Comparison of erythrocyte uridine sugar nucleotide levels in normals, classic galactosemics, and patients with other metabolic disorders

By limiting galactosylation mechanisms, a cellular deficiency of the uridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long-term complications seen in patients with classic galactosemia despite dietary treatment. As a result, great interest has been generated in the accurate assessment of UDPgalactose, as well as UDPglucose, from which UDPgalactose may be derived by the function of a ubiquitous, active UDPgalactose-4-epimerase. Since several series of values for the concentration of these compounds in red blood cells (RBCs) of galactosemics have been flawed by the use of methods subsequently shown to be unsuitable, we have quantified erythrocyte UDPgalactose and UDPglucose levels by an accurate high-performance liquid chromatography (HPLC) assay in 116 normals, 76 galactosemics, and 39 patients with other metabolic disorders. These large groups have permitted the evaluation of age, diet, and genotype as influential factors in the steady-state RBC levels of the sugar nucleotides. The data show that age is an important determinant of RBC levels, with children younger than 10 years having higher values than individuals older than 10 years. Mean UDPgalactose levels in galactosemic children younger than 10 years and those older than 10 years were 30% and 18% lower, respectively, than levels in comparable normals. Although the mean differences were highly significant, there was considerable overlap of individual values. There was no difference in UDPglucose levels between galactosemics and normals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular mechanisms of biocatalytic desulfurization of fossil fuels

The development of biocatalytic desulfurization of petroleum fractions may allow its use in place of conventional hydrodesulfurization (HDS). Dibenzothiophene (DBT) is representative of a broad range of sulfur heterocycles found in petroleum that are recalcitrant to desulfurization via HDS. Rhodococcus sp. strain IGTS8 has the ability to convert DBT to 2-hydroxybiphenyl (HBP) with the release of inorganic sulfur. The conversion of DBT to HBP is catalyzed by a multienzyme pathway consisting of two monooxygenases and a desulfinase. The final reaction catalyzed by the desulfinase appears to be the rate limiting step in the pathway. Each of the enzymes has been purified to homogeneity and their kinetic and physical properties studied. Neither monooxygenase has a tightly bound cofactor and each requires an NADH-FMN oxidoreductase for activity. An NADH-FMN oxidoreductase has been purified from Rhodococcus and is a protein of approximately 25,000 molecular weight with no apparent sequence homology to any other protein in the databases. We describe a unique sulfur acquisition system that Rhodococcus uses to obtain sulfur from very stable heterocyclic molecules.     

Paracoccidioidoma: case record and review

The ulcer resulting from snake-bite injury was characterized by deep and wide tissue necrosis and secondary infection. The patient was at high risk of loss of function of his extremity. From 1989 to 1996, 16 cases with deep ulcer of the upper extremity resulting from snake-bite injury were treated with different types of axial thoraco-abdominal skin flaps, depending on the location of the ulcer. Thoraco-umbilical skin flap was used in 2 cases, lateral thoracoabdominal skin flap in 1 case, iliolumbar skin flaps in 5 cases, lower abdominal skin flaps in 6 cases, lower abdominal divided foliated skin flap in 1 case and Y-shaped hypogastric skin flap in 1 case. Reparative operation was carried out within 3 weeks after injury and primary repair were undertaken in 6 of them. The pedicles were divided in 17 to 24 days after operation. Twelve flaps survived. Three of the 6 flaps had mild signs of inflammation which disappeared after administration of antibiotics. One had necrosis of the distal part of the flap, and was healed with split skin graft. This type of skin flap was an ideal method for the treatment of snake-bite injury of the upper extremity.     

Evidence for a selectively favourable reduction in the mutation rate of the X chromosome

The equilibrium per-genome mutation rate in sexual species is thought to result from a trade-off between the benefits of reducing the deleterious mutation rate and the costs of increasing fidelity. We propose that selection will often favour a lower mutation rate on the X chromosome than on autosomes, owing to the exposure of deleterious recessive mutations on hemizygous chromosomes. We tested this hypothesis by examining 33 X-linked genes that have been sequenced in both mouse and rat, and compared their rate of evolution against 238 autosomal genes. The X-linked genes were found to have a significantly lower rate of synonymous substitution than the autosomal genes. Neither the supposed higher mutation rate in males nor stronger purifying selection against slightly deleterious mutations on the X chromosome can account for the low value. The most parsimonious explanation is that rodents have a lower mutation rate on the X chromosome than on autosomes. It is therefore likely that previous indirect estimates of the excess male mutation rate are inaccurate. Indeed, after correction we find no evidence for a male-biased mutation rate in rodents. Furthermore, the rate of synonymous substitution in Y-linked genes is not significantly different from that in autosomal ones. The extent to which enhanced male mutation rates are problematic for the mutational deterministic model of the evolution of sex must, in turn, be questioned.     

Entry of US medical school graduates into family practice residencies: 1997-1998 and 3-year summary

This is the 17th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each US medical school's graduates entering family practice residency programs. Approximately 16.6% of the 15,894 graduates of US medical schools between July 1996 and June 1997 were first-year family practice residents in October 1997, compared with 15.9% in 1996 and 14.6% in 1995. This is the highest percentage since this series of studies began in 1980-1981 (12.8%). Medical school graduates from publicly funded medical schools were almost twice as likely to be first-year family practice residents in October 1997 than were residents from privately funded schools, 19.8% compared with 11.8%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1997 at 25.8%; the Middle Atlantic and New England regions reported the lowest percentages at 11.7% and 10.7%, respectively. Nearly half of the medical school graduates (48.1%) entering a family practice residency program as first-year residents in October 1997 entered a program in the same state where they graduated from medical school. The percentages for each medical school have varied substantially from year to year since the AAFP began reporting this information. This article reports the average percentage for each medical school for the last 3 years. Also reported are the number and percentage of graduates of colleges of osteopathic medicine who entered Accreditation Council for Graduate Medical Education-accredited family practice residency programs, based on estimates provided by the American Association of Colleges of Osteopathic Medicine.     

Thyroid cancer: relationship to radiation exposure and to pregnancy

Exposure to radiation results in an increased occurrence of nodularity to the thyroid and, more important, the development of cancer in a significant proportion of patients. Near-total thyroidectomy is recommended in those patients with a history of irradiation who are found on physical examination of the thyroid to have one or more nodules. Although pregnancy appears to have no effect on the course of thyroid carcinoma and the tumor has no effect on pregnancy, because of the numerous stimuli to thyroid growth during pregnancy, we feel that pregnancy is best avoided by women with known residual disease.