Spatial distribution of DNA-synthesizing cells in colonic crypts of the guinea pig

The ascending colon of a guinea pig injected with tritiated thymidine was cut serially, autoradiographed and stained with periodic-acid-Schiff-hematoxylin. Maps of transversely sectioned crypts were prepared with the use of a microscope eye-piece projector. The number and angular positions of pulselabelled (DNA-synthesizing) cells around the circumference of transverse sections of the crypt were recorded. A method of “statistics of the circumference” was applied in order to find the variances of angular distances between labelled cells and thereby to find the type of arrangement of DNA-synthesizinbg cells in the crypt. The spatial distribution of DNA-synthesizing cells, both around the crypt circumference and along the crypt, was found to be non-random. While the pattern of nonrandomness around the crypt circumference is such that the DNA-synthesizing cells tend to occupy positions in the crypt circumference at maximal distances from each other, DNA-synthesizing cells along the crypt tend to occupy positions at minimal distances from each other. DNA-synthesizing cells are arranged in the crypt in rows, each consisting of several cells and each parallel to the long axis of the crypt. Apparently the dividing cell of the crypt produces either two proliferating or two differentiating cells. No evidence of differential mitosis could be found.     

Dependence of cross-bridge kinetics on myosin light chain isoforms in rabbit and rat skeletal muscle fibres

Cross-bridge kinetics underlying stretch-induced force transients was studied in fibres with different myosin light chain (MLC) isoforms from skeletal muscles of rabbit and rat. The force transients were induced by stepwise stretches (< 0.3% of fibre length) applied on maximally Ca²⁺-activated skinned fibres. Fast fibre types IIB, IID (or IIX) and IIA and the slow fibre type I containing the myosin heavy chain isoforms MHC-IIb, MHC-IId (or MHC-IIx), MHC-IIa and MHC-I, respectively, were investigated. The MLC isoform content varied within fibre types. Fast fibre types contained the fast regulatory MLC isoform MLC2f and different proportions of the fast alkali MLC isoforms MLC1f and MLC3f. Type I fibres contained the slow regulatory MLC isoform MLC2s and the slow alkali MLC isoform MLC1s. Slow MLC isoforms were also present in several type IIA fibres. The kinetics of force transients differed by a factor of about 30 between fibre types (order from fastest to slowest kinetics: IIB > IID > IIA ≫ I). The kinetics of the force transients was not dependent on the relative content of MLC1f and MLC3f. Type IIA fibres containing fast and slow MLC isoforms were about 1.2 times slower than type IIA fibres containing only fast MLC isoforms. We conclude that while the cross-bridge kinetics is mainly determined by the MHC isoforms present, it is affected by fast and slow MLC isoforms but not by the relative content of MLC1f and MLC3f. Thus, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the cross-bridge kinetics.     

Accumulation of radioiodinated tyrosine derivatives in the adrenal medulla and in melanomas

Because tyrosine and dopa can be regarded as precursors of adrenomedullary hormones and melanin, radioiodinated derivatives of these compounds were tested for their accumulation in the adrenal medulla and in melanomas of various animal species. The highest level of accumulation in the adrenal medulla was attained in mice and rats with iodinated -hydroxy--methyltyramine, and in melanomas of mice with iodinated -methyltyrosine. The results could not be reproduced to the same extent in other species.     

HER2-targeted therapy reduces incidence and progression of midlife mammary tumors in female murine mammary tumor virus huHER2-transgenic mice.

PURPOSE: This study examined the effectiveness of early and prolonged mu4D5 (the murine form of trastuzumab/Herceptin) treatment in transgenic mice that overexpress human HER2 (huHER2), under the murine mammary tumor virus promoter, as a model of huHER2-overexpressing breast cancer. EXPERIMENTAL DESIGN: Mice were randomly assigned to one of three treatment groups and received i.p. injections from 17 weeks of age until either 52 weeks of age or morbidity. Fourteen mice received 100 mg/kg mu4D5, 14 mice received 100 mg/kg antiherpes simplex virus glycoprotein D control antibody, and 11 mice received a diluent control. RESULTS: High levels of huHER2 expression were detectable in mammary glands of young virgin founder mice. Mammary adenocarcinomas were frequently found in female founders and progeny at an average age of 28 weeks, with some progressing to metastatic disease. The incidence of mammary tumors was significantly reduced, and tumor growth inhibition was observed in mice receiving mu4D5 compared with control mice. In addition, Harderian gland neoplasms, highly associated with overexpression of huHER2 in this transgenic line, were entirely absent in the mu4D5 treatment group, indicating down-regulation of huHER2 in vivo activity. CONCLUSIONS: Early intervention with mu4D5 was of benefit in our transgenic mice at high risk for developing huHER2-overexpressing breast cancer. This study suggests a potential benefit of early treatment with Herceptin in HER2-positive primary breast cancer.     

Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat

Conjugated linoleic acid (CLA) may decrease adiposity and improve blood lipid profiles under some conditions. The goal of this study was to determine the effects of CLA supplementation on blood lipid profiles and adiposity of rats fed a diet containing a primarily saturated fat versus a diet containing a primarily unsaturated fat. Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four diets containing coconut oil, coconut oil with CLA, corn oil or corn oil with CLA. After 28 days, blood was collected and serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TG) were assessed. Food intake, body weights, and epididymal fat pads were measured. No significant differences (p>0.05) were noted among groups for amount of food consumed, weight gained, food efficiency ratio or serum TG concentrations. TC concentrations were lower (p<0.05) in the CLA-supplemented rats that were fed coconut oil but not those consuming corn oil. Serum HDL-C was lower (p<0.05) in rats consuming corn oil but was not significantly different (p>0.05) for CLA supplemented groups. Epididymal fat pads weighed significantly more (p<0.05) in the coconut oil fed group compared to the corn oil fed group, but there was no significant difference (p>0.05) between the corn oil and coconut oil + CLA group. Overall, this study suggests that CLA is more beneficial for control of blood lipids and adiposity when supplemented to a diet rich in saturated versus unsaturated fat.     

Osseointegration of porous titanium and tantalum implants in ovariectomized rabbits: A biomechanical study

BACKGROUNDToday, biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty. Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant, and their ability to withstand functional loads.AIMTo compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits.METHODSThe study was performed in 50 female California rabbits divided into non-ovariectomized (non-OVX) and ovariectomized groups (OVX) at 6 mo of age. Rabbits were sacrificed 8 wk after the implantation of four biomaterials [TTM, CONCELOC, Zimmer Biomet''s Trabecular Metal (TANTALUM), and ATLANT] in a 5-mm diameter defect created in the left femur. A biomechanical evaluation of the femur was carried out by testing implant breakout force. The force was gradually increased until complete detachment of the implant from the bone occurred.RESULTSThe breakout force needed for implant detachment was significantly higher in the non-OVX group, compared with the OVX group for all implants (TANTALUM, 194.7 ± 6.1 N vs 181.3 ± 2.8 N; P = 0.005; CONCELOC, 190.8 ± 3.6 N vs 180.9 ± 6.6 N; P = 0.019; TTM, 186.3 ± 1.8 N vs 172.0 N ± 11.0 N; P = 0.043; and ATLANT, 104.9 ± 7.0 N vs 78.9 N ± 4.5 N; P = 0.001). In the OVX group, The breakout forces in TANTALUM, TTM, and CONCELOC did not differ significantly (P = 0.066). The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC, and by 2.2 compared with TTM (P = 0.001). In the non-OVX group, the breakout force for ATLANT was significantly different from all other implants, with a reduction in fixation strength by a factor of 1.9 (P = 0.001).CONCLUSIONTANTALUM, TTM, and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone. ATLANT had significantly decreased osseointegration (P = 0.001) in healthy and in osteoporotic bone.