Human hypertension caused by mutations in WNK kinases.

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.

Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter.

We isolated and characterized a novel K-Cl cotransporter, KCC3, from human placenta. The deduced protein contains 1,150 amino acids. KCC3 shares 75-76% identity at the amino acid level with human, pig, rat, and rabbit KCC1 and 67% identity with rat KCC2. KCC3 is 40 and 33% identical to two Caenorhabditis elegans K-Cl cotransporters and approximately 20% identical to other members of the cation-chloride cotransporter family (CCC), two Na-K-Cl cotransporters (NKCC1, NKCC2), and the Na-Cl cotransporter (NCC). Hydropathy analysis indicates a typical KCC topology with 12 transmembrane domains, a large extracellular loop between transmembrane domains 5 and 6 (unique to KCCs), and large NH(2) and COOH termini. KCC3 is predominantly expressed in kidney, heart, and brain, and is also expressed in skeletal muscle, placenta, lung, liver, and pancreas. KCC3 was localized to chromosome 15. KCC3 transiently expressed in human embryonic kidney (HEK)-293 cells fulfilled three criteria for increased expression of K-Cl cotransport: stimulation of cotransport by swelling, treatment with N-ethylmaleimide, or treatment with staurosporine.

Serum cholesterol levels in selected air force cadets compared with levels in the West Point study.

In the USAFSAM Cardiovascular Disease Followup Study, the surprising rise in average cholesterol levels in West Point cadets during the 6 years following their entry into the U.S. Military Academy in 1952 implied a significant increase in risk of heart disease in later years. To ascertain whether that pattern of change suggested increased risk is characteristic of cadets at military academies, a similar study on a smaller scale was conducted on U.S. Air Force Academy cadets beginning in 1972. Randomly selected cadets were monitored throughout their 4-year training at the U.S. Air Force Academy. Mean levels of serum cholesterol were similar at the beginning and end of the study; values between those times were generally somewhat lower. Average body fat never exceeded 12.6%; the average remained close to 12% during the last 3 years. Possible reasons for the differences between the pattern of change in serum cholesterol in the West Point cadets in earlier years (1952-56) and in the U.S. Air Force Academy cadets are discussed. Differences in exercise or stress levels were ruled out as likely explanations. Changes in dietary fat intakes may account for the differences, while unidentified changes in the social environment are possible contributory factors.

Determination of ammonia inhibition in fabric impregnated with antimicrobials.

A new method is described for determining the presence or absence of ammonia produced by urealytic microorganisms, using fabric which has been treated with an antimicrobial. Circular disks of fabric treated with various concentrations of an antimicrobial are placed in the bottoms of snap-on lid petri dishes. Nutrient medium containing urea, an indicator, and a dilution of an overnight culture of Proteus mirabilis is applied to the fabric disks. The lids are snapped on and the dishes are incubated at 37 degrees C. By examination of the fabric disks at regular intervals of time for a color change from white to red, one may determine whether the concentration of antimicrobial in the fabric is sufficient to inhibit the production of ammonia by a urealytic microorganism.

Corrected identification of a test organism (ATCC 4352) previously thought to be Escherichia coli.

A gram-negative test organism (ATCC 4352) previously identified as Escherichia coli was found to be Klebsiella pneumoniae.