Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition.     

US-guided pseudoaneurysm repair with a compression device

A simple commercially available compression device allowed intermittent ultrasound scanning of the compression site during compression repair of a femoral artery pseudoaneurysm in six patients. All six of the pseudoaneurysms (five superficial femoral and one common femoral) were compressed without compression of the underlying vessels. The procedure was successful in four of the six patients, without complications. Use of this device may decrease operator fatigue during compression repair of pseudoaneurysm.     

A zero-voltage and zero-current switching three-level DC/DC converter

This paper presents a novel zero-voltage and zero-current switching (ZVZCS) three-level DC/DC converter. This converter overcomes the drawbacks presented by the conventional zero-voltage switching (ZVS) three-level converter, such as high circulating energy, severe parasitic ringing on the rectifier diodes, and limited ZVS load range for the inner switches. The converter presented in this paper uses a phase-shift control with a flying capacitor in the primary side to achieve ZVS for the outer switches. Additionally, the converter uses an auxiliary circuit to reset the primary current during the freewheeling stage to achieve zero-current switching (ZCS) for the inner switches. The principle of operation and the DC characteristics of the new converter are analyzed and verified on a 6 kW, 100 kHz experimental prototype.     

Changes in myocardial hemodynamics and contractile function in patients under surgical treatment for prostatic adenoma

Hemodynamics and left ventricular myocardial contractility in 170 patients who underwent surgery of prostatic adenoma were examined in preoperative period and 16 days after single-stage transvesical adenomectomy. The age of the patients varied from 52 to 85 years. Echocardiography and the dilution method were used for the evaluation. The increase of end-diastolic and end-systolic volumes, stroke volume, cardiac index, was registered. The combined pharmacological treatment made it possible to decrease the number of operative and postoperative cardiovascular complications.     

PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression

Deletion of PHR1, a pH-regulated gene of Candida albicans, results in pH-conditional defects in growth, morphogenesis, and virulence evident at neutral to alkaline pH but absent at acidic pH. Consequently, we searched for a functional homolog of PHR1 active at low pH. This resulted in the isolation of a second pH-regulated gene, designated PHR2. The expression of PHR2 was inversely related to that of PHR1, being repressed at pH values above 6 and progressively induced at more acidic pH values. The predicted amino acid sequence of the PHR2 protein, Phr2p, was 54% identical to that of Phr1p. A PHR2 null mutant exhibited pH-conditional defects in growth and morphogenesis analogous to those of PHR1 mutants but manifest at acid rather than alkaline pH values. Engineered expression of PHR1 at acid pH in a PHR2 mutant strain and PHR2 at alkaline pH in a PHR1 mutant strain complemented the defects in the opposing mutant. Deletion of both PHR1 and PHR2 resulted in a strain with pH-independent, constitutive growth and morphological defects. These results indicate that PHR1 and PHR2 represent a novel pH-balanced system of functional homologs required for C. albicans to adapt to environments of diverse pH.     

Tissue fixation security in transosseous rotator cuff repairs: a mechanical comparison of simple versus mattress sutures

The primary purpose of this investigation was to compare tissue fixation security by simple sutures versus mattress sutures in transosseous rotator cuff repair. These two repair techniques were each performed in 17 human cadaver shoulders, with two bone tunnels being used for the repair by two simple sutures and two other bone tunnels being used for the repair by one mattress suture. The repairs were loaded to failure in a servohydraulic materials test system. Rotator cuff repair by simple sutures was found to be significantly stronger than repair by mattress sutures (P = .0007). The average ultimate load to failure for the simple suture construct (189.62 N) was 39.72% greater than that for the mattress suture construct (135.71 N). Most of the failures occurred by suture breakage at the knot. Load-sharing by multiple suture tails and multiple knots in the simple suture configuration likely contributed to its superior strength characteristics compared with the mattress suture configuration.     

Plastic changes in the cholinergic innervation of the rat cerebral cortex after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA): effects of basal forebrain transplants into neocortex

Since the beginning of the twentieth century, different methods to control the quality of analyses have been in use. The advent of modern analytical instruments has prompted the need for such controls. In a modern clinical chemistry laboratory, quality control is an important tool to maintain the high predictive value of the methods in use. In this article the most important aspects of quality control are outlined. For further study, I recommend the references listed at the end of this article.