Mammographically detected ductal carcinoma in situ: are we overdiagnosing breast cancer?
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Biomedical subjects
Publications and source records attributed to M Baum.
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Randomized clinical trials are powerful tools to refute old prejudices and establish new therapeutic regimes. We propose that they should be afforded a more widespread application in modern clinical medicine.
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The object of this study was to review and delineate the presenting complaints, signs, symptoms, and Emergency Department (ED) management of pediatric heart transplant recipients who presented to Loma Linda University Medical Center's (LLUMC) Emergency Department. A retrospective chart review was made of all of the pediatric heart transplant patients who presented to the ED at LLUMC from January 1986 through February 1993. The department is part of a 600-bed university hospital with an associated 250-bed children's hospital that includes a pediatric heart transplant center and an ED that sees over 38,000 patients per year. The retrospective review collected information relating to chief complaint, physical findings, laboratory analysis, and diagnoses. Forty-seven patients (23%) presented to the ED for a total of 76 visits. The patients presented a median of 278 days (range 19 days to 6.5 years) after transplantation. The most common chief complaints were related to the respiratory tract, and the most common diagnoses (55%) were related to infectious processes. Fever was present in 21% of the visits. Three of 13 blood cultures obtained were positive. Cardiac symptoms were present in 14% of the visits with two rejection episodes. Hospital admission was required for 22 (29%) of the ED visits. Results showed that pediatric heart transplant recipients are most likely to present to the ED with infections. Although infections from opportunistic organisms and bacteremia must be considered, most infections are similar to those in the nontransplanted child. Life-threatening conditions such as graft rejection are less likely. Nevertheless, the emergency physician should maintain caution in the evaluation of these patients. Close cooperation and consultation with the transplant team will assure the optimal outcome for these patients.
The diagnosis of brucellosis in cattle and small ruminants requires the use of more than one serological test. The complement fixation test (CFT), the rose bengal test (RBT), and the serum agglutination test (SAT) are among the most useful tests for routine diagnosis. The microagglutination test (MAT) was developed as a simpler and more efficient test than the SAT. The relative efficacy of this test compared with that of the SAT was evaluated by using brucella-free sheep and goats prior to and after vaccination treatment. The specificities of the MAT and the SAT were 100%. Of the ewes and goats with a vaccination history, one ewe, expectedly a negative responder, had reactions in the MAT, the complement fixation test, and the rose bengal test but not in the SAT, suggesting a lower sensitivity of the SAT in this case. The calculated sensitivities of the MAT and the SAT were 93.9%. The agreement between MAT and SAT results from nonresponders was examined by using sera from unvaccinated lambs and kids (95.2% agreement), unvaccinated ewes and goats (84.4%), and ewes and goats with a vaccination history (43.9%). For the latter group higher levels of agglutination units were observed by the MAT than by the SAT in 51.5% of the samples. In testing sera from positive reactors after vaccination neither method was superior (MAT values were greater than SAT values for 23.5% of the samples, and MAT values were less than SAT values for 21.9% of the samples). Comparison of the methods on the individual sample level revealed a significant correlation between the MAT and the SAT (r = 0.96 +/- 0.005; P < 0.001). Since the MAT is simpler to perform than the SAT and can potentially be automated, the inclusion of the MAT as a supplementary test in brucellosis control programs is recommended.
The centromeric DNAs of Schizosaccharomyces pombe chromosomes resemble those of higher eukaryotes in being large and composed predominantly of repeated sequences. To begin a detailed analysis of the mode of replication of a complex centromere, we examined whether any sequences within S. pombe centromere II (cen2) have the ability to mediate autonomous replication. We found a high density of segments with such activity, including at least eight different regions comprising most of the repeated and unique centromeric DNA elements. A physical mapping analysis using two-dimensional gels showed that autonomous replication initiated within the S. pombe sequences in each plasmid. A two-dimensional gel analysis of replication on the chromosomes revealed that the K and L repeat elements, which occur in multiple copies at all three centromeres and comprise approximately 70% of total centromeric DNA mass in S. pombe, are both sites of replication initiation. In contrast, the unique cen2 central core, which contains multiple segments that can support autonomous replication, appears to be repressed for initiation on the chromosome. We discuss the implications of these findings for our understanding of DNA replication and centromere function.
The present study examined the effect of epidermal growth factor (EGF) on Na-Pi cotransport in a tubular epithelial cell line derived from the opossum kidney (OKP cells). EGF caused a time- and dose-dependent decrease in Na-Pi cotransport. The inhibition of Na-Pi cotransport by 10(-8) M EGF was first demonstrable after 18 h with maximal effect seen at 24 h. EGF inhibited Na-Pi cotransport by decreasing the maximal velocity (10.8 +/- 0.9 in control vs. 4.9 +/- 0.8 nmol 32Pi.4 min-1.mg protein-1 in EGF, P < 0.001). Northern blot analysis indicated that EGF caused a significant decrease in NaPi-4 mRNA abundance. The abundance of NaPi-4 mRNA relative to beta-actin and/or glyceraldehyde-3-phosphate dehydrogenase mRNA was decreased by twofold in OK cells treated with EGF for 4 h and threefold in OKP cells treated with EGF for 24 h. Thus the decrease in NaPi-4 mRNA abundance preceded the decrease in Na-Pi cotransport activity. Inhibition of transcription with actinomycin D and protein synthesis with cycloheximide prevented the inhibition of Na-Pi cotransport. Furthermore, inhibition of phospholipase C activity with U-73,122 also significantly blocked the inhibitory effect of EGF on Na-Pi cotransport. The results indicate that EGF-induced decrease in OKP Na-Pi cotransport is mediated through a decrease in NaPi-4 mRNA and activation of the phospholipase C signaling pathway.
The neonatal proximal tubule has a lower rate of bicarbonate absorption and Na+/H+ antiporter activity than the proximal tubule of adult animals. Two isoforms of the Na+/H+ antiporter have been localized to the proximal tubule. NHE3 is located on the apical membrane, whereas NHE1, the isoform found on most mammalian cells, is present on the basolateral membrane. The Na+/H+ antiporter isoforms that increase with renal maturation are unknown. The purpose of the present study was to examine the maturation of rabbit renal cortical NHE3 and NHE1 mRNA and protein abundance and to determine whether the rate of maturation of these isoforms was affected by glucocorticoids. Renal cortex from neonatal rabbits (1 wk) had approximately one-fourth the NHE3 mRNA and protein abundance as that from adult animals. Renal cortical NHE1 mRNA and protein abundance did not change significantly during maturation. Glucocorticoids have been shown to accelerate the maturation of neonatal bicarbonate absorption and apical membrane Na+/H+ antiporter activity. Daily subcutaneous administration of dexamethasone starting at 4 days of age (10 micrograms/100 g body wt) for 3 days and 2 h before being killed resulted in a twofold increase in NHE3 mRNA abundance and a threefold increase in NHE3 protein abundance. NHE1 mRNA and protein abundance were unaffected. These data show that there is selective maturation of NHE3 during renal cortical development, which can be accelerated by administration of glucocorticoids.
Active transcellular NaCl transport in the proximal convoluted tubule (PCT) is via apical parallel Na/H and Cl/base exchange. The mechanism of Cl/base exchange remains unclear. The present in vitro microperfusion study examined the mechanism of Cl/base exchange in superficial and juxtamedullary PCT by examining the rate of change in intracellular pH in response to luminal Cl removal. In superficial PCT the rate of Cl/base exchange was 24.0 +/- 2.3 without formate, 36.4 +/- 6.6 with 10 microM formate (P < 0.05), and 43.6 +/- 2.8 pmol.mm-1.min-1 (P < 0.001) with 1 mM luminal formate. Cl/base exchange was inhibited by luminal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in the presence and absence of formate. In juxtamedullary PCT, Cl/base exchange was 22.2 +/- 3.8 without formate and 25.0 +/- 5.4 pmol.mm-1.min-1 in the presence of 1 mM luminal formate [P = not significant (NS)]. Cl/base exchange was inhibited by luminal DIDS in juxtamedullary PCT. The rates of Cl/base exchange in both superficial and juxtamedullary PCT were not affected by 0.1 mM acetazolamide and 2 mM cyanide and were the same in the presence and absence of HCO3/CO2, consistent with Cl/OH rather than Cl/HCO3 exchange. To examine the effect of formate on PCT transport, tubules were perfused with a high-Cl solution without organics simulating late proximal tubular fluid. In superficial PCT net volume absorption (JV) was 0.00 +/- 0.05 in the absence of formate and 0.14 +/- 0.06 nl.mm-1.min-1 in the presence of 1 mM formate (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The present study investigated the signal-transduction pathway responsible for the epidermal growth factor (EGF) stimulation of phosphate transport (JPhos) in the rabbit proximal convoluted tubule (PCT). Genistein, 10(-4) M, bath and lumen, an inhibitor of EGF receptor tyrosine kinase activity, blocked the EGF effect on JPhos, consistent with a role for tyrosine kinase in the signal-transduction pathway. Both staurosporine (5 x 10(-8) M) and calphostin C (10(-8) M), inhibitors of protein kinase C, blocked the EGF stimulation of JPhos, indicating that protein kinase C is involved in EGF signaling. Intracellular calcium (Ca2+i) concentrations were measured in perfused tubules using fura PE3 to determine whether changes in Ca2+i were also part of the signaling pathway. After addition of 3 nM EGF, there was no change in Ca2+i, suggesting that stimulation of protein kinase C is not from phosphatidylinositol hydrolysis by phospholipase C-gamma. To determine whether phospholipase A2 (PLA2) is involved, the inhibitor mepacrine was used. Mepacrine (5 x 10(-5) M) had no direct effect on PCT transport but blocked the stimulatory effect of EGF on JPhos. PLA2 activity, assessed as free arachidonic acid release from proximal tubules in suspension, increased by 18.8% with 3 nM EGF. Thus the stimulation of JPhos by EGF is mediated via a signal-transduction pathway involving tyrosine kinase, protein kinase C, and PLA2.
Young people are facing very serious problems of unemployment and underemployment in the current job market. Disadvantaged youth are enduring the most difficult struggle. One plausible reason is that youth are undereducated and insufficiently skilled to meet job requirements. This article explores forty in-depth interviews with young people from three high-unemployment neighborhoods to closely examine experiences in high school and in the post-high school work entry phase. The purpose was to determine whether the youths were receiving the skill set components advanced by Comprehensive Collaborative Models. Policy implications are drawn from the lack of fit between model prescriptions and actual experiences.
We present a case of hematocolpos due to congenital imperformed hymen in an 16-year-old girl. The symptoms, the diagnostic methods and the treatment of the malformation are reported and discussed. Severe complications, such as the hematometra or the hematosalpinx, can be ruled out preoperatively by ultrasound examination.
Cloning of a nitric oxide synthase (NOS) from RAW 264.7 mouse macrophages (Xie, Q.-w., Cho, H. J., Calaycay, J., Mumford, R. A., Swiderek, K. M., Lee, T. D., Ding, A., Troso, T., and Nathan, C. (1992) Science 256, 225-228) yielded two sets of cDNA: one with a longer coding region of 1144 amino acids, whose sequence matched that of the purified protein, and another with a shorter coding region of 1122 amino acids, in which the last 10 carboxyl-terminal amino acids differed completely from those of the long form. We have now found that the short form lacks NOS activity. To determine the basis of this defect, we prepared recombinant chimeric, deletional, and point mutants of the long and short NOS variants, monitored their expression by immunoblot, and tested their enzymatic activity. By itself, lack of the 22-carboxyl-terminal residues of the long form NOS was scarcely consequential. Mutation of Phe1122, the only aromatic residue within one of the longest conserved regions shared by all NOSs of reported sequence, reduced enzymatic activity by 41%. Deletion of 23 carboxyl-terminal amino acids (including Phe1122) reduced activity by 71%. Further loss of Ile1121, another completely conserved residue, reduced activity by 95%, and with the deletion of the rest of the conserved region, NOS activity was undetectable. Normal dimerization and binding of heme and calmodulin by the short variants militated against distortions of tertiary structure affecting the amino-terminal half or middle portion of the protein. In contrast, the short variants were deficient in binding to NADPH, as predicted by a model of tertiary structure based on that of spinach ferredoxin-NADP+ reductase. This is the first demonstration that the carboxyl terminus of NOS is a functionally critical region.
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