Analyses of brains from six infants whose birth weights were "small for gestational age"... more Analyses of brains from six infants whose birth weights were "small for gestational age" (SGA) and ten infants whose birth weights were ‘appropriate for gestational age" (AGA) show the cerebellum to be the area of the brain most greatly affected by intrauterine underdevelopment. The SGA cerebellar weight was reduced 37% and cellularity 35%, compared to reductions of only 21% and 19% for weight and cellularity in the remainder of the brain. The myelin lipids, cerebroside and sulfatide, were significantly reduced (p < .01) in concentration or total quantity in the brains of SGA infants, in contrast to phospholipids, cholesterol, and gangliosides which did not show a similar reduction. Galactolipid sulfotransferase activity, important in sulfatide formation, was also significantly reduced (p < .01) in the brains from SGA infants.
A two stage assay procedure has been developed for the estimation of dihydroxyacetone (DHN). DHA ... more A two stage assay procedure has been developed for the estimation of dihydroxyacetone (DHN). DHA is at first phosphorylated to dihydroxyacetone phosphate (DHAP) by glycerokinase (GK) and ATP at pH 8.5. The DHAP formed is then measured enzymatically using glycerol-3P dehydrogenase (GDH) and NADH at pH 7.6. The sensitivity of this method is found to be adequate for both routine
Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal a... more Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal amounts of normal and shortened pro alpha 2(I) chains of type I procollagen. Nuclease S1 probe protection experiments with mRNA demonstrated that the pro alpha 2(I) chains were shortened because of a deletion of most or all of the 54 nucleotides in exon 6, the exon that contains codons for the cleavage site for procollagen N-proteinase. Sequencing of genomic clones revealed a single-base mutation that converted the first nucleotide of intron 6 from G to A. Therefore, the mutation was a change, in the -GT-consensus splice site, that produced efficient exon skipping. Allele-specific oligonucleotide hybridizations demonstrated that the proband's mother, father, and brother did not have the mutation. Therefore, the mutation was a sporadic one. Analysis of potential 5' splice sites in the 5' end of intron 6 indicated that none had favorable values by the two commonly employed techniques for evaluating such sites. The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene. No other mutations in the two type I procollagen genes have been found in the syndrome. Therefore, such mutations may be a common cause of the phenotype. The primers developed should be useful in screening for the same or similar mutations causing the disease.
Journal of Medical Education and Curricular Development
The medical humanities, an umbrella term for the fields of ethics, social science, and fine arts,... more The medical humanities, an umbrella term for the fields of ethics, social science, and fine arts, are increasingly recognized as an important component of medical education. Since the Flexner report, the primacy of science and evidence-based medicine has replaced subjectivity and nuance. While this has been critical for standardization of care and patient safety, an exclusive emphasis on science in undergraduate medical education can devalue more humanistic pursuits. Modern medicine is now plagued with burnout, pandemics, and societal ills that permeate into medicine. Addressing these requires a thoughtful, holistic approach where we extend our sights beyond strict evidence-based medicine.
Limb-bud proteoglycans are heterogeneous molecules which vary in their chemical and physical prop... more Limb-bud proteoglycans are heterogeneous molecules which vary in their chemical and physical properties with development. This report describes proteoglycan intermediates (PG-I) that predominate in stage-34 limbs, and compares them with proteoglycan aggregates (PG-A) in stage-38 limbs. We analysed proteoglycans and their components extracted with guanidinium chloride by subjecting them to density gradient centrifugation, molecular sieve chromatography, electrophoretic separation, and selective enzymatic degradation. PG-I and PG-A have similar chondroitin sulphate composition, amino sugars, chondroitin sulphate side-chain length, glycoprotein link factors, and hyaluronic acid binding capacity, and both cross react with antisera prepared against cartilage-specific chick sternal proteoglycans. However, PG-I has lower molecular weight, lower buoyant density, and fewer chondroitin sulphate side chains on the protein core. The PG-I in the developing limb can be considered a mixture of sma...
Analyses of brains from six infants whose birth weights were "small for gestational age"... more Analyses of brains from six infants whose birth weights were "small for gestational age" (SGA) and ten infants whose birth weights were ‘appropriate for gestational age" (AGA) show the cerebellum to be the area of the brain most greatly affected by intrauterine underdevelopment. The SGA cerebellar weight was reduced 37% and cellularity 35%, compared to reductions of only 21% and 19% for weight and cellularity in the remainder of the brain. The myelin lipids, cerebroside and sulfatide, were significantly reduced (p < .01) in concentration or total quantity in the brains of SGA infants, in contrast to phospholipids, cholesterol, and gangliosides which did not show a similar reduction. Galactolipid sulfotransferase activity, important in sulfatide formation, was also significantly reduced (p < .01) in the brains from SGA infants.
A two stage assay procedure has been developed for the estimation of dihydroxyacetone (DHN). DHA ... more A two stage assay procedure has been developed for the estimation of dihydroxyacetone (DHN). DHA is at first phosphorylated to dihydroxyacetone phosphate (DHAP) by glycerokinase (GK) and ATP at pH 8.5. The DHAP formed is then measured enzymatically using glycerol-3P dehydrogenase (GDH) and NADH at pH 7.6. The sensitivity of this method is found to be adequate for both routine
Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal a... more Fibroblasts from a proband with Ehlers-Danlos syndrome type VII synthesized approximately equal amounts of normal and shortened pro alpha 2(I) chains of type I procollagen. Nuclease S1 probe protection experiments with mRNA demonstrated that the pro alpha 2(I) chains were shortened because of a deletion of most or all of the 54 nucleotides in exon 6, the exon that contains codons for the cleavage site for procollagen N-proteinase. Sequencing of genomic clones revealed a single-base mutation that converted the first nucleotide of intron 6 from G to A. Therefore, the mutation was a change, in the -GT-consensus splice site, that produced efficient exon skipping. Allele-specific oligonucleotide hybridizations demonstrated that the proband's mother, father, and brother did not have the mutation. Therefore, the mutation was a sporadic one. Analysis of potential 5' splice sites in the 5' end of intron 6 indicated that none had favorable values by the two commonly employed techniques for evaluating such sites. The proband is the fourth reported proband with Ehlers-Danlos syndrome VII with a single-base mutation that causes skipping of exon 6 in the splicing of RNA from either the COL1A1 gene or COL1A2 gene. No other mutations in the two type I procollagen genes have been found in the syndrome. Therefore, such mutations may be a common cause of the phenotype. The primers developed should be useful in screening for the same or similar mutations causing the disease.
Journal of Medical Education and Curricular Development
The medical humanities, an umbrella term for the fields of ethics, social science, and fine arts,... more The medical humanities, an umbrella term for the fields of ethics, social science, and fine arts, are increasingly recognized as an important component of medical education. Since the Flexner report, the primacy of science and evidence-based medicine has replaced subjectivity and nuance. While this has been critical for standardization of care and patient safety, an exclusive emphasis on science in undergraduate medical education can devalue more humanistic pursuits. Modern medicine is now plagued with burnout, pandemics, and societal ills that permeate into medicine. Addressing these requires a thoughtful, holistic approach where we extend our sights beyond strict evidence-based medicine.
Limb-bud proteoglycans are heterogeneous molecules which vary in their chemical and physical prop... more Limb-bud proteoglycans are heterogeneous molecules which vary in their chemical and physical properties with development. This report describes proteoglycan intermediates (PG-I) that predominate in stage-34 limbs, and compares them with proteoglycan aggregates (PG-A) in stage-38 limbs. We analysed proteoglycans and their components extracted with guanidinium chloride by subjecting them to density gradient centrifugation, molecular sieve chromatography, electrophoretic separation, and selective enzymatic degradation. PG-I and PG-A have similar chondroitin sulphate composition, amino sugars, chondroitin sulphate side-chain length, glycoprotein link factors, and hyaluronic acid binding capacity, and both cross react with antisera prepared against cartilage-specific chick sternal proteoglycans. However, PG-I has lower molecular weight, lower buoyant density, and fewer chondroitin sulphate side chains on the protein core. The PG-I in the developing limb can be considered a mixture of sma...
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