Inosine monophosphate dehydrogenase and myeloid cell maturation

In previous studies of purine ribonucleotide metabolism in the human myeloid leukemia cell line HL-60, we observed that there is a down- regulation of guanine ribonucleotide biosynthesis from the central intermediate, inosine monophosphate (IMP) and a depletion of intracellular guanosine triphosphate (GTP) and guanosine diphosphate (GDP) pools that occur during the induced maturation of these cells. We also found that inhibitors of IMP dehydrogenase, the enzyme that catalyzes the first step of guanylate synthesis from IMP, are potent inducers of HL-60 maturation. Because of these observations we specifically investigated the activity of IMP dehydrogenase in HL-60 cells and in a new inducible human myeloid leukemia cell line, RDFD2- 25, both during maintenance culture and during induced maturation of the cells. Enzyme activity was examined directly in cell extracts with a radiometric assay that measures free 3H2O formed from [2-3H] IMP during the conversion of IMP to XMP. Uninduced HL-60 and RDFD2 cells in maintenance culture were found to have high levels of IMPD activity (5.2 to 5.7 pmol IMP metabolized/10(7) cells/min) compared with normal neutrophils and monocytes that had been purified from blood (less than 1.5 pmol IMP metabolized/10(7) cells/min). However, when HL-60 and RDFD2-25 cells were induced to mature with retinoic acid (10(-6) mol/L), dimethylformamide (6 X 10(-2) mol/L), or a known IMPD inhibitor, tiazofurin (10(-6) mol/L), IMPD activity in the cells fell by 51% to 80% within three to six hours. These changes in IMPD activity preceded detectable functional and antigenic maturation of the cells by at least 12 hours and were not temporally related to changes in cellular proliferation. These findings are consistent with the concept that the regulation of myeloid cell maturation may be influenced by intracellular concentrations of guanine ribonucleotides because IMP dehydrogenase activity is known to be rate limiting for the production of these nucleotides.     

Palpable prostatic nodules: comparison of US and digital guidance for fine-needle aspiration biopsy

This study was undertaken to evaluate the use of transrectal sonographically guided fine-needle aspiration biopsy and to compare sonographic with digital guidance for biopsy. In 62 patients in whom prostatic carcinoma was suspected at digital rectal examination, fine-needle aspiration biopsies were performed transperineally under sonographic guidance and transrectally under digital guidance. These patients had 89 nodules, 73 of which were sampled with both techniques. Malignant cells were obtained under digital guidance in 17 of 73 nodules (23%) and under sonographic guidance in 16 (22%). An additional seven nodules, which were not seen sonographically, were sampled under digital guidance and proved to be negative. In nine other nodules that were nonpalpable and evident only with sonography, malignant cells were obtained under sonographic guidance in three. These findings indicate that sonographic guidance for fine-needle aspiration biopsy is as good as digital guidance for palpable lesions.     

Perioperative blood transfusion and cancer recurrence: meta-analysis for explanation

BACKGROUND: Meta-analysis was used to explain disagreements across observational studies in regard to the association between perioperative transfusion and cancer recurrence. STUDY DESIGN AND METHODS: Observational studies published in English from 1982 through 1994 were retrieved. Five or more articles published in complete form were identified for each of six cancer sites: colorectum, breast, head and neck, lung, prostate, and stomach. Necessary information for building a 2 × 2 contingency table could be extracted from 60 studies. Summary relative risks (RR) reflecting the "average" adverse transfusion effect were computed for each cancer site by the random- effects method. Seven study characteristics were examined as potential explanations for the disagreements among the published studies. RESULTS: Before any adjustment for the effect of confounding, computed crude summary RRs suggested a significant (p < 0.05) deleterious transfusion effect in all cancer sites, except for breast. The RR of an adverse outcome was 1.49 in colorectal cancer (95% CI, 1.23-1.79) and ranged from 1.06 in breast cancers to 3.62 in head and neck cancers. The disagreements among published studies were most marked in the case of colorectal and gastric cancers. These discrepancies could be explained, in part, by study design, because prospective investigations had not produced a significant unadjusted transfusion effect (RR = 1.18; 95% CI, 0.93-1.51 in the case of colorectal cancer). CONCLUSION: A reduction in the size of the computed unadjusted transfusion effect (of an appropriate magnitude to adjust for the effect of confounding) might eliminate the significance of the average adverse effect in most studied cancer sites. Whether the entire unadjusted transfusion effect should be ascribed to the effect of confounding or whether a true, deleterious transfusion effect also exists can be resolved only by randomized controlled trials.     

用FAB—MS／MS对γB—晶体蛋白非酶糖基化位点的研究

鉴定γＢ－晶体蛋白非酶糖基化位点。方法用离子交换ＨＰＬＣ纯化小牛晶状体γＢ－晶体蛋白，与果糖保温后用糜蛋白酶水解。糖基化的肽用Ａｆｆｉ－Ｇｅｌ６０１柱层析纯化，并用ＲＰ－ＨＰＬＣ分离各肽。     

Effect of delta-opioid receptor agonist deltorphin on circulating concentrations of luteinizing hormone and follicle stimulating hormone in healthy fertile women

There is evidence that endogenous opioid peptides exert an inhibitory effect on pituitary luteinizing hormone (LH) secretion both in animals and in humans, by interacting with mu-opioid receptors. However, a role for delta-opioid receptors in the regulation of gonadotrophin releasing hormone (GnRH) secretion has recently been suggested. In the present study, we evaluated the effect of the highly selective delta-opioid receptor agonist deltorphin on the LH and follicle stimulating hormone (FSH) responses to naloxone in six healthy fertile women during the luteal phase of the menstrual cycle. Deltorphin infusion alone (7 microg/kg/min for 60 min) did not significantly change the basal serum concentrations of LH in this group of women. The intravenous (i.v.) bolus administration of naloxone (15 mg) induced a significant (P < 0.001) increase in serum LH concentrations (from a mean basal value of 4.24+/-1.10 IU/l to a peak of 13.27+/-1.8 IU/l). The LH response to naloxone was significantly (P < 0.001) blunted by preinfusion of deltorphin (13.27+/- 1.80 IU/l versus 4.80+/-1.18 IU/l). No significant changes in FSH concentrations were observed during deltorphin, naloxone or deltorphin plus naloxone administration. These data indicate that activation of delta-opioid receptors can reduce naloxone-induced LH release, suggesting a possible role of delta receptors in opioidergic modulation of LH secretion in women.      

Low-oxygen-affinity red cells produced in a large-volume, continuous- flow electroporation system

BACKGROUND: Human red cells containing inositol hexaphosphate (IHP) have a lowered O2 affinity, though they are able to bind and carry about the same amount of oxygen as native cells. These modified cells therefore deliver oxygen more efficiently to the tissues, which is a property of potential clinical utility. Investigators set out to devise a system and procedure by which large volumes of IHP-containing red cells, suitable for transfusion, could be produced quickly and efficiently. STUDY DESIGN AND METHODS: The encapsulation of IHP into human red cells by use of several variations of static electroporation was performed to define the conditions necessary for optimal IHP incorporation and cell survival. These conditions were used as a starting point for optimization of a flow electroporation system. RESULTS: When fresh human red cells in a 35 mM IHP solution are subjected to three exponential pulses of field strength of 2.98 +/− 0.064 kV per cm per pulse and pulse length of 2.0 +/− 0.2 msec per pulse while flowing through a cooled electroporation chamber, the condition of the resultant cells, according to the criteria used here, is optimized. After storage for 24 hours in plasma at 37 degrees C, the cells show more than 85-percent survival (in vitro) and hematologic indices nearly identical to those of unpulsed control cells. The p50 value of these cells, however, has doubled to 50.4 +/− 2.0 torr. The processing time for 1 unit of blood is 90 minutes. CONCLUSION: These data indicate that the system described here can efficiently produce low-oxygen-affinity red cells in volumes that are useful in clinical applications.     

Infant growth and aorta total lipid fatty acids

Abnormal fetal and infant growth have increasingly been correlated with adult onset cardiovascular disease. To date, there is little known about the lipid fatty acid profiles in infant cardiovascular tissue. Therefore, we analysed total lipid fatty acids from thoracic and abdominal aorta intima and media from 24 normally grown sudden infant death syndrome cases. Aorta from small for gestational age (n = 2), failure to thrive from birth (n = 3), and premature (n = 1) infants were also examined. Dihomo-gamma-linolenic acid (C20:3n-6) and oleic acid (C18:1n-9) concentrations were significantly lower in the thoracic than in the abdominal aorta. Similar dietary related differences were found in the subgroup (n = 15) of infants fed on formula milks. Both abdominal and thoracic intimal arachidonic (C20:4n-6) to dihomo-gamma-linolenic acid ratios were greater in the infants with retarded growth after birth than in their normally grown counterparts. Growth restriction in infancy might disrupt the normal accretion of vascular endothelial polyunsaturated fatty acids.     

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91)

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.     

Readjustment of the biological exposure limit applied to blood lead levels in Brazil

We randomly selected twenty lead workers from an electric accumulator factory in the State of S?o Paulo, Brazil, whose blood lead level and urinary d-aminolevulinic acid level were below 60 mg/dL and 10 mg/L, respectively. The workers were submitted to a standard motor nerve conduction velocity study of the right radial nerves, in addition to blood lead dosage. Based on these measures, a first-order linear regression model was adjusted, where the dependent variable was conduction velocity and the independent variable was the blood lead level. Analyzing the fitted model, we inferred that the negative predictive value of the Brazilian biological exposure limit is 0.63. In order for the above biological exposure limit to have a negative predictive value of 0.99, the study suggests that it be reduced from its present value (60 mg/dL) to 32 mg/dL.