Multiple Chromosomal Aberrations in a Patient with Acute Granulocytic Leukemia Associated with Down's Syndrome and Twinning: Study of a Family with a Possible Tendency to Nondisjunction

1. A case of Down's syndrome (G 21 trisomy) in a boy, age 4, associatedwith twinning and AGL is described. Multiple chromosomal aberrationswere found prior to and during antileukemic chemotherapy.

2. The initial modal number ranged from 47 to 53 and subsequently 49to 53, and 42 to 52 chromosomes respectively. The overwhelming leukemiccell population was represented by 51 chromosomes on three occasions (74.2,80 and 79.5 per cent respectively).

3. The autosomal aberrations—trisomies and polysomies—were constant,involving predominantly the chromosomes of the G, F and D series.

4. Heterokaryotic twinning with one normal and one affected was encountered twice in this family (G 21 trisomy and normal) and (normal andmentally affected) sets of twins.

5. A possible tendency to nondisjunction has been demonstrated in threehealthy members of the family.

6. Multiple mitotic nondisjunction anomalies might be of etiologic importance in the leukemic process.

7. The implication of different injurious agents and factors, such as ionizing radiation, x-ray exposure, chemicals and parental age in the developmentof trisomic syndromes and/or neoplasia are briefly discussed.

Submitted on November 12, 1963 Accepted on January 7, 1964     

Synthesis of Riboflavin Nucleotides by Mature Human Erythrocytes

Intact human red blood cells can synthesize FAD and FMN from riboflavin.The rate of synthesis of FAD is linearlyproportional to the concentration of riboflavin in the medium at levels below 0.9µM. With 0.9 µM riboflavin, the rate ofsynthesis is about 0.1 mµmole FAD/ml.red blood cells/hour. Incubation of redblood cells with riboflavin can result inincreased red cell glutathione reductaseactivity when the enzyme is measured inthe absence of added FAD. This indicates that the FAD concentration in thered cells increased during the incubation. The rate of incorporation of radioactive riboflavin into red blood cells isthe same whether the cells are suspendedin plasma or in a phosphate-saline-glucose medium. The time it takes for halfthe FAD in normal human red bloodcells to turn over is calculated to beabout 6 days, assuming a single mixingpool of red cell FAD.

Submitted on March 9, 1970 Revised on April 28, 1970 Accepted on May 8, 1970     

Simplified Determination of Blood Adenosine Triphosphate Using the Firefly System

A simplified method is described for the determination of red cell ATPusing the firefly lantern extract method. Variables investigated include theeffect of the time of reading, dilution of firefly extract and the effective rangeof the method. Excellent recoveries were obtained. Optimal extraction of ATPfrom red cells was achieved with a hypotonic buffer at pH 9.2. The methodcould be used with acid-citrate-dextrose, heparin or EDTA as an anticoagulant. The method was found to be highly specific when the nucleotides foundin normal human blood were investigated; only adenosine diphosphate andguanosine triphosphate gave slight readings, neither of which would significantly affect ATP determinations of human blood. Normal human valueswere found to be 5.45 µmoles of ATP/Gm. of hemoglobin or 1.83 µmoles/ml.red cells in heparinized blood samples. This method is believed to be morerapid, more reproducible and more accurate than any previously describedmethod of ATP determination.

Submitted on October 1, 1963 Accepted on December 3, 1963     

ENALAPRIL: A POWERFUL IN VITRO NON-THIOL ACANTHOLYTIC AGENT

Drugs containing sulfhydryl groups (thiol drugs) (e.g., penicillamine, captopril, thiopronine) can induce pemphigus in vivo and provoke acantholysis in vitro. Enalapril, like captopril, is an angiotensin-converting enzyme (ACE) inhibitor largely used as an antihypertensive drug; it has recently been reported to induce pemphigus, though it is not a thiol drug. In this study we investigated the possible in vitro acantholytic effect of enalapril on normal human skin from donors. The drug induced severe acantholytic changes of keratinocytes and complete suprabasal splitting at one tenth the concentration required by thiol drugs in similar experiments, even after a shorter period of culture. All skin samples from different donors was highly susceptible to the acantholytic effect of enalapril. In our experience, enalapril is the most powerful acantholytic drug in vitro.     

Application of acetamidomethyl and 9-fluorenylmethyl groups for efficient side protection of penicillamine in solid-phase peptide synthesis

Synthesis of S-acetamidomethyl and S-fluorenylmethyl derivatives of penicillamine is described. Both groups are completely stable to all the usual reagents in solid-phase peptide synthesis, including the HF cleavage step, and show an excellent degree of orthogonality to each other. Treatment of the protected peptides Ac-L-Pen(X)-L-Pro-D-Val-L-Cys(X)-NH₂ with thallium (III) trifluoroacetate or iodine for X = Acm or piperidine/DMF (1:1) for X = Fm induced with good yield the formation of the intramolecular disulfide bridge. This cyclic peptide appears to assume a type II β-turn conformation in d₆-DMSO as evidenced by ¹H-NMR spectra.     

Alcohol-related problems among Aboriginal drinkers in the Kimberley region of Western Australia

This paper reports on the prevalence of alcohol-related problems among drinkers in a stratified random sample of the adult Aboriginal population of the Kimberley region of Western Australia. Subjects were 265 current drinkers who were identified in the total sample of 516 Kimberley Aboriginal men and women over the age of 15 years. Participants' reports were obtained on their frequency and quantity of alcohol consumption, and their lifetime experience of 16 alcohol-related problems. The majority of Aboriginal drinkers in the Kimberley consumed harmful amounts of alcohol, and there was a high prevalence of the 16 alcohol-related problems which showed a high degree of internal coherence, with the first principal component accounting for 45% of the total variance. The number of alcohol-related problems which respondents reported was strongly related to the quantity and frequency of self-reported alcohol consumption.     

Anchoring of Fmoc-amino acids to hydroxymethyl resins

A method to anchor Fmoc-amino acids to p-alkoxybenzyl ester resins without using DMAP is described. Esterification takes place with 3–4 equiv. of Fmoc-amino acid plus DCC and a slightly lower excess of HOBt in good yields, without racemization or dipeptide formation. Addition of N-methylmorpholine to the reaction medium enhances the reaction yield but is accompanied by a small amount of racemization and dipeptide formation. Coupling via Fmoc-amino acid chlorides has also been evaluated.     

UNBOUND PLASMA SALICYLATE CONCENTRATION IN RHEUMATOID ARTHRITIS PATIENTS

This study was designed to investigate the relationship of freeplasma salicylate to total plasma salicylate and to determinethe clinical utility of monitoring the free plasma salicylateconcentration. Analysis of 46 patient samples indicated a closecorrelation between the free and total plasma concentrationand that there is no additional advantage to monitoring thefree plasma salicylate concentration. Also this study re-emphasizesthe unique pharmacokinetic characteristics of salicylate, wherebythe amount of free plasma salicylate increases disproportionatelywith increased total plasma salicylate concentration. KEY WORDS: Rheumatoid arthritis, Plasma salicylate, Protein binding ^*Submitted as partial fulfilment of the requirements for thedegree of Master of Science in Pharmacy, University of Illinoisat the Medical Center.