Haemoglobin H disease in 2 Filipino families.

Haemoglobin H disease is described in successive generations of 2 Filipino families. The condition was asymptomatic. The inheritance pattern of haemoglobin H disease in these families appeared to be like that described for Thais.     

In vivo human muscle structure and function: adaptations to resistance training in old age

This study investigated changes in elderly muscle joint angle-torque relation induced by resistance training. Older adults were assigned to either training (n = 9, age 74.3 +/- 3.5 years; mean +/-s.d.) or to control groups (n = 9, age 67.1 +/- 2 years). Leg-extension and leg-press exercises were performed three times per week for 14 weeks. Maximal isometric knee extension torque was measured across the knee joint angle range of movement. Vastus lateralis muscle architecture was examined in vivo using ultrasonography. The vastus lateralis muscle fascicle force was estimated from the measured joint torque, enabling construction of the fascicle length-force relation. Electromyographic (EMG) activity was measured from representative agonist and antagonist muscles. Training altered the angle-torque relation: (a) displacing it by 9-31% towards higher torque values (P < 0.05); and (b) shifting the optimal angle from 70 deg (corresponding torque: 121.4 +/- 61 N m) before to 60 deg (134.2 +/- 57.2 N m; P < 0.05) after training. Training also altered the fascicle length-force relation: (a) displacing it by 11-35% towards higher force values; and (b) shifting the optimal fascicle length from 83.7 +/- 8 mm (corresponding force: 847.9 +/- 365.3 N) before to 93.2 +/- 12.5 mm (939.3 +/- 347.8 N; P < 0.01) after training. The upward displacement of the angle-torque relation was mainly due to a training-induced increase in agonist activation, whilst the shift in the optimal angle was associated with changes in muscle-tendon properties.     

Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.     

The acetyltransferase enzyme method for the assay of serum gentamicon concentrations and a comparison with other methods.

The adenylytransferase/acetyltransferase methods of gentamicin assay have been evaluated for accuracy, speed, and cost. For a comparable cost of materials the latter method is more accurate than that using the adenylytransferase enzyme. The acetyltransferase method is much quicker than the adenyltransferase due to the shorter time necessary for radioactive counting. Sonication is an easier method of enzyme preparation than the previously used osmotic shock technique. The acetyltransferase method is reproducible and there was a very good correlation between it and a microbiological agar-plate diffusion method.     

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.      

Biochemical, genetic, and epidemiologic characterization of Haemophilus influenzae biogroup aegyptius (Haemophilus aegyptius) strains associated with Brazilian purpuric fever.

Brazilian purpuric fever (BPF) is a recently recognized fulminant pediatric disease characterized by fever, with rapid progression to purpura, hypotensive shock, and death. BPF is usually preceded by purulent conjunctivitis that has resolved before the onset of fever. Both the conjunctivitis and BPF are caused by Haemophilus influenzae biogroup aegyptius (formerly called H. aegyptius). Isolates from 15 BPF cases, mainly from blood or hemorrhagic cerebrospinal fluid, case-associated isolates from 42 persons in towns where BPF cases occurred, and control strains from 32 persons in towns without BPF cases were characterized biochemically, genetically, and epidemiologically. Results indicated that a single clone was responsible for all BPF cases identified in six Brazilian towns from 1984 through 1986. All of 15 (100%) case strains were the same clone as was 1 of 32 (3%) control strains (P = less than 10(-8). Isolates of the clone were preferentially intrarelated by DNA hybridization (99% relatedness, hydroxyapatite method at 60 and 75 degrees C) and were separable from other H. influenzae biogroup aegyptius strains (approximately 90% relatedness at 60 degrees C and 82% relatedness at 75 degrees C). All isolates of the BPF clone and no other strains contained a 24-megadalton plasmid of restriction endonuclease type 3031, were of a single multilocus enzyme mobility type, were of a single sodium dodecyl sulfate-polyacrylamide gel electrophoresis type, and were in one of two ribosomal DNA restriction patterns. All BPF clone isolates reacted with monoclonal antibodies produced from a case strain; only 3 of 62 (5%) other strains reacted with this monoclonal antibody. Ninety percent of BPF clone strains and 27% of other strains were relatively resistant to sulfamethoxazole-trimethoprim.     

Lung vascular smooth muscle as a determinant of pulmonary hypertension at high altitude.

The pulmonary hypertensive response to chronic hypoxia varies markedly among mammalian species. An explanation for this variability was sought by exposing seven species to hypobaric hypoxia (PB equal to 435 mmHg) for 19-48 days. Control animals were studied at 1,600 m (PB equal to 630 mmHg). The pulmonary hypertension that developed varied in the following order of decreasing severity: calf and pig (severe); rat and rabbit (moderate); sheep, guinea pig, and dog (mild). Right ventricular hypertrophy developed in proportion to the elevation in right ventricular systolic pressure. These interspecies variations in response were not correlated with the degree of arterial hypoxemia, degree of polycythemia, elevation in heart rate, or postnatal age. However, the medial thickness of the small pulmonary arteries in control animals was highly correlated with the development of pulmonary hypertension and right ventricular hypertrophy in hypoxic animals. Thus, the amount of lung vascular smooth muscle inherent within each species is a major determinant of the pulmonary hypertensive response to high altitude and contributes to the interspecies variability in this response.