WOK.1W rats. A potential animal model of the insulin resistance syndrome.
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Biomedical subjects
Publications and source records attributed to B Voigt.
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In this study the spontaneously hypertensive rat (SHR/Mol) and the spontaneously diabetic BB/OK rat were crossed, and the F1 hybrids were backcrossed onto the BB/OK rat in order to search for cosegregation between blood pressure and loci on chromosomes 4 and 13. Cosegregation of microsatellites on chromosomes 4 (Spr, Npy, D4mit6, Il-6) and 13 (Atp1a2, D13Mit1, D13Uwm1) with blood pressure was evaluated using one-way analysis of variance. On chromosome 4 linkage of the Npy and D4Mit6 markers to systolic blood pressure was observed. A blood pressure QTL was also found on chromosome 13 within the renin locus. Surprisingly, alleles of the SHR strain at loci showing linkage to blood pressure on chromosome 4 and 13 promote lower blood pressure than the same alleles from the BB/OK strain. The transfer of D4Mit6 and renin locus from the SHR rat onto the genetic background of BB/OK rat will probably not lead to a model of diabetic hypertension, but the thorough characterisation of such congenics could contribute to the explanation of genetics and pathophysiology of hypertension in the SHR rat.
Hypertension and diabetes mellitus are known to be frequently associated. The genetic dissection of diseases such as hypertension or diabetes mellitus is possible by using experimental crosses, which allow identification of loci influencing phenotypic traits (quantitative trait loci - QTLs). In this study the spontaneously hypertensive rat (SHR) and spontaneously diabetic, but normotensive rat (BB/OK) were crossed and the F2 population was analysed in order to search for QTLs on selected chromosomes (1, 10, 18) for blood pressure and some metabolic traits related to diabetes, renal function and hypertension. There were 3 regions found on chromosome 1 which showed linkage to blood pressure. The strongest evidence for linkage was observed between loci Igf2 and D1Mgh12. On chromosome 10 there was a QTL for blood pressure found between Ppy and Abp and on chromosome 18 there were three regions (Ttr-Grl, Tilp-Gja1, Olf-D18Mit9) with linkage to blood pressure. Since the 24 hr albumin and phosphate excretion correlated with blood pressure in F2 hybrids, the same regions were linked to both parameters. Region with linkage to serum concentrations of cholesterol (probably located beyond the terminal marker Ttr of the linkage group) were also found. The results of this study with a new F2(BB x SHR) population confirm the existence of previously described blood pressure loci (Sa and Bp2) and showed novel QTLs on chromosomes 1, 10 and 18.
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We report on the synthesis of the brassinosteroid analogs (22R,23R)-3 beta, 7 beta, 22,23-tetrahydroxy-stigmast-5-ene (13), (22R,23R)-3 beta, 7 alpha, 22,23-tetrahydroxy-stigmast-5-ene (15), and (22R,23R)-3 beta, 22,23-trihydroxy-stigmast-5,7-diene (18) by means of the osmium-catalyzed asymmetric dihydroxylation of intermediate 1, available from stigmasterol. This reaction sequence produced the expected (22S,23S)- and (22R,23R)-triols 6 and 7 as well as the 22,23-diketo derivatives 2 and 3. The phytohormone activity of the new brassinosteroid analogs is discussed.
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BACKGROUND: This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions. METHODS: Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation. RESULTS: College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure. CONCLUSIONS: Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.
Spectral substructure and ultrafast excitation dynamics have been investigated in the chlorophyll (Chl) a and b Qy region of isolated plant light-harvesting complex II (LHC II). We demonstrate the feasibility of Nonlinear Polarization Spectroscopy in the frequency domain, a novel photosynthesis research laser spectroscopic technique, to determine not only ultrafast population relaxation (T1) and dephasing (T2) times, but also to reveal the complex spectral substructure in the Qy band as well as the mode(s) of absorption band broadening at room temperature (RT). The study gives further direct evidence for the existence of up to now hypothetical "Chl forms". Of particular interest is the differentiated participation of the Chl forms in energy transfer in trimeric and aggregated LHC II. Limits for T2 are given in the range of a few ten fs. Inhomogeneous broadening does not exceed the homogeneous widths of the subbands at RT. The implications of the results for the energy transfer mechanisms in the antenna are discussed.
OBJECTIVE: To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis. DESIGN: Prospective randomized open label study. SETTING: Tertiary care university-affiliated reproductive medicine program. PATIENTS: Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis. INTERVENTIONS: All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III volunteers (n = 18) were untreated and followed for bone density changes. MAIN OUTCOME MEASURES: Disease extent at follow-up laparoscopy; pain, vasomotor, and vaginal symptom scores; bone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge. RESULTS: Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group III untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II. CONCLUSIONS: The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved.
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A recently developed ultrasonic integrated backscatter imaging system allows automated border detection (ABD) of the blood-tissue interface in real time and provides instantaneous measurement of left ventricle cavity area in a beat-to-beat fashion. Three validations of this new system have been performed. 1) In 70 subjects (38 normal volunteers and 32 patients) the on-line ABD-derived areas (end-diastole, -systole = EDA, ESA) and the resulting fractional area change (FAC) of the left ventricle (apical four-chamber view) were compared with the off-line areas and FAC traced manually. All correlations were close (EDA r = 0.97, ESA r = 0.98, FAC r = 0.92; p < 0.0001). 2) In 36 patients with mitral regurgitation (MR), ABD-FAC was compared to the Doppler-derived systolic rate of pressure rise (RPR) which corresponds to systolic dP/dt, as simultaneous studies with high-fidelity pressure measurements have shown. Linear regression analysis yielded a significant correlation with r = 0.91; p < 0.0001. 3) In 26 patients undergoing routine heart catheterization, ABD-echo was performed on the same day. ABD-derived areas (end-diastole, -systole) and FAC (apical two- and four-chamber view) were compared to the corresponding angiographic data derived from biplane projection in 30 degrees RAO and 60 degrees LAO. Linear regression analysis yielded significant values for all correlations (EDA r = 0.88, ESA r = 0.95, FAC 0.90; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
UNLABELLED: Automated border detection (ABD) is a new on-line technique that instantaneously calculates cavity areas from automatic tracking of the endocardial-blood interface with a modified ultrasonic integrated backscatter imaging system. After validation of this new method in comparison with off-line echocardiographic, Doppler- and angiographic analyses, we studied dynamic systolic and diastolic function of the left (LV) and right ventricle (RV) in 50 normal volunteers (31 +/- 9 years) in order to establish ranges of normality for the ABD-parameter. The averaged areas of the LV (apical chamber view) were 25.7 +/- 4.9 sq cm in end-diastole and 14.7 +/- 3.3 sq cm in end-systole, resulting in a fractional area change (FAC) of 43.2 +/- 4.8%. The peak filling (PFR) and peak ejection rate (PER) were 69.3 +/- 11.2 and -61.5 +/- 11.1 sq cm/s. Normalization for end-diastolic area (EDA) yielded 2.7 +/- 0.28 and -2.4 +/- 0.42 EDA/s. The areas of the RV (apical chamber view) were 17.1 +/- 3.8 sq cm in end-diastole and 9.0 +/- 2.0 sq cm in end-systole, resulting in a FAC of 47.3 +/- 9.2%. PFR and PER were 58.2 +/- 13.7 and -51.6 +/- 10.1 sq cm/s. Normalization for EDA yielded 3.4 +/- 0.74 and -2.9 +/- 0.62 EDA/s. The interobserver- and day-to-day-variability for all measured values was less than 10%. CONCLUSION: ABD permits reproducible on-line quantification of systolic and diastolic ventricular function and offers a non-invasive approach for longitudinal monitoring of cardiac patients.
24-Epicastasterone and 24-epibrassinolide, two naturally occurring phytohormones of the brassinosteroid type, were transformed by the fungus Cunninghamella echinulata to give the corresponding 12 beta-hydroxylated compounds. The structures of these compounds were determined by spectroscopic methods, especially heterocorrelated two-dimensional nuclear magnetic resonance investigations. In the rice lamina inclination test the 12 beta-hydroxylation lowered the bioactivity at 0.1 ppm to 10% in comparison with that of the corresponding parent hormones. The described hydroxylations represent the first biotransformations of native brassinosteroids.
OBJECTIVE: To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone. METHODS: Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially. RESULTS: The significant vasomotor instability (P < .01) and bone mineral density loss (-4.8 +/- 0.9%; P < .05) experienced by patients in group III was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state. Bone density changes in groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone. CONCLUSION: These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.
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20 patients with biopsy-proven Wegener's granulomatosis (WG) and 95 control patients underwent determination of anticytoplasmic antibodies (ACPA) by the indirect immunofluorescence technique to assess the specificity and sensitivity of ACPA for WG. Of 14 untreated patients with WG, 13 were ACPA-positive. All these patients became ACPA-negative under immunosuppressive treatment. 4 patients treated with immunosuppressive drugs and 2 patients in remission after termination of therapy had a negative ACPA-test. ACPA were detected in 9 patients of the control group (two patients with Henoch Schoenlein purpura, two patients with systemic vasculitis, 2 patients with systemic diseases, and 1 patient with systemic lupus erythematodes). With that we achieved a specificity of 90.5% and a sensitivity 65.0%. In conclusion the ACPA-determination is very helpful for diagnosis and follow-up of WG.