Urinary thromboxane and 6-keto-prostaglandin F1 alpha are early markers of acute rejection in experimental pancreas transplantation.
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6-Ketoprostaglandin F1 alpha↗
Biomedical subjects
M Fox
Publications and source records attributed to M Fox.
Identification of YAC and cosmid clones encompassing the ZFX-POLA region using irradiation hybrid cell lines.
The human Xp21.3-p22.1 region is poorly mapped relative to other X chromosome regions. To target cosmid and YAC clones specifically from Xp21.3-p22.1 for rapid contig construction, a hybridization-based screening approach using irradiation hybrids has been used. Alu-PCR products generated from hybrid lines containing small overlapping fragments from Xp21-p22 were hybridized to an X chromosome cosmid library, and cosmids predicted by their hybridization pattern to map to the region of interest were analyzed by fluorescence in situ hybridization (FISH). Hybridization of the cosmids in pools to gridded YAC libraries identified 15 YACs, which were verified and tested for chimerism by FISH. Cosmid content analysis of the YACs defined two contigs, one with 12 YACs covering about 1.5 Mb and one with 3 YACs. Five YACs from the 12-YAC cluster had been previously recognized by DNA polymerase alpha (POLA). ZFX identified a single YAC; hence, the physical linkage of ZFX and POLA was demonstrated within the contig. Four YACs had been isolated previously with ZFX and these extend the contig to 2 Mb. Restriction mapping of several YACs demonstrates that ZFX and POLA are about 700 kb apart, a distance similar to that reported in the mouse between Zfx and Pola. The order of these two loci and two additional loci identified by homologous mouse linking clones was found to be conserved between human and mouse: tel-ZFX-DXCrc57-DXCrc140-POLA-cen. We have shown that YAC contigs can be rapidly constructed from targeted regions without the need for time-consuming YAC end rescue and chromosomal walking.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regional localization of DPP4 (alias CD26 and ADCP2) to chromosome 2q24.
A panel of microcell hybrids containing fragments of chromosome 2 was analyzed for the presence of human DPP4, the gene that codes for dipeptidyl peptidase IV (or CD26), by specific PCR amplification of a fragment of the 3' untranslated region of the gene. This analysis placed DPP4 between LCT and GAD in bands q21 to q31. The localization was confirmed by in situ hybridization using two genomic probes that each revealed a hybridization signal in band q24. We also use the recent identification of the ADA binding protein as DPPIV to propose that the gene ADCP2 should be renamed DPP4.
Animals↗
Predicting oliguria following indomethacin for treatment of patent ductus arteriosus.
Fifty-two consecutive infants who received intravenous indomethacin, 0.2 mg/kg, were reviewed to determine factors associated with the occurrence of oliguria. Serum creatinine and concentration prior to indomethacin did not predict the occurrence of oliguria. A mean urine output of less than 4.5 mL/kg/hr prior to the administration of indomethacin was the only factor that we determined to be associated with a significant risk of oliguria. Two infants developed symptomatic oliguria and both had a pre-indomethacin urine output less than 1.5 mL/kg/hr.
Creatinine↗
Vasectomy reversal--microsurgery for best results.
OBJECTIVE: To determine whether microsurgery achieves a better result in vasectomy reversal than other macroscopic techniques. PATIENTS AND METHODS: A series of 103 consecutive patients with a median age of 36 years (range 26-58) who underwent microsurgical vasovasostomy was studied. The method employed was a modification of a two-layer anastomotic technique. In the first 49 patients 8/0 Vicryl was used to create a two-layer anastomosis whereas in 54 patients 10/0 Ethilon was used. RESULTS: Sperm were present in the ejaculate in 85% of patients who underwent bilateral vasovasostomy. The rate increased to 94% in those in whom 10/0 Ethilon had been used as the suture material but the difference was not statistically significant. In half of the patients sperm concentration, quality and motility improved over the 12 months following reversal. The fertility rate, measured between 8 months and 5 years after vasovasostomy, was 64% if the vasectomy had been performed within 10 years and fell to 39% if 10 years or more had elapsed. In the 10 patients who had undergone a failed reversal attempt elsewhere four had sperm in the ejaculate and two of these patients became fertile. CONCLUSION: The additional time and effort required for a microsurgical approach to vasovasostomy were worthwhile to obtain patency and fertility rates which were superior to those of other techniques.
Adult↗
Selective decontamination of the gut.
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Critical Care↗
AICAR is not an endogenous mutagen in Escherichia coli.
A number of observations in the Escherichia coli and Salmonella typhimurium literature could be explained by the hypothesis that a particular purine ribonucleotide precursor can be converted to the corresponding deoxyribonucleotide triphosphate, thereby becoming a base-analogue mutagen. The metabolite in question, AICAR (5-amino-4-carboxamide imidazole riboside 5'-phosphate), is also a by-product of histidine biosynthesis, and its (ribo)triphosphate derivative, ZTP, has been detected in E. coli. We constructed E. coli tester strains that had either a normal AICAR pool (pur+ his+ strains cultivated without purines or histidine) or no AICAR pool (purF hisG mutant strains, lacking the first enzyme of each pathway and cultivated in the presence of adenine and histidine). Using a set of lacZ mutations, each of which can revert to Lac+ only by a specific substitution mutation, we found that no base substitution event occurs at a higher frequency in the presence of an AICAR pool. We conclude that the normal AICAR pool in E. coli is not a significant source of spontaneous base substitution mutagenesis.
Aminoimidazole Carboxamide↗
The pleiotropic effects of his overexpression in Salmonella typhimurium do not involve AICAR-induced mutagenesis.
Inhibition of cell division associated with overexpression of hisH and hisF in Salmonella typhimurium is strongly reminiscent of a cellular response to DNA damage. On these grounds, we investigated the involvement of a metabolite which appeared to represent a possible candidate for an endogenous mutagen: the base analog 5-amino-4-carboxamide imidazole riboside 5'-phosphate (AICAR), a by-product of HisH and HisF activity. However, we showed that AICAR is not an endogenous mutagen in S. typhimurium. Other types of DNA damage induced by his overexpression seem also unlikely, since similar mutation rates are found in hisO+ and hisOc strains. We also show that AICAR production is not involved in the pleiotropic effects of his overexpression, since these are still observed in strains devoid of AICAR. Thus inhibition of cell division resulting from HisH and HisF overexpression must operate through a mechanism unrelated to the role of these proteins in histidine biosynthesis.
Aminoimidazole Carboxamide↗
A cosmid library specific for human chromosome regions 6p21.3 and 6q27.
We have explored the potential of irradiation-fusion gene transfer (IFGT) hybrids as a source of well-defined human chromosome fragments from which probes can be derived. Extensive characterization of the IFGT hybrid 4J4 with a full panel of markers from Chromosome (Chr) 6 showed that the human DNA content derives largely from 6p21.3 and 6q27. A cosmid library has been constructed from 4J4 DNA, and 370 recombinants containing human DNA have been isolated and overlapping clones ordered into 20 contigs. Regional localization of representative clones from each contig, determined by fluorescent in situ hybridization (FISH), places 13 contigs in 6q27 and 6 in 6p21.3. Preliminary screening of cDNA libraries with selected cosmids has identified two expressed sequences. Since there are a number of medically important genes in both these regions of human Chr 6 with several disease loci linked to the HLA-A region in 6p21.3 and various tumor suppressor genes to 6q27, this library will provide a valuable resource to aid the isolation of candidate genes for these diseases. In addition, unique markers for detailed physical and genetic mapping of these regions of human Chr 6 can be easily obtained.
Base Sequence↗
HNF4 and HNF1 as well as a panel of hepatic functions are extinguished and reexpressed in parallel in chromosomally reduced rat hepatoma-human fibroblast hybrids.
Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.
Albumins↗
Thromboxane and prostacyclin synthesis in experimental pancreas transplantation. Changes in parenchymal and vascular prostanoids.
The principal causes of failure of a pancreas transplant are rejection and vascular thrombosis. There is an unusually high attrition rate for pancreas transplants, but study models have been difficult to develop. In a rat model that allows study of acute rejection to the exclusion of nonspecific effects of transplant surgery on the pancreas, in vitro synthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) by transplanted pancreas and the blood vessels transplanted with it was measured using an RIA for their stable hydrolysis products 6-keto-prostaglandin F1 alpha and thromboxane B2 (TXB2). TXB2 synthesis was significantly greater in allotransplanted pancreas than isotransplanted pancreas from the 5th day after transplantation. Rejection was complete in the allografted group 7-9 days after transplantation. 6-Keto-prostaglandin F1 alpha synthesis was similar in the pancreas for both allografts and isografts. Similar changes were seen in aorta, celiac artery, superior mesenteric artery, and portal vein transplanted with the pancreas. In the transplanted aorta, TXB2 was significantly greater in the allograft group from the third posttransplant day. A group of CsA-treated allografts sampled after 9 days had transplanted pancreatic parenchymal and vascular prostanoid synthesis in the isograft range. The changes in PGI2 and TXA2 synthesis that accompany cellular rejection may mediate vascular failure in rejecting pancreas transplants, and changes in PGI2 and TXA2 synthesis in blood vessels transplanted with the pancreas could promote early vascular thrombosis.
6-Ketoprostaglandin F1 alpha↗
Combined inhibition of neutral endopeptidase and angiotensin converting enzyme in cardiomyopathic hamsters with compensated heart failure.
Inhibition of the metallopeptidase neutral endopeptidase 3.4.24.11 (NEP) protects endogenous natriuretic peptides and potentiates their vasodepressor effects. Inhibition of angiotensin converting enzyme (ACE) attenuates the formation of angiotensin II and enhances the vasodepressor effect of endogenous kinins. A combination of NEP inhibition and ACE inhibition can potentially interact to shift the balance of vasoactive peptides toward vasodilation. This potential interaction was examined in conscious cardiomyopathic hamsters with low cardiac output and compensated heart failure. Neither the selective NEP inhibitor SQ 28,603 nor the selective ACE inhibitor enalaprilat (each at 30 mumol/kg, i.v.) caused significant changes in left ventricular end diastolic pressure or left ventricular systolic pressure when administered separately. However, the combination of these inhibitors, each at that dose, caused significant peak decreases in left ventricular end diastolic pressure and left ventricular systolic pressure of -12 +/- 1 and -18 +/- 4 mm Hg, respectively. In separate cardiomyopathic hamsters, this same combination of treatments resulted in significant decreases in mean arterial pressure (-13%) and total peripheral resistance (-37%) and an increase in cardiac output (36%) as compared with vehicle effects (P < .05). At 90 min after administration of SQ 28,603 alone, plasma atrial natriuretic peptide concentration was double that in the vehicle group. In the group receiving the combination of inhibitors, plasma atrial natriuretic peptide at 90 min was maintained at the high basal levels associated with this model despite the decrease in cardiac filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Alanine↗
Vasectomy reversal by microsurgery.
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Adult↗
Medical student indebtedness and choice of specialization.
This study's purpose was to examine the impact of indebtedness on medical student choice of specialty. Nonprimary care was disaggregated into distinct specialties. The study found that indebtedness induced medical students to choose the remunerative field of anesthesiology but had the opposite effect on the decision to choose the comparably remunerative field of radiology. The results imply that if specialties are aggregated into broad categories, such as primary and nonprimary care, the estimated impact of indebtedness on specialty choice may be misleading. Such estimates may also be biased if the type of medical school attended (public or private) is not included as a control variable.
Adult↗
Measurement of cardiovascular and renal function in unrestrained hamsters.
We describe a preparation for measuring blood pressure, left ventricular end diastolic pressure, heart rate, and renal excretory variables (volume, electrolytes, glomerular filtration rate) in hamsters. The new approach offers an advantage over previously described methods by eliminating the problems associated with restraint. Hamsters were surgically implanted with venous and arterial catheters. A specially constructed bladder catheter, which allows flushing to minimize errors due to dead space and permits urine collection without restraining the animals, was also implanted. The hamsters were allowed to recover from surgery for 3 hours before being studied in a specially designed lucite housing unit. Representative results were obtained in cardiomyopathic and healthy hamsters.
Animals↗
Red cell filterability determined using the cell transit time analyzer (CTTA): effects of ATP depletion and changes in calcium concentration.
Cell transit time analysis (CTTA) is a new filtrometric technique for assessing red blood cell deformability by measuring the conductivity change caused by passage of erythrocytes through a polycarbonate filter. Most reported studies to date using CTTA have focused on the transit time (TT), the duration of passage of an individual red cell through a micropore. Bulk flow rate has not been previously measured via CTTA. The use of new enzyme based cleaning solutions make it possible to reduce clogging in micropore filters. Therefore, valid measures of the number of red cell transits per unit time (counts/s: C/S) can now be obtained. We evaluated both parameters, TT and C/S, as indicators of red cell filterability. Our goal was to evaluate the effect of metabolic changes shown by alternative techniques to affect red cell deformability. The two best established factors are changes in intracellular [ATP] and [Ca2+]. ATP depletion produces a very small increase in TT but a very marked decrease in C/S. In contrast, the addition of low concentrations of calcium produces an increase in TT with minimal decrease in C/S. The effects of calcium appear to be complex. The substantial changes in intracellular calcium induced by the ionophore A23187 result in a curvilinear pattern of increase in transit times and reduction in counts per s. Lanthanum, which inhibits egress of intracellular calcium, causes an increase in TT with a drop in C/S. We conclude that CTTA demonstrates the same changes in red cell deformability measurable by alternative filtrometric techniques; however, CTTA furnishes two separate and independent parameters which may be used to evaluate red cell deformability.
Adenosine Triphosphate↗
Regional localization of a trophoblast antigen-related sequence and 16 other sequences to human chromosomes 6q using somatic cell hybrids.
Using a panel of 13 hybrid cell lines, we have regionally localized 22 markers to the long arm of chromosome 6. Revised or new locations are provided for 17 of the markers, and preliminary assignments to chromosome 6 of 11 loci are confirmed. The location of NT5, previously determined by antigen expression in hybrids, has been confirmed at 6q14-q15 by using a cDNA probe. Other DNA probes include one new anonymous sequence, designated D6S130, that maps to 6q12 and 4 VNTR probes that map to the proterminal band, 6q27. Probe CRI-L1065 also maps to 6q21, CRI-994 maps to 6q21-qter, and CRI-L322 maps to 6q14-15, information that may assist the merging of physical and genetic maps.
Antibodies, Monoclonal↗