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Biomedical subjects

L Johnson

Publications and source records attributed to L Johnson.

At least 19 recordsLinked to original sources
PubMed2001

Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families.

Type 1 diabetes (T1D) is a genetically complex disorder of glucose homeostasis that results from the autoimmune destruction of the insulin-secreting cells of the pancreas. Two previous whole-genome scans for linkage to T1D in 187 and 356 families containing affected sib pairs (ASPs) yielded apparently conflicting results, despite partial overlap in the families analyzed. However, each of these studies individually lacked power to detect loci with locus-specific disease prevalence/sib-risk ratios (lambda(s)) <1.4. In the present study, a third genome scan was performed using a new collection of 225 multiplex families with T1D, and the data from all three of these genome scans were merged and analyzed jointly. The combined sample of 831 ASPs, all with both parents genotyped, provided 90% power to detect linkage for loci with lambda(s) = 1.3 at P=7.4x10(-4). Three chromosome regions were identified that showed significant evidence of linkage (P<2.2x10(-5); LOD scores >4), 6p21 (IDDM1), 11p15 (IDDM2), 16q22-q24, and four more that showed suggestive evidence (P<7.4x10(-4), LOD scores > or =2.2), 10p11 (IDDM10), 2q31 (IDDM7, IDDM12, and IDDM13), 6q21 (IDDM15), and 1q42. Exploratory analyses, taking into account the presence of specific high-risk HLA genotypes or affected sibs' ages at disease onset, provided evidence of linkage at several additional sites, including the putative IDDM8 locus on chromosome 6q27. Our results indicate that much of the difficulty in mapping T1D susceptibility genes results from inadequate sample sizes, and the results point to the value of future international collaborations to assemble and analyze much larger data sets for linkage in complex diseases.

Adolescent↗
PubMed1992

Reduced Leydig cell volume and function in adult rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin without a significant effect on spermatogenesis.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to alter testicular function. However, its effect on the efficiency of spermatogenesis or on Leydig cell volume has not been determined in adult rats. In two replicas, adult male rats received a single intraperitoneal injection of TCDD at a rate of 0, 12.5, 25.0, or 50.0 micrograms/kg body weight. Rats were sacrificed 4 weeks after treatment. The cytosolic Ah receptor in the testis was estimated at 10.3 +/- 1.2 fmol/mg protein in these adult rats. The presence of the Ah receptor at this concentration in the testis reveals that the testis is a possible target organ for TCDD-induced responses. Left testes were homogenized and testicular spermatids were counted by phase contrast cytometry to determine daily sperm production. Right testes were vascularly perfused with glutaraldehyde, embedded in Epon 812, sectioned at 0.5 micron, stained with toluidine blue and evaluated by stereology for germ cells or Leydig cells. Body weight was reduced (P < 0.01) in a dose-dependent fashion. Testicular weight and daily sperm production per testis were not significantly reduced by TCDD. Androgen receptor concentrations in the testis and prostate were not affected. Weights of two androgen-sensitive organs (seminal vesicles and epididymis) were reduced (P < 0.01) in a dose-dependent fashion and serum concentrations of testosterone were reduced in a dose-dependent fashion in Replica 2. Due to low numbers of animals in Replica 1, the reduced Leydig cell volume was not significant after TCDD treatment; however, in Replica 2 there was a dose-dependent reduction (P < 0.01) in volume per testis of Leydig cell cytoplasm, nuclei, or total Leydig cell volume. Production of testosterone was sufficient to maintain spermatogenesis quantitatively; however, TCDD caused a dose-dependent reduction in Leydig cell function and Leydig cell volume per testis. This study showed for the first time that TCDD-induced androgen deficiency of male rats may be explained by the loss of total volume of Leydig cell cytoplasm. This study also further illustrates the reserve capacity of Leydig cell function to maintain spermatogenesis when the volume of these cells is significantly reduced.

Animals↗
PubMed1992

Magnetic resonance imaging of body fat of athletes compared with controls, and the oxidative metabolism of estradiol.

The extent of 2-hydroxylation of estradiol (E2), which yields a non-estrogenic metabolite (2-OHE1), increased significantly with decreasing subcutaneous fat (ScF)/total volume percent (TV%) and total fat (TF)/TV% evaluated by magnetic resonance imaging (MRI) for five athletes during low- and high-intensity training, and four controls. The increase in 2-hydroxylation with decreasing adiposity was associated with anovulation and amenorrhea among the athletes.

Adipose Tissue↗
PubMed1992

Removal of toxic metals and nonmetals from contaminated water.

The effects of the application of potassium ferrate to remove possible toxic compounds are presented. Potassium ferrate (K2FeO4) is shown in this work to be an effective means to remove toxic metals and nonmetals from aqueous solution. The toxic material present in water is precipitated from aqueous solution and readily removed. Potassium ferrate removes itself from solution. Discolored contaminated water may be made clear by utilizing potassium ferrate. In addition, turbidities of solutions induced by dissolved substances are eliminated by the action of potassium ferrate. The efficacy of potassium ferrate in cleaning contaminated water shows great potential in application to municipal and industrial waste water.

Chemical Precipitation↗
PubMed1992

Missing generations of spermatocytes and spermatids in seminiferous epithelium contribute to low efficiency of spermatogenesis in humans.

Daily sperm production per gram parenchyma (DSP/g) in humans is only 25 or 35% of that for most species including rats and nonhuman primates. To explain the low efficiency of spermatogenesis in humans, the number of generations of germ cells (spermatocytes and spermatids) and the number of these germ cells in each generation were determined for each spermatogenic stage in men with varied efficiencies. Testes were obtained at autopsy, fixed by vascular perfusion with glutaraldehyde, further fixed in osmium, and embedded in Epon 812 before 0.5-micron sections were stained with toluidine blue. Tubular cross sections were photographed, and spermatogenic stages were determined by two observers. Testes were divided into three groups on the basis of DSP/g. The number of generations of spermatocytes and spermatids was greater (p < 0.05) in the high (2.01 +/- 0.05) and intermediate (1.77 +/- 0.04) than in the low (1.45 +/- 0.15) DSP/g group. All groups had a lower number of generations of spermatocytes and spermatids compared to the optimum value of three. The number of these generations per cross section was related (r = 0.85; p < 0.01) to DSP/g in these men. The number per cross section of spermatocytes, spermatids, and the combined number of germ cells was higher (p < 0.01) in the high than in the low DSP/g group. The combined number of germ cells per cross section was related (r = 0.85; p < 0.01) to DSP/g. The combined number of germ cells was higher in the high versus the low DSP/g group in stages I through V, but this difference was significant only in stages IV and V.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Stable nucleosome positioning and complete repression by the yeast alpha 2 repressor are disrupted by amino-terminal mutations in histone H4.

Nucleosomes are positioned in the presence of the yeast repressor alpha 2 in minichromosomes containing the alpha 2 operator and on the promoters of a-cell-specific genes regulated by alpha 2. To investigate the possibility that alpha 2 directs nucleosome position through an interaction with a component of the core particle, we analyzed chromatin structures adjacent to the operator in alpha cells containing mutations in the amino-terminal region of histone H4. Deletion or point mutation of specific amino acids in histone H4 altered the location and/or stability of nucleosomes adjacent to the alpha 2 operator. These changes in chromatin structure were accompanied by partial derepression of a beta-galactosidase reporter construct under alpha 2 control, even though alpha 2 remained bound to its operator sequence. Our data suggest that complete repression by alpha 2 requires stable positioning of nucleosomes in promoter regions and this positioning involves the conserved amino-terminal region of histone H4.

Base Sequence↗
PubMed1992

Onset of retinopathy of prematurity as related to postnatal and postconceptional age.

The hypothesis that both perinatal events and stage of retinal development are important factors in determining the age at onset of retinopathy of prematurity (ROP) was tested by comparing gestational age at birth with postnatal and postconceptional age when ROP (using ICROP) was first seen. The study population consisted of 207 infants (111 placebo (P) treated, 96 vitamin E (E) treated) who developed ROP among a group of 914 premature infants (460 P, 454 E) enrolled in a randomised clinical trial of the effect of prophylactic use of vitamin E at pharmacological serum levels on incidence and severity of retinopathy. The mean postnatal age at onset of retinopathy was delayed in E treated infants compared with P treated infants by 1.4 weeks (t = 4.004, p < 0.0001). For both P and E treated infants postnatal age at onset of ROP (which reflects the state of retinal development at which birth insults occur) and postconceptional age at onset of ROP which defines state of maturity) were correlated with gestational age at birth. This suggests that both the event of premature birth and the extent of retinal development are important in determining when ROP will first be observed.

Aging↗
PubMed1992

Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice.

Reproductive performance was studied in transgenic males from lines expressing and transmitting four hybrid genes: mouse metallothionein-I/human growth hormone (GH) (MT/hGH), MT/hGH placental variant (MT/hGH.V), MT/bovine GH (MT/bGH) and phosphoenolpyruvate carboxykinase/bGH (PEPCK/bGH). Each male was exposed to three normal females for 1 week and to three different normal females for another week. Females were examined for vaginal plugs and necropsied on day 14 of pregnancy. Males were killed for analysis of organ weights, numbers of testicular spermatids, numbers of epididymal sperm and measurements of plasma glucose concentration. Fertility of MT/hGH and MT/hGH.V transgenic males was significantly lower than in normal males, primarily because most males failed to impregnate any females. In females that became pregnant, the numbers of corpora lutea, total fetuses and live fetuses did not differ from those in females mated to normal (nontransgenic) males. Fetal crown-rump length on day 14 of pregnancy did not differ between litters sired by normal or by transgenic males. Weights of testes and seminal vesicles were significantly greater in all four types of transgenic male, but daily sperm production per unit weight (g-1) of testis was not affected and epididymal sperm reserves were either normal or slightly higher than normal. Plasma glucose concentrations were significantly higher in PEPCK/bGH mice than in other mice. Average or individual reproductive performance of transgenic males from the various lines did not correlate with any of the parameters examined except for significantly heavier seminal vesicles in MT/hGH and MT/hGH.V males than in normal males; these transgenic males exhibited a high incidence of infertility. Since hGH and hGH.V, but not bGH, are lactogenic in rodents, it was concluded that chronic stimulation of GH and prolactin receptors by ectopically produced human GHs in transgenic mice compromises male fertility by an unknown mechanism. Reduced fertility of transgenic males with MT/hGH or MT/hGH.V hybrid genes is due to failure to inseminate or impregnate females rather than to reduced numbers of spermatozoa or gross changes in the male reproductive system.

Animals↗
PubMed1992

Changes in the hypothalamic-hypophyseal axis of mares in relation to the winter solstice.

In mares, the amount of gonadotrophin-releasing hormone (GnRH) is low in the hypothalamus during seasonal anoestrus, but by early spring, concentrations of GnRH are high. The timing of this response was characterized more precisely by determining concentrations of GnRH in hypothalamic tissue collected immediately before and at various times after the winter solstice (22 December 1986). Ovaries, pituitary gland, hypothalamus and a blood sample were collected from six groups of mares (6-12 mares per group) at death, 1 week before day of the winter solstice and 1, 2, 3 and 12 weeks afterwards. No significant changes in weight of the anterior pituitary gland or concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were observed in the anterior pituitary gland (P > 0.1). Mean diameter of the largest follicle, number of follicles > or = 20 mm in diameter and concentrations of LH and FSH in serum remained unchanged for weeks -1 to +3 (P < 0.05), then increased significantly by week 12 (P < 0.001). Content and concentration of GnRH in the median eminence was low at -1 week, increased gradually (P < 0.05) to a maximum by +1 week, then decreased gradually (P < 0.05) to low values at 12 weeks. Means (+/- SEM) for -1, +1 and +12 weeks were 33.5 +/- 5.5, 117.7 +/- 18.6 and 29.8 +/- 3.7 ng GnRH, respectively. Mean content of GnRH in the preoptic area of the hypothalamus showed a reciprocal pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Specific and diversive curiosity in gifted elementary students.

Twenty-nine gifted students in Grades 2 to 6 from the small school districts in north central Kansas completed the Maze test and the Which-to-Discuss test. Background information such as age, sex, grade, and marital status of parents was also collected. There were no significant differences between boys and girls or for students from divorced and nondivorced parents on either the Which-to-Discuss test (specific curiosity) or the Maze test scores (diversive curiosity). The students scored significantly higher on the former test than chance guessing which suggests the students were displaying specific curiosity. Scores of these gifted students on these two tests of curiosity were significantly and positively correlated.

Attention↗
PubMed1992

Reference hematologic values and morphologic features of blood cells in healthy adult llamas.

Hematologic values and cellular morphologic features were evaluated for 38 healthy adult llamas. Reference ranges were determined for PCV, reticulocyte concentration, leukocyte concentration, and leukocyte differential counts. The approach used in this study was to focus on hematologic values that may be determined by use of techniques readily available to the practicing veterinarian and nonveterinary laboratory. Unique cellular morphologic features commonly observed and interpreted as normal included large granular lymphocytes, hyposegmented eosinophil nuclei, folded erythrocytes, and hemoglobin crystals.

Animals↗
PubMed1992

Characterization of erythrocytic indices and serum iron values in healthy llamas.

An electronic particle counter with attached particle-size analyzer was configured to directly determine concentration, mean cell volume, and volume distribution of erythrocytes in llama blood. Blood from 38 healthy llamas was used to characterize erythrocytic measurements and serum iron values for this species. Volume distribution curves for llama erythrocytes were similar in shape to those of other species. These curves had a unimodal, symmetric shape with a tail skewed to the right. Reference ranges for directly measured mean cell volume, erythrocyte concentration, hemoglobin concentration, and mean cell hemoglobin concentration were 21 to 28 fl, 11.3 x to 17.5 x 10(6) cells/microliters, 12.8 to 17.6 g/dl, and 43.2 to 46.6 g/dl, respectively. Reference ranges for serum iron concentration, total iron-binding capacity, and transferrin saturation were determined to be 70 to 148 micrograms/dl, 230 to 370 micrograms/dl, and 22 to 50%, respectively.

Animals↗
PubMed1992

Peripheral blood mononuclear cell subsets in patients with severe inherited forms of epidermolysis bullosa.

BACKGROUND AND DESIGN: Epidermolysis bullosa (EB) is a group of inherited disorders in which slight trauma to the skin results in blister formation. Patients with severe types of EB suffer cutaneous infections that sometimes progress to septicemia and cutaneous and gastrointestinal carcinomas that are locally aggressive and frequently metastasize. Previous studies have shown deficits in natural killer (NK) cell activity as well as in lymphokine and monokine production in patients with severe forms of EB. Alterations in peripheral blood mononuclear cells, however, which may reflect on immune functions in patients with EB, have received little attention. A prospective study was designed to ascertain if differences existed between subsets of peripheral blood mononuclear cells in patients with severe forms of EB vs healthy control subjects. Thirty patients with clinical and histologic diagnoses of EB and 30 healthy volunteers were studied. Flow cytometric analysis of labeled cells was performed. RESULTS: Absolute numbers of CD3+, CD2+, CD4+, CD19+, NK+, CD29+, and CD45R+ cells were lower in patients with severe types of EB in comparison with controls. The T cells showed decreased numbers of interleukin 2 receptors. An increase in numbers of CD20+, CD4+ CD8+, and CD4-CD8- cells was also observed in patients with severe types of EB. CONCLUSION: Alterations in monocyte and lymphocyte subsets known to affect host immune response were observed in patients with severe forms of EB. Quantitative changes relative to controls included decreased total numbers of T cells with greater decreases in helper cells, decreased NK cells, and a diminished number of interleukin 2 receptors. Such changes have been associated previously with a lower resistance to infections and to neoplasia. The changes in subsets correlated with the severity of the cutaneous and extracutaneous disease in the patients with EB.

Antibodies, Monoclonal↗