Biomedical subjects
Publications and source records attributed to E O'Leary.
Preoperative preparation for the patient with adrenal disorders is directed toward restoring the intravascular volume and the electrolyte concentrations to normal. Hypertension and hypokalemia may be controlled by restricting sodium intake and administration of the aldosterone antagonist spironolactone. Patients taking steroids preoperatively must be adequately replaced throughout the perioperative phase at times of maximum stress.
The Krüppel-associated box A (KRAB-A) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the Cys2-His2 type. Using the yeast two-hybrid system, we report the isolation of a cDNA encoding a novel murine protein, KRAB-A interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region. KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4, family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction. The KRIP-1 protein has high homology to TIF1, a putative modulator of ligand-dependent activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1 fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase reporter construct with five GAL4 binding sites, there is dose-dependent repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity.
We have assessed the potential for myocardial ischaemia during laparoscopic cholecystectomy in 16 otherwise healthy patients. Continuous ambulatory ECG monitoring was commenced 12 h before operation and continued for 24 h after operation. The neuroendocrine stress response was assessed by measuring plasma concentrations of adrenaline and noradrenaline, human growth hormone, cortisol, renin and aldosterone, and prolactin, at specified times during surgery. Acute ST segment changes in the ECG occurred in only two patients. These episodes were independent of creation of pneumoperitoneum and changes in position. Acute intraoperative increases in MAP were noted during insufflation of carbon dioxide and reverse Trendelenburg positioning (P < 0.05). A four-fold increase in plasma concentrations of renin and aldosterone was noted after pneumoperitoneum and reverse Trendelenburg positioning (P > 0.05). There was a linear correlation between changes in plasma renin and aldosterone concentrations and MAP (r = 0.97 and r = 0.85, respectively). Prolactin concentrations increased four-fold after induction of anaesthesia. Cortisol, HGH, adrenaline and noradrenaline concentrations increased after deflation of the pneumoperitoneum. The time profile-concentration changes of increased MAP and renin-aldosterone suggests a cause-effect relationship. Increased intra-abdominal pressure and reverse Trendelenburg positioning may reduce cardiac output and renal blood flow. The early increase in prolactin concentration was probably secondary to the effect of the opioid fentanyl.
We have previously reported the cloning, sequencing, and partial characterization of Kid-1, a zinc finger-encoding cDNA from the rat kidney. The Kid-1 protein and approximately one-third of all other zinc finger proteins contain a highly conserved region of approximately 75 amino acids at their NH2 terminus named Krüppel-associated box (KRAB), which is subdivided into A and B domains. The evolutionary conservation, wide distribution, and genomic organization of the KRAB domains suggest an important role of this region in the transcriptional regulatory function of zinc finger proteins. The functional significance of the KRAB domain was evaluated by studying transcriptional activities of yeast GAL4-rat Kid-1 fusion proteins containing various regions of the non-zinc-finger domain of Kid-1. Transcriptional repressor activity of GAL4-Kid-1 fusion proteins maps to the KRAB-A domain. The KRAB-A domain of another zinc finger protein, ZNF2, also has repressor activity. Site-directed mutagenesis of conserved amino acids in this motif results in decreased repressor activity. Thus, we have established a functional significance for the KRAB-A domain, a consensus sequence common in zinc finger proteins.
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Expression of newly cloned cDNAs in mammalian cell lines is an essential tool for the functional analysis of the proteins encoded by these cDNAs. In many instances, however, evaluation of the protein is difficult because of the difficulty in purification of the expressed protein and/or the lack of specific antibodies which react with the proteins on Western blots or for immunocytochemistry or immunoprecipitation. A number of gene fusion systems have been employed in which a known peptide is fused to the expression product of interest and the fusion protein is purified using affinity chromatography and identified in extracts or by immunocytochemistry using antibodies directed against the affinity handle peptide. The DNA-binding domain of the yeast transcription factor GAL4 is widely used to construct fusion proteins with putative transcription factors to evaluate potential trans-acting domains. Because of the lack of commercially available anti-GAL4 antibodies, the further biochemical characterization of these fusion proteins has remained difficult. We describe the construction of two mammalian expression vectors, pMFH/GAL4 and pMFH2/GAL4 (where pMFH stands for pM2, Flag, Histidine tail), which encode the DNA-binding domain of the yeast transcription factor GAL4 with a Flag peptide (consisting of the 11-amino-acid leader peptide of the gene 10 product from bacteriophage T7) at the NH2-terminus and a tail of six histidines at the COOH-terminus. Unique restriction sites allow both the construction of fusion proteins with the GAL4 DNA-binding domain and the replacement of the GAL4 fragment with another insert.(ABSTRACT TRUNCATED AT 250 WORDS)
We have identified a new putative transcription factor from the rat kidney, termed Kid-1 (for kidney, ischemia and developmentally regulated gene 1). Kid-1 belongs to the C2H2 class of zinc finger genes. Its mRNA accumulates with age in postnatal renal development and is detected predominantly in the kidney. Kid-1 mRNA levels decline after renal injury secondary to ischemia or folic acid administration, two insults which result in epithelial cell dedifferentiation, followed by regenerative hyperplasia and differentiation. The low expression of Kid-1 early in postnatal development, and when renal tissue is recovering after injury, suggests that the gene product is involved in establishment of a differentiated phenotype and/or regulation of the proliferative response. The deduced protein contains 13 C2H2 zinc fingers at the COOH end in groups of 4 and 9 separated by a 32-amino-acid spacer. There are consensus sites for phosphorylation in the NH2 terminus non-zinc finger region as well as in the spacer region between zinc fingers 4 and 5. A region of the deduced protein shares extensive homology with a catalytic region of Raf kinases, a feature shared only with TFIIE among transcription factors. To determine whether Kid-1 can modulate transcription, a chimeric construct encoding the Kid-1 non-zinc finger region (sense or antisense) and the DNA-binding region of GAL4 was transfected into COS and LLC-PK1 cells together with a chloramphenicol acetyltransferase (CAT) reporter plasmid containing GAL4 binding sites, driven by either a minimal promoter or a simian virus 40 enhancer. CAT activity was markedly inhibited in cells transfected with the sense construct compared with the activity in cells transfected with the antisense construct. To our knowledge, this pattern of developmental regulation, kidney expression, and regulation of transcription is unique among the C2H2 class of zinc finger-containing DNA-binding proteins.
Delayed, profound respiratory depression occurred in a 4-year-old boy, who had been premedicated with trimeprazine 4 h after tonsillectomy. This is a rare, but potentially fatal idiosyncratic reaction.
To determine the interfamilial and intrafamilial variation in the expression of the Bardet-Biedl syndrome (a form of Laurence-Moon-Biedl syndrome), we looked for the five recognized features of the disorder (retinal dystrophy, obesity, polydactyly, mental retardation, and hypogonadism), plus possible renal manifestations, in some or all of 32 patients with this disorder. All 28 patients examined had severe retinal dystrophy, but only 2 had typical retinitis pigmentosa. Polydactyly was present in 18 of 31 patients, but syndactyly, brachydactyly, or both were present in all. Obesity was present in all but 1 of 25 patients. Only 13 of 32 patients were considered mentally retarded. Scores on verbal subtests of intelligence were usually lower than scores on performance tasks. Seven of eight men had small testes and genitalia, which was not due to hypogonadotropism. All 12 women studied had menstrual irregularities, and 3 had low serum estrogen levels (1 of these had hypogonadotropism, and 2 had primary gonadal failure). The remaining women who were of reproductive age had endocrinologic evidence of reproductive dysfunction. Diabetes mellitus was present in 9 of 20 patients. Renal structural or functional abnormalities were universal (n = 21), and three patients had end-stage renal failure. We conclude that the characteristic features of Bardet-Biedl syndrome are severe retinal dystrophy, dysmorphic extremities, obesity, renal abnormalities, and (in male patients only) hypogenitalism. Mental retardation, polydactyly, and hypogonadism in female patients are not necessarily present.
We report on a patient with congenital absence of the left pectoralis major muscle, whose second cousin had the full Poland sequence. This suggests that isolated pectoralis major muscle defect should be included in the spectrum of anomalies characterized as the Poland sequence, postulated to result from disruption of blood supply in the embryonic subclavian and vertebral arteries, the site and degree of obstruction determining the sites and severity of the resulting anomalies. Very few cases are familial; in these the family pattern is compatible with an autosomal dominant mutant gene with reduced penetrance or delayed mutation.
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A simple method was devised for recording dermatoglyphics in a form suitable for sweat pore counting. Fifteen members of a family with a hypohidrotic X-linked ectodermal dysplasia made their own hand prints using our method and mailed the results to us for interpretation. The simplicity of the technique also makes it practical to use on new-born males at risk for the condition, or where dermatoglyphic records are required for other purposes. Preliminary data suggest that patchiness of sweat pore distribution on the fingers and palms may be useful in the discrimination of heterozygotes.
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OBJECTIVE: This paper analyzes the longitudinal relationship between serum uric acid level and a natural disaster. METHODS: The sample consists of factory workers who were participating in a longitudinal epidemiological study of coronary heart disease risk factors. Participants were seen in 1975 (baseline), 1980 (5 year follow-up), and 1987 (12 year follow-up). The 5 year (1980) follow-up examination was interrupted by a major earthquake and resumed 2 weeks after the quake. At this examination, participants seen after the quake had, on the average, significantly lower serum uric acid than those seen before the earthquake. In 1987 (7 years after the quake), participants were questioned whether or not (in their own perception) they were still suffering from damages due to the 1980 earthquake. RESULTS: At the examination in 1987, participants who reported suffering from damage due to the 1980 quake showed on the average significantly increased serum uric acid compared with participants who reported not suffering from damages due to the 1980 quake. The analyses of the data of 578 individuals who participated in all three examinations confirmed these findings and showed that they were independent from levels of uric acid measured prior to the disaster. CONCLUSIONS: The reason for this apparent different association with uric acid and acute and long-term exposure to the quake remains to be clarified but these findings are consistent with the existence of diverse patterns of physiologic response to different stressors.