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T E Johnson

Publications and source records attributed to T E Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Secondary squamous cell carcinoma of the orbit.

OBJECTIVE: To evaluate the origin and biological behavior of secondary orbital squamous cell (SCC) and mucoepidermoid carcinoma. METHODS: A retrospective review of 30 consecutive patients with SCC and mucoepidermoid carcinoma of the orbit seen over a period of 8 years at a large ophthalmic hospital in Saudi Arabia. RESULTS: A total of 51 secondary orbital tumors were seen in the 8-year period from 1983 through 1991; 30 (60%) of the 51 cases were SCC. There were 16 male and 14 female patients, with an age range of 38 to 80 years and a mean age of 65 years. In 28 (93%) of the 30 patients, the tumor originated in the conjunctiva. Orbital involvement by conjunctival SCC was the most common cause of secondary orbital tumors encountered in patients older than 19 years. Four patients had concomitant paranasal sinus involvement, 4 patients exhibited intraocular invasion, and 2 others were found to have intracranial extension of the SCC. Six (20%) of the 28 patients developed regional lymph node metastases during the course of their illness. All patients were treated by orbital exenteration, with or without radiation therapy. Seven (23%) of the 28 patients died of their disease. CONCLUSIONS: Orbital SCC is an aggressive and life-threatening condition. Most cases result from secondary extension of conjunctival SCC, a common disease in Saudi Arabia. Several factors contribute to the aggressiveness of conjunctival SCC in this geographic location, including continual exposure to UV rays, chronic irritation, and genetic factors. Delay in presentation for treatment, inadequate initial resection of conjunctival lesions, and the aggressive mucoepidermoid carcinoma variant of SCC are also factors contributing to orbital invasion.

Adult↗
PubMed1997

Murine albino-deletion complex: high-resolution microsatellite map and genetically anchored YAC framework map.

The murine albino-deletion complex developed as part of the Oak Ridge specific-locus test covers 6-11 cM of chromosome 7. This complex has proven to be a valuable resource for localizing traits to a small target region for positional cloning. In this study, we mapped the endpoints of deletions in this complex using all of the available Mit simple-sequence length polymorphism (SSLP) markers. Concurrently, this mapping has determined the map order of nearly all of the SSLP markers, most of which were previously unresolved. The SSLP-based deletion map was confirmed and genetic distances were determined using the European Collaborative Interspecific Backcross panel of nearly a thousand mice. The average SSLP marker resolution is 0.3-0.4 cM, comparable to the cloning capacity of yeast artificial chromosomes (YACs). The SSLP markers were then used to construct a genetically anchored YAC framework map that further confirms the deletion map. We find that the largest deleted region distal to Tyr is about two to three times larger than the largest proximal deletion region, and the original C3H/101 regions flanking the deletions (moved to an St2A cch/cch background) are smaller than anticipated, which we suggest may result from increased recombination rates immediately flanking the deleted regions.

Animals↗
PubMed1997

Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice.

Initial insensitivity to alcohol is a strong predictor of human alcoholism, a widespread and heritable health problem. The Long Sleep and Short Sleep lines of mice were developed by genetic selection for high or low alcohol sensitivity. We have identified seven quantitative trait loci (QTLs) specifying differences in alcohol sensitivity using intercross progeny from these selected strains. These QTLs (Lorel-Lore7) together account for approximately 60% of the total genetic variance for this trait. This represents the first report of linkages for genes influencing alcohol action in any mammalian system using stringent, genome-wide mapping criteria.

Alcoholic Intoxication↗
PubMed1997

Common quantitative trait loci for alcohol-related behaviors and central nervous system neurotensin measures: hypnotic and hypothermic effects.

Genetic correlations were found between high-affinity neurotensin receptor (NTR(H)) densities and NT-immunoreactivity (NT-ir) levels in specific brain regions and sensitivity to hypnotic and hypothermic effects of ethanol in LSXSS recombinant inbred strains of mice. Simple sequence length polymorphisms were used to identify quantitative trait loci (QTL) influencing hypnotic and hypothermic sensitivity to ethanol, NTR(H) and low-affinity neurotensin receptor densities and NT-ir levels in LSXSS recombinant inbred strains. Common QTL for NTR(H) receptor densities, NT-ir levels and these ethanol actions were identified. One of the QTL (chromosome 2, 80 cM) for NTR(H) density and hypnotic sensitivity is linked to the NTR(H) gene, Ntsr. Also, QTL for NTR(H) density were found in common with confirmed QTL for hypnotic sensitivity on chromosomes 1 (43 cM), 11 (57 cM) and 15 (56 cM) and with an unconfirmed QTL on chromosome 3 (19 cM). Two common QTL for NT-ir levels, but not NTR(H) or low-affinity neurotensin receptor receptors, and ethanol-induced hypothermia were observed on chromosomes 4 (43 cM) and 6 (41 cM). Two common QTL for NT-ir levels and sleep time were identified on chromosomes 3 (19 cM) and 9 (55 cM). Common QTL indicate that genes regulating NT receptor and/or NT-ir expression may be the same as those regulating sensitivity to ethanol.

Alcoholism↗
PubMed1997

Quick method for confirmation of quantitative trait loci.

Numerous algorithms for the identification and genetic mapping of quantitative trait loci (QTL) have been developed. Methods for confirming QTL maps involve either examination of independent segregating populations or the construction of congenic lines differing only in the QTL of interest. Because these projects require a minimum of several years or thousands of marker assessments in laboratory mice, an alternative, faster congenic method has been proposed. In a preliminary study, we tested this method for confirming QTLs identified in crosses between the ILS and ISS selected lines of mice for differential sensitivity to the hypnotic effects of ethanol. Herein, we report the construction of "segregating congenic" strains in which each QTL is made homozygous in a single generation, whereas the remainder of the genetic background is allowed to segregate. Sensitivity to ethanol among the progeny of such mice is consistent with predictions. Phenotypic variation is high, as expected, due to the background segregation, and statistical significance was attained in only 2 of 7 comparisons. Such segregating congenic populations may be a valuable research tool for confirming QTL map positions and for subsequent assessment of individual pathways and mechanisms of action of individual QTLs.

Alcoholism↗
PubMed1997

Fitting the pieces together: treatment planning in the geriatric dental patient.

Treatment planning older patients often becomes a complex process as dental professionals, patients, family, and caregivers attempt to prioritize and balance the influences of multiple age-associated dental, systemic, and psychosocial factors. To assist clinicians in identifying and weighing numerous factors that can influence planning dental care for older patients, clinicians should be wary of relying on chronological age as a factor, but should focus on the issues of biologic age and life expectancy, which may be greater than many older adults believe. The longevity of dental interventions is another factor that is helpful to consider in determining the most appropriate treatment plan for older adults. Among many issues influencing the treatment planning process, the quality of communication between clinicians and older patients is critical, along with the influence of third parties, including families and professional caregivers. Due to the lack of objective information on the outcomes of dental care in the older population, clinicians inevitably face many situations in which there is uncertainty about the best course of therapy. Practitioners can adopt specific strategies to help minimize difficulties that may be associated with the provision of care under such circumstances.

Age Factors↗
PubMed1996

Growth regulation by peroxisome proliferators: opposing activities in early and late G1.

Peroxisome proliferators (PPs) are a diverse group of nongenotoxic rodent liver carcinogens. One potential mechanism for the carcinogenicity of PPs is epigenetic modulation of growth-regulatory signal transduction pathways. We investigated the effects of PPs on growth-regulatory gene expression and cell proliferation in immortalized mouse liver cells, comparing PPs with other growth regulators and tumor promoters of known activity. The PPs Wy-14643, mono-ethylhexyl phthalate, clofibrate, and ciprofibrate ethyl-ester were found to be potent inducers of immediate-early gene expression (including c-fos, c-jun, junB, egr-1, NUP475, and to a lesser extent fosB, JE, and KC, with maximal expression seen 1 h after treatment of serum-deprived quiescent cells. The gene induction was potently inhibited by protein kinase inhibitor H7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride] but not by H8 [N-¿2-(methyl-amino)ethyl¿-5-isoquinolinesulfonamide dihydrochloride], indomethacin, or nordihydroguaiaretic acid. Compared with other growth regulators, the profile of PP-induced gene expression was most similar to that induced by arachidonic acid and eicosatetraynoic acid. The induction of immediate-early gene expression by PPs was followed by enhanced progression into S phase (DNA synthesis) when quiescent cells were treated with the PPs for only 1 h, washed, and then incubated without PPs. However, no stimulation of DNA synthesis was seen when the PPs were continually present. Furthermore, the PPs inhibited serum-induced DNA synthesis, even when they were added 6 h after serum stimulation (in late G1). Dehydroepiandrosterone-sulfate, a unique PP in being a steroid, had no detectable effect on immediate-early gene expression, did not stimulate DNA synthesis when applied for only 1 h, but did inhibit serum-induced DNA synthesis. Thapsigargin and A23187 mimicked this mitoinhibitory activity of PPs, suggesting that calcium mobilization by PPs might be involved. Our results demonstrate that PPs can modulate cell proliferation either by a stimulatory activity that functions in early G1, associated with activation of immediate-early gene expression, or by an inhibitory activity that functions in late G1; both activities could potentially play a role in tumor promotion by PPs.

Animals↗
PubMed1996

Human liver S-9 metabolic activation: proficiency in cytogenetic assays and comparison with phenobarbital/beta-naphthoflavone or aroclor 1254 induced rat S-9.

Induced rat liver S-9 is routinely used for metabolic activation in cytogenetic assays. When a compound gives a positive test result only with rat S-9, the significance for humans should be assessed. To evaluate the use of human S-9, we used sister-chromatid exchanges (SCEs) and chromosome aberrations (Abs) in Chinese hamster ovary cells to test five pro-mutagens, each preferentially activated by a different family of P-450: benzo(a)pyrene (BP), dimethylnitrosamine (DMN), diethylnitrosamine (DEN), aflatoxin B1 (AFB), and 2-acetylaminofluorene (2-AAF). We tested two human S-9 preparations, one from a single liver and a second pooled from two livers known to have good activity for several P-450s. Concentrations and ratios of NADP and isocitrate were adjusted to optimize NADPH generation by the S-9. Abs were scored 20 hr, and SCEs 29-45 hr, after the beginning of a 3 hr treatment. P-450 enzyme activities were generally higher in rat than human S-9. With the single-liver human S-9, increase in SCEs were seen with all chemicals; with both human S-9s, increases in Abs were seen with all chemicals except BP. (The level of P-450 1A1, required for BP activation, is very low in human liver.) Compared with rat S-9, generally higher concentrations of human S-9 and of promutagens were required to see positive results. However, human S-9 effectively activated 2-AAF, whereas neither of the two types of rat S-9 produced Abs with 2-AAF. We also compared rat S-9s induced with Aroclor 1254 or phenobarbital/ beta-naphthoflavone (PB/beta NF). Although there were some differences in P-450 enzyme activities, these did not translate into differences in Abs induction. At low doses of AFB and of BP, PB/beta NF induced S-9 appeared more effective than Aroclor 1254 induced S-9.

2-Acetylaminofluorene↗
PubMed1996

Direct isolation of longevity mutants in the nematode Caenorhabditis elegans.

We have isolated several new EMS-induced, long-lived mutants of Caenorhabditis elegans, using a novel screen that eliminates the need for replica plating. Three new alleles of age-1 (z10, z12, and z25) were identified by failure to complement age-1 (hx546) for life span extension; these alleles had life spans ranging from 18.9 to 25.9 days at 25 degrees C, with an average 46% increase in life span. After backcrossing, alleles were examined in a wild-type background for resistance to several environmental stresses: heat (35 degrees C), ultraviolet (UV) light (20 J/m2), and hydrogen peroxide (H2O2) (0.5 M). Two replicates of the test of thermotolerance were completed on each strain, giving mean survivals of 842 min (hx546), 810 min (z10), 862 min (z12), and 860 min (z25), compared to 562 min for wild type. All the age-1 alleles were significantly tolerant, compared with wild type (P < 0.001). Two replicates for UV resistance were also completed with mean survivals of 103, 118, 108, and 89 hr, respectively, compared to 72 hr for wild type. One test of hydrogen peroxide resistance has shown that z12 and N2 had a mean survival of 41 hr, while the other age-1 alleles had mean survival of 54 hr (z10), and 62 hr (z25); H2O2 resistance is the only environmental stress that differentiates among the age-1 alleles.

Animals↗
PubMed1996

Quantitative trait loci for ethanol sensitivity in the LS x SS recombinant inbred strains: interval mapping.

We are mapping the genes (quantitative trait loci or QTLs) that are responsible for individual differences in ethanol sensitivity, measured as the duration of loss of righting, reflex (LORR) and blood ethanol concentrations upon recovery of the righting reflex (BEC). The Long-Sleep (LS) and Short-Sleep (SS) selected lines of mice manifest an 18-fold difference in LORR and serve as a rodent model for ethanol sensitivity. The LS x SS recombinant inbred (RI) series, developed from LS and SS lines, are an important resource for QTL mapping of ethanol-related responses. The current report summarizes the initial QTL analysis of LORR and BEC in the LS x SS strains and compares the results of correlational analysis with an interval-mapping approach. The data provide strong evidence for QTLs that influence ethanol sensitivity on mouse chromosomes 1 and 2 and possible QTLs on chromosomes 1, 3, 4, 5, 6, 7, 12, 13, 16, and 18. These results are compared to those from an F2 cross which confirms QTLs on chromosomes 1, 2, 4, and 18.

Alcohol Drinking↗
PubMed1996

Strain distribution patterns for genetic markers in the LSXSS recombinant-inbred series.

We present the strain distribution patterns (SDPs) of 118 SSLP markers and three pigmentation genes that have been characterized in 27 strains from the LSXSS RI series. This coarse map provides a resource for linkage studies of phenotypes that are heritable in the LSXSS RI series. The LSXSS recombinant inbred (RI) strains were derived from the Long-Sleep (LS) and Short-Sleep (SS) selected lines of mice that were selected for differential sensitivity to ethanol but are also differentially sensitive to a variety of other alcohols, barbiturates, sedative hypnotics, and general anesthetics. Since the parents were not inbred, two atypical factors are present in these SDPs. First, more than two alleles are frequently found in these RIs, and second, some alleles can be uniquely associated with one or the other parent while other alleles may be found in both parental lines. To validate the markers found in the parental line, we genotyped all parental mice from one generation of both the LS and SS lines, thus leading to a set of marker SDPs that are useful for further phenotypic association and identification of provisional QTLs.

Alleles↗
PubMed1996

Genetic models in the study of anesthetic drug action.

This chapter reviews the use of genetic models in the study of anesthetic drug action. Genetic model systems provide a novel approach to understanding mechanisms of anesthetic drug action. Many models have been derived using selection processes that emphasize differential drug sensitivity, producing animal lines that differ in their CNS drug response. Studies of vertebrate (rodent) and invertebrate (Drosophila, Caenorhabditis elegans) animal model systems are covered. The review discusses studies employing lines derived from spontaneous and induced mutagenic processes, selectively bred lines, and inbred lines possessing inherent differential drug sensitivities. The primary focus of included studies is the general anesthetic drugs that are commonly used in the clinical setting. These are drugs such as the inhalational agents (halothane, enflurane, isoflurane, nitrous oxide) and the intravenous induction agents (propofol and diazepam). Rodent lines with differential sensitivity to opiates are also discussed. Finally, an approach to identifying and isolating the genes that control anesthetic sensitivity is discussed in a section on mapping quantitative trait loci (QTL) in recombinant inbred lines.

Anesthetics↗
PubMed1996

Orbital infections in patients with human immunodeficiency virus infection.

BACKGROUND: Opportunistic infections frequently involve the anterior and posterior segments of the eye but rarely occur in the orbit in patients with human immunodeficiency virus (HIV) infection. The authors managed eight patients with HIV and unilateral orbital infections who presented between July 1988 and March 1995. METHODS: Records of the patients were reviewed. A literature review of orbital infections in patients infected with HIV also was conducted. RESULTS: There were five men and three women, with a mean age of 33.8 years. The mean CD-4 cell count from five of the eight patients was 18.4 cells/mm3. Invasive aspergillosis was the most common orbital infection occurring in four patients, all of whom had contiguous sinus involvement and intracranial extension. Orbital cellulitis with subperiosteal abscesses secondary to ethmoiditis caused by Propionibacterium acnes and Pseudomonas aeruginosa developed in two patients. Orbital cellulitis and panophthalmitis secondary to Staphylococcus aureus endogenous endophthalmitis developed in one patient, and one patient had presumed syphilitic optic neuritis, orbital periostitis, and necrotizing vasculitis. Five patients had permanent visual loss, including four who had loss of light perception. Four patients died of orbital diseases within 1 year of presentation, and three deaths were attributed to intracranial spread of Aspergillus fumigatus. Other organisms reported in the literature that caused orbital infections in patients with HIV include Rhizopus arrhizus, Toxoplasma gondii, and Pneumocystis carinii. CONCLUSION: Opportunistic infections of the orbit from bacterial, fungal, and parasitic organisms should be recognized as a serious complication of systemic HIV infection and are associated with a high ocular morbidity and mortality rate.

AIDS-Related Opportunistic Infections↗
PubMed1996

Genetic analysis of ageing: role of oxidative damage and environmental stresses.

Evolutionary theory predicts substantial interspecific and intraspecific differences in the proximal mechanisms of ageing. Our goal here is to seek evidence for common ('public') mechanisms among diverse organisms amenable to genetic analysis. Oxidative damage is a candidate for such a public mechanism of ageing. Long-lived strains are relatively resistant to different environmental stresses. The extent to which these stresses produce oxidative damage remains to be established.

Aging↗
PubMed1996

Mapping quantitative trait loci affecting life history traits in the nematode Caenorhabditis elegans.

We have identified chromosomal regions containing quantitative trait loci (QTLs) specifying life history traits in recombinant-inbred strains of the nematode Caenorhabditis elegans. This approach also allows us to examine epistatic interactions between loci and pleiotropic effects on different traits at specific loci. QTLs for mean life span were identified on chromosomes II (near stP101), IV (stP5) and the X (stP61), and QTLs for fertility were identified on II (maPI), III (stP19) and IV (stP51). The QTLs for mean life span accounted for 90% of the genetic component of variance. The loci for mean fertility accounted for 88% of the genetic component of variance. Additional QTLs for temperature-sensitive fertility [II (stP36) and V (stP6)] and internal hatching [IV (stP5)] were also mapped in these crosses. We found evidence for epistatic effects on mean life span between maP1 and bP1 (V), and for epistatic effects on mean fertility between stP36 and stP6, between stP98 (II) and stP192 (V), between maP1 and stP127 (III), between maP1 and stP103 (X), and between stP5 and stP6. Negatively correlated, pleiotropic effects on mean life span and internal hatching were found linked to stP5.

Animals↗
PubMed1996

A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans.

A variety of mechanisms have been proposed to explain the extension of adult life span (Age) seen in several mutants in Caenorhabditis elegans (age-1: an altered aging rate; daf-2 and daf-23: activation of a dauer-specific longevity program; spe-26: reduced fertility; clk-1: an altered biological clock). Using an assay for ultraviolet (UV) resistance in young adult hermaphrodites (survival after UV irradiation), we observed that all these Age mutants show increased resistance to UV. Moreover, mutations in daf-16 suppressed the UV resistance as well as the increased longevity of all the Age mutants. In contrast to the multiple mechanisms initially proposed, these results suggest that a single, daf-16-dependent pathway, specifies both extended life span and increased UV resistance. The mutations in daf-16 did not alter the reduced fertility of spe-26 and interestingly a daf-16 mutant is more fertile than wild type. We propose that life span and some aspects of stress resistance are jointly negatively regulated by a set of gerontogenes (genes whose alteration causes life extension) in C. elegans.

Animals↗
PubMed1996

Hypothesis: interventions that increase the response to stress offer the potential for effective life prolongation and increased health.

In the last decade it has become evident that many laboratory manipulations, both genetic and environmental, can lead to significant life extension. All or almost all of the observed life-extension phenotypes are associated with increased resistance and/or ability to respond to environmental stress. These observations show dramatically that life span is not maximized. We suggest that latent within many species-perhaps even humans-is the ability for large increases of life expectancy. The striking correlation between the increased stress resistance of all long-lived mutants in C. elegans and other species and the increased resistance of dietary restricted rodents to environmental toxins is consistent with an evolutionary conservation of a life-span maintenance/environmental stress resistance program. We suggest that it may be possible to develop methods for life extension in mammals, including humans, using relatively straightforward manipulations, such as drug treatments. It should be obvious that these findings have tremendous implications for human society at large, and we suggest that the implications of these findings should be explored.

Aging↗