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Biomedical subjects

L K Johnson

Publications and source records attributed to L K Johnson.

At least 37 records · Page 2Linked to original sources

Aging of a class of arteries in various mammalian species in relation to the life span.

Age-related sclerosis of human renocortical arteries is associated with essential hypertension and limitation of the life span by cardiovascular mortality. Arteries in the kidneys of nonprimate species, examined here, showed near absence of arteriosclerosis when the average life span was less than 12 years and small amounts of sclerosis in longer-lived species. The fastest progression of arteriosclerosis was, paradoxically, in the longest-lived species, the human and the macaque. Results are incompatible with theories of aging that include arteriosclerosis within the framework of mechanisms that are proposed to explain the life spans of species.

Adolescent↗

Amelioration of effects of severe dietary copper deficiency by food restriction in rats.

To test the effect of food restriction on responses to dietary copper deficiency, male weanling rats were fed two amounts of dietary copper via five dietary-intake regimens ranging from ad libitum to 70% of ad libitum intake. Copper-deficient rats exhibited characteristic signs, including depressed organ copper content, reduced activity of copper-dependent enzymes, enlarged hearts, and anemia. Food restriction attenuated the cardiac enlargement, red blood cell defects, and reduction of superoxide dismutase activity in copper-deficient rats. Mineral and enzyme assays suggested that possible mechanisms for this amelioration are the correction of copper status and/or the improvement of antioxidant status. Also, food restriction depressed serum cholesterol and enhanced cytochrome c oxidase activity in both copper-adequate and copper-deficient rats, which compensated for effects of copper deficiency. A second experiment illustrated that the mortality associated with severe copper deficiency was also inhibited by food restriction.

Animals↗

Parasitic meningoencephalitis in nurse sharks (Ginglymostoma cirratum).

Based on microscopic examination of the brains of seven wild-caught nurse sharks (Ginglymostoma cirratum), we observed a severe meningoencephalitis associated with numerous parasitic granulomas. The parasites were larval nematodes with morphological characteristics of the Superfamily Dracunculoidea. Although meningeal larval aggregates were associated with chronic inflammation, additional parasitic nodules found on the endocardial surface and perimandibular region did not provoke an inflammatory response. Neither the route of infection nor life cycle were determined.

Animals↗

Detection of ovine lentivirus in seronegative sheep by in situ hybridization, PCR, and cocultivation with susceptible cells.

Serological surveys for ovine lentivirus (OvLV), a worldwide cause of pneumonia and chronic debilitation in sheep, have demonstrated a wide range of seroprevalence rates. This study analyzed OvLV infection in a purebred sheep flock with a history of OvLV disease (flock 1), and compared the prevalence with that of a flock lacking previous OvLV-associated disease (flock 2). Serological tests (ELISA and Western blot assay) indicated that 25% of sheep of all ages in flock 1 (Group A) and 33% of animals of all ages in flock 2 (Group B) had antibodies to OvLV. In situ hybridization, however, detected viral RNA in a much larger proportion of sheep (72 and 67%, respectively). Animals less than 1 year of age rarely had antibodies to OvLV, although most harbored viral RNA. Twenty animals in this age group from flock 1 (Group C) were therefore studied more closely for infection. These yearling animals were tested serologically by ELISA and their peripheral blood-derived macrophages were cultured for 14 days to amplify any infection in these target cells. The macrophages were then tested by in situ hybridization, PCR, and cocultivation with susceptible target cells. The results of these tests showed that while only 10% of animals in Group C were seropositive, 70% were positive by in situ hybridization, PCR, and cocultivation. These data suggest that latent OvLV infection is common in sheep and that infection is frequently undetected by serological tests.

Age Factors↗

Dietary protein, as egg albumen: effects on bone composition, zinc bioavailability and zinc requirements of rats, assessed by a modified broken-line model.

The effect of dietary protein concentration on zinc bioavailability, requirements and incorporation into bones was investigated in growing rats. Zinc requirements were determined by the broken-line method. Protein did not affect either absorption or biological half-life of 65Zn added to the diet. Zinc requirements based on weight gain or tibia zinc were generally greater when rats were fed 30% rather than 15% egg white. When fed 30% rather than 15% egg white, zinc-deficient rats gained less weight and tended to incorporate less zinc into bone, whereas zinc-adequate rats gained weight similarly and incorporated more zinc into bone. Dietary protein concentration apparently elevated the maximum amount of zinc incorporated into bones of rats fed adequate zinc. When dietary zinc was adequate (25 mg/kg diet), tibia zinc concentrations increased linearly with dietary concentrations of 15, 25, 35 and 45% egg white. When dietary zinc was adequate, higher protein diets resulted in lower tibia nitrogen, and higher tibia zinc, without substantial changes in tibia size or calcium concentration. These results indicate that high protein diets increase zinc requirements and bone zinc deposition, the latter being a consequence of altered bone zinc metabolism, rather than improved zinc bioavailability.

Administration, Oral↗

Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial.

A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described. Eighteen patients with rheumatoid arthritis, who acted as their own controls, were brought to a minimum symptom state through conventional means, trained, and allowed to control subsequent flares by a patient-initiated, flare-response prednisone regimen. The six-month trial was double-blind with a crossover at midpoint. While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies, the patients averaged additional 57% and 75% reductions from baseline in tender joint count and total pain score, respectively, on the prednisone therapy. The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated. The adverse events were no more frequent with prednisone than with placebo use. The efficacy of prednisone was increased threefold while reducing consumption by 40% when compared to the predecessor 5-mg prednisone/day clinical trial.

Adult↗

Short- and long-term variability of selected indices related to nutritional status. II. Vitamins, lipids, and protein indices.

Five free-living women (ages 23-38 years) who consumed a self-selected diet and five women (ages 23-44 years) residing in a metabolic unit who were fed constant diet were assessed for variation in vitamin and general chemistry indices. Blood was drawn from these women once a month for five months, once a week for five weeks, and once a day for five days to assess analytical and biological variability of the indices. Analytical variability was determined by concurrently analyzing control samples prepared from plasma and serum pools. All samples were analyzed in duplicate. Of the measured indices, vitamins and lipids seemed to be the most variable. Diet had a significant effect only on ascorbic acid. We were unable to show any seasonal change for these analytes. Estimations of analytical variability, along with estimates of biological variability, and knowledge of dietary practices are essential when interpreting differences in analytes.

Adult↗

Adolescent pregnancy: maternal weight effects on fetal heaviness: possible route to improved outcomes.

In a previous report of a zinc supplementation trial in pregnant adolescents zinc effect varied according to maternal weight (wt) status--normal (90-110% of expected wt), light or heavy, prompting this analysis of effects of wt status and gestational wt gain on fetal heaviness relative to length and gestational age (GA) and other pregnancy outcomes. One-third of adolescents shifted in or out of normal wt by delivery, creating seven outcome groups--light-light, light to normal, normal to light, normal-normal, normal to heavy, heavy to normal, and heavy-heavy. These wt class change groups varied significantly as to intrauterine growth (SGA, low AGA, high AGA, and LGA); by weekly grams gain per cm height (ht), birth wt, infant wt/length ratio, and occurrence of low birth wt (LBW). Infants with above average intrauterine growth had an advantage in: absolute size, length of hospital stay, rates of LBW, fetal demise, rates of low Apgar score, and "other" complications. This association between intrauterine growth and maternal wt class change suggests that promotion of wt gain might lower rates of LBW. Birthwt varied by quartiles of weekly wt change (gm) per cm ht in women grouped by their percent of expected wt: in the lowest quartile (Q1) only one group in seven reached average Bwt (3025 grams); with Q4 gain all groups did. Thus, the parameter wt gain/wk/cm ht deserves study as a tool for monitoring wt status and gain to identify those pregnant adolescents in greatest need for nutritional counseling and to set wt gain goals.

Adolescent↗

Insertion of Tn916 into Bacillus pumilus plasmid pMGD302 and evidence for plasmid transfer by conjugation.

As part of an effort to develop systems for genetic analysis of strains of Bacillus pumilus which are being used as a microbial hay preservative, we introduced the conjugative Enterococcus faecalis transposon Tn916 into B. pumilus ATCC 1 and two naturally occurring hay isolates of B. pumilus. B. pumilus transconjugants resistant to tetracycline were detected at a frequency of approximately 6.5 x 10(-7) per recipient after filter mating with E. faecalis CG110. Southern hybridization confirmed the insertion of Tn916 into several different sites in the B. pumilus chromosome. Transfer of Tn916 also was observed between strains of B. pumilus in filter matings, and one donor strain transferred tetracycline resistance to recipients in broth matings at high frequency (up to 3.4 x 10(-5) per recipient). Transfer from this donor strain in broth matings was DNase-resistant and was not mediated by culture filtrates. Transconjugants from these broth matings contained derivatives of a cryptic plasmid (pMGD302, approx 60 kb) from the donor strain with Tn916 inserted at various sites. The plasmids containing Tn916 insertions transferred to a B. pumilus recipient strain at frequencies of approx 5 x 10(-6) per recipient. This evidence suggests that pMGD302 can transfer by a process resembling conjugation between strains of B. pumilus.

Bacillus↗

The effects of changes in health care delivery on the reported incidence of cutaneous melanoma in western Washington State.

The reported incidence of malignant melanoma of the skin has steadily increased in the United States during the past three decades. Since the treatment of melanoma increasingly has been provided solely on an outpatient basis in recent years, it is likely that some cases of this disease are being missed by population-based tumor registries that do not consistently ascertain cases from sources outside the hospital setting. The population-based tumor registry of western Washington state has been identifying office-treated cases of cutaneous melanoma from records of private and hospital pathology laboratories. However, since laboratory records have often lacked information on place of residence, these cases have not been previously included in the calculation of incidence rates. In the present study, by determining the place of residence of these cases at the time of their diagnosis (by contacting the physician listed on their pathology reports), the authors found that there had been a growing amount of underreporting of cutaneous melanoma from 1974 through 1984. In western Washington state, the incidence of melanoma of the skin had been underestimated in registry rates by approximately 2% in 1974 and approximately 21% in 1984. This trend in the level of underenumeration has spuriously blunted the true increasing incidence of melanoma and may limit the ability to monitor and study this disease in the future.

Delivery of Health Care↗

Localization and evolution of two human phospholipase A2 genes and two related genetic elements.

Mammals are now known to contain at least two distinct classes of phospholipases A2, the progenitors of which can be seen in the venoms of snakes. Mammalian "Type I" PLA2, synthesized primarily by the pancreas, is also present in smaller amounts in other tissues including lung, spleen, and kidney. Recently, a mammalian "Type II" PLA2 has been sequenced, and shown to occur in platelets, synovial cells and fluid, cells of inflammatory peritoneal exudate, liver, intestine, kidney, and placenta. This form, referred to here as Type IIA PLA2, could play a key role in arachidonate release in both normal and pathologic inflammation. The genes encoding both forms have also been recently cloned. Here, the sites of synthesis and respective roles of the two known enzymes are discussed, along with an analysis of the evolutionary conservation of Type IIA PLA2 gene sequence. In addition, two related genetic elements containing sequences homologous to a portion of Type II PLA2 are described, which map to the same chromosome as the Type IIA PLA2 gene (chromosome 1). Either or both of these could also encode a portion of additional mammalian PLA2s.

Amino Acid Sequence↗

Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid.

Synovial fluid from arthritic patients contains multiple forms of phospholipase A2 (PLA2), as resolved by high performance liquid chromatography (Seilhamer, J.J., Plant, S., Pruzanski, W., Schilling, J., Stefanski, E., Vadas, P., and Johnson, L. K. (1989) J. Biochem. (Tokyo), submitted for publication). Here we describe the cloning of a human 4.5-kilobase gene and 800-base pair cDNA encoding the form representing the major peak of activity and protein mass (peak A). The clones encode a mature peptide of 124 amino acids, which follows a prepeptide of 20 residues. The deduced amino acid sequence constitutes an enzyme of the "Type II" class of PLA2s, and resembles PLA2s from other mammalian sources. This represents the first report of a full length mammalian non-pancreatic PLA2 sequence. Active transcription of this PLA2 gene was detected in two different inflammatory cell sources. Recombinant human peak A PLA2 was expressed in vaccinia as a secreted protein which accumulated in conditioned medium.

Amino Acid Sequence↗

Novel gene exon homologous to pancreatic phospholipase A2: sequence and chromosomal mapping of both human genes.

We described previously the cloning and DNA sequence of the human gene encoding pancreatic phospholipase A2 [DNA 5, 519]. When pancreatic phospholipase A2 (PLA2) cDNA was used to screen a human genomic library, two classes of clones were obtained. One class encoded the pancreatic enzyme, and a second class encoded one exon of an apparently related PLA2. No additional PLA2 gene exons displayed sufficient homology to be detected by the probe. A homologous sequence in both rat and porcine genomic DNA was detected by DNA blot hybridization, and the corresponding gene fragments were cloned and sequenced. Within the deduced amino acid sequences, the presence of known functional residues along with the high degree of interspecies conservation suggests the genes encode a functional PLA2 enzyme form. The encoded sequence lacks Cys11, as do the "type II" viperid venom and other nonpancreatic mammalian PLA2 enzymes. The sequence is distinct from porcine intestinal PLA2 and appears not to be a direct homolog of the recently published rabbit ascites and rat platelet enzymes. Hybridization of DNA probes containing sequences from these genes to genomic DNA blots of mouse/human somatic cell hybrids permitted chromosomal assignment for both. The pancreatic gene mapped to human chromosome 12, and the homologous gene mapped to chromosome 1.

Animals↗

Adolescent pregnancy: associations among body weight, zinc nutriture, and pregnancy outcome.

In a double-blind zinc trial in low-income, pregnant adolescents thought to be at risk for poor zinc nutriture, subjects were randomly assigned to receive 30 mg zinc (gluconate) or placebo. Response to zinc was related to maternal weight. Infants of normal-weight mothers given zinc had reduced rates of prematurity (p = 0.05) and assisted respiration (p = 0.006). Underweight multiparas given zinc had longer gestational lengths (p = 0.008) than did subjects given the placebo. Multiple stepwise regression analysis, used to identify predictors of infant size, revealed that 14-26% more variance was accounted for in the zinc than in the placebo group. Except for gestational age, the predictors selected were entirely different in the two groups. The zinc group had a positive toxemia screen more often, which did not appear to affect outcome. Zinc supplementation improved pregnancy outcome in normal-weight women and in underweight multiparas. The nonresponse in underweight primiparas was perhaps due to multiple limiting factors.

Adolescent↗

Multiple forms of phospholipase A2 in arthritic synovial fluid.

Phospholipase A2 (PLA2) has been purified to homogeneity from human arthritic synovial fluid. The activity resolved into multiple peaks by preparative HPLC. The most abundant peak (A) was present in synovial fluid from patients with rheumatoid arthritis, osteoarthritis, and psoriatic arthritis. A second major peak (B) was variable and lower in relative abundance, but was distinguishable from peak A by its stimulated activity in the presence of either 0.5 M Tris or 0.1% sodium deoxycholate (DOC), in addition to its longer HPLC column retention time. Both peaks required Ca2+ and showed optimal activity in DOC/phosphatidylcholine (PC) mixed micelle assays between pH 8.0 and 9.0. Both peaks showed higher activity with PC as substrate than with PI, however peak A exhibited higher activity with PE than PC. Upon preparative SDS-polyacrylamide gel electrophoresis, both peaks of PLA2 activity were resolved as proteins of approximately 14,000 Da. The N-terminal sequence obtained from purified peak A material matched that of a recent similar isolate (Hara et al. (1988) J. Biochem. 104, 326-328).

Animals↗

How to diagnose and treat chemical dependency in the elderly.

1. It is difficult to assess what percentage of the older population is chemically dependent; available literature cites between 2% and 70% of adults over age 60 have illnesses or other serious consequences as a result of alcohol abuse. 2. It is often difficult to differentiate between the signs and symptoms of chemical dependency and other physical, emotional, and social changes that occur with aging. 3. Chemical dependency often goes unrecognized in the older adult because of poor assessment skills and tools available to health-care professionals. 4. Once identified and treated, the recovery rate of the older adult alcoholic is equal to that of the younger alcoholic; however, there are specific treatment needs unique to the older adult that must be recognized and addressed in rehabilitation programs.

Aged↗