A 32-33 bp highly repeated DNA sequence, TkS1, has been isolated from genomic DNA of the newt Triturus karelini digested with the restriction endonucleases HaeIII or AluI. TkS1 is known to be ...localised in the centromeric heterochromatin of all the chromosomes in T. karelini and the related species T. cristatus. TkS1 has been shown to be present in varying amounts in the genomic DNA of a range of species of Triturus, including representatives of the two main subgenera Triturus and Palaeotriton. A programme of sequencing of monomers, dimers and trimers of TkS1 was carried out in order to determine the level of conservation of the sequence within and between species of Triturus. Altogether 204 monomer (32/33 bp) clones were made of TkS1 from three individuals of T. karelini, and one individual each of T. cristatus, T. carnifex, T. dobrogicus and T. marmoratus, all members of the subgenus Triturus and the cristatus species group. A number of dimer (64 bp) and trimer (96 bp) clones were also made from DNA of a single specimen of T. karelini digested with HaeIII or AluI. Three distinct types of TkS1 were identified in all species examined, except for T. marmoratus where only two of the types were found. The types were distinguished on the basis of certain recurring divergent patterns in monomers sequenced from T. karelini. Type 1 is mainly characterised by the presence of an AluI site at positions 24-27 and type 3 mainly by the presence of an additional base (C) at position 14. Type 2 normally lacks the AluI site and the C at position 14, as well as having a number of other distinguishing features. TkS1 and its three types have remained remarkably constant in sequence since before the divergence of T. marmoratus from other species in the cristatus species group, about 10 million years ago. Examination of all 204 monomer clones and comparison with consensus sequences for the three types shows less than 5% divergence at any one position in the sequence. There is good evidence from examination of dimer and trimer clones of TkS1 that the different types are intermingled with each other, and all three types are likely to be present on all chromosomes. Dimeric (64 bp) TkS1 clones constructed from AluI fragments of T. karelini DNA show evidence of a trimeric (96 bp) "supertype" with the pattern type 1-type 3-type 1 that is much more common than would be expected on a random basis.
Objectives: The sensitivity of one plasma and two urinary methods to assess zinc absorption after oral dosing were compared over the dose range of 10 to 100 mg. Methods: Eleven healthy subjects ...participated in this four-way crossover design study. After an overnight fast, the subjects received a single oral dose of zinc acetate corresponding to 10, 25, 50, or 100 mg of elemental zinc. Plasma zinc concentrations were measured at baseline (pre-zinc administration) and hourly intervals post-zinc administration for 9 hours. Urine was collected for 24 hours prior to and for 24 hours after zinc administration. During this 48-hour period, subjects consumed an isocaloric, caffeine-free diet containing 18 mg of elemental zinc per day. Results: The area under the plasma zinc concentration versus time curve (PZAUC) increased linearly with doses between 10 and 50 mg, then flattened out. By contrast, urinary zinc excretion was approximately linear with doses in the 25 to 100 mg range, but no differences were observed in urinary zinc excretion after doses of 10 and 25 mg. Conclusions: Plasma zinc concentration is a useful method of evaluating oral zinc absorption from doses of 10 to 50 mg. Urinary zinc excretion is an alternative method of assessing zinc absorption, particularly when doses of 50 to 100 mg of elemental zinc are administered
The distribution and number of Peyer's patches (5) in two species of marsupial mice, Antechinus swainsonii and Antechinus stuartii was found to be the same even though the length of the intestine in ...the latter species was half that of the former. Both species lack a caecum and appendix. The position of the Peyer's patches is unusual in that the first three Peyer's patches are on the right side of the small intestine whereas the penultimate and ultimate Peyer's patches are large, contain many lymphoid follicles and are in an anti-mesenteric position in the small intestine and sometimes in the large intestine (ultimate Peyer's patch). The number of Peyer's patches in eutherian mice of similar size, and intestinal length is greater (13) although the number of Peyer's patch lymphoid follicles per centimeter intestine is less (1.8) than in A. swainsonii (4) and A. stuartii (4.4). Marsupial mice have most of their lymphoid follicles confined to a few large Peyer's patches, whereas eutherian mice have fewer lymphoid follicles per unit intestinal length, more Peyer's patches (with fewer lymphoid follicles) evenly distributed along the intestine and more single lymphoid follicles interspersed between them.
Involution of the thoracic thymus in two species of marsupial mouse, Antechinus swainsonii (Waterhouse) and Antechinus stuartii (Macleay) was shown to be unrelated to corticosteroid action and to be ...complete before puberty. A stress response in male marsupial mice is caused by an androgen related drop in the plasma corticosteroid binding globulin concentration which gives rise to an increase in the plasma free glucocorticoid concentration. The high concentrations of free glucocorticoids in the plasma just prior to the breeding season causes a rapid involution of the spleen and lymph nodes while the gut associated lymphoid tissues remain unaffected. The concentration of free glucocorticoids also rises in females, but it never attains the high concentrations observed in males. Nevertheless, the spleen and lymph nodes do involute to some extent in some females and the degree of involution appears to be related to the relative concentration of plasma free glucocorticoids. At the conclusion of the breeding season, there is a complete mortality in males of the population, due to a stress response in which the compromised immune system clearly plays a role.
We assessed the efficacy of a high-molecular-weight hydroxypropylmethylcellulose (K8515) as a cholesterol-lowering agent, the dose-response profile of its action, and the ability of adult subjects to ...tolerate its ingestion at effective doses.
These studies were conducted at the Clinical Research Center of The University of Michigan Hospitals, Ann Arbor. Efficacy was assessed in 10 normal and 12 mildly hyperlipidemic subjects in double-blind, randomized crossover trials of 1 and 2 weeks' duration, respectively. The dose-response profile was studied in 12 mildly hypercholesterolemic subjects in a nonrandomized control trial with doses given in escalating order. Tolerance was assessed by a questionnaire of adverse effects and bowel movement habits in all subjects.
We found that 10 g of K8515 ingested in a prehydrated form three times a day with meals lowered total cholesterol levels by an average of 1.45 mmol/L (56 mg/dL) (32%) in normal subjects within 1 week. In two studies in subjects with mildly elevated cholesterol levels (with entry levels ranging from 5.35 mmol/L 207 mg/dL to 6.70 mmol/L 260 mg/dL), average reductions of 1.00 mmol/L (39 mg/dL) (18%) and 1.15 mmol/L (45 mg/dL) (20%) were observed within the same period. The effect was primarily due to a reduction in low-density lipoprotein cholesterol levels. Low-density lipoprotein levels in normal subjects were an average of 1.10 mmol/L (42 mg/dL) (38%) lower after a week of 10 g of K8515 three times a day with meals, and in the two studies in subjects with mild hyperlipidemia, the reductions in low-density lipoprotein levels after 1 week were 0.95 mmol/L (37 mg/dL) (23%) and 1.05 mmol/L (40 mg/dL) (25%). Although there was a tendency for high-density lipoprotein cholesterol levels to decrease, this was significant only in normal subjects. Decreases in cholesterol levels were not accompanied by any rise in triglyceride levels. Dose-response studies in those with mildly elevated cholesterol levels indicated that it is possible to achieve a 15% decrease in low-density lipoprotein cholesterol levels within 1 week at a dose of 6.7 g three times a day, with minimal adverse effects.
These results suggest a role for high-molecular-weight hydroxypropylmethylcellulose in the clinical treatment of mild hypercholesterolemia.
