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Biomedical subjects

J L Adams

Publications and source records attributed to J L Adams.

At least 73 records · Page 4Linked to original sources

Mycobacterium paratuberculosis monoassociated nude mice as a paratuberculosis model.

In this study, a paratuberculosis (Johne's disease) model was developed by intragastrically dosing gnotobiotic athymic nude mice with Mycobacterium paratuberculosis. The mice infrequently shed bacilli from their intestinal tracts during the first 4 months after inoculation. Following this time, increasing numbers of M. paratuberculosis (greater than 4.0 log10 bacilli per fecal pellet by 40 weeks) were recovered from the feces of the 12 mice that remained in the isolator. A similar pattern of recovery of M. paratuberculosis was obtained from the ileum, cecum, colon, and liver. Histopathologic lesions and acid-fast bacilli were rare during the first 4 months of infection and then, with time, increased in prevalence and severity. Mice maintained for 7 months or longer exhibited severe granulomatous inflammation and large numbers of acid-fast bacilli in the gastrointestinal tract and liver (up to 10(8) log10 colony forming units per gram wet weight). Five mice maintained for 7 months or more developed clinical signs consistent with those seen in paratuberculosis (weight loss, chronic diarrhea); three of these mice eventually died or became moribund and were euthanatized. M. paratuberculosis monoassociated mice released increased levels of tumor necrosis factor activity into their sera, as compared to uninfected control mice, when they were injected with bacterial lipopolysaccharide. The clinical signs, fecal shedding of M. paratuberculosis, granuloma formation, and progressive bacillary multiplication observed with these mice are consistent with naturally occurring M. paratuberculosis infection of ruminants (Johne's disease). This model will be useful for future studies of immunoregulation and antimicrobial therapy of paratuberculosis.

Animals↗

Bacterial lipopolysaccharide induces release of tumor necrosis factor-alpha from bovine peripheral blood monocytes and alveolar macrophages in vitro.

In this study, we demonstrate that freshly adherent bovine monocytes release tumor necrosis factor-alpha (TNF-alpha) in response to stimulation with bacterial lipopolysaccharide (LPS). TNF-alpha was detected using actinomycin D-treated WEHI-164 murine fibrosarcoma cells as targets in an 18 hr cytotoxicity assay. Doses of LPS from 20 ng/ml to 20 micrograms/ml were capable of inducing bovine TNF-alpha. The kinetics of TNF-alpha release from bovine monocytes demonstrated peak levels of cytotoxic activity at 1-3 hr post-LPS treatment, with a subsequent decline to background levels by 18 hr post-LPS treatment. A monoclonal antibody that neutralizes recombinant human TNF-alpha (rHuTNF-alpha) significantly reduced the cytotoxicity of LPS-stimulated bovine monocyte culture supernatants. Size exclusion high-performance liquid chromatography (HPLC) analysis of LPS-stimulated monocyte and alveolar macrophage culture supernatants resulted in a molecular weight elution profile similar to that of recombinant human TNF-alpha. These elution profiles are consistent with the presence of multimers of TNF-alpha. This is believed to be the first report of the in vitro production of bovine TNF-alpha.

Animals↗

Administration of bacterial lipopolysaccharide elicits circulating tumor necrosis factor-alpha in neonatal calves.

The presence of tumor necrosis factor-alpha (TNF-alpha) during endotoxemia in ruminants has not been reported previously. In this study, we detected the in vivo release of bovine TNF-alpha by using WEHI-164 murine fibrosarcoma cells as targets in an 18-h cytotoxicity assay. Treatment of the WEHI-164 cells with 1 microgram of actinomycin D (dactinomycin) enhanced approximately twofold the susceptibility of the cells to TNF-alpha activity. TNF-alpha activity in sera from neonatal calves injected intravenously with 2.7 micrograms of Escherichia coli lipopolysaccharide (LPS) increased rapidly within the first 2 h postinjection and then declined until it was undetectable by 4 h postinjection. Sera taken before LPS administration had no TNF-alpha activity. LPS (10 micrograms/ml) and fetal, newborn, and pooled adult bovine sera alone and in combination had no direct cytotoxic effects on WEHI-164 cells. TNF-alpha cytotoxic activity is probably not due to the presence of interleukin-1 (IL-1), alpha interferon, or gamma interferon in the sera since recombinant human IL-1, natural bovine IL-1, and recombinant bovine alpha and gamma interferons had no direct cytotoxic effects on WEHI-164 cells. A monoclonal antibody that neutralizes recombinant human TNF-alpha significantly reduced the cytotoxic activity of sera from LPS-injected calves.

Animals↗

Mechanism and inhibition of delta 24-sterol methyltransferase from Candida albicans and Candida tropicalis.

The S-adenosyl-L-methionine: delta 24-sterol methyltransferase from Candida albicans has been solubilized with a mixture of octyl glucoside and sodium taurodeoxycholate. The enzyme has an apparent molecular weight of approximately 150,000 as measured by gel filtration chromatography. Zymosterol is the preferred substrate for the microsomal methyltransferase. Other nuclear double bond isomers support reduced rates of methenylation, while sterols which bear methyl groups at C-4 or C-14 are not substrates. Initial velocity and product inhibition studies are consistent with a rapid equilibrium ordered kinetic mechanism. A series of novel sterol analogues which contain heteroatoms substituted for C-24 or C-25 have been kinetically characterized as dead-end inhibitors of the methyltransferase, revealing three distinct mechanisms of interaction with the enzyme. Sterols which contain positively charged moieties in these positions are particularly potent inhibitors, supporting the proposed intermediacy of C-24 and C-25 carbocations. The methyltransferase is reversibly inhibited by low concentrations of 24-thiasterols, while behavior consistent with mechanism-based enzyme inactivation is apparent at higher concentrations. Possible mechanisms for this novel inactivation reaction are discussed.

Candida↗

Cerebrospinal fluid leakage complicating orbital exenteration.

In three cases of cerebrospinal fluid leakage complicating orbital exenteration, leakage occurred intraoperatively following relatively low-power (0 to 25 W), high-frequency monopolar cautery to the orbital roof. Six cadaver orbits and 25 dried skulls were examined to investigate possible causes of intraoperative cerebrospinal fluid leakage. In this experimental model, monopolar cautery to the orbital roof did not cause cerebrospinal fluid leakage; however, cautery to preexistent foramina or experimentally created defects in the orbital bones did. In exenteration, monopolar cautery may transmit thermal energy through extant body defects in the orbital roof directly to the dura, resulting in its disruption. These defects may be congenital, tumor related, or iatrogenic. Alternative methods of hemostasis should probably be employed to control bleeding that occurs along the orbital roof during exenteration.

Aged↗

cis-4-Carboxy-6-(mercaptomethyl)-3,4,5,6-tetrahydropyrimidin-2(1 H)-one , a potent inhibitor of mammalian dihydroorotase.

A series of cis- and trans-4-carboxy-3,4,5,6-tetrahydropyrimidin-2(1H)-ones possessing either a carboxy, hydroxymethyl, or mercaptomethyl substituent at C-6 were prepared and tested for their ability to inhibit mammalian dihydroorotase. Of these compounds, only the cis-6-mercaptomethyl compound, cis-1, was found to be a potent competitive inhibitor of the enzyme (Ki = 140 nM at pH 7.4 and 8.5) when assayed in the direction of dihydro-L-orotate hydrolysis. These results suggest that the inhibition arises from the ligation of the thiolate to the zinc atom which is thought to be located in the enzyme's active site. Although analysis of cis-1 with 2,2'-dithiobis(5-nitrobenzoic acid) revealed significant loss of the free thiol group under enzymatic assay conditions, the addition of the reducing agent, dithiothreitol, to the enzymatic reaction mixtures afforded cis-1 complete protection against this chemical decomposition, as evidenced by lowering of the inhibition constant in the presence of dithiothreitol. Compound cis-1 had no significant antiproliferative activity against B16 melanoma cells in tissue culture, possibly due to the rapid decomposition of the compound or poor permeability into cells.

Amidohydrolases↗

Immediate cranial nerve paralysis during removal of a mandibular third molar.

Cranial nerve palsy is a rare complication of dental extraction. This article presents a report of an incomplete seventh nerve paralysis and branch third nerve palsy occurring during extraction of a mandibular third molar. Diagnostic and treatment considerations are discussed, including a review of pertinent neuroanatomy.

Adult↗

Temporary nonincisional tarsorrhaphy.

A simple and effective method of temporary tarsorrhaphy, which is referred to as intermarginal serpentine temporary tarsorrhaphy, is presented. The tarsorrhaphy is created by passing a 6-0 Prolene suture in a serpentine manner across the eyelids, entering and exiting from the eyelid margin. This type of tarsorrhaphy is easy to perform, has few disadvantages, and is very effective.

Eyelids↗

Effects of information on patient stereotyping.

The influence of information on nurse attitudes and behavior toward a member of a stereotyped group was investigated. Responsibility for the decision to be childless and the intelligence of the person making that decision were manipulated. Student nurses individually interacted with a hypothetical, childless, female patient, presented via audiotape, who was about to undergo surgery for sterilization. The patient was described (a) as seeking sterilization either voluntarily or because of medical necessity, and (b) as either retarded or not classified intellectually. It was hypothesized that the patient who freely chose childlessness would be viewed and treated less positively when thought to be of normal intelligence. When the patient was mildly retarded or seeking sterilization out of medical necessity, however, more positive attitudes and behavior were expected. Both of these hypotheses were supported. The results of this study support the importance of contextual variables on perceptions of patients.

Adult↗

Infants' home environments: a study of screening efficiency.

The predictive efficiency of Caldwell's Home Observation for Measurement of the Environment (HOME) with a sample of infants from low-income families at-risk for developmental retardation was assessed. The home environments of 51 infants were assessed with the HOME at 6 and 18 months. Multiple discriminant functions composed of the six HOME subscale scores predicted whether the child would be low IQ (below 75), low average (75 to 89), or average to superior (90 and above) at age 3. At both 6 and 18 months, the discriminant function of the HOME was found to be moderately sensitive in identifying children in the low-IQ group (62% correctly identified); 56% were false positives. Additional research is necessary to differentiate with precision among families at elevated risk levels.

Child Development↗

The use of obstetrical procedures in the care of low-risk women.

Data from birth certificates were used to examine the pattern of obstetrical procedures used in the care of a sample of low-risk women. The data suggests that hospitals with greater technological capabilities and more specialized medical manpower have a greater tendency to use the obstetrical procedures of cesarean section, forceps delivery and drug induced labor. However, the utilization rates of these procedures also varied considerably between hospitals with comparable technology and medical staffs.

Adult↗

Structural aspects of maternal speech to infants reared in poverty.

Mother-infant dyads (N = 27) were seen as part of a longitudinal study of lower-socioeconomic-status infants at high but varying risk for mild mental retardation. A 20-min unstructured interaction session was videotaped in a laboratory setting when the infants were 6 months old. Transcriptions were made of mothers' speech to their infants. Measures of maternal language included sentence form, amount of speech, and syntactic complexity. It was found that the proportion of imperatives, but not the amount of maternal speech, was positively correlated with a composite measure of risk status (High Risk Index) and negatively correlated with maternal education and WAIS IQ. Similar to previous findings for maternal speech to older infants, syntactic complexity was not significantly related to social risk indices. In terms of descriptive aspects of the data, there was a high degree of variability on the language measures-indicative of wide individual differences in maternal language style.

Adolescent↗