The effect of compressive loading on proteoglycan turnover in cultured fetal tendon

A fibrocartilaginous tissue develops in tendon at the point where the tendon wraps under bone and is subjected to transverse compressive loading in addition to tension. This tissue is characterized by a high level of large proteoglycan (aggrecan), which could accumulate because of increased synthesis, diminished turnover, or both. To examine the effect of loading on proteoglycan turnover segments of fetal tendon in sterile culture were subjected to cyclic, uniaxial compression loading to 30% of initial thickness once every 6 sec. for 72 h, and then allowed to incorporate 35S-sulfate for 12 h. The rate of loss of newly-synthesized 35S-proteoglycans from tissue was determined during subsequent culture for up to 12 days, with or without continued loading. Proteoglycan was lost from fetal tendon segments rapidly during the first 3 days of culture and slowly thereafter. Loss of newly-synthesized proteoglycan from adult tendon fibrocartilage was linear, with a half life of 12 d. Segments of fetal tendon subjected to cyclic compression before labeling synthesized more proteoglycan. These segments lost a greater percent of labeled proteoglycan to medium during a subsequent 12-day culture period than matched segments that had not experienced loading. Analysis of medium and tissue proteoglycans by SDS polyacrylamide gel electrophoresis and sieve chromatography indicated that small proteoglycans (decorin and biglycan) were retained in both loaded and non-loaded tissue whereas large proteoglycans (migrating in the Vo of a Sepharose CL-4B column) were readily lost. It is concluded that the 3-day loading regimen did not diminish turnover of large proteoglycan. To the contrary, although synthesis of large proteoglycan was enhanced by the loading regimen, these proteoglycans were still rapidly lost from the fetal tissue.     

Dissolution kinetics of phenylbutazone

This study investigated the possible effects of simultaneous, noninstantaneous, reversible chemical ionization of carbon acids on the dissolution of a typical pharmaceutical carbon acid, phenylbutazone, and its deutero analog. The dissolution rate versus pH profile for phenylbutazone was consistent with phenylbutazone acting as if it were an acid where the ionization can be considered instantaneous. In view of the dissolution behavior of phenylbutazone under various conditions, it is unlikely that the noninstantaneous ionization kinetics demonstrated for this compound play a major role in determining the dissolution rate, either in vitro or in vivo, since the average residence time in a typical aqueous diffusion layer for phenylbutazone dissolution is longer than the reaction time for its ionization. Slowing the reaction time with a primary isotope effect by deuterium substitution for the ionizable proton caused significant deviation from classical behavior for d-phenylbutazone.     

Changes of bone-perfusion in osteosynthesis of the femur with a marrow-nail (author's transl)

The perfusion of the bone in the hind leg after osteosynthesis (nailing of the bone-marrow) was studied. In 11 shepherd dogs (bastards) an osteotomy of the femur was done; it was treated with a marrow-nail without boring the marrow-cavity. With the "tracer-microsphere"-method the perfusion of femur, tibia and talus of both hind legs was measured. Measurements were performed before and after surgery, in 10 dogs 2 weeks and in 8 dogs 6 weeks after surgery. Immediately after the operation the perfusion was reduced considerably in all the examined bones of the operated leg. Two weeks later the perfusion was increased in all bones of both hind limbs. In the cancellous bone of the femur the perfusion reached the original preoperative values after 6 weeks; in cortical bone a further increase of the perfusion was noted. This increase was most marked in the cortical bone of the operated femur; it was less in the cortical bone of the other bones.     

Renal resistive index in experimental partial and complete ureteral obstruction

RATIONALE AND OBJECTIVES: Recent clinical work suggests that the Doppler resistive index (RI) may be useful in distinguishing obstructive from nonobstructive hydronephrosis. We evaluated the usefulness of the RI in a rabbit model of hydronephrosis. METHODS: Unilateral partial ureteral obstruction was produced in nine rabbits and complete obstruction in another nine. Three sham operations were performed, and these animals served as control subjects. The RI was measured in all kidneys before and 6 hr after surgery and on days 1, 4, and 7 postoperatively. The RI and the difference in RI (delta RI) between the obstructed and normal kidney were evaluated over time using a two-way analysis of variance. The intravenous urography and Whitaker tests served as gold standards. RESULTS: Hydronephrosis was observed on sonograms in all obstructed kidneys. Comparing groups, there was no significant difference in mean RI or delta RI between the three groups at any time point. Looking at individual groups over time, there was no significant change in mean delta RI, whereas the change in mean RI was significantly elevated above baseline only in the complete obstruction group at 6 hr (p = .002) and on days 4 (p = .008) and 7 (p = .006). In evaluating varying thresholds of RI and delta RI, we could not consistently discriminate between normal and obstructed kidneys. CONCLUSION: Although complete obstruction caused a significant increase in RI, partial obstruction failed to do so. RI and delta RI values proved to be insensitive predictors of obstruction in this rabbit model.     

Structural and functional characterization of proteolytic fragments derived from the C-terminal regions of bovine fibrinogen

A number of new as well as previously described fragments derived from the D region of bovine fibrinogen by limited proteolysis have been characterized by sequence analysis, differential scanning calorimetry and circular dichroism. Determination of the extremities of the polypeptide chains forming individual fragments allowed the scheme of proteolysis and the borders between domains in the D region of fibrinogen to be established. It was also found that the most thermostable region of the D fragment (TSD) can be substantially reduced in size without loss of its compact structure. The alpha-helical content of the newly prepared 21-kDa TSD2 and 16-kDa TSD3 fragments were 82% and 75%, respectively, strongly supporting a coiled-coil structure for this region of the fibrinogen molecule. The DX and DZ fragments, prepared from a chymotryptic digest of the DLA fragment, were found to be similar to the DL and DY fragments, respectively, except for an internal cleavage at K393-T394 in their beta chains. This cleavage leads to destabilization of all thermolabile domains, indicating interaction between them. The DL and DY fragments, containing only one polymerization site in their beta chains, were able to inhibit fibrin polymerization at high concentration. However, these same fragments failed to bind to fibrin-Sepharose under conditions where their structural analogues, DX and DZ, were tightly bound, indicating that cleavage after K393 substantially increases the affinity of this site.     

Prenatal diagnosis of partial monosomy 13q associated with occipital encephalocoele in a fetus

The pre- and postnatal findings of a fetus with a de novo del(13)(pter-->q21:) and an occipital encephalocoele are described. Maternal serum alpha-fetoprotein (AFP) screening at 19 weeks' gestation demonstrated a high level of 2.5 multiples of the median (MOM) and ultrasonography at 27 weeks' gestation showed severe intrauterine growth retardation, cardiomegaly, an occipital encephalocoele, and a calvarial defect. Genetic amniocentesis revealed a karyotype of 46,XX,del(13)(pter-->q21:). The proband postnatally displayed additional abnormalities such as microphthalmia, hypertelorism, large low-set ears, and micrognathia. We discuss the association of central nervous system (CNS) malformations with 13q deletions and emphasize that pregnancies with neural tube defects warrant cytogenetic analysis, especially when additional fetal abnormalities and neonatal dysmorphism are observed.     

Resurgence of derived stimulus relations

Resurgence has been shown in human and nonhuman operant behavior, but not in derived relational responses. The present study examined this issue. Twenty-three undergraduates were trained to make conditional discriminations in a three-choice matching-to-sample paradigm. The training resulted in three equivalence classes, each consisting of four arbitrarily configured visual stimuli. The same 12 stimuli were then reorganized, and the conditional discrimination training was repeated such that three new classes were possible. In a subsequent test of derived relations, most subjects showed response patterns that were consistent with the altered conditional discriminations. Subjects were then exposed to conditional discrimination trials under extinction. Most subjects continued to respond consistently with the most recently reinforced conditional discrimination trials. During the next phase, subjects were exposed to symmetry and equivalence trials. Responses consistent with the most recent training produced feedback saying that the responses were incorrect, whereas other responses produced no feedback. Most subjects showed a resurgence of responding that was consistent with their earlier training. Finally, subjects were exposed to conditional discrimination trials carried out in extinction. Most subjects continued to show a resurgence of responding that was consistent with their early training.