Biomedical subjects
Publications and source records attributed to M Gross.
Eight classes of human leukocyte interferon (LeIFN) cDNA clones have been identified in a cDNA library prepared from a myeloblastoid cell line. The nucleotide sequences demonstrate that the multiple human LeIFN genes code for a family of homologous, yet distinct proteins. One of the cDNA clones may have been derived from the transcription of a LeIFN pseudogene.
We have investigated whether the phosphorylation of the Mr = 35,000 subunit of eukaryotic initiation factor 2 (eIF-2 alpha) by the hemin-controlled translational repressor (HCR), which appears to mediate the regulation of protein synthesis by hemin in rabbit reticulocytes, occurs at a single or multiple sites. Following phosphorylation of highly purified ribosomal or soluble eIF-2 with [gamma-32P]ATP and highly purified HCR, eIF-2 alpha was isolated by elution from a 7% sodium dodecyl sulfate-polyacrylamide gel, subjected to trypsin digestion, and analyzed on 20% sodium dodecyl sulfate-polyacrylamide gels. By 9 h of digestion none of the original, Mr = 35,000 subunit remained, and after 24 h the 32P radioactivity was distributed in multiple polypeptides in the range of Mr = 4,000 to 8,000. After 4 days of trypsinization, however, all of these peptides were reduced to a low level except for a minor band with Mr = 4,500, and a Mr = 1,500 component became the predominant 32P-labeled product. After 6 days of trypsin digestion the minor Mr = 4,500 component was much less but still detectable, and the Mr = 1,500 component represented 85% (ribosomal eIF-2 alpha) and 90% (soluble eIF-2 alpha) of the total radioactivity. The Mr = 1,500 component, when eluted fro 20% gels, showed a single spot when fingerprinted on thin layer cellulose sheets that was identical whether derived from ribosomal or soluble eIF-2 alpha. These findings suggest that HCR phosphorylates eIF-2 alpha at one specific site, although we cannot exclude the possibility that a second, minor site may also become phosphorylated to a very limited degree.
A comprehensive method of evaluating the feet of patients with adolescent hallux valgus both before and after surgical correction is described. Serial clinical, photographic and radiological studies were made and a dynamic assessment of gait was carried out using a load-sensitive walkway. Observations were made on 36 feet in which hallux valgus was treated by a modification of the Wilson oblique metatarsal osteotomy, with removal of a wedge of bone and screw fixation. In the first six months after operation, there was a lateral shift of the weight-bearing pattern in the forefoot and less weight was taken on the toes, but there was a tendency to return to the pre-operative distribution of weight during the next four years. Persistence of the lateral shift of weight-bearing appeared to result from elevation of the first metatarsal head secondary to shortening of the first metatarsal during the osteotomy. This can be avoided by deliberate depression of the first metatarsal head at the time of operation and fixation of the fragments in the required position with a screw.
A comparison of the efficacy of prostacyclin and heparin as anticoagulants during hemodialysis in uremic dogs was evaluated. Prostacyclin was infused continuously into the arterial limb of the dialyzer (100 ng/kg/min) while heparin was administered as a 5000 unit bolus at the beginning of dialysis. Prostacyclin and heparin were alternated and a total of 4 dialyses/dog were performed. Parameters followed to assess the efficacy of dialyses included: dialysance (ml/min) of urea, creatinine, ultrafiltration rate (ml/hr), residual volume and platelet count (% of baseline). A lesser degree of hemodialysis associated thrombocytopenia, and a higher ultrafiltration rate were observed with prostacyclin. These studies demonstrate that prostacyclin can be used alone as an anticoagulant in a uremic dog model, and in contrast to heparin it maintains the platelet count and improves the ultrafiltration rate during hemodialysis.
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Diallinas-Amalric syndrome is characterized by a combination of central pseudoretinopathia pigmentosa and pancochlear hearing loss. The dystrophy of the macula may occur in patients in whom hearing was unpaired in the prenatal, perinatal and/or postnatal periods. This fact indicates that Diallinas-Amalric syndrome must be seen as a nonspecific manifestation of a bisensorial impairment of very varied etiology.
The gene for human leukocyte interferon alpha 2 (designated either LeIF A or HuIFN-alpha 2) has been isolated from a human genome library. The DNA sequence of this gene demonstrates that it lacks introns. The 3' noncoding sequences of the IFN-alpha 2 gene correspond to two types of IFN-alpha 2 cDNA clones we have isolated that have alternate sites of polyadenylylation. A comparison of seven human IFN-alpha sequences shows that they are homologous in the 5' flanking region and contain identical "TATA box" sequences. The recombinant lambda clone containing the IFN-alpha 2 gene also contains two copies of the "Alu family" repeat sequence.
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Retinol and Retinol-binding protein are estimated in the plasma of 91 children with hearing impairments of different etiology and 35 normal children of similar age. The concentrations of Retinol and Retinol-binding protein are age-dependent but in a given age class the concentrations of these substances are found to be similar in both groups. It is obvious, however that the concentrations in children with Alport-syndrome lie mainly in the upper range, while these with Pendred-syndrome have values in the lower range of the total distribution curve.
A modified method for the diagnosis of the Pendred Syndrome in children by the Perchlorate discharge test using 123I is described. The older child, who has the Pendred Syndrome and the obligatory hearing deficit, frequently has neither a goitre nor hypothyroidism, but other investigations (bone growth, scars and function tests) can also show changes. However a more certain diagnosis of this disorder in children is possible by the Perchlorate discharge test using 123I. The test using 131I is no longer justified in the face of more recent radiobiological knowledge.
It is reported about the measuring of voice area as a completion of phoniatric diagnosis. This is a more objective procedure that is qualified for the documentation of voice disorders, especially for medical certificates. It gives valuable information for qualification ratings and supports the developmental control of voice therapy and training of singers. The whole procedure lasts about 10 minutes usually.
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Addition of glucose to Ehrlich-Landschütz ascites tumour cells preincubated for 30-60 min in phosphate-buffered Krebs-Ringer salt solution ("starved cells") resulted within 1-2 min in an approx. 90% decline of their ATP content and a massive accumulation of fructose 1,6-bisphosphate. These alterations, which took place under both aerobic and anaerobic conditions, were followed by a gradual spontaneous recovery with restoration of normal ATP and fructose 1,6-bisphosphate values. The transient derangement of the energy metabolism after glucose addition to starved ascites tumour cells by preventable by simultaneous addition of pyruvate or 2-oxobutyrate, or by preincubating the cells in the presence of glucose. The protective effect of pyruvate was duplicated by addition of phenazine methosulphate or NAD+ to the incubation medium. The data seem to warrant the conclusion that the glucose-induced ATP depletion is determined by a blockade of glycolysis at the stage of glyceraldehyde phosphate dehydrogenase caused by the failure of the cells to oxidize the NADH produced in the same reaction. The continued unrestrained action of 6-phosphofructokinase results in accumulation of fructose 1,6-bisphosphate, which constitutes a trap for the high-energy phosphate bonds of ATP. The primary metabolic disturbance appears to consist of a transient inhibition of pyruvate kinase with the resultant inability of the cells to maintain an unimpaired supply of pyruvate, as required for the lactate dehydrogenase-mediated oxidation of NADH. The regulatory mechanism underlying this phenomenon is discussed.
A human leukocyte interferon cDNA was enzymatically synthesized, inserted into the vector pBR322, and cloned in Escherichia coli. The DNA sequence codes for a 23-amino acid signal peptide followed by an interferon polypeptide of 165 amino acids. An expression plasmid was constructed which permits the synthesis in E. coli of 2.5 x 10(8) units of interferon per litre of culture. This LeIF protected squirrel monkeys from lethal encephalomyocarditis virus infection.
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