Biomedical subjects
Publications and source records attributed to H M Rubinstein.
A comparison of methods for preparing a jellyfish nematocyst suspension from sea nettle (Chrysaora quinquecirrha) fishing tentacles at the beachside was conducted. Autolysis of the tentacle followed by straining and sedimentation on ice was found to be a satisfactory technique. This procedure utilized a tea strainer, plastic cup and conical centrifuge tube, all of which could be made available at a minimally equipped laboratory.
The fluoride variant of human butyrylcholinesterase owes its name to the observation that it is resistant to inhibition by 0.050 mM sodium fluoride in the in vitro assay. Individuals who are heterozygous for the fluoride and atypical alleles experience about 30 min of apnea, rather than the usual 3-5 min, after receiving succinyldicholine. Earlier we reported that the atypical variant has a nucleotide substitution which changes Asp 70 to Gly. In the present work we have identified two different point mutations associated with the fluoride-resistant phenotype. Fluoride-1 has a nucleotide substitution which changes Thr 243 to Met (ACG to ATG). Fluoride-2 has a substitution which changes Gly 390 to Val (GGT to GTT). These results were obtained by DNA sequence analysis of the butyrylcholinesterase gene after amplification by PCR. The subjects for these analyses were 4 patients and 21 family members.
Genomic DNA from two families exhibiting the K-variant phenotype of serum butyrylcholinesterase was amplified by PCR and sequenced to determine the molecular basis of this variant. The K-variant phenotype was found to be associated with a DNA transition from guanine to adenine at nucleotide 1615, which caused an amino acid change from alanine 539 to threonine (GCA----ACA; Ala539----Thr). There was a 30% reduction of serum butyrylcholinesterase activity associated with this mutation. Amplification and sequencing of DNA from a random sample of 47 unrelated people gave a frequency of .128 for the K-variant allele. Thus, 1 person in 63 should be homozygous for the K-variant, making the K-variant the most common butyrylcholinesterase variant. The K-variant mutation was also found to be present in 17 (89%) of 19 butyrylcholinesterase genes containing the point mutation which causes the atypical phenotype of butyrylcholinesterase (GAT----GGT; Asp70----Gly). The presence of the K-variant in the same molecule as the atypical variant does not contribute to the qualitative change in the atypical enzyme, but it most likely accounts for the approximately one-third reduction in Vmax of butyrylcholinesterase activity in atypical serum. Two additional point mutations located in noncoding regions of the gene were also observed to be in linkage disequilibrium with the K-variant mutation. As many as four different point mutations have been identified within a single butyrylcholinesterase gene. Inhibition tests of the enzyme in plasma are usually used to distinguish the K-variant from the usual enzyme when the former is present with the heterozygous atypical variant (AK phenotype vs. UA phenotype). Inhibition tests were performed on plasma enzyme from the four possible genotypic combinations of the heterozygous atypical mutation with or without the K-variant mutation on either allele; we found that the AK phenotype was caused by three genotypes (A/K, AK/K, and U/A) and that the UA phenotype was caused by two genotypes (U/A and U/AK).
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Crude venoms of three poisonous jellyfish produce membrane depolarization as determined by the loss of fluorescence intensity of 3,3'-dipentyloxacarbocyanine iodide loaded cells measured by flow cytometry. This method for detecting jellyfish cytotoxicity was reproducible and more sensitive than mouse lethality assays.
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Two families segregating for the atypical (E1a) allele at cholinesterase locus 1 are described. Unusual results for dibucaine inhibition led to the recognition of a new allele (E1k) also segregating in these families. The enzymatic and immunological data are consistent with the hypothesis that E1k causes reduction of 'usual' (E1u) molecules by about 33%. Whether the reduction of E1u caused by E1k is caused by retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.
Two patients with profound decrease of alpha1-antitrypsin (PiZZ) presented with severe pannicultis (Weber-Christian disease); one had systemic panniculitis including pancreatitis. Another possible case is quoted from the literature. Although milder forms of panniculitis can have normal Pi phenotypes and alpha1-antitrypsin levels, the marked reduction of antiproteolytic activity found in PiZZ homozygotes may predispose to or aggravate the lesions of Weber-Christian disease.
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A case of Candida albicans arthritis involving a knee and cuneiform bone is presented. As with other forms of candidiasis, multiple antibiotic treatment and hyperalimentation predisposed to the infection. Fourteen previously published cases are reviewed. The knee is the most common site of infection and there is a high frequency of associated osteomyelitis. Treatment with both amphotericin and 5-fluorocytosine seems to be effective. The case presented was treated successfully with a small dose of amphotericin followed by five and one-half months of 5-fluorocytosine.
A family (H-J pedigree) segregating for the A and F alleles at cholinesterase locus 1 is described. Apparent anomalous results led to the recognition of a new allele (E1j) also segregating in the family. The data are consistent with the hypothesis that the the E1j causes reduction of 'usual' (E1u) molecules by about 66%. Whether this is because of retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.
Sera of various phenotypes at serum cholinesterase locus 1, including the newly recognized phenotypes E1 aE1j, E1 uE1j, and E1 fE1J, were studied by immunodiffusion and rocket immunoelectrophoresis. The sera containing the E1j allele show reduced numbers of immunologically active cholinesterase molecules. This finding is consistent with the previously advanced hypothesis that E1j results in reduced numbers of circulating 'usual' (E1u) molecules. Whether this reduction is the result of the low rate of synthesis or of an increased rate of degradation of the cholinesterase remains to be determined.
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