Transmembrane domain inversion blocks ER release and insulin receptor signaling

Activation of the insulin receptor, like other tyrosine kinase receptors, appears to require dimerization. We have shown previously that, even in the absence of insulin, full receptor activation can be induced by changes in the receptor transmembrane domain (TMD), suggesting that TMD dimerization is sufficient for receptor activation. To further understand the importance of the TMD in insulin receptor activation, we have inverted the entire TMD sequence including flanking basic amino acids, residue-for-residue. This mutation was predicted to alter the ability of a TMD alpha-helix to form homodimers and higher level aggregates. Despite apparently normal protein folding on either side of the membrane, this mutation caused ER retention and, for those receptors that reached the cell surface, blockade of insulin-stimulated kinase signal transmission. However, the signaling blockade could be overcome by proteolytic activation with trypsin. In contrast, shifting only the basic cytoplasmic residues to the opposite side of the TMD or mutation to neutral residues had no detectable effect on assembly, biosynthesis, topology, or signaling. These findings extend our previous observations to suggest that TMD interactions within the membrane are not only sufficient for receptor activation, but may be required. TMD interactions also appear to be necessary for oligomeric assembly and biosynthetic maturation of the insulin receptor.     

Velocity of peristaltic propagation in distal esophageal segments

Recent studies of the peristaltic pressure wave have suggested the presence of two sequential but overlapping contraction segments in the distal esophageal body. In this report, propagation velocity of esophageal peristalsis was determined in these segments in normal subjects (N = 35) and in patients with high-amplitude peristalsis (nutcracker esophagus, N = 25) to see if intersegment differences were present in the normal or abnormal setting. Velocity measurements were made from conventional manometric tracings in two 4-cm regions representing the distal smooth-muscle segments. A novel method of velocity measurement was employed that used regression lines established from contraction onset times. In normal subjects, propagation velocity decreased significantly from the proximal to distal segment (4.9 +/- 0.5 cm/sec, vs 3.2 +/- 0.2 cm/sec, P < 0.01). Velocity also decreased across segments in nutcracker-esophagus patients (5.3 +/- 0.6 cm/sec, vs 3.6 +/- 0.7 cm/sec, P = 0.06), but the difference reached statistical significance only when the subset with highest amplitudes (> or = 180 mm Hg) was analyzed separately. Greater variance in velocity in the distal smooth-muscle segment of nutcracker-esophagus patients (P < 0.01) was, in part, responsible for this statistical observation. We conclude that normal propagation velocity decreases across regions corresponding to the smooth-muscle contraction segments defined by recent studies of peristalsis, supporting the assumption that they represent separate neuromuscular units. The mechanisms responsible for contraction wave abnormalities in the nutcracker esophagus have a minimal effect on propagation velocity, an effect that is restricted to the distal smooth-muscle segment of the esophageal body.     

Electron microscope studies of conditional spore cortexless mutants of Bacillus sphaericus

Spore cortex of conditional cortexless mutants of Bacillus sphaericus 9602 was not detectable by electron microscopy unless the medium was supplemented with meso-alpha,epsilon-diaminopimelic acid during sporulation. Other spore structures appeared normal. Spore shape was quite irregular in the absence of meso-alpha,epsilon-diaminopimelic acid.     

Apparent total alpha1-antitrypsin deficiency: report of a case

A 29-year-old female, with chronic renal failure and chronic bilateral emphysema, was admitted with severe uremia and septicemia secondary to multiple abscesses in the right kidney. Her condition improved after right nephrectomy. Pulmonary function studies showed marked obstructive and restrictive lung disease consistent witht the diagnosis of primary emphysema. On biochemical and histological examination, the liver was found to be normal. Alpha1-antitrypsin could not be demonstrated in the patient's serum at normal pH by any of the known techniques, but protein molecules with alpha1-antitrypsin antigencity were found at pH 4.8; this suggests a pH-dependent structural difference in alpha1-antitrypsin protein. Starch gel electrophoresis gave a multibanding pattern not previously described. A new form of apparent total alpha-1-antitrypsin deficiency is postulated.     

Arterial radio-anatomy of the extrahepatic biliary system (author's transl)

The uni-arterial vascularisation of the lateral bilary duct makes it impossible to systematise the arteries which supply the common bile duct. Only the cystic artery is seen at coelio-mesenteric catheterization. The techniques essential for visualisation of the cystic artery are discussed, on the basis of one hundred coelio-mesenteric arteriograms: frequency of demonstration, origin, course, termination, calibre and length. The frequent finding of opacification of the wall of the gall bladder under normal conditions is stressed.     

Benign oesophageal stricture following oral potassium chloride therapy

A patient is described who developed a benign oesophageal stricture following cardiac surgery. A brief review of the literature is given and the possible dangers of oral potassium cholride therapy in patients with dysphagia are highlighted.     

Characteristics of streptolysin S hemolysis

The MCD spectra of ferri- and ferro-heme in high and low spin states and zinc porphyrin for reference have been measured in the ultraviolet region. Zinc porphyrin offered an A term at 325 nm attributable to the N transition. A ferrous low-spin complex with CO or CN exhibited MCD spectra composed of B terms around 325 nm. This striking difference from that of zinc porphyrin in the ultraviolet region is noted from the fact that their Soret and visible MCD's gave A terms similar to those of zinc porphyrin. A ferric complex with high spin had MCD spectrum different from that of low spin, the former showing a negative C term at 287 nm and a B term at 339 nm, but the latter positive C terms at 275 nm and 320 nm. Some of these Faraday parameters were ascribed to charge-transfer transitions.