Structural analysis of heparin by methylation and g.l.c.-m.s.: preliminary results

Heparin is a complex mixture of polysaccharides differing in biological activity and structure, and attempts to relate this activity to structure have suffered, owing to a lack of sufficiently sensitive and specific analytical methods. Application of methylation analysis to determination of the structure of heparin is described. Carboxyl-reduced heparin was converted into its pyridinium salt, this was dissolved in Me2SO, and free OH and NH groups were methylated with dimethylsulfinyl anion. Sulfate groups were removed by solvolysis, and after dialysis, the polymer was acetylated and depolymerized by acetolysis. The resulting monosaccharides were converted into alditol acetates, which were separated by capillary, gas-liquid chromatography, and identified by both electron impact and chemical ionization mass spectrometry. Seventeen different monosaccharides were identified in the hydrolyzate. All of the expected internal hexosaminyl and glycosyluronic residues were identified. Although several sugars were identified as nonreducing termini, only a hexosamine 6-sulfate was identified as a reducing-terminus sugar. The results indicate that methylation analysis of heparins and other complex, sulfated glycosaminoglycans is feasible.     

Human leukocyte interferon subtypes have different antiproliferative and antiviral activities on human cells

The antigrowth effects of 5 different cloned human leukocyte IFN subtypes (IFN-alpha A, B, C, D, F) and 2 molecular hybrids between them (IFN-alpha AD(Bg1II) and IFN-alpha DA(Bg1II)) were examined on 6 different human cell lines. The results indicate that the interferons sort into two distinct groups: IFN-alpha B, C and F showed comparable antiproliferative activity which was greater than that of IFN-alpha A, D, AD(Bg1II) and DA(Bg1II). The interferons could also be assigned to one of two groups on the basis of their antiviral activity. IFN-alpha A, D and AD(Bg1II) were observed to be more protective than IFN-alpha B, C and F against HSV-2 and EMCV infections, i.e. the relative antiviral efficacies of the cloned IFN subtypes were the reverse of their antiproliferative activities.     

Anticonvulsant activity of glycylglycine and delta-aminovaleric acid: evidence for glutamine exchange in amino acid transport

We have proposed that glutamine serves in a facilitated diffusion process, mediated by the enzyme gamma-glutamyl transferase (gamma-glutamyl transpeptidase; gamma GT) and that it leaves the brain in exchange for entering amino acids. Glutamine is also a precursor of gamma-aminobutyric acid (GABA). Thus, providing an alternate substrate for gamma GT should spare brain glutamine, raise GABA, and cause an anticonvulsant effect. We have found that glycylglycine, the best-known substrate for gamma GT, and delta-aminovaleric acid (DAVA), a structural analog, have anticonvulsant activity in DBA/2J mice. Both compounds can decrease the incidence and severity of seizures induced by L-methionine-RS-sulfoximine or electroconvulsive shock. DAVA was also tested and found to be active against seizures caused by pentylenetetrazol or picrotoxin. [14C]DAVA entered the brain at the rate of 18.7 nmol/g/min. The activity of DAVA as a substrate of gamma GT was intermediate to that of glycylglycine and glutamine. Preliminary studies have shown that brain glutamine and perhaps GABA are elevated 3 h after administration of DAVA (7.5 mmol/kg). These findings support the theory that glutamine exchange plays a role in amino acid transport across the blood-brain barrier and suggests a new concept in anticonvulsant therapy.     

A single column method to measure hydrogen-tritium exchange by gel chromatography

Employment of a commercially integrated gel chromatography system together with the utilization of cross-linked polyacrylamide as the chromatographic medium simplifies the methodology of hydrogen-tritium exchange measurements. The system described allows the execution of hydrogen-tritium exchange measurements with as little as 0.5 mg protein per time point and with only a single pass of sample through the column for out-exchange of <1 min to at least 24 h. The accuracy and precision of this system are comparable to those of existing methodologies.     

Chloroform-soluble alkaloids of the root bark of Fagara viridis

Three alkaloids have been isolated from the root bark of Fagara viridis A. Cheval. (Rutaceae). One of these, canthin-6-one, is reported for the first time from an African species of Fagara while the others are the quaternary benzophenanthridine alkaloids chelerythrine and nitidine.     

Applicants to Canadian Medical Schools for 1966-67

An examination of applicants to Canadian medical schools for 1966-67 revealed that 4534 applications were received for the approximately 974 available places. The number of Canadian applications was 2866 and these were made by 1815 individual applicants, an increase of 48 over 1965-66. United States applicants declined from 1143 to 1013.Evaluations made by the schools concerning the acceptability of the Canadian applicants disclosed that 55 applicants who rated as “acceptable” by one or more schools failed to gain admission to any medical school in 1966-67 (as compared to 36 in 1965-66). However, of those applicants who did find a place 76 were evaluated as “marginal” or “unacceptable”, while another 126 were rated as “acceptable” by one school but “marginal” and/or “acceptable” by one or more other schools.These results were interpreted to imply that the Canadian medical schools were still experiencing difficulty in attracting well-qualified applicants for study in medicine.     

Medical Students in Canadian Universities: Report of Statistics, 1966-67

Enrolment in the 13 Canadian medical schools in 1966-67 reached a new high of 4230, an increase of 5.1% over 1965-66. The percentage of women among medical students (12.1%) was close to that of the preceding three years. There has been a levelling off in the decline of students from outside Canada in 1966-67, when 9.5% of medical students were non-Canadian. The decline had been primarily in the number of American students, which continues. The number of students from Commonwealth countries has shown a steady increase during the eight-year period under review; in 1966-67, they make up nearly one-half of all non-Canadian students. It was noted that 18.5% of overseas students came to Canada under governmental or intergovernmental sponsorship. Of the Canadian students, 94% came from the “home” provinces of the medical schools.