Search PubMed⌕ Search

Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 433 records · Page 24Linked to original sources
PubMed1995

Improved survival in homozygous sickle cell disease: lessons from a cohort study.

OBJECTIVE: To examine whether simple interventions in a sickle cell clinic improve survival in sickle cell disease. DESIGN: Survival curve analysis and hazard ratios in a cohort study followed from birth. SETTING: MRC Laboratories (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital, Kingston, Jamaica. SUBJECTS: 315 patients with homozygous sickle cell disease detected during the screening of 100,000 consecutive non-operative deliveries between June 1973 and December 1981 at the main government maternity hospital, Kingston, Jamaica. INTERVENTIONS: Prophylactic penicillin to prevent pneumococcal septicaemia, parental education in early diagnosis of acute splenic sequestration, close monitoring in sickle cell clinic. MAIN OUTCOME MEASURES: Survival. RESULTS: Survival appeared to improve, the log rank test for trend comparing the first, second, and last third of the study reaching borderline significance (P = 0.05). Combined deaths from acute splenic sequestration and pneumococcal septicaemia-meningitis declined significantly (test for trend, P = 0.02). CONCLUSION: Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease.

Adolescent↗
PubMed1995

Neuroticism: a vulnerability marker for depression evidence from a family study.

INTRODUCTION: We investigated the relationship between depressive illness and personality traits from the Eysenck Personality Inventory (EPI) using data from a family study. METHODS: The first-degree relatives of a series of 89 probands with RDC major depression (MD) were subdivided by their lifetime RDC diagnosis into: (1) relatives recovered from MD (n = 34); (2) never-ill relatives (n = 45). The neuroticism (N) and extraversion (E) scores of these two groups were compared using a multilevel linear model, allowing for potential confounders. The relationship between age of onset and recurrence of MD and N scores in group 1 was also examined. RESULTS: (1) Raised N scores were associated with a past history of major depression. (2) There was no such relationship for E scores. (3) Current depressive symptoms were also associated with an increased N score but this did not explain the relationship between previous major depression and N scores. (4) Recurrent episodes of major depression in the recovered MD relatives were significantly associated with increased N scores. CONCLUSION: These data suggest that raised N may be a vulnerability marker for major depression.

Adult↗
PubMed1995

Structure-activity relationship of omeprazole and analogues as Helicobacter pylori urease inhibitors.

Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

Ammonia↗
PubMed1995

CpG islands in human ZFX and ZFY and mouse Zfx genes: sequence similarities and methylation differences.

The human ZFX, human ZFY, and mouse Zfx genes have CpG islands near their 5; ends. These islands are typical in that they span about 1.5 kb, contain transcription initiation sites, and encompass some 5' untranslated exons and introns. However, comparitive nucleotide sequencing of these human and mouse islands provided evidence of evolutionary conservation to a degree unprecedented among mammalian 5' CpG islands. In one stretch of 165 nucleotides containing 19 CpGs, mouse Zfx and human ZFX are identical to each other and differ from human ZFY at only 9 nucleotides. In contrast, we found no evidence of homologous CpG islands in the mouse Zfy genes, whose transcription is more circumscribed than that of human ZFX, human ZFY, and mouse Zfx. Using the isoschizomers HpaII and MspI to examine a highly conserved segment of the ZFX CpG island, we detected methylation on inactive mouse X chromosomes but not on inactive human X chromosomes. These observations parallel the previous findings that mouse Zfx undergoes X inactivation while human ZFX escapes it.

Animals↗
PubMed1995

Helicobacter pylori and gastric neoplasia: evolving concepts.

There is evidence that Helicobacter pylori infection is associated with gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and possibly with non-ulcer dyspepsia. Eradication therapy for confirmed H. pylori infection may therefore become mandatory in patients with non-ulcer dyspepsia severe enough to warrant endoscopy and in first-degree relatives of patients with gastric cancer. However, routine treatment of asymptomatic carriers awaits confirmation of the association with cancer.

Adenocarcinoma↗
PubMed1995

Benign marrow progenitors are enriched in the CD34+/HLA-DRlo population but not in the CD34+/CD38lo population in chronic myeloid leukemia: an analysis using interphase fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) was used to discriminate between benign and malignant cells in sorted populations of chronic myelogenous leukemia (CML) marrow. FISH has the advantage of allowing for a cell by cell analysis of the breakpoint cluster region (BCR) gene rearrangement immediately after flow sorting in nondividing G0/G1 cells that are potentially transcriptionally inactive. We initially selected CD34+ cells with very low expression of the activation antigen CD38 as a candidate phenotype for an immature and hypothetically more benign cell population, but found no enrichment for Ph negativity in that subtype. In five CML samples, 55% +/- 3.3% (mean +/- SE) of CD34+/CD38hi cells had the BCR gene rearrangement, similar to 57% +/- 3.7% seen in the CD34+/CD38lo population. In contrast, subsequent experiments (n = 4) determined that the CD34+/HLA-DRlo population in CML marrow does contain an increased proportion of benign cells: 15% +/- 1% of the CD34+/DRlo cells were BCR rearranged, compared with 52% +/- 5.8% of the CD34+/DRhi cells (P = .001). Our results indicate that benign progenitors in CML are enriched within the CD34+ cells with low DR antigen expression, but not low CD38 expression. One possible interpretation of these observations is that low CD38 antigen expression is not as useful as low HLA-DR expression for isolating immature cells.

ADP-ribosyl Cyclase↗
PubMed1995

Gene disruption of a G4-DNA-dependent nuclease in yeast leads to cellular senescence and telomere shortening.

The yeast gene KEM1 (also named SEP1/DST2/XRN1/RAR5) produces a G4-DNA-dependent nuclease that binds to G4 tetraplex DNA structure and cuts in a single-stranded region 5' to the G4 structure. G4-DNA generated from yeast telomeric oligonucleotides competitively inhibits the cleavage reaction, suggesting that this enzyme may interact with yeast telomeres in vivo. Homozygous deletions of the KEM1 gene in yeast block meiosis at the pachytene stage, which is consistent with the hypothesis that G4 tetraplex DNA may be involved in homologous chromosome pairing during meiosis. We conjectured that the mitotic defects of kem1/sep1 mutant cells, such as a higher chromosome loss rate, are also due to failure in processing G4-DNA, especially at telomeres. Here we report two phenotypes associated with a kem1-null allele, cellular senescence and telomere shortening, that provide genetic evidence that G4 tetraplex DNA may play a role in telomere functioning. In addition, our results reveal that chromosome ends in the same cells behave differently in a fashion dependent on the KEM1 gene product.

Blotting, Southern↗
PubMed1995

Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus.

The salivary glands of mammals synthesize and secrete a number of peptide growth factors that play important roles in cell/tissue homeostasis and embryonic development. Using a radioimmunoassay, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) were detected in saliva from mice. Unlike epidermal growth factor (EGF), there was no sexual dimorphism in the concentrations of the insulin growth factor family. Immunohistochemical localization of IGF-I and IGF-II was confined to the duct cells of both the parotid and the submandibular glands. Reverse transcriptase-polymerase chain reaction amplification of total RNA from parotid and submandibular glands confirmed the presence of all three hormone/growth factor mRNAs in both glands. The levels of insulin and IGF-I were higher in saliva from an animal model for autoimmune type 1 diabetes, the non-obese diabetic (NOD) mouse, than in a second inbred strain, BALB/c. In contrast, the IGF-II levels were decreased relative to the BALB/c strain. With the onset of diabetes in NOD mice, insulin levels declined, while IGF-I and IGF-II levels showed trends toward lower levels of these growth factors when compared with non-diabetic animals. These changes were reflected in the concentrations from parotid and submandibular gland cell lysates.

Animals↗
PubMed1995

Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients.

We studied 346 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML) for the presence of the bcr-abl transcript detected by the polymerase chain reaction (PCR) to understand the frequency and implication of a positive test. A total of 634 samples of BM and/or peripheral blood were obtained for PCR analysis between 3 and 192 months after BMT. A positive PCR test at 3 months post-BMT was not statistically significantly associated with an increased risk of relapse compared with PCR-negative patients. However, a positive PCR assay at 6 months and beyond was highly associated with subsequent relapse. The Kaplan-Meier estimate of relapse for patients testing PCR-positive at 6 to 12 months was 42% versus 3% for PCR-negative patients (P < .0001). The Kaplan-Meier estimate of survival at 4 years for the PCR-positive patients was 74% compared with 83% for the PCR-negative group (P = .002). Multivariable analysis indicated that a PCR-positive result at 6 to 12 months post-BMT, the type of BMT donor (allogeneic matched donor v mismatched or unrelated), and the presence of acute GVHD were independent risk factors for subsequent relapse. The relative risk (RR) for relapse for patients PCR-positive at 6 to 12 months post-BMT was 26.1 (95% confidence interval, 8.9 to 76.1, P < .0001). The outcome of long-term patients (> 36 months post-BMT) who tested PCR-positive was much better, as 15 of 59 (25%) tested positive for bcr-abl, but only one patient relapsed. There was a 91% concordance between PCR tests of simultaneously obtained BM and peripheral blood. These analyses show that the PCR assay of the bcr-abl fusion transcript 6 to 12 months post-BMT is an independent predictor of subsequent relapse which provides an opportunity for early therapeutic intervention.

Adolescent↗
PubMed1995

Rey 15-item memorization and Dot counting scores in a "stress" claim worker's compensation population: relationship to personality (MCMI) scores.

The relationship between apparent faking of cognitive impairment (as detected by such "malingering" tests as 15-item Memorization and Dot Counting) and faking of psychiatric symptoms has not been investigated formally. In addition, no empirical literature is available on the relationship between personality traits and faking of cognitive symptoms. Of 154 subjects who claimed "stress" psychiatric injury, 12% appeared to be faking cognitive impairment; 4.5% failed the 15-item Memorization Test, and 10% failed the Dot Counting task. Faking of cognitive symptoms occurred in only 23% of subjects who were faking/exaggerating psychological symptoms on the MCMI. Malingering test failure was associated with significant elevations on MCMI personality scales, although this appeared to be an artifact of attempts to fake/exaggerate on the MCMI, rather than a reflection of "true" personality traits.

Adolescent↗
PubMed1995

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension.

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.

Adult↗
PubMed1995

Fixation of whole eyes: the role of fixative osmolarity in the production of tissue artifact.

BACKGROUND: Whole eyes fixed in 4% buffered formaldehyde (10% neutral buffered formalin) demonstrate a variety of artifacts, including separation of the neurosensory retina from the retinal pigment epithelium. We postulate that the osmolarity of 4% buffered formaldehyde causes contraction of the internal compartments of the eye leading to several artifactual changes commonly observed in routine histologic sections. METHODS: In part I of the study, enucleated animal eyes were examined histologically after immersion in different concentrations of formaldehyde. The variables of fixation and processing were kept constant except for the concentration and osmolarity of formaldehyde. In part II, enucleated animal eyes were used to empirically determine the optimal mixture of formaldehyde and glutaraldehyde for fixation based on subjective assessment of histologic sections. RESULTS: In the first part of the study, the post-fixed volume of the anterior chamber and vitreous increased as the concentration (and osmolarity) of formaldehyde decreased. In part II of the study, fixation of whole eyes was optimal with a mixture of 1% buffered formaldehyde and 1.25% glutaraldehyde. The neurosensory retina was less likely to detach from the retinal pigment epithelium, and the anterior chamber retained a more normal shape with this fixative. CONCLUSIONS: Volume contraction of whole eyes fixed in 4% buffered formaldehyde is caused by the relatively high osmolarity of the fixative. Immersion fixation of whole eyes for 36 h (or longer) in 1% buffered formaldehyde/1.25% glutaraldehyde reduces tissue distortion without compromising cellular preservation.

Animals↗
PubMed1995

The importance of local acid production in the distribution of Helicobacter felis in the mouse stomach.

BACKGROUND/AIMS: Helicobacter felis colonizes the gastric mucosa of rodents. Preliminary studies showed differences in the distribution of the organism in different parts of the stomach that seemed related to the secretory capacity of the mucosa. The aim of this study was to determine the localization of H. felis in the mouse stomach and to investigate the influence of acid-suppressive agents. METHODS: Specific-pathogen-free BALB/c mice were infected with H. felis. Colonization was assessed in longitudinal sections of gastric tissue from animals untreated or treated with omeprazole or ranitidine. RESULTS: In untreated H. felis-infected animals, the preferred ecological niche was the antrum and cardia equivalent. The density of colonization correlated with the number of parietal cells per gland. Partial acid suppression with ranitidine produced a slight increase in the colonization of the body but was restricted to the upper portions of the gastric gland. Omeprazole treatment produced a greater colonization of the body with bacteria traversing the entire gland. Some reduction in antral colonization occurred. CONCLUSIONS: These results are consistent with the hypothesis that local acid output is a crucial determinant in the distribution of Helicobacter species in the stomach. Differences in local acid output may explain the different patterns of Helicobacter pylori-induced gastric pathology.

Animals↗
PubMed1995

Migration of a novel DQA1* allele (DQA1*0502) from African origin to North and South America.

A PCR-based strategy termed DHDA has recently been developed which reveals DQA1 and DQB1 allelic polymorphism through gel retardation following electrophoresis. This HLA-typing strategy improves the efficiency of identifying previously undetected DNA sequence polymorphisms. DHDA has been utilized to perform DQA1 genotypic analysis in non-Caucasian populations and has resulted in the identification of a novel allele, DQA1*0502 (designated by the WHO nomenclature committee). This new allele has been found in Africans and South and North Americans of black racial ancestry and is geographically consistent with the African diaspora during the 15th-19th centuries. DQA1*0502 represents a single C-to-G transversion in codon 59 (exon 2) and results in an amino acid change from proline to arginine. Although MHC genes are highly polymorphic, this DQA1*0502 substitution is unique, as it represents an amino acid change at a position assessed previously to be conserved in the human DQ alpha polypeptides.

Africa↗
PubMed1995

Animal models and vaccine development.

Following the demonstration of Helicobacter pylori as a major gastroduodenal pathogen there was a need to develop animal models in order to investigate mechanisms of pathogenesis and to be able to test new treatment strategies. Helicobacter pylori will only colonize a limited number of hosts including non-human primates, germ-free or barrier raised piglets, germ-free dogs and recently laboratory raised cats. Although these models have proved useful there is a need for more convenient small animal models. The ferret infected with its natural gastric organism, Helicobacter mustelae, is the only other animal to show peptic ulceration and has been successfully used to investigate gastritis and antimicrobial agents. The other commonly used animal model is the laboratory mouse or rat infected with either Helicobacter felis or Helicobacter heilmannii, bacteria that normally colonize cat or dog gastric mucosae. Active/chronic gastritis, gastric atrophy, and lymphoma-like lesions have been shown to develop in H. felis infected mice. The most recent and exciting use of an animal model has been the use of the H. felis mouse model in the development of human vaccines against H. pylori. Mice can be protected against infection with large doses of viable H. felis by oral immunization using sonicates of H. felis or H. pylori or recombinant H. pylori urease together with cholera toxin or cholera toxin-B subunit as the mucosal adjuvant. More importantly it has been shown that immunization of already infected animals results in eradication of infection. This raises the intriguing possibility that therapeutic immunization might be a viable option in the management of Helicobacter-associated disease. If immunization as a therapy of peptic ulcers was combined with short-term acid suppression, the possibility of reinfection may also be eliminated. In those countries where H. pylori infection rates are very high and infection occurs at an early age, large scale oral immunization of sections of the community would not only protect the young from the deleterious consequences of long-term H. pylori infection but could also cure existing disease.

Animals↗
PubMed1995

Prevention of emesis after strabismus repair in children: a prospective, double-blinded, randomized comparison of droperidol versus ondansetron.

STUDY OBJECTIVE: To compare the effectiveness of ondansetron with droperidol in preventing postoperative emesis in children after strabismus repair. DESIGN: Randomized, double-blind study. PATIENTS AND SETTING: 57 ASA physical status I and II children aged 3 to 14 years, undergoing outpatient strabismus repair in two separate study centers. INTERVENTIONS: Patients were randomized to receive either 0.15 mg/kg intravenous (i.v.) ondansetron or 0.075 mg/kg i.v. droperidol shortly after induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Number of episodes of emesis and times to discharge from the recovery room and ambulatory center were assessed. Twenty-nine (94%) of 31 children who received ondansetron and 21 (81%) of 26 children who received droperidol were emesis-free (p = NS). There were no significant differences in the number of episodes of emesis on the day after surgery or times to discharge. CONCLUSIONS: Ondansetron is at least as effective as droperidol in reducing the frequency of emesis in children after strabismus repair, and it did not shorten times to discharge home. The low number of patients in our study may have masked a difference in effect between the two groups. The clinician should decide whether the increased cost of ondansetron justifies its use over other antiemetics.

Adolescent↗