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Biomedical subjects

C Kowalczyk

Publications and source records attributed to C Kowalczyk.

14 recordsLinked to original sources

Pediatric and Adolescent Gynecology experience in academic and community OB/GYN residency programs in Michigan.

OBJECTIVES: The purpose of this study is to assess training in Pediatric and Adolescent Gynecology (PAG) at the Obstetrics and Gynecology (OB/GYN) resident level. SETTING: Two large Michigan programs were studied: a university-based, inner-city program, and a suburban, community-based program. Seventy-one questionnaires were distributed to the residents, and descriptive and inferential analysis of answers to demographic, training, attitude, and knowledge-based questions regarding PAG was performed. RESULTS: Sixty-one questionnaires were returned, a response rate of 86%. The majority of respondents reported no PAG rotations or clinics and recalled limited didactic sessions with only 0-2 lectures. Ninety-eight percent of university residents and 94% of community residents requested more PAG training. Comfort levels about PAG issues were assessed on a 5 point scale (1 = low, 5 = high comfort); university residents scored 3.7 with pediatric patients and 4.4 with adolescents, and community residents scored 4.0 with the pediatric age group and 4.3 with adolescents. However, both groups responded with familiarity to knowledge based questions only 61% of the time. CONCLUSIONS: OB/GYN residents in both academic and community programs report little experience and scant training in PAG but express interest in obtaining the skills and information needed. It is concerning that residents lack the basic knowledge that is required for the routine daily care of this patient population. More emphasis needs to be placed on these issues in OB/GYN residency training programs.

Adolescent↗

Coiled-coil assembly by peptides with non-heptad sequence motifs.

BACKGROUND: The seven-residue heptad repeat is the accepted hallmark of coiled coils. In extended filamentous proteins, however, contiguous patterns of heptads are often disrupted by 'skips' and 'stammers'. The structural consequences and roles of these digressions are not understood. RESULTS: In a cytoskeleton protein from Giardia lamblia, heptads flank eleven-residue units (hendecads) to give a 7-11-7 motif that dominates the sequence. Synthetic peptides made to the consensus sequence of this motif fold in solution to fully helical, parallel dimers. Both the sequence pattern and these experimental data are consistent with the coiled-coil model. We note that breaks in other extended coiled coils can also be reconciled by hendecad insertions. CONCLUSIONS: The heptad paradigm for the coiled coil must be expanded to include hendecads. As different combinations of heptads and hendecads will give different overall sequence motifs, we propose that these provide a mechanism to promote cognate protein pairings during the folding of extended coiled coils in the cell.

Amino Acid Sequence↗

Deletion in HCDR3 rescues T15 antibody mutants from a secretion defect caused by mutations in HCDR2.

We recently described mutants of the murine anti-phosphocholine Ab T15, with changes in heavy chain complementarity determining region 2 (HCDR2) that caused loss of secretion. Surprisingly, the T15 HCDR2 mutations did not alter secretion when placed into the related anti-phosphocholine Ab D16, which differs from T15 only in HCDR3 and light (L) chain. Here, we exploit the differences between these two Abs to assess the basis of the secretion defect. The T15 L chain is not secreted in the absence of heavy (H) chain. In contrast, D16 L chain is secreted in the absence of H chain, as are most L chains. We co-expressed the T15 wild-type (wt) and mutant H chains with the D16 L chain, as well as with another secreted L chain, J558L. The mutant H chains were not secreted when expressed with either heterologous L chain. These results establish that the T15 L chain is not uniquely associated with the defect. The T15 and D16 Abs also differ in HCDR3 length in that D16 lacks four amino acid residues (Ser99, Ser100, Tyr100a, Trp100b) present in T15. We deleted these four residues from T15 wt and mutant H chains. Secretion of T15 wt was unaffected by the deletion, but shortening HCDR3 restored secretion in the HCDR2 mutants regardless of L chain association. Together these data demonstrate that both the HCDR2 and HCDR3 domains contain structural information that may affect the secretion competence of Abs.

Amino Acid Sequence↗

Thrombosis and hormone replacement therapy in postmenopausal women.

OBJECTIVE: The effects of postmenopausal hormone replacement therapy on thrombosis remain controversial. We tested the hypothesis that estrogen or progesterone has no significant effect on thrombosis by means of newly developed markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin generation. STUDY DESIGN: A prospective study that included 106 women, 68 postmenopausal women on hormone replacement therapy and 38 postmenopausal controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured by enzyme-linked immunosorbent assay. Multivariate analysis of the covariance was used for statistical analysis, controlling for patient's age because the hormone replacement therapy group was older. RESULTS: There were no statistically significant differences between the hormone replacement therapy and control groups in either of the clotting parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex in patients receiving estrogen alone or estrogen plus progestin also revealed no differences. CONCLUSIONS: Current doses of postmenopausal hormone replacement therapy do not appear to enhance in vivo clotting. Thromboembolic complications among postmenopausal women receiving hormone replacement therapy may therefore be secondary to congenital or other acquired coagulation defects.

Adult↗

Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and preeclampsia in urban black women.

BACKGROUND: Although preeclampsia is an important and relatively common medical problem, its pathophysiology remains unresolved and the search for a biochemical marker that precedes the hemodynamic abnormalities of preeclampsia continues. We designed a study to investigate the hemodynamic changes that characterize preeclampsia and to evaluate the metabolism of platelet intracellular calcium as a possible predictor of the development of preeclampsia. METHODS: Hemodynamic measurements and spectrofluorometric determinations of the levels of intracellular calcium in platelets in the basal state and after stimulation with an agonist were performed in 48 nulliparous black women during each trimester of pregnancy. The data on the 14 women (29 percent) in whom preeclampsia developed were then compared with the data on the other 34, who served as normotensive controls. RESULTS: There was no significant difference between the two groups in the basal levels of intracellular calcium at any time. In contrast, the levels measured after arginine vasopressin was administered during the first trimester indicated an exaggerated response in the group with preeclampsia as compared with the control group (1494 +/- 388 [+/- SEM] percent vs. 545 +/- 55 percent of base line; P less than 0.0002), which was sustained through the second and third trimesters. All but three of the women with preeclampsia had responses higher than the highest response among the controls. Platelet intracellular calcium responses to arginine vasopressin during the first trimester were a sensitive predictor of the subsequent development of preeclampsia (P less than 0.00009). Although vascular resistance was similar in the two groups during the first trimester, it subsequently decreased in the control group (P less than 0.02) but not in the group with preeclampsia. CONCLUSIONS: Our findings indicate that preeclampsia is characterized by the absence of the normal pregnancy-related decrease in vascular resistance, which is preceded in most instances by an exaggerated response of platelet intracellular calcium to arginine vasopressin early in pregnancy. We therefore propose that an increase in the sensitivity of platelet calcium to arginine vasopressin can be used as an early predictor of subsequent preeclampsia.

Adolescent↗

Factors affecting graft force in surgical reconstruction of the anterior cruciate ligament.

The effect of the maximum unloaded graft length (Lo) and femoral fixation hole location on graft force with the knee under anteriorly directed tibial loads was measured in five fresh cadaver knees with a reconstruction of the anterior cruciate ligament (ACL). The reconstruction was performed using a composite graft consisting of the semitendinosus and gracilis tendons augmented with the Kennedy ligament augmentation device (LAD). Buckle transducers were used to measure ligament and graft forces. The total graft force was adjusted to match the intact ACL at 30 degrees flexion using a force-setting method so that a standardized reference configuration could be repeatedly obtained. The graft force was highly sensitive to Lo, typically changing by 50% with a change in Lo of 3 mm. Variation in femoral hole location of 5 mm anterior, posterior, proximal, and distal to the anatomic position produced changes in graft force, particularly at 60 degrees and 90 degrees flexion; however, these changes were not statistically significant. The effect of femoral hole location varied considerably between knees. This variability makes predicting proper hole placement difficult, and suggests the need to adjust each knee at surgery to account for this variable femoral hole position sensitivity.

Adult↗

Method for setting total graft force and load sharing in augmented ACL grafts.

The objective of this study was to develop a method for obtaining a controllable and reproducible immediate postoperative mechanical state in a knee with an anterior cruciate ligament (ACL) reconstruction. This method, called the force-setting technique, was demonstrated using a composite graft consisting of the middle third of the patellar tendon with bone blocks (PT) and the ligament augmentation device (LAD). The total graft force was set to match the force in the intact ACL at 30 degrees flexion with the knee under the same standardized external load, while at the same time the load sharing between the biologic and augmentation components was controlled. The total graft force was set to match the ACL force three separate times in each knee, with ratios of load sharing set at the following levels: 50% PT-50% LAD, 25% PT-75% LAD, and 75% PT-25% LAD. ACL, PT, LAD, and collateral forces were measured using buckle transducers, and three-dimensional knee motion was measured using an instrumented spatial linkage as 90 N anteriorly directed tibial loads were applied to eight specimens at 0 degree, 30 degrees, 60 degrees, and 90 degrees flexion with an intact ACL, an excised ACL, and the three load-sharing reconstruction states. The total graft force could be consistently set to within an average of 2% of the intact ACL force at 30 degrees flexion, and load sharing between the graft segments could be set to within an average of 5.1% of the desired ratio at 30 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver↗

The biochemical ecology of Biomphalaria glabrata, a snail host of Schistosoma mansoni: short chain carboxylic and amino acids as phagostimulants.

1. A buccal mass olfactometer was used to investigate the responses of the fresh-water pulmonate snail Biomphalaria glabrata to carboxylic and amino acids. 2. The snails proved very discriminating as only 6 (14.6%) of the 41 chemical species tested were effective as phagostimulants. These are ranked as follows in order of potency:- butanoate greater than propanoate greater than D-malate greater than 2-hydroxybutanoate = L-tartrate = L-aspartate. 3. The structure-activity relationships of the active compounds, and their significance to the ecology and control of the snails are discussed.

Amino Acids↗

Load sharing and graft forces in anterior cruciate ligament reconstructions with the Ligament Augmentation Device.

Buckle transducers were used to directly measure load sharing and overall force in three segment (semitendinosus, gracilis, Ligament Augmentation Device) and two segment (patellar tendon, LAD) composite ACL grafts during the application of anteriorly directed loads to a series of five fresh knee specimens with a pneumatic load apparatus. The total graft forces generated in the two segment and three segment composite reconstructions during this immediate postoperative state were highly variable when compared to the normal ACL in each specimen, and were irreproducible among the five specimens. Load sharing among the graft components occurred and was also variable in both reconstructions, with this variation being greater in the three segment graft. The LAD carried an average of 45% of the total graft force in the three segment graft and 28% in the two segment graft. Further work is required to clarify the source of the variability in the total graft force and load sharing observed in this study.

Biomechanical Phenomena↗

Graft force-setting technique in reconstruction of the anterior cruciate ligament.

The objective of this work was to present a method for controlling the mechanical state of the knee during graft fixation in an ACL reconstruction; that is, adjusting the unloaded length of the graft at the time of fixation so that the force-carrying characteristics of the graft match that of the intact ACL, when the normal and reconstructed knees are subjected to the same external load. To demonstrate the new method, an experimental knee testing system was used to measure ligament and graft forces with buckle transducers, as external loads were applied to five fresh knee specimens with a pneumatic load apparatus. ACL and collateral ligament force data were collected as anteriorly directed loads of 90 N (20 pounds) were applied at 0 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion in the normal intact knee and the same knee following ACL excision. A composite graft was prepared, consisting of distally based semitendinosus and gracilis autogenous tissue augmented with the Kennedy Ligament Augmentation Device. Femoral fixation was obtained using a fixation plug that was inserted through the lateral femoral condyle. With a 90 N anterior tibial load applied at 30 degrees of flexion and a single buckle transducer measuring the total composite graft force, the graft length was varied using the fixation plug until the force matched that seen by the intact ACL under the same loading condition. The graft was then clamped in the fixation plug and the anterior load sequence at the four flexion angles was applied to this reconstructed knee state.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗