Analysis of mutational changes at the HLA locus in single human sperm

Using a simple and efficient single sperm PCR and direct sequencing method, we screened for HLA-DPB1 gene mutations that may give rise to new alleles at this highly polymorphic locus. More than 800 single sperm were studied from a heterozygous individual whose two alleles carried 16 nucleotide sequence differences clustered in six polymorphic regions. A potential microgene conversion event was detected. Unrepaired heteroduplex DNA similar to that which gives rise to postmeiotic segregation events in yeast was observed in three cases. Control experiments also revealed unusual sperm from DPB1 homozygous individuals. The data may help explain allelic diversity in the MHC and suggest that a possible source of human mosaicism may be incomplete DNA mismatch repair during gametogenesis.     

Efficacy and safety of pravastatin in African Americans with primary hypercholesterolemia

BACKGROUND: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia. METHODS: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio. RESULTS: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%. CONCLUSION: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.     

Disproportionation of Q m (0 ≤ m ≤ 4) species in partially devitrified Li2Si2O5 glasses with small amounts of P2O5

The effect of addition of small amounts of P₂O₅ in the lithium disilicate glasses results in the scavenging of lithium metal ions by a phosphate group, Li₃PO₄. As a consequence of the scavenging, the silicate network partially repolymerises. The phosphate group remains intact during heat treatment of the optically clear, X-ray amorphous and slightly nucleated base glasses. However, the relative amounts of the silicate species, Q_m (0 ≤ m ≤ 4), are dependent on the state of the glasses. These amounts, in the optically clear and X-ray amorphous, do not change with heat treatment but they do change, i.e. disproportionation occurs in the slightly nucleated and milky coloured glasses. The disproportionation follows the relation 2Q₃ → Q₂ + Q₄ which is evident from the relative intensity of the different peaks.     

M?bius syndrome: classification and grading system

M?bius syndrome is characterized by facial abnormalities, but the limbs, chest wall, spine, and soft tissues also can be involved. There is no system for categorizing the various anomalies, grading phenotypic severity, designing treatment protocols, or assessing therapeutic results. This is a retrospective analysis of 27 patients with M?bius syndrome seen in our craniofacial unit from 1980 to 1994. We categorized and graded the cranial nerve deficits and diverse musculoskeletal abnormalities of the face, upper and lower limbs, and trunk. The first letter for each of five potentially involved structures, i.e., cranial nerve, lower limb, upper limb, face, and thorax, formed the acronym CLUFT. The structural and/or functional deficits for each component were graded on a scale of 0 to 3. Complete facial nerve paralysis was documented in 11 patients and paresis in 16. Facial nerve paralysis was bilaterally symmetric in 17 of 26 patients. Sixth nerve paralysis was present in 23 of 27 patients; other cranial nerves were affected in 8 of 27 patients. Lower limbs were involved in 10 of 27 patients and upper limbs in 7 of 27 patients. Facial structures were affected in 17 of 27 patients (e.g., microtia, micrognathia, and microphthalmia), and chest wall deformities were found in 8 of 27 patients (e.g., scoliosis, hypoplasia of the breast, pectoral muscles, and scapula). We noted that microtia primarily involved second pharyngeal arch-derived structures. The CLUFT system permits categorization and comparison of M?bius patients for phenotypic and management outcome studies. Documentation of the widespread structural anomalies suggests that pathogenesis involves vascular disruption; a detailed prenatal history is indicated.     

Binding of human monoclonal IgG rheumatoid factors to Fc is influenced by carbohydrate

OBJECTIVE: The precise nature of the epitope on the Fc portion of the IgG molecule to which IgG rheumatoid factors (RF) bind has not been identified. As patients with rheumatoid arthritis (RA) have abnormal glycosylation of the Fc portion of IgG, we investigated the impact of the sugar present in the Fc on the binding of IgG RF. METHODS: Binding of monoclonal IgG RF to Fc fragments with varying oligosaccharide chains was detected using an immunoblot assay. RESULTS: We demonstrated that the binding of human hybridoma derived monoclonal IgG RF was strongly influenced by the presence of carbohydrate and was maximal when the carbohydrate molecule was intact. The RF did not bind directly to the carbohydrate moiety itself. CONCLUSION: This suggests that conformational changes in the polypeptide chain induced by the carbohydrate are responsible for the observed binding patterns.     

A clinical and histological comparative study of the effect of nifedipine and phenytion on human gingiva

Ten patients manifesting gingival enlargement were chosen for this study. Five patients had been treated with 4 mg nifedipine per day as a treatment for angina pectoris, while the other five patients treated with phenytion as an anticonvulsant drug. Clinical and histological data showed that nefidipine induced gingival hyperplasia which is of close similarity to that induced by phenytion despite the differences in target tissue.     

Anemia severity and missed dialysis treatments in erythropoietin-treated hemodialysis patients

A comparative study was conducted of the results of venous end-to-end and end-to-side anastomosis in 948 clinical cases of microvascular free-tissue transfers for head and neck reconstruction following tumor resection. End-to-side anastomosis to the internal jugular vein was achieved uneventfully in the present series, while a variety of recipient veins was used for end-to-end anastomosis. The incidence of thrombosis was 1.8% (15/835) in the end-to-end anastomosis group and 2.7% (3/113) in end-to-side venous anastomosis. No statistical difference was observed between the two groups. One may hesitate to perform end-to-side anastomosis because of unfamiliarity, concern over technical difficulty, and unreliability. As a result of our statistical analysis, we are convinced that end-to-side anastomosis directly to the internal jugular vein, whenever available, is the preferred procedure in microvascular free-tissue transfers for reconstruction of the head and neck following tumor resection.