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Biomedical subjects

C L Johnson

Publications and source records attributed to C L Johnson.

At least 19 recordsLinked to original sources

Loss of heterozygosity on chromosome 11 in sporadic gastrinomas.

Gastrinomas are pancreatic endocrine neoplasms that arise either sporadically or are inherited as part of the multiple endocrine neoplasia type I syndrome (MENI). Loss of heterozygosity (LOH) in the region flanking the MENI gene at chromosome 11q13 has been documented in a few sporadic and familial pancreatic endocrine tumors, but not previously in sporadic gastrinomas. It has therefore been suggested that gastrinomas develop by a mechanism different from other tumors associated with the MENI syndrome. We report LOH on chromosome 11 in 5 of 11 sporadic gastrinomas. Four of these tumors have LOH for markers flanking the MENI region. Molecular evaluation of segments of chromosomes 3, 13, and 17 known to contain cloned or putative tumor suppressor genes fail to show LOH except at one locus in one tumor. These data suggest that a tumor suppressor DNA segment exists at 11q13 that may be involved in the development of sporadic gastrinomas.

Blotting, Southern

Management of catastrophic neonatal midgut volvulus with a silo and second-look laparotomy.

The case of a neonate with midgut volvulus and severe intestinal ischemia extending from the ligament of Treitz to the midtransverse colon is presented. Management consisted of abdominal silo application at the initial exploration to obviate the adverse physiological consequences of increased intraabdominal pressure from reperfusion edema of the intestine. The majority of the intestine was salvaged, and a short segment of ileum was resected. This method of treatment resulted in optimal ventilatory status, renal function, and cardiac performance. The advantages of temporary prosthetic wound coverage in selected cases of midgut volvulus include greater physiologic stability through the avoidance of "intraabdominal hypertension" and the ability to monitor the status of the intestine at the bedside.

Duodenal Obstruction

Family functioning in late late life.

This study of 150 individuals, 85 years and older, focused on their families and social networks. Using both structured and open-ended questions, we explored the extent to which the family functions as a source of support for the oldest old. The findings indicate that those with children are significantly more active with all relatives, most likely because children link them to grandchildren, great-grandchildren, and their relatives by marriage. For the 30 percent who are childless and unmarried, other relatives are not usually active providers of support, a finding which suggests that the principle of substitution does not operate effectively for this age group. Case studies illustrate the variations in family functioning in the support of their oldest members.

Aged

Characterization of receptors for substance P in human astrocytoma cells: radioligand binding and inositol phosphate formation.

UC11 cells, derived from a human astrocytoma, have a high density of functional substance P receptors. Radioligand binding studies were conducted with the highly selective neurokinin-1 receptor ligand [3H][Sar9,Met(O2)11]-substance P. Kinetic binding experiments conducted at 4 degrees C yielded an association rate constant k1 of 1.86 x 10(7) M-1 min-1, a dissociation rate constant k-1 of 0.00478 min-1, and a calculated kinetic KD of 257 pM. Saturation binding experiments yielded average values of KD = 447 +/- 103 pM, Bmax = 862 +/- 93 fmol/mg of protein. This Bmax corresponds to more than 150,000 binding sites/cell. Competition binding experiments with unlabeled [Sar9,Met(O2)11]-substance P yielded average values of KD = 491 +/- 48 pM and Bmax = 912 +/- 67 fmol/mg of protein. In [3H]inositol-labeled cells, substance P induced a robust inositol phosphate formation. Inositol trisphosphate levels increased as much as 20-fold within approximately 15 s of addition of substance P. This inositol trisphosphate formation was transient and had returned to baseline within the first 60-120 s. Inositol monophosphate formation, however, was linear for at least 2 h. Structure activity data on binding and inositol monophosphate formation confirmed the presence of a neurokinin-1 receptor subtype in these cells. Thus, the UC11 cell should be a useful model cell for delineating the physiological role of substance P receptors in astrocytes.

Astrocytoma

Effects of skirting on processing characteristics of Targhee wool.

Ninety mature Targhee ewes were randomly allocated to nine lots. Lots were randomly assigned to three fleece preparation treatments: 1) nonskirted (control); 2) bellies removed, in which bellies and topknots were removed on the shearing floor; and 3) skirted, in which bellies and topknots were removed and remaining fleece was thrown on a table and lightly skirted. Bellies and topknots composed about 6 to 7% of the fleece weight. An additional 6.6% was removed when fleeces were skirted. Top fiber diameters were not affected (P greater than .10) by skirting. Although not significant (P greater than .10), percentage yield, vegetable content, percentage of noilage, top fiber length, and yellowness indexes tended to be most desirable for skirted lots and least desirable for unskirted lots. Lots with bellies removed were intermediate. Removal of bellies reduced vegetable contamination by 8.4%, with an additional reduction of about .5% by further skirting. Skirting reduced the number of fibers less than 25.4 mm (P less than .10) by 42%. Minimal colored fiber contamination of top was observed. One colored fiber per 15 g of top was detected in two lots of the treatment with bellies removed. All other lots contained no colored fibers. All wools evaluated were well below industry limits set for use in high-quality white or pastel fabrics. All skirted lots of wool evaluated in this study had improved processing characteristics for all processing traits evaluated.

Animal Husbandry

Estimation of genetic parameters for wool fiber diameter measures.

Genetic and phenotypic correlations and heritability estimates of side, britch, and core diameters; side and britch CV; side and britch diameter difference; and clean fleece weight were investigated using 385 western white-faced ewes produced by 50 sires and maintained at two locations on a selection study. Data were analyzed using analysis of variance procedures, and effects in the final model included breed of sire-selection line combination, sire within breed-selection line, and location. Heritabilities were estimated by paternal half-sib analysis. Sires within breed-selection line represented a significant source of variation for all traits studied. Location had a significant effect on side diameter, side and britch diameter difference, and clean fleece weight. Age of ewe only affected clean fleece weight. Phenotypic and genetic correlations among side, britch, and core diameter measures were high and positive. Phenotypic correlations ranged from .68 to .75 and genetic correlations ranged from .74 to .89. The genetic correlations between side and britch diameter difference and side diameter or core diameter were small (-.16 and .28, respectively). However, there was a stronger genetic correlation between side and britch diameter difference and britch diameter (.55). Heritability of the difference between side and britch diameter was high (.46 +/- .16) and similar to heritability estimates reported for other wool traits. Results of this study indicate that relatively rapid genetic progress through selection for fiber diameter should be possible. In addition, increased uniformity in fiber diameter should be possible through selection for either side and britch diameter difference or side or britch CV.

Age Factors

Tumor necrosis factor and interleukin-1 down-regulate receptors for substance P in human astrocytoma cells.

This study examined the influence of cytokines on substance P (SP) receptors (NK1 subtype) in the human astrocytoma cell line UC11. Following trypsinization and passage, the density of SP receptors in these cells was rather low but gradually increased several fold over the course of a few days in culture. Frequent replacement of the growth medium enhanced the density of receptors even more, suggesting that growth factors in the culture medium may determine the levels of receptor. Exposure of the cells to sub-nanomolar concentrations of tumor necrosis factor (TNF alpha) or interleukin-1 beta (IL1 beta), but not interleukin-2 or interleukin-6, decreased the density of SP receptors. This was accompanied by a decrease in the ability of SP to stimulate inositolphosphate formation. The ability of histamine to activate inositolphosphate formation was not influenced by the cytokines. The decrease in SP receptor density was readily reversible on washout of the cytokines. The EC50 for TNF alpha was approximately 0.5 ng/ml, the EC50 for IL1 beta was approximately 0.1 ng/ml. Radioligand binding studies with [125I]TNF alpha indicated the presence of a low density of high affinity binding sites for this ligand: Kd = 2.5 +/- 0.6 ng/ml, Bmax = 14.8 +/- 2.7 fmol bound/mg protein (assuming trimeric form of ligand bound). The most likely explanation for the cytokine effect is an inhibition of the synthesis of new receptors.

Astrocytoma

Response of 7- to 15-month-old infants to sequential immunization with Haemophilus influenzae type b-CRM197 conjugate and polysaccharide vaccines.

OBJECTIVE: To evaluate the immunologic potential of infants 7 to 15 months of age to respond to Haemophilus influenzae type b polysaccharide vaccine following immunization with H influenzae b oligosaccharide-CRM197 conjugate vaccine. STUDY DESIGN: One hundred seventy-one infants, aged 7 to 15 months, were consecutively and alternatively assigned to one of three immunization protocols. Group 1 (n = 71) received three doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine, group 2 (n = 47) received two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine followed by one dose of H influenzae type b polysaccharide vaccine, and group 3 received one dose of H influenzae b oligosaccharide-CRM197 conjugate vaccine followed by two doses of H influenzae type b polysaccharide vaccine. Immunizations were given on day 0 and at 2 months and 6 months. Anti-H influenzae type b polysaccharide antibody levels were measured on day 0 and 2, 3, 6, 7, and 12 months after the study began. RESULTS: Haemophilus influenzae type b polysaccharide vaccine given as a second dose stimulated an antibody rise but did so less effectively than H influenzae b oligosaccharide-CRM197 conjugate vaccine. Two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine were highly immunogenic; geometric means were 31 and 35 micrograms/mL in the 7- to 11-month and 12- to 15-month age groups, respectively. Following two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine, both immunization protocols resulted in (1) equally high geometric mean antibody levels 1 month after immunization and (2) similar geometric mean antibody levels 6 months after immunization. CONCLUSIONS: Haemophilus influenzae b oligosaccharide-CRM197 conjugate vaccine induces antibody levels that would be expected to protect infants from initial invasion and primes the immune system for an anamnestic response. Our data indicate that if a booster immunization is needed, H influenzae type b polysaccharide vaccine could be an alternative to H influenzae b oligosaccharide-CRM197 conjugate vaccine.

Antibodies, Bacterial

Dihydropyridine receptor binding sites in the cardiomyopathic hamster heart are unchanged from control.

An increase in the number of voltage dependent calcium channels has been implicated in the overload of calcium found in cardiac tissue of the cardiomyopathic hamster. We examined the binding of [3H]-(+)PN200110 to dihydropyridine receptors in cardiac muscle membranes from TO cardiomyopathic hamsters. When compared to random bred controls, there were no differences in either the Bmax or the KD for [3H]-(+)PN200110 binding using homogenates from 35 to 41-day-old TO cardiomyopathic hearts. In 8 to 9-month-old myopathic animals there were only small decreases in Bmax with no change in KD. We suggest that the calcium overload observed in cardiomyopathic hamster heart may not be due to an increased density of calcium channels as estimated by high affinity dihydropyridine receptor binding sites.

Animals

Prediction of responses in milk constituents to changes in the nutrition of dairy cows.

Milk quotas, based on an average fat content, severely limit milk production on UK farms. Predictions of the time-course of lactation are incorporated into most computerized herd management programs but these models take no account of food inputs, body weight change or milk composition. Dynamic models are generally used to simulate metabolic pathways and, as such, have little direct relevance to commercial milk production. Dynamic models can be converted to an adaptive-predictive model that partitions food energy into milk and non-milk constituents. This paper reports the development of an adaptive-predictive model to partition food into milk and non-milk components. Additional functions further partition milk energy into the principal constituents, fat, protein and lactose.

Animal Feed

A multipoint linkage map of the distal short arm of the human X chromosome.

The distal portion of the short arm of the human X chromosome (Xp) exhibits many unique and interesting features. Distal Xp contains the pseudoautosomal region, a number of disease loci, and several cell-surface markers. Several genes in this area have also been observed to escape X-chromosomal inactivation. The characterization of new polymorphic loci in this region has permitted the construction of a refined multipoint linkage map extending 15 cM from the Xp telomere. This interval is known to contain the loci for the diseases X-linked ichthyosis, chondrodysplasia punctata, and Kallmann syndrome, as well as the cell-surface markers Xg and 12E7. This region also contains the junction between the pseudoautosomal region and strictly X-linked sequences. The locus MIC2 has been demonstrated by linkage analysis to be indistinguishable from the pseudoautosomal junction. The steroid sulfatase locus has been mapped to an interval adjacent to the DXS278 locus and 6 cM from the pseudoautosomal junction. The polymorphic locus (STS) DXS278 was shown to be informative in all families studied, and linkage analysis reveals that the locus represents a low-copy repeat with at least one copy distal to the STS gene. The generation of a multipoint linkage map of distal Xp will be useful in the genetic dissection of many of the unique features of this region.

Alleles

Effect of dose and route of administration of thyroid releasing hormone (TRH) on the concentration of prolactin (PRL) and thyroxine (T4) in cyclic gilts.

Our objective was to examine the ability of thyroid releasing hormone (TRH) to stimulate not only the release of the thyroid hormones, but also prolactin (PRL) in the female pig. An experiment was conducted to determine the effect of dose and route of administration of TRH on the concentration of PRL and thyroxine (T4) in cyclic gilts. Six gilts were injected with 0, 5, 25, 125, and 625 micrograms TRH and fed 0, 5, 2.5, 12.5 and 62.5 mg TRH. Gilts received TRH once daily. During the 10-day treatment period, route of TRH administration alternated between i.v. injection and feeding. The dose of TRH progressed from the lowest to the highest. Blood samples were taken prior to TRH injection and thereafter at 15-min intervals for 3 hr. Sampling continued for an additional 3 hr at 30-min intervals when TRH was fed. Concentrations of PRL and T4 were determined by radioimmunoassay. Intravenous injection of gilts with 125 and 625 micrograms TRH resulted in an increase in PRL from 0 to 15 min (P less than .05). All doses of TRH given i.v. elevated T4 over a 2-hr period (P less than .01). TRH failed to increase PRL when TRH was fed (P greater than .5). The feeding of 62.5 mg TRH elevated T4 from 0 to 6 hr (P less than .01). Thus, TRH injection increased PRL rapidly and T4 gradually. When TRH was fed, only a gradual elevation in T4 was observed. We conclude that TRH can elicit the release of both PRL and T4 in the cyclic gilt, but magnitude and duration of the PRL and T4 response depends on the dose and route of TRH administration.

Administration, Oral

Inhibition of human skin fibroblast proliferation by histamine and phorbol esters is mediated by protein kinase C.

The proliferation of human skin fibroblasts in culture was examined using a [3H]thymidine incorporation assay. Histamine inhibited thymidine incorporation with an IC50 of about 0.2 microM. This effect was blocked by the H1 receptor antagonist mepyramine but not by the H2 receptor antagonist cimetidine. Protein kinase C activators, including several phorbol esters and mezerine, also inhibited thymidine incorporation. The IC50 for beta-phorbol 12,13-didecanoate was less than 0.1 nM. The alpha-isomer of this compound was inactive. Long-term treatment of cells with the beta-isomer eliminated the ability of both histamine and phorbol ester to inhibit thymidine incorporation, presumably due to downregulation of protein kinase C. Our results suggest that histamine H1 receptors are linked to activation of protein kinase C and that activation of this enzyme leads to an inhibition of cell proliferation.

Blood

Rationale of feeding systems for lactating dairy cows.

Manipulations of the lactation cycle are achieved through nutritional regimens and generally result in a restriction of the physiological lactation cycle. Most models of lactation used in management programmes only describe the average time course of lactation for groups of cows on a given feeding regimen. This is inadequate for the variety of feeding systems in use on British farms. In the present paper several existing models of lactation have been critically evaluated. An integral equation approach has been developed to rationalize experimental observations and currently accepted biological concepts.

Animal Nutritional Physiological Phenomena