Gregor Johann Mendel and Modern Evolutionary Biology: Gregor Johann Mendel: From peasant to priest,pedagogue, and prelate

Gregor Mendel was an Augustinian priest in the Monastery of St. Thomas in Brünn (Brno, Czech Republic) as well as a civilian employee who taught natural history and physics in the Brünn Modern School. The monastery’s secular function was to provide teachers for the public schools across Moravia. It was a cultural, educational, and artistic center with an elite core of friar-teachers with a well-stocked library and other amenities including a gourmet kitchen. It was wealthy, with far-flung holdings yielding income from agricultural productions. Mendel had failed his tryout as a parish priest and did not complete his examination for teaching certification despite 2 y of study at the University of Vienna. In addition to his teaching and religious obligations, Mendel carried out daily meteorological and astronomical observations, cared for the monastery''s fruit orchard and beehives, and tended plants in the greenhouse and small outdoor gardens. In the years 1856 to 1863, he carried out experiments on heredity of traits in garden peas regarded as revolutionary today but not widely recognized during his lifetime and until 16 y after his death. In 1868 he was elected abbot of the monastery, a significantly elevated position in the ecclesiastical and civil hierarchy. While he had hoped to be elected, and was honored to accept, he severely underestimated its administrative responsibilities and gradually had to abandon his scientific interests. The last decade of his life was marred by an ugly dispute with civil authorities over monastery taxation.     

Total correction of tetralogy of Fallot at age 40 years and older: long-term follow-up

Whether total surgical correction of tetralogy of Fallot in adults aged 40 years old or older has acceptable operative risk and gratifying long-term results is unknown. The Mayo Clinic experience (June 1960 to May 1982) with 30 patients 40 to 60 years old (mean 47) who had total surgical correction of tetralogy of Fallot was reviewed. Preoperatively, 4 patients (13%) were in functional class I, 9 (30%) in class II and 17 (57%) in classes III and IV. Eight patients (27%) had had preoperative complications: five had a cerebrovascular accident and three had infective endocarditis. Only 11 patients (37%) had had palliative surgery 16 to 34 years (mean 22) before total surgical correction. Total surgical correction was successful in all patients. Right ventricular to left ventricular (RV/LV) pressure ratio of 0.65 or less was achieved in 28 (93%) of the 30 patients. One patient died of ventricular fibrillation (RV/LV ratio = 0.8) 2 days postoperatively, one had complete heart block and one had a cerebrovascular accident 7 days after operation. At follow-up of 5 to 266 months (mean 110), there were seven late deaths: two sudden at 5 and 21 years, respectively, after operation, one from myocardial infarction at 11 years, one from cerebrovascular accident at 11 years, one from congestive heart failure (RV/LV ratio = 1.0) at 8 years and two from noncardiac causes. Of the 22 patients who survived, 16 are in class I, 5 are in class II and 1 is in class III.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tracking of high- and low-density-lipoprotein cholesterol from childhood to young adulthood in a single large kindred with familial hypercholesterolemia

Tracking of high- and low-density-lipoprotein cholesterol (HDLC, LDLC) from childhood to young adulthood was assessed in 77 children and in 53 adults from a single large pedigree with familial hypercholesterolemia who were respectively less than or equal to 19 and greater than or equal to 20 years old when first studied in 1973, with reassessment in 1984. No children and only five of the adults had received LDLC lowering therapy from 1973 to 1984. The rank correlations between the 1973 and 1984 measurements for LDLC were 0.73, 0.74, and 0.87; and for HDLC were 0.55, 0.73, and 0.65 (P less than 0.0001 for all correlations), respectively for relatives who were less than or equal to 12, 13 to 19, and greater than or equal to 20 years old in 1973. The 1973:1984 LDLC and HDLC correlations, categorized by relationships to the proband, were as follows: (1) unrelated, LDLC = 0.16, HDLC = 0.56;* (2) first-degree relatives, LDLC = 0.90, HDLC = 0.30; (3) second-degree relatives, LDLC = 0.79, HDLC = 0.39; and (4) other relatives, LDLC = 0.62, HDLC = 0.64. All nine of the probands' first-degree relatives who were above the age-sex specific LDLC 95th percentile in 1973 were also greater than the 95th percentile for LDLC in 1984. Similarly, seven of eight second-degree relatives with LDLC greater than the 95th percentile in 1973 were greater than the 95th percentile in 1984, as were ten of 15 other relatives. LDLC levels in childhood in this extended kindred were highly predictive of adult values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate and short-term benefit of multilesion coronary angioplasty: influence of degree of revascularization

The safety and short-term therapeutic benefit of multilesion percutaneous transluminal coronary angioplasty was assessed in 135 patients, 66 of whom had a minimum of 6 months of follow-up study. Primary success, defined as successful dilation of the most critical lesion or all lesions attempted without major in-hospital complications was obtained in 117 (87%) of the 135 patients. Cardiac complications associated with the procedure were uncommon; prolonged angina occurred in 5% and myocardial infarction in 3%; emergency coronary bypass surgery was performed in 4% of the patients. There were no deaths. Complete revascularization was achieved in 46% of the 117 patients with a primary success. Of the 66 patients eligible for 6 month follow-up, 80% had an uncomplicated course and required no further procedures. Clinical improvement by at least one angina functional class was observed in 90% of the patients. Cardiac events such as the need for a second revascularization procedure were significantly more common in patients who had incomplete versus complete revascularization (35 versus 9%; p = 0.018). Repeat coronary angiography performed an average of 5 months after angioplasty revealed restenosis in 18 of 22 symptomatic patients and 3 of 9 asymptomatic patients. Restenosis occurred at the site of a single dilation in 12 patients, at two sites in 8 patients and at three sites in 1 patient. Thus, multilesion coronary angioplasty is an important therapeutic option for selected patients with multivessel disease and can be performed with relatively low risk. Improvement in angina status can be expected even in patients who have incomplete revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diabetic lipoprotein deficient serum: Its effect in low density lipoprotein (LDL) uptake and degradation by fibroblasts

Low density lipoproteins (LDL) isolated from poorly controlled diabetic patients are known to be taken up and degraded by fibroblasts at a lower rate than LDL isolated from normal subjects. This aberrant metabolic behavior has been attributed to a diabetic-related abnormality in LDL composition yet to be characterized. The studies reported in this article show that the decrease in uptake and intracellular degradation of LDL from diabetic patients is further enhanced when the cells are exposed to lipoprotein deficient serum (LPDS) isolated from the same poorly controlled diabetic patients. Comparative studies of the composition of LPDS obtained from normal donors and poorly controlled diabetic patients showed an increase in saturated and total unesterified fatty acids (UFA), lecithin, apolipoprotein A1, and immunoreactive insulin in the LPDS from diabetic patients. We postulate that exposure of cells to LPDS obtained from poorly controlled diabetic patients may induce changes in the composition of the fibroblast membrane and alter its fluidity, leading to further decrease in the uptake and degradation of LDL. During poor diabetic control, cell membrane changes, and modification of LDL composition are likely to act either additively or synergistically to induce an abnormal LDL-cell interaction. This abnormal interaction may be a relevant factor to explain the greater incidence of arteriosclerosis in diabetes mellitus.     

Regulation of hepatic glycogen metabolism: effects of diabetes, insulin infusion, and pancreatic islet transplantation

Insulin-deficient diabetes mellitus results in diminished capacity of the liver to accumulate glycogen. One site of metabolic lesion in the diabetic liver is at the level of the synthase-activating enzyme, synthase phosphatase. This activity is progressively diminished with increasing severity of chemically induced diabetes in both soluble and smooth endoplasmic reticulum (SER) associated subfractions. Insulin administration via an implanted miniosmotic pump or via intrahepatic islet transplantation increased synthase phosphatase activity, particularly in SER. Hepatic glycogen synthesis and accumulation was enhanced as well. The data support a role for insulin in maintenance of the ability of the liver to synthesize and accumulate glycogen mediated either directly or indirectly through SER-synthase phosphatase activity.     

Plasma lipoprotein abnormalities associated with acquired hepatic triglyceride lipase deficiency

Two enzymes, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL), are released into human plasma after intravenous injection of heparin. LPL is the major enzyme responsible for initiating catabolism of chylomicrons and very-low-density lipoproteins (VLDL). The physiological role of HTGL is less certain. HTGL has been postulated to be an alternate enzyme to LPL in hydrolysis of triglyceride in VLDL and to be an important enzyme for removal of phospholipid from both low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In this latter role, this enzyme would convert larger, lighter lipoprotein particles to smaller denser particles. HTGL deficiency has been found in severe liver disease and with a genetic deficiency of this enzyme. A unique patient is described with acquired hepatic triglyceride lipase deficiency and vitamin A intoxication. This patient developed hypercholesterolemia with an increase in both LDL and HDL. An increased proportion of lighter LDL (LDL1) and HDL (HDL2) was noted. In addition, after administration of heparin there was no shift in the distribution of apoE in plasma fractionated using a column containing 4% agarose. These findings are consistent with a postulated role of HTGL in metabolism of light LDL and HDL particles and some classes of apoE containing lipoproteins.     

Left Ventricular Mass Regression After Implantation of St. Jude Medical Cardiac Valves in Small Aortic Roots

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty-eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow-up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4 % at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long-term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.