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Experimental leprosy with Mycobacterium lepraemurium in hairless mice (Mus musculus).

Forty-three homozygous albino hairless mice (Mus musculus) were inoculated intradermally on the head, back, sides and base of the tail with suspensions of lepromatous tissue containing numerous Mycobacterium lepraemurium (Hawaiian strain). Visible nodules were noted in all mice. These lepromatous nodules enlarged slowly and often merged with each other, covering up to two thirds of the dorsum. Several mice became blind during the course of the infection. All of the mice died or were killed 68 to 287 days following inoculation. Post-mortem examinations on representative mice showed, in addition to observed cutaneous lesions, generalized systemic murine leprosy. Smears and histological sections from nodules, skin, lymph nodes, spleen, liver, kidney, heart and lung were positive for acid-fast bacilli. The cysts in the skin (which are degenerated hair follicles filled with keratin-like material and which are one of the characteristics of hairless mice) contained scattered acid-fast bacilli, but no acid-fast globi. Ten mice with hair (M. musculus) which were used as controls did not reveal noticeable cutaneous nodules; however, all developed generalized visceral leprosy similar to that of the hairless M. musculus. Thus, hairless mice (with thymus) can be looked upon as a model for studying experimental cutaneous leprosy.

Animals↗

The combined procedures of Ficoll-Paque centrifugation and anion exchange separation for the recovery of trypanosomes from blood and other tissues.

The conventional method of separating African trypanosomes from infected blood using a DEAE-cellulose (Whatman Chromedia, DE-52) column was modified by the inclusion of an initial centrifugation step employing the density gradient medium, Ficoll-Paque. On centrifugation in this medium using diluted infected rodent blood the trypanosomes moved into the buffy coat interphase which consisted mainly of lymphocytes with a few contaminating RBCs and neutrophils. The buffy coat interphase layer was withdrawn, washed, resuspended and the trypanosomes finally separated from the contaminating blood cells by passage through buffer-equilibrated DE-52 packed in a 25 ml syringe barrel, representing a considerable saving of DE-52 over the conventional method. The centrifugation step was applied to the investigation of other tissues of infected rodents, such as bone marrow, brain, spleen, liver, lymph nodes, kidney and testis, for the presence of trypanosomes. Using the combined procedure, high recoveries of purified brucei group trypanosomes were obtained from bone marrow, brain, spleen and lymph nodes.

Animals↗

Alcohol dehydrogenase (ADH) independent ethanol metabolism in deermice lacking ADH.

To assess the importance of non-ADH ethanol metabolism, ADH-negative (ADH-) and ADH-positive (ADH+) deermice were fed for 2-4 weeks liquid diets containing ethanol or isocaloric carbohydrate. They consumed progressively increasing amounts of ethanol. Blood ethanol clearance (BEC) increased significantly in both strains. It remained almost unchanged at low ethanol concentrations (5-10 mM), but at high levels (40-70 mM) BEC was strikingly increased with significant differences between ethanol-fed and control animals. Kinetics were consistent with the activity of a non-ADH high Km system such as the microsomal ethanol-oxidizing system (MEOS). Naive ADH- had a more active MEOS and more abundant SER than naive ADH+. After ethanol feeding, MEOS was increased 3-4 times in both strains. There was striking proliferation of SER and cytochrome P-450 was enhanced significantly. Expressed per P-450, MEOS activity was higher in ADH- than ADH+. Thus despite absence of ADH, ADH- deermice can consume large amounts of ethanol: this is associated with increased BEC, SER proliferation, enhanced MEOS activity and quantitative and qualitative changes of cytochrome P-450.

Alcohol Dehydrogenase↗

Antigenic variation in African trypanosomes by gene replacement or activation of alternate telomeres.

We have analyzed antigenic variants with a known lineage and show that there are several telomeres on which variant surface glycoprotein (VSG) genes can be expressed. These telomeres have similar restriction maps 5' to the barren region. In addition, the same VSG gene was expressed on different telomeres. Some antigenic switches in the lineage were accomplished by duplicative replacement of one VSG gene with another. Other switches occurred without duplication by transcriptional activation of an alternate telomeric VSG gene. We call the latter process telomeric activation and propose that these two processes can occur independently. We further propose that antigenic switching by telomeric activation is mediated by the regulatory system that controls which telomere is transcriptionally active, while the duplicative mechanism does not.

Animals↗

ICAAC 1993.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Neuroendocrine regulation of seasonal reproductive activity in the male golden hamster.

Golden (Syrian) hamsters are seasonal breeders. Under natural photoperiodic conditions, their reproductive systems are functional during spring and summer and atrophic during the fall and winter. This reproductive cycle can be duplicated in the laboratory by exposing the animals to artificially-created photoperiods. The endocrine correlates of photoperiod-induced changes in reproductive activity of the male hamster are fairly well characterized, but the neural control of seasonal reproductive activity has not been as extensively studied. Recent studies indicate that short day (less than 12.5 hr light/day) exposure leads to complex changes in central neurotransmitter metabolism, as well as neurotransmitter and hormonal receptor content, which, in turn, are reversed by exposure to long days or during the period of spontaneous testicular recrudescence. Many of these endocrine and neuroendocrine changes are dependent on the presence of the pineal gland, but photoperiod-induced changes in neurotransmitter metabolism have also been described in pinealectomized hamsters. Further studies of the neuroendocrine transduction of photoperiodic signals will not only provide a better understanding of seasonal reproductive and metabolic activities, but will increase our basic understanding of the neural control of the endocrine system.

Animals↗

The development of visual acuity in the Mongolian gerbil (Meriones unguiculatus).

The development of visual acuity for vertically oriented gratings was followed in gerbil pups from 34 days of age until adulthood using a jumping stand procedure. Acuity was found to improve gradually from an initial level of about 0.7 cycles/degree to asymptotic values of 1.2-1.6 cycles/degree by 70 days of age. Acuity did not vary as a function of viewing distance over the range tested (17.5-46 cm). Practice was found to play some role in the acuity changes seen but cannot alone explain the results. The contributions of other performance variables and of neural development are considered.

Animals↗

Molecular characterization of initial variants from the IsTat I serodeme of Trypanosoma brucei.

Variant surface glycoproteins (VSGs) were isolated from variant antigen types (VATs) of the IsTat 1 serodeme. Molecular weight and isoelectric focusing analysis demonstrate that seven early VSGs possess properties generally attributed to VSGs isolated from other trypanosome serodemes. Six of the seven VSGs characterized are distinct from one another, while two (D and 1) appear identical. The presence of VSG specific mRNA in corresponding VATs was demonstrated by in vitro translation of RNA from each of the VATs, followed by immunoprecipitation with homologous and heterologous antisera. Hybridization of VSG cDNA clones with RNA from each VAT confirm that VSG mRNA is present only in homologous VATs and verifies the transcriptional control of these VSG genes. The two VATs D and 1 express indistinguishable VSGs by a variety of biochemical criteria, as well as by reactivity with 24 monoclonal antibodies. The VSG mRNAs in VATs D and 1 also appear identical. However, this identity is not reflected at the genomic level. Data is presented which establishes that DNA rearrangements can occur around both expressed and non-expressed VSG genes without qualitatively affecting VSG gene expression.

Animals↗

Genomic organization of Trypanosoma brucei variant antigen gene families in sequential parasitemias.

cDNA libraries were made from mRNA purified from each of seven sequentially isolated variant antigen types (VATs) of the IsTat 1 serodeme. Plasmids containing variant surface glycoprotein (VSG) sequences corresponding to each of the isolates were used in Southern analyses to examine the genomic organization of VSG nucleotide sequences. In most cases, cells expressing a given VSG were shown to have an extra copy of the corresponding VSG gene. In one case an expression-linked copy (ELC) was not detectable. VSG gene rearrangements not obviously correlated with the expression of homologous sequences were detected in four of six VSG gene families. Thus, even cDNAs which detected an ELC revealed additional genomic reorganization in regions flanking VSG sequences. The cells used to initiate the chronic infection expressed the same VSG as those isolated from the first parasitemia. The extent of genomic rearrangement observed between these two sequentially derived populations was comparable to that observed between any of the other serially derived VATs. Thus, within a short period of time and in the absence of detectable antigenic variation, the amount of genetic flux in sequences associated with VSG genes can be substantial.

Animals↗

Preferential activation of telomeric variant surface glycoprotein genes in Trypanosoma brucei.

During an infection, Trypanosoma brucei expresses diverse variant surface glycoprotein (VSG) genes in a quasi-sequential order. Numerous VSG genes have intrachromosomal locations but many are located adjacent to telomeres. We have tested whether telomeric VSG genes are preferentially activated compared to intrachromosomal VSG genes during an antigenic switch. The frequency with which the IsTat 11 VSG gene is expressed in first relapse populations has been compared for variant antigenic types (VATs) A3 and A11. These VATs express the same A VSG gene from the same chromosome but VAT A11 contains an inactive telomeric 11 VSG gene which is absent in VAT A3. The 11 gene is activated at a much higher frequency in first relapse populations from VAT A11 than from VAT A3. A resultant VAT 11 clone was examined in detail and shown to have reactivated the telomeric 11 VSG gene. These results suggest that a telomeric location can result in a greater frequency of activation of a VSG gene. This preferential activation may explain, in part, the order of expression of VSG genes.

Animals↗

Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species.

Urate has been shown to be a major antioxidant in human serum and was postulated to have a biological role in protecting tissues against the toxic effects of oxygen radicals and in determining the longevity of primates. This possibility has been tested by determining if the maximum lifespan potentials of 22 primate and 17 non-primate mammalian species are positively correlated with the concentration of urate in serum and brain per specific metabolic rate. This analysis is based on the concept that the degree of protection a tissue has against oxygen radicals is proportional to antioxidant concentration per rate of oxygen metabolism of that tissue. Ascorbate, another potentially important antioxidant in determining longevity of mammalian species, was also investigated using this method. The results show a highly significant positive correlation of maximum lifespan potential with the concentration of urate in serum and brain per specific metabolic rate. No significant correlation was found for ascorbate. These results support the hypothesis that urate is biologically active as an antioxidant and is involved in determining the longevity of primate species, particularly for humans and the great apes. Ascorbate appears to have played little or no role as a longevity determinant in mammalian species.

Aging↗

Sex differences in the effects of neuropeptide FF and IgG from neuropeptide FF on morphine- and stress-induced analgesia.

There is evidence suggesting that the endogenous mammalian octapeptide FLFQPQRFamide (F8Fa or neuropeptide FF, NPFF) has modulatory effects on opioid-mediated analgesia in rodents. There is also substantial evidence for sex differences in opioid analgesia, whereby male rats and mice display greater levels of opioid-mediated analgesia than females. In the present study, determinations were made of the effects of NPFF and IgG from antiserum against NPFF on morphine- and restraint stress-induced opioid analgesia in male and female deer mice. Intracerebroventricular (ICV) administrations of NPFF (0.10-10 micrograms) reduced in a dose-dependent manner morphine- and stress-induced analgesia in both male and female mice, with NPFF having markedly greater antagonistic effects in the male than female mice. Additionally, ICV administrations of NPFF-IgG increased the levels of morphine- and stress-induced analgesia and significantly reduced basal nociceptive sensitivity in male mice, whereas, in female mice, NPFF-IgG had no significant effects on either opioid-mediated analgesia or nociceptive sensitivity. These results indicate that there are sex differences in the modulatory effects of NPFF on opioid-mediated analgesia.

Analgesia↗