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Biomedical subjects

J D Hull

Publications and source records attributed to J D Hull.

13 recordsLinked to original sources

Transposition of domains between the M2 and HN viral membrane proteins results in polypeptides which can adopt more than one membrane orientation.

The influenza A virus M2 polypeptide is a small integral membrane protein that does not contain a cleaved signal sequence, but is unusual in that it assumes the membrane orientation of a class I integral membrane protein with an NH2-terminal ectodomain and a COOH-terminal cytoplasmic tail. To determine the domains of M2 involved in specifying membrane orientation, hybrid genes were constructed and expressed in which regions of the M2 protein were linked to portions of the paramyxovirus HN and SH proteins, two class II integral membrane proteins that adopt the opposite orientation in membranes from M2. A hybrid protein (MgMH) consisting of the M2 NH2-terminal and membrane-spanning domains linked precisely to the HN COOH-terminal ectodomain was found in cells in two forms: integrated into membranes in the M2 topology or completely translocated across the endoplasmic reticulum membrane and ultimately secreted from the cell. The finding of a soluble form suggested that in this hybrid protein the anchor function of the M2 signal/anchor domain can be overridden. A second hybrid which contained the M2 NH2 terminus linked to the HN signal anchor and ectodomain (MgHH) was found in both the M2 and the HN orientation, suggesting that the M2 NH2 terminus was capable of reversing the topology of a class II membrane protein. The exchange of the M2 signal/anchor domain with that of SH resulted in a hybrid protein which assumed only the M2 topology. Thus, all these data suggest that the NH2-terminal 24 residues to M2 are important for directing the unusual membrane topology of the M2 protein. These data are discussed in relationship to the loop model for insertion of proteins into membranes and the role of charged residues as a factor in determining orientation.

Animals↗

Integration of a small integral membrane protein, M2, of influenza virus into the endoplasmic reticulum: analysis of the internal signal-anchor domain of a protein with an ectoplasmic NH2 terminus.

The M2 protein of influenza A virus is a small integral membrane protein of 97 residues that is expressed on the surface of virus-infected cells. M2 has an unusual structure as it lacks a cleavable signal sequence yet contains an ectoplasmic amino-terminal domain of 23 residues, a 19 residue hydrophobic transmembrane spanning segment, and a cytoplasmic carboxyl-terminal domain of 55 residues. Oligonucleotide-mediated deletion mutagenesis was used to construct a series of M2 mutants lacking portions of the hydrophobic segment. Membrane integration of the M2 protein was examined by in vitro translation of synthetic mRNA transcripts prepared using bacteriophage T7 RNA polymerase. After membrane integration, M2 was resistant to alkaline extraction and was converted to an Mr approximately equal to 7,000 membrane-protected fragment after digestion with trypsin. In vitro integration of M2 requires the cotranslational presence of the signal recognition particle. Deletion of as few as two residues from the hydrophobic segment of M2 markedly decreases the efficiency of membrane integration, whereas deletion of six residues completely eliminates integration. M2 proteins containing deletions that eliminate stable membrane anchoring are apparently not recognized by signal recognition particles, as these polypeptides remain sensitive to protease digestion, indicating that in addition they do not have a functional signal sequence. These data thus indicate that the signal sequence that initiates membrane integration of M2 resides within the transmembrane spanning segment of the polypeptide.

Animals↗

Resistance of a measles virus mutant to fusion inhibitory oligopeptides is not associated with mutations in the fusion peptide.

The nucleotide sequence and predicted amino acid sequence has been obtained for the fusion (F) protein gene of the R93 strain of measles virus and compared to that of the parental strain, Edmonston B. The R93 strain is a mutant measles virus which is able to grow and induce cell fusion in the presence of the fusion inhibiting oligopeptide, Z-D-Phe-L-Phe-L-(NO2)Arg (SV4814). Primer extension sequencing on isolated R93 mRNA demonstrated the presence of three nucleotide changes leading to three amino acid changes, none of which are in the hydrophobic NH2-terminal region of the F1 polypeptide.

Amino Acid Sequence↗

Renal vein renin activity and prostaglandins A and E in hypertension.

The relation between renal vein renin activity (RVRA) and renal vein-prostaglandin A (PGA) and prostaglandin E (PGE) concentrations was examined in 50 patients with hypertension who underwent renal vein catheterizations for suspected renovascular hypertension. In 14 patients wih unilateral renal artery stenosis, mean renal vein PGE concentrations were higher in the renal vein draining the nonischemic kidney, while RVRA was increased in the renal vein draining the ischemic kidney. PGE ratios from the two sides were inversely related to RVRA ratios in this group. In the other 36 patients with either bilateral renal artery stenosis, essential hypertension or nonrenovascular unilateral renal disease, RVRA and PGE concentrations were similar in both kidneys. No relation between RVRA and PGA could be established for any group.

Adolescent↗

Low incidence of renal failure after angiography.

One hundred consecutive patients with serious illnesses that required angiography were studied prospectively for the development of radiocontrast-induced acute renal failure. The study included 24 diabetics (six diabetics had chronic renal insufficiency), 19 patients with chronic renal insufficiency of other causes, 15 patients with concentrated urine, and 56 patients who received 100 mL or more of a contrast agent. Acute renal failure developed in only one patient. Previous series that indicated much higher incidences were retrospective and not inclusive of all patients, or these studies were composed mainly of patients with diabetic nephropathy and chronic renal failure to whom high doses of a contrast agent were given. Angiography is unlikely to produce acute renal failure except in an occasional patient with well-defined risk factors.

Acute Kidney Injury↗

Reflex anuria from unilateral ureteral obstruction.

A 20-year-old woman had 18 hours of pain and anuria associated with a calcium oxalate stone impacted in the distal left ureter. The stone passed spontaneously and the urine output returned. There was no abnormality of the right kidney on excretory urography. We believe that this is a cause of reflex anuria not previously described. Severe pain may be the initiating event in this unusual but interesting syndrome and mechanisms proposed by previous authors are reviewed.

Adult↗

Elevation of serum lactate dehydrogenase levels in renal infarction.

The diagnostic value of a strikingly elevated serum lactate dehydrogenase (LDH) level in association with only small or no increases in SGOT and alkaline phosphatase levels was noted in five patients with proved renal infarction. Four had renal artery embolism and infarction in association with atrial arrhythmias; one had an acute extension of an abdominal aortic aneurysm occluding the renal artery. Other causes of a considerable isolated increase in the serum LDH level such as hemolysis and myocardial infarction can usually be easily excluded.

Aged↗

Transomental hernia.

Transomental hernia is a very rare condition with less than 50 cases reported. This hernia nearly always causes bowel obstruction and may result in a high mortality rate because of strangulation and gangrene. A typical case of transomental hernia is presented and the literature is reviewed with emphasis on the need for early diagnosis and operation.

Aged↗

Agenesis of the dorsal mesentery without jejunoilial atresia ("apple peel small bowel").

Agenesis of the dorsal mesentery with apple peel or Christmas tree deformity but without small-bowel atresia can occur beyond the neonatal period. The recognition of this entity is imperative as it is also associated with a marginal artery which may be the only blood supply to the majority of small bowel. Preservation of this vessel is necessary to avoid catastrophic bowel death.

Child, Preschool↗