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Biomedical subjects

L Johnson

Publications and source records attributed to L Johnson.

At least 91 records · Page 5Linked to original sources

A polyadenylylation-specific RNA-contact site on the surface of the bifunctional vaccinia virus RNA modifying protein VP39 that is distinct from the mRNA 5' end-binding "cleft".

VP39 is a bifunctional mRNA-modifying protein that acts as both an mRNA cap-specific 2'-O-methyltransferase and a processivity factor for VP55, the vaccinia poly(A) polymerase catalytic subunit. Although regions of the protein surface required for methyltransferase function are well defined, it has been unclear whether the protein polyadenylylation function requires direct RNA contact and, if so, where the contact site(s) might be located on the protein surface. Here, we show that the VP55-VP39 heterodimer forms a stable complex with a 50mer oligonucleotide bearing a U2-N25-U motif, as opposed to the U2-N15-U motif that is optimal for stable complex formation with VP55 alone. An oligonucleotide bearing a U2-N25-U motif in which the downstream U residue is replaced with 4thioU can be efficiently photocrosslinked to VP39, but only in the context of the VP55-VP39 heterodimer. By partial proteolysis of end-labeled VP39, the site of oligonucleotide photocrosslinking was localized to the region of VP39 between residues Lys90 and Arg122. Peptide microsequencing and confirmatory mutagenesis identified the side-chain of Arg107 as the photocrosslinking site. Substitution of this residue with lysine abolished photocrosslinking entirely, consistent with the established RNA binding role of arginine in other RNA-binding proteins. This study provides clear evidence for a polyadenylylation-specific RNA-contact site on the surface of VP39, which is distinct from the RNA-binding methyltransferase "cleft" characterized in recent crystallographic and biochemical studies.

Base Sequence↗

The early diagnosis project: a collaborative approach to risk management.

Diagnostic errors account for one-fifth of lawsuits against hospitals and physicians. Virtually all medical specialties are at risk for these lawsuits. To this point, risk managers have done little to assist physicians to reduce their risk of failure-to-diagnose (FTD) lawsuits. This article describes a collaborative effort to reduce FTD lawsuits in the primary care setting.

Breast Neoplasms↗

Are we getting the message out to all? Health information sources and ethnicity.

BACKGROUND: Over 80% of the excess deaths in minority and economically disadvantaged populations are from diseases with preventable or controllable contributing factors. However, mainstream health education targeting behavior change often fails to reach minority populations. OBJECTIVE: To identify the health and cancer information sources used by a multi-ethnic population and to determine whether information sources differ by ethnic group, age, gender, and socioeconomic status. METHODS: A multilingual, random-digit dial telephone survey of 2,462 Hispanic (Colombian, Dominican, Ecuadorian, and Puerto Rican) and black (Caribbean, Haitian, and U.S.-born) persons, aged 18-80 years, from a population-based quota sample, New York City, 1992. RESULTS: All ethnic and age groups cited a health professional as the most common source of health information (40% overall). The next most commonly cited sources overall were: television (21%), hospitals or doctor's offices (18%), books (17%), magazines (15%), brochures/pamphlets (11%), and radio (8%). Responses on sources of cancer information followed a similar pattern. Black subgroups were all significantly more likely than Hispanic subgroups to get their health information from a doctor or other health professional (p = 0.001). Use of the radio as a source of health information was highest among Haitians (20.8%) and Colombians (12.5%), and lowest among U.S.-born blacks (4.2%) (p = 0.001), but there was no difference in the use of television. Among immigrants, as the proportion of life spent in mainland U.S. rose, increasing percentages cited magazines (p = 0.001) and decreasing percentages cited radio (p = 0.025) as a health information source. Less educated persons and more recent immigrants were most likely to report inability to get health information (p = 0.001). CONCLUSIONS: Given the variation in sources of health and cancer information, identification of those most commonly used is important to health educators' and public health practitioners' efforts to target hard-to-reach ethnic minorities.

Adult↗

Diagnosis of pulmonary hypertension.

Pulmonary hypertension may complicate a variety of congenital or acquired cardiac and pulmonary conditions. This vascular disorder results from conditions that lead to a chronic increase in left atrial pressure, increased pulmonary blood flow, or increased pulmonary vascular resistance. Definitive diagnosis requires cardiac catheterization and detection of systolic and mean pulmonary artery pressures exceeding 30 and 20 mm Hg, respectively. Clinical signs and historical complaints reflect underlying cardiac or pulmonary conditions, although syncope may be a predominant finding. Radiographic changes are nonspecific; however, right ventricular enlargement and enlarged pulmonary arteries should increase suspicion for the disorder. Estimates of pulmonary arterial pressure may be obtained through Doppler echocardiography. This requires detection of a high-velocity regurgitant jet across the tricuspid or pulmonic valve. Further investigation is required to determine how pulmonary hypertension impacts therapy and prognosis for dogs and cats with cardiac and pulmonary diseases.

Animals↗

Effects of smoking on local delivery of controlled-release doxycycline as compared to scaling and root planing.

This paper examines the effects of smoking on the treatment outcomes of two nonsurgical therapies: (1) scaling and root planing alone (SRP) or (2) controlled-release of subgingivally delivered doxycycline hyclate in a polylactic acid based polymer gel. Subjects from 2 9-month multicenter studies were classified as nonsmokers (never smoked: 100 subjects), former smokers (137 subjects), and current smokers (> or = 10 cigarettes/day: 121 subjects). Clinical parameters were analyzed for treated sites with baseline probing depths > or = 5 mm and for a subset of treated sites with baseline probing depths of > or = 7 mm. Clinical parameters (plaque levels, clinical attachment levels, pocket depths, and bleeding on probing) were analyzed at baseline, 4, 6, and 9 months. In the doxycycline treated group in general, there were neither marked significant differences in clinical attachment gain nor differences in probing depth reduction among the 3 smoking groups. On the other hand, in the scaling and root planing treated group in general, there were significant differences in clinical attachment gain and pocket depth reduction, with non-smokers responding better than former smokers and current smokers at 6 and 9 months. These differences in clinical response between scaling and root planing alone versus controlled-release of locally-delivered doxycycline hyclate among these 3 smoking groups are discussed in relation to treatment implications for smokers.

Administration, Topical↗

The distribution and mortality impact of chronic energy deficiency among adult Nigerian men and women.

OBJECTIVE: To determine the prevalence of chronic energy deficiency (CED) and associated mortality risk in a cohort of adult Nigerians followed from 1992 to 1997. RESEARCH METHODS AND PROCEDURES: The data for this investigation were derived from an international collaborative study on chronic diseases in populations of the African diaspora. Body mass index (BMI) was used to define three grades of CED in 4061 men and women aged 25 years and older: Grade I (mild CED) as BMI 17.5-18.4, Grade II (moderate CED) as BMI 16.0-17.4, and Grade III (severe CED) as BMI < 16.0 and BMI > or = 18.5 was considered normal. The odds of mortality associated with differing grades of CED was estimated with logistic regression analysis. RESULTS: The prevalence of CED (BMI < 18.5) increased from 14.3% in 1992 to 19.6% in 1997, both genders combined. The prevalence of CED was similar for both sexes in 1992 (14%) but increased to 22.4% in men and 17.4% in women by 1997. The prevalence of CED was 8.5%, 7.6 and 3.4 for Grades I, II and III, respectively. Two hundred and seven deaths occurred during the follow-up period. The mortality rate for the 5.5 y of follow-up was 5.1% (207/4061). The odds ratios (95% CIs) for all cause mortality were 1.4 (0.5, 3.8), 2.4 (1.2, 4.9) and 2.5 (1.0, 6.2), respectively, for CED grades I, II and III adjusting for age and sex. CONCLUSION: Under nutrition is an increasing problem in Nigerian men and women. The economic reforms (structural adjustment program (SAP)) introduced in 1986 in combination with the continued economic woes brought on by political instability, corruption and nepotism have been advanced by several investigators as the main factors in the growing problem of inadequate calorie intake. Intervention strategies both at the government and private sectors are urgently needed to increase food availability.

Adult↗

Specialty care for patients with epilepsy must become standard of care. Promotion of Specialty Care for Epilepsy Group.

Epilepsy is a complex, common disorder with severe consequences for patients. The authors believe that a significant percentage of patients are receiving suboptimal care. The national standard of care needs to be upgraded to include the notion that patients with less than total seizure control or those suffering from any medication side-effects should be given the opportunity to receive specialty care by physicians with specific expertise in the field of epilepsy.

Epilepsy↗

A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome).

Mucopolysaccharidosis type III A (MPS III A, Sanfilippo syndrome) is a rare, autosomal recessive, lysosomal storage disease characterized by accumulation of heparan sulfate secondary to defective function of the lysosomal enzyme heparan N- sulfatase (sulfamidase). Here we describe a spontaneous mouse mutant that replicates many of the features found in MPS III A in children. Brain sections revealed neurons with distended lysosomes filled with membranous and floccular materials with some having a classical zebra body morphology. Storage materials were also present in lysosomes of cells of many other tissues, and these often stained positively with periodic-acid Schiff reagent. Affected mice usually died at 7-10 months of age exhibiting a distended bladder and hepatosplenomegaly. Heparan sulfate isolated from urine and brain had nonreducing end glucosamine- N -sulfate residues that were digested with recombinant human sulfamidase. Enzyme assays of liver and brain extracts revealed a dramatic reduction in sulfamidase activity. Other lysosomal hydrolases that degrade heparan sulfate or other glycans and glycosaminoglycans were either normal, or were somewhat increased in specific activity. The MPS III A mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.

Animals↗

A comparative morphological study of human germ cells in vitro or in situ within seminiferous tubules.

For many infertile couples, intracytoplasmic germ cell/spermatozoon injection into unfertilized eggs may be their only hope for producing their own biological children. Thus far, success with injection of pre-spermatozoan germ cells such as round spermatids has not been as great as that of spermatozoon injection. This could be due in part to the difficulty of identifying younger (less mature) male germ cells in testicular biopsy dispersions. To improve the identification of various types of live, dispersed, human testicular cells in vitro, a comparative study of the morphological characteristics of human spermatogenic germ cells in vitro or in situ within seminiferous tubules was conducted. Live human testicular tissue was obtained from an organ-donating, brain-dead person with a high density of various germ cells. A cell suspension was obtained by enzymatic digestion, and cells were cultured for 3 days in an excessive volume (100-fold medium:cells; v:v) of HEPES-TC 199 medium at 5 degrees C and observed live with Nomarski optics (interference-contrast microscopy). For comparative purposes, testes from ten men obtained at autopsy were fixed, embedded in epoxy resin, sectioned at 20 microm, and observed unstained by Nomarski optics. This approach allowed comparison of morphological characteristics of individual germ cells seen in vitro or in situ in the human testis. In both live and fixed preparations from control men with varied daily sperm production rates, Sertoli cells have oval to pear-shaped nuclei with indented nuclear envelopes and large nucleoli, which makes their appearance distinctly different from germ cells. The size, shape, and chromatin pattern of nuclei, and the presence of meiotic metaphase figures, acrosomic vesicles/structures, tails, and/or mitochondria in the middle piece of germ cells are characteristically seen in live cells in vitro and in those cells observed in the fixed seminiferous tubules. Hence, this comparative approach allows verification of the identity of individual germ cells seen in vitro and provides a checklist of distinguishing characteristics of live human germ cells, to be used by scientists and technical staff in infertility clinics when selecting specific germ cells from a testicular aspirate or enzymatically digested biopsy.

Adult↗

Use of intraosseous blood to assess blood chemistries and hemoglobin during cardiopulmonary resuscitation with drug infusions.

OBJECTIVE: To compare intraosseous with central venous blood samples for biochemical analyses and hemoglobin levels during cardiopulmonary resuscitation (CPR) and during cardiopulmonary resuscitation with infusion of sodium bicarbonate, epinephrine, and saline boluses through the intraosseous site. DESIGN: Prospective, complete repeated measures study. SETTING: An animal laboratory at a university medical center. SUBJECTS: Thirty-two piglets (mean weight, 30 [range, 24-35] kg). INTERVENTIONS: Animals were anesthetized, instrumented, and subjected to hypoxic cardiac arrest. An intraosseous cannula was inserted into the tibia, and animals were randomly assigned to one of five groups: heparinized saline (n = 6), epinephrine infusions only (n = 6), saline infusions only (n = 6), sodium bicarbonate infusions only (n = 8), and epinephrine, saline, and sodium bicarbonate infusions through the same site (n = 6). CPR (chest compressions and mechanical ventilation) was performed in all groups. Simultaneous blood samples were taken from the central venous and intraosseous sites before arrest and after 5 and 30 mins of CPR. MEASUREMENTS AND MAIN RESULTS: There were no differences (p < .05) in sodium, potassium, magnesium, lactate, and calcium values of intraosseous and central venous blood at the baseline and during 5 mins of CPR with infusions through the intraosseous cannula. At 30 mins, differences were apparent in magnesium, potassium, and sodium values between groups when the intraosseous cannula was used for infusions as well as sampling. Intraosseous potassium, glucose, and magnesium values were lower and sodium values were higher than central venous blood levels. No differences were seen at all sampling intervals if small-volume heparinized saline was given through the intraosseous site. Hemoglobin values were lower in the intraosseous group after 30 mins of CPR and infusions through the intraosseous site. After 30 mins of CPR, all hemoglobin values from the intraosseous site were <10 g/100 mL. CONCLUSION: Intraosseous and central venous blood biochemical and hemoglobin values were similar during hemodynamic stability and throughout 30 mins of resuscitation if no drugs were given through the intraosseous site. However, differences existed after 30 mins of CPR and infusions through the intraosseous site. Laboratory values may be erroneous when intraosseous blood is used during periods of resuscitation of >5 mins if drugs and fluid boluses have also been infused through the site. For reliable values, an intraosseous site for sampling only may be reasonable.

Animals↗

Acid-base status of blood from intraosseous and mixed venous sites during prolonged cardiopulmonary resuscitation and drug infusions.

OBJECTIVES: a) To determine the relationship of acid-base balance (pH, PCO2) of blood samples from the intraosseous and the mixed venous route during prolonged cardiopulmonary resuscitation; b) to compare the effect of separate infusions of epinephrine, fluid boluses, or sodium bicarbonate through the intraosseous sites on the acid-base status of intraosseous and mixed venous blood during cardiopulmonary resuscitation; and c) to compare pH and Pco2 of intraosseous and mixed venous blood samples after sequential infusions of fluid, epinephrine, and sodium bicarbonate through a single intraosseous site. DESIGN: Prospective, randomized study. SETTING: Animal laboratory at a university center. SUBJECTS: Thirty-two mixed-breed piglets (mean weight, 30 kg). INTERVENTIONS: Piglets were anesthetized and prepared for blood sampling and cardiopulmonary resuscitation. After anoxic cardiac arrest, ventilation was resumed and chest compression was resumed. Blood gas samples from the pulmonary artery and both intraosseous sites were obtained simultaneously at baseline, at cardiac arrest, and at 5, 10, 15, 20, and 30 mins of cardiopulmonary resuscitation for group 1 (control group) and after drug (epinephrine and sodium bicarbonate) and saline infusions via one of the intraosseous cannulas in groups 2 through 5. MEASUREMENTS AND MAIN RESULTS: We found no differences between intraosseous and mixed venous pH and Pco2 during periods of <15 mins of cardiopulmonary resuscitation. However, this relationship was not maintained during prolonged cardiopulmonary resuscitation and after bicarbonate infusion. After large volume saline infusion, the pH and Pco2 of mixed venous and intraosseous blood were similar. During epinephrine infusion, the relationship between intraosseous and mixed venous pH and Pco2 was similar to that found in the control group. CONCLUSIONS: The intraosseous blood sample could be used to assess central acid-base balance in the early stage of arrest and cardiopulmonary resuscitation of <15 mins. However, during cardiopulmonary resuscitation of longer duration, drug infusions may render the intraosseous site inappropriate for judging central acidosis.

Acid-Base Equilibrium↗

Influences on the inclusion of children in family therapy.

This study examined factors that influence family therapists to include children in or exclude them from therapy sessions. We hypothesized that therapist comfort, child problem type (internalizing vs. externalizing), family composition (one- vs. two-parent families), and presenting problem (child-oriented problem vs. adult-oriented problem) affect therapists' inclusion of children. A survey of clinical members of AAMFT found that half of the therapists excluded children on the basis of their comfort and that those who felt more comfortable were more likely to include children in sessions. Therapists included children more frequently in cases of an internalizing vs. an externalizing child, more with single-parent than two-parent families, and more often when the presenting problem focused on a child than on an adult. Implications of the findings are discussed.

Attitude of Health Personnel↗

The use of child-centered play therapy and filial therapy with Head Start families: a brief report.

Play therapy and filial therapy show promise as effective ways to provide direct services to Head Start, addressing the needs of the children, the families, and the Head Start teachers and staff. This paper examines the utility of play and filial therapies for the Head Start population, presents a systemic explanation for the benefit of filial therapy, and provides a case example for illustration.

Anxiety, Separation↗

Early hemodynamic changes during uncontrolled intra-abdominal bleeding.

Central hemodynamics was studied in 32 pigs during the first 10 min after making a 5-mm laceration in the infrarenal aorta. Blood flow probes were placed proximally and distally to the site of the bleeding and also over the portal vein and renal artery. We found that the bleeding, which was indicated by a difference in the rate of blood flow between the two aortic probes, stopped spontaneously after about 3 min. The short-term changes in blood flow rates closely followed simple monoexponential functions with mean half-times of 34 (proximal aorta), approximately 10 (lower aorta), 27 (splanchnic) and 21 s (kidney) to reach steady-state levels amounting to 20, 20, 27 and 8% of the baseline flow rates, respectively.

Adaptation, Physiological↗

Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns.

OBJECTIVE: To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week. METHODS: Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined. RESULTS: The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%). CONCLUSIONS: An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.

Bilirubin↗

Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis.

BACKGROUND: The clinical efficacy and safety of doxycycline hyclate (8.5% w/w) delivered subgingivally in a biodegradable polymer (DH) was compared to placebo control (VC), oral hygiene (OH), and scaling and root planing (SRP) in 2 multi-center studies. METHODS: Each study entered 411 patients who demonstrated moderate to severe periodontitis. Patients had 2 or more quadrants each with a minimum of 4 qualifying pockets > or =5 mm that bled on probing. At least 2 of the pockets were > or =7 mm. Treatment with DH, VC, OH, or SRP was provided at baseline and again at month 4. Clinical parameters were recorded monthly. RESULTS: DH and SRP resulted in nearly identical clinical changes over time in both studies. Mean 9 month clinical attachment level gain (ALG) was 0.8 mm for the DH group and 0.7 mm for the SRP group in Study 1, and 0.8 mm (DH) and 0.9 mm (SRP) in Study 2. Mean probing depth (PD) reduction was 1.1 mm for the DH group and 0.9 mm for the SRP group in Study 1 and 1.3 mm for both groups in Study 2. Frequency distributions showed an ALG > or =2 mm in 29% of DH sites versus 27% of SRP sites in Study 1 and 31% of DH sites versus 34% of SRP sites in Study 2. PD reductions > or =2 mm were seen in 32% of DH sites versus 31% of SRP sites in Study 1 and 41% of DH sites versus 43% of SRP sites in Study 2. Comparisons between DH, VC, and OH treatment groups showed DH treatment to be statistically superior to VC and OH. Safety data demonstrated a benign safety profile with use of the DH product. CONCLUSIONS: Results of this trial demonstrate that treatment of periodontitis with subgingivally delivered doxycycline in a biodegradable polymer is equally effective as scaling and root planing and superior in effect to placebo control and oral hygiene in reducing the clinical signs of adult periodontitis over a 9-month period. This represents positive changes resulting from the use of subgingivally applied doxycycline as scaling and root planing was not limited regarding time of the procedure or use of local anesthesia.

Absorbable Implants↗

Nutritive value of corn silage as affected by maturity and mechanical processing: a contemporary review.

Stage of maturity at harvest and mechanical processing affect the nutritive value of corn silage. The change in nutritive value of corn silage as maturity advances can be measured by animal digestion and macro in situ degradation studies among other methods. Predictive equations using climatic data, vitreousness of corn grain in corn silage, starch reactivity, gelatinization enthalpy, dry matter (DM) of corn grain in corn silage, and DM of corn silage can be used to estimate starch digestibility of corn silage. Whole plant corn silage can be mechanically processed either pre- or postensiling with a kernel processor mounted on a forage harvester, a recutter screen on a forage harvester, or a stationary roller mill. Mechanical processing of corn silage can improve ensiling characteristics, reduce DM losses during ensiling, and improve starch and fiber digestion as a result of fracturing the corn kernels and crushing and shearing the stover and cobs. Improvements in milk production have ranged from 0.2 to 2.0 kg/d when cows were fed mechanically processed corn silage. A consistent improvement in milk protein yield has also been observed when mechanically processed corn silage has been fed. With the advent of mechanical processors, alternative strategies are evident for corn silage management, such as a longer harvest window.

Animals↗