotoxin GI at 1.2 A resolution.

Predatory marine snails of the genus Conus paralyze their fish prey by injecting a potent toxin. The alpha-conotoxin GI is a 13-residue peptide isolated from venom of Conus geographus. It functions by blocking the postsynaptic nicotinic acetylcholine receptor. After crystallization in deionized water, the three-dimensional structure of the GI neurotoxin was determined to 1.2 A resolution by X-ray crystallography. This structure, which can be described as a triangular slab, shows overall similarities to those derived by NMR, CD, and predictive methods. The principal framework of the molecule is provided by two disulfide bonds, one linking Cys 2 and Cys 7 and the other Cys 3 and Cys 13. Opposite ends of the sequence are drawn together even further by hydrogen bonds between Glu 1 and Cys 13 and between Cys 2 and Ser 12. Since the C-terminus is amidated, only one negative charge is present (carboxylate of Glu 1), and this is not implicated in receptor binding. Two positively charged regions (the alpha-amino group of Glu 1 and the guanido group of Arg 9) are situated 15 A apart at the corners of the triangular face of the molecule. phi, psi angles characteristic of a 3(10) helix were observed for residues 5-7. For residues 8-11, these angles were consistent with either a type I beta-turn or a distorted 3(10) helix.

Amino Acid Sequence↗

Convergence of Lewy bodies and neurofibrillary tangles in amygdala neurons of Alzheimer's disease and Lewy body disorders.

Amygdalae of patients with Alzheimer's disease (AD), Parkinson's disease, Down's syndrome, diffuse Lewy body disease or a combination of these diseases were probed with antibodies to neurofilament proteins as well as with Lewy body (LB)- and paired helical filament-specific antibodies. The results indicate that the amygdala is severely affected by the accumulation of both neurofibrillary tangles (NFTs) and LBs in most cases of the diseases mentioned above, and that amygdala LBs have a similar epitope composition to that of LBs in the brain stem and cerebral cortex. While large numbers of both LBs and NFTs were seen in different neurons within the amygdala, these two lesions frequently occurred together in the same neurons of the amygdala. These findings are in contrast to other sites that accumulate LBs and NFTs, but rarely both lesions in the same neuron. Thus, amygdala neurons may be selectively vulnerable to developing both LBs and NFTs, and these inclusions may play a role in the massive degeneration of these neurons in AD and LB disorders of the elderly.

Aged↗

Who should rate candidates in an objective structured clinical examination?

PURPOSE: To determine who is the better rater of history taking in an objective structured clinical examination (OSCE): a physician or a standardized patient (SP). METHOD: During the 1991 pilot administration of an OSCE for the Medical Council of Canada's qualifying examination, five history-taking stations were videotaped. Candidates at these stations were scored by three raters: a physician (MD), an SP observer (SPO), and an SP rating from recall (SPR). To determine the validity of each rater's scores, these scores were compared with a "gold standard", which was the average of videotape ratings by three physicians, each scoring independently. Analysis included both correlations with the standard and a repeated-measures analysis of variance (ANOVA) comparing raters' mean scores on each station with mean scores of the gold standard. RESULTS: Ninety-one videotapes were scored by the "gold-standard" physicians. Correlations with the standard showed no clear preference for MD, SPO, or SPR raters. ANOVAs revealed significant differences from the standard on three stations for the SPR, two stations for the SPO, and one stations for the MD. CONCLUSIONS: An MD rater is less likely to differ from a standard established by a consensus of MD ratings than are SP raters rating from recall. If an MD cannot be used, an SP observer is preferable to an SP rating from recall.

Analysis of Variance↗

Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer's disease PHFtau.

Neurofibrillary tangle (NFT)-rich brain samples from patients with progressive supranuclear palsy (PSP) or Alzheimer's disease (AD) were probed with a large panel of anti-tau antibodies to compare the species of tau present in PSP and AD NFTs by immunohistochemistry and Western blot methods. These antibodies have been shown to recognize phosphate-independent or -dependent epitopes that extend from the amino to the carboxy terminal domains of normal brain tau and the abnormal tau in the paired helical filaments (PHFs) of AD NFTs (PHFtau). The immunohistochemical studies showed that all of the tau epitopes detected in brainstem PSP NFTs also were found in hippocampal AD NFTs and vice versa. While Western blots demonstrated 2 PHFtau-like immunobands in PSP brainstem, a triplet of PHFtau proteins were seen in the AD and PSP hippocampus. Despite differences in the distribution, ultrastructure and immunoblot profile of NFTs in PSP and AD, the same constellation of tau epitopes is present in the abnormal tau proteins in PSP and AD NFTs. Thus, the generation of abnormal tau proteins in PSP (PSPtau) and AD (PHFtau) may have similar adverse biological consequences in both diseases.

Aged↗