Covariance among premating, post-copulatory and viability fitness components in Drosophila melanogaster and their influence on paternity measurement.

In polyandrous mating systems, male fitness depends on success in premating, post-copulatory and offspring viability episodes of selection. We tracked male success across all of these episodes simultaneously, using transgenic Drosophila melanogaster with ubiquitously expressed green fluorescent protein (i.e. GFP) in a series of competitive and noncompetitive matings. This approach permitted us to track paternity-specific viability over all life stages and to distinguish true competitive fertilization success from differential early offspring viability. Relationships between episodes of selection were generally not present when paternity was measured in eggs; however, positive correlations between sperm competitive success and offspring viability became significant when paternity was measured in adult offspring. Additionally, we found a significant male × female interaction on hatching success and a lack of repeatability of offspring viability across a focal male's matings, which may underlay the limited number of correlations found between episodes of selection.

Factors related to the eating habits of students in grades 9-12.

This study examined the influence of demographic characteristics and selected family factors on consumption of a healthy breakfast and lunch and consumption of fruits and vegetables among adolescents. A cross-sectional survey was completed by a representative sample (n = 3,155) of students from all high schools in a suburban county near Atlanta, Georgia. Students consuming healthy breakfasts, healthy lunches, and more fruits and vegetables were more likely to be White or Asian (lunch/fruits and vegetables only), better able to communicate with parents or guardians on serious issues, closely monitored by their parents, living with one or both parents, spending less time at home without adults, perceiving themselves at about the right weight or underweight (lunch/breakfast only), male (lunch/breakfast only), and in 9th or 10th grade (breakfast only). These results suggest family factors should be considered in the development and implementation of nutrition interventions.

The acrodermatitis enteropathica mutation transiently affects zinc metabolism in human fibroblasts.

The acrodermatitis enteropathica (AE) mutation has been shown to affect zinc transport in human intestinal biopsies. However, whether the mutation is also expressed in human fibroblasts has not been determined. The activity of the zinc-dependent enzyme, 5' nucleotidase, and cell zinc content were measured in normal and AE fibroblasts 2 and 4 d after subculturing to determine the effect of the AE mutation on zinc metabolism. The activity of 5' nucleotidase in AE cells was 68% of normal at 2 d after subculturing. Although 5' nucleotidase activity had decreased significantly in both normal and AE fibroblasts at 4 d after subculturing, there was no significant difference between the two genotypes. The zinc content of AE fibroblasts was also significantly reduced. Acrodermatitis enteropathica fibroblasts contained 62% less zinc than normal fibroblasts at 2 d. By 4 d the normal fibroblast zinc content had decreased to that of the AE fibroblasts. The uptake and transport of 65Zn into AE fibroblasts at 2 d was measured because these cells exhibited reduced 5' nucleotidase activity and cell zinc content at this time. The uptake of zinc over a 90-min time period was the same in the two genotypes. However, AE fibroblasts incubated with 2-10 mumol Zn/L for 15 min had significantly slower zinc transport compared with normal fibroblasts. In both genotypes, Michaelis-Menten kinetics were observed. Normal and AE fibroblasts had similar affinities for zinc (Km), but AE fibroblasts exhibited a Vmax which was reduced by 38%. These results indicate that the phenotypic expression of the AE mutation occurs in a time-dependent manner, is not restricted to the intestine and is also transiently expressed in human fibroblasts, resulting in abnormal zinc metabolism in these cells.

Impact of the saponin adjuvant QS-21 and aluminium hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi.

The impact of the adjuvants QS-21 and aluminium hydroxide (alum) on the immunogenicity of recombinant outer surface proteins A (OspA) and B (OspB) of Borrelia burgdorferi was investigated. Both non-acylated OspA and OspB derived from strain B31 were expressed in Escherichia coli and purified by reversible citraconylation and anion-exchange chromatography. Antisera to OspA or OspB were prepared in mice with antigens formulated with QS-21 or alum, and evaluated for specific immunoglobulin G isotypes, agglutination and borreliacidal activity. QS-21 significantly enhanced IgG2a and IgG2b antibody responses to OspA and OspB, and IgG1 response to OspA when compared with the formulation containing antigen alone. In contrast, alum significantly inhibited the induction of IgG2a and IgG2b responses to OspA. Alum had no significant effect on IgG1 response to OspA, or IgG2a and IgG2b responses to OspB, but significantly enhanced IgG1 antibody response to OspB. Antisera to OspA or OspB formulated by QS-21 possessed higher titres of agglutinating antibody than antisera to OspA or OspB alone. Borreliacidal activity was eight- to 64-fold higher in antisera to OspA formulated with QS-21 than in antisera to OspA formulated with or without alum. These antisera were highly borreliacidal to New York strain B31, a California isolate CA-2-87, German isolate Fr, and Swedish isolate G25. Antisera to OspB formulated with QS-21 were highly borreliacidal to strains B31 and Fr, but not to CA-2-87 and G25. Antisera to OspB formulated with alum were borreliacidal only to B31. Thus, OspA was superior to OspB and QS-21 superior to alum at eliciting functional antibody responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Unique wounds and wound emergencies.

Unique wounds and wound emergencies include a variety of environmental assaults including bites, stings, electrical and chemical injury, and severe reactions to medications. This article reviews the clinical manifestations and treatment options essential to the management of these environmental assaults.

The presence of the enhanced K/Na discrimination trait in diploid Triticum species.

A number of accessions of the three species of diploid wheat, Triticum boeoticum, T. monococcum, and T. urartu, were grown in 50 mol m(-3) NaCl+2.5 mol m(-3) CaCl2. Sodium accumulation in the leaves was low and potassium concentrations remained high. This was not the case in T. durum grown under the same conditions, and indicates the presence in diploid wheats of the enhanced K/Na discrimination character which has previously been found in Aegilops squarrosa and hexaploid wheat. None of the accessions of diploid wheat showed poor K/Na discrimination, which suggests that if the A genome of modern tetraploid wheats was derived from a diploid Triticum species, then the enhanced K/Na discrimination character became altered after the formation of the original allopolyploid. Another possibility is that a diploid wheat that did not have the enhanced K/Na discrimination character was involved in the hybridization event which produced tetraploid wheat, and that this diploid is now extinct or has not yet been discovered.

Low-dose ultraviolet-B irradiation of donor corneal endothelium and graft survival.

Donor rabbit corneal endothelium was pretreated with different doses of ultraviolet (UV-B) irradiation (302 nm) before grafting to test whether allograft survival could be favorably affected in comparison with untreated corneas grafted into the same recipients. Endothelial rejection was observed in 19 of 32 (59%) eyes that received no treatment compared with five of 32 (16%) eyes that received UV-B (P less than 0.001), and increasing doses of UV-B were associated with lower rejection rates (P less than 0.05). Although exposure of donor endothelium significantly reduced endothelial rejection at all doses tested, it resulted in primary graft failure in a substantial proportion of corneas treated at high doses. Class II (Ia) antigen staining of corneal tissue was present in conjunction with clinical evidence of rejection, and the magnitude of staining correlated with the histologic extent of inflammation. Scanning electron microscopy revealed various endothelial cell surface irregularities and membrane defects in high-dose UV-treated corneas. Endothelial cell cultures exposed in vitro to UV-B light showed a dose-dependent loss in cell viability. These data suggest that UV-B pretreatment of donor corneal endothelium prolongs graft survival but that toxic side effects must be carefully controlled.

Rapid induction of Thy-1 antigenic markers on keratinocytes and epidermal immune cells in the skin of mice following topical treatment with common preservatives used in topical medications and in foods.

Earlier experiments from our laboratory revealed that the medication most commonly used for depigmenting patients with vitiligo, monobenzyl ether of hydroquinone (MBEH), when applied to the skin of DBA/2 mice caused an increase in the population density (cells/mm2) of identifiable Ia+ and ATPase+ Langerhans cells. Further, this increase in Langerhans cell density could be correlated with an increase of contact hypersensitivity (CHS) reactivity to dinitrofluorobenzene (DNFB). The current experiments demonstrated that other compounds chemically similar to MBEH, such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), which are used as preservatives/antioxidants in many topical medications, cosmetics, food, and rubber products, can in five days significantly increase the population density of Thy-1+ dendritic epidermal cells. These compounds had no effects on Ia+ cells. This observation suggests that the Thy-1+ DEC cells may be more mobile and/or their surface markers may be readily expressed and are not a slowly mobile (trafficking) population of cells as suggested by the results of previous work. In addition, these parasubstituted phenolic compounds behaved like pertussis toxin and induced Thy-1 and Ia expression on keratinocytes. These changes in Thy-1 immune markers were not accompanied by functional alterations in the immune response to contact allergens as measured by the ear swelling technique.

Non-polarizable collagen in dermatofibrosarcoma protuberans: a useful diagnostic aid.

The stroma in dermatofibrosarcoma protuberans (DFSP) stains with trichrome, but is not polarizable (birefringent, doubly refractile). The usefulness of polarizing neoplastic stroma as a diagnostic aid in distinguishing DFSP from dermatofibroma and fibromatosis was evaluated. Forty cases of dermatofibroma of all types, 12 cases of dermal fibromatosis, and 15 cases of DFSP were examined. None of DFSPs contained polarizable collagen, whereas 11 of the 12 (92%) fibromatoses and 35 of the 40 (88%) dermatofibromas did. Of the 5 dermatofibromas that did not polarize, all were composed primarily of round to polyhedral histiocytic cells, including foam cells, frequently surrounding small obliterated capillaries. Although not pathognomonic, the presence of nonpolarizable collagen appears to be an additional histological marker useful in differentiating DFSP from dermatofibroma and fibromatosis.

Giant cell fibroblastoma: an immunohistochemical study.

Giant cell fibroblastoma is a rare, benign soft tissue tumor occurring in childhood. A 34-year-old woman presented with a giant cell fibroblastoma involving the chest wall. Histologic features include an infiltrating spindle-cell tumor involving the dermis and subcutaneous fat containing characteristic sinusoidal spaces rimmed by spindle cells and multinucleate giant cells. Immunohistochemical studies support a fibrohistiocytic differentiation.

Reactions of oxaprozin-1-O-acyl glucuronide in solutions of human plasma and albumin.

Hydrolysis and rearrangement (isomerization by acyl migration) of oxaprozin glucuronide are greatly accelerated by plasma and human serum albumin. Albumin accounts for all the hydrolytic activity in plasma and no esterase is involved. The isomeric esters formed by rearrangement are also good substrates for the hydrolysis reaction. Another reaction between oxaprozin glucuronide and albumin leads to covalent binding of the aglycone. Similar reactions leading to covalent binding have been described for other acyl glucuronides by several investigators. In the case of oxaprozin, there is little or no potential for biological significance of covalent binding because the reaction is almost entirely inhibited by low concentrations of the drug. All three reactions are pH dependent but not to the same extent. They can be considered to be transacylations to the hydroxyl ion (hydrolysis), to a different OH-group of the glucuronic acid moiety (rearrangement) or to a nucleophilic group on the albumin molecule (covalent binding). All three reactions are greatly inhibited by the same compounds suggesting a common reaction site. This site has certain features in common with the indole or benzodiazepine binding site of human serum albumin. A scheme is proposed in which the first step is reversible binding of the acyl glucuronide to this site in analogy to the known reversible binding of reactive esters (such as p-nitrophenyl acetate) to the same site. All three reactions are inhibited by compounds such as naproxen and decanoic acid which are known to also inhibit the acylation of albumin by reactive esters and the reversible binding of benzodiazepines.

Metabolic formation of N- and O-glucuronides of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid. Rearrangement of the 1-o-acyl glucuronide.

Excretion of 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid (I) and its metabolites was studied in rats, beagle dogs, and rhesus monkeys given 20-mg/kg doses of 14C-labeled drug. The urine of rhesus monkeys contained two metabolites in addition to unchanged drug. Both metabolites were hydrolyzed to I by beta-glucuronidase and the hydrolysis was inhibited by 1,4-saccharolactone, indicating that they were glucuronides of I. One of the metabolites (III) was not hydrolyzed by dilute alkali. Its NMR spectrum indicated that the site of conjugation was one of the nitrogen atoms, i.e., it was a quaternary N-glucuronide. The FAB mass spectrum was in conformity with this assignment. This metabolite was not present in the urine of dogs or rats given labeled drug. The other metabolite (II) was excreted in the urine of all three species as well as in the bile of the rat. It was readily hydrolyzed by dilute alkali (pH 11 for 0.5 hr at 37 degrees C), indicating that this metabolite was an acyl glucuronide. The metabolite was stable at pH 4.5 but it was readily converted to three isomers at 37 degrees C within 1 hr at pH 6.5 and above. The mass spectra of the derivatized isomers and metabolite were similar. The isomers were hydrolyzed to I by dilute alkali but not by beta-glucuronidase. They exhibited reducing properties (whereas metabolite II did not), suggesting that they were formed by acyl migration of the aglycone to the second, third, and fourth carbon atoms of the glucuronic acid moiety. Acyl migration probably plays a role in the disposition of I as well as other drugs that form labile glucuronides.

Effect of sex hormones on the disposition in rats of 1-aminocyclohexane carboxylic acid, a metabolite of semisynthetic penicillin.

The renal clearance of 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of the semisynthetic penicillin, cyclacillin, is about 10 times faster in female than in male rats. The slower clearance in males is attributed to a higher net rate of reabsorption of the compound from the tubule of the kidney. Because ACHC is not metabolized, it is apparently continuously recirculated through the kidney of the male, resulting in the longer half-life. The sex-related disposition of the metabolite can be modified by gonadectomy and/or treatment with sex hormones. Castrated males show increased urinary excretion and decreased plasma half-life of ACHC relative to intact males. In ovariectomized females, less ACHC is excreted and the half-life is longer than in intact females. Thus, in both sexes, gonadectomy shifts the excretion and the residence time in plasma toward the values of these parameters for the opposite sex. Treatment of castrated males with estradiol markedly enhances the effect of castration, but treatment of ovariectomized females with testosterone propionate has little or no additional effect over ovariectomy. Treatment of intact males with estradiol modifies both excretion and residence time in plasma to a great extent, but treatment of intact females with testosterone has a lesser effect on the disposition of ACHC. These results indicate that excretion and residence time of ACHC in both male and female rats are influenced by sex hormones. The described effect is an example of the action of sex hormones on the transport of foreign compounds in this species. Its mechanism is quite different from the well known influence of sex hormones on the microsomal metabolism of foreign compounds in rats.