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M Baum

Publications and source records attributed to M Baum.

At least 73 records · Page 4Linked to original sources

Effect of dipyridamole on serum and urinary phosphate in X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with hypercalcuria and nephrocalcinosis. Recently, intravenous and oral dipyridamole has been reported to decrease fractional excretion of phosphate in adults with idiopathic hyperphosphaturia. Our objective was to determine whether oral dipyridamole therapy reduces urinary phosphate excretion and increases serum phosphate concentration in children with XLH. A prospective study was performed in six children with XLH. The average age of the patients at the start of the study was 12.5+/-1.0 years. The effects of 12 weeks of oral dipyridamole therapy, at 4.4+/-0.4 mg/kg body weight per day, on serum phosphorous, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D, osteocalcin, tubular maximum for phosphate reabsorption (TmP/GFR), urinary calcium excretion, and cyclic adenosine 3',5'-monophosphate (cAMP) excretion, were compared to baseline levels. Our results show that there was no change in serum phosphorous concentration or TmP/GFR after 12 weeks of dipyridamole therapy. Dipyridamole therapy also had no effect on serum PTH, serum 1,25 (OH)2 vitamin D, alkaline phosphatase, osteocalcin levels, urinary calcium or cAMP excretion. We therefore concluded that in children with XLH, a 12-week course of dipyridamole had no effect on serum phosphorous or its urinary excretion. Dipyridamole therapy is unlikely to improve the bone disease in children with XLH.

Adolescent↗

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Albumins↗

Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible?

OBJECTIVE: To evaluate the feasibility of conducting a large randomized trial of HRT in symptomatic women with early-stage breast cancer. DESIGN: Open randomized study. SETTING: Outpatient clinics at The Royal Marsden and St. George's Hospitals, London. PATIENT(S): One hundred postmenopausal women with early-stage breast cancer, experiencing vasomotor symptoms and/or vaginal dryness. INTERVENTION(S): Randomization (1:1) to HRT or no HRT for 6 months. MAIN OUTCOME MEASURE(S): Acceptance, continuance rates, and the reasons eligible women declined study entry. RESULT(S): Acceptance (38.8%) and continuance rates (>80%) were encouraging. The efficacy of HRT did not appear to be antagonized with concomitant tamoxifen. Seventy-five percent of women continued HRT after the study ended. Three women developed metastatic disease. Two used HRT. CONCLUSION(S): Despite informed consent, a national UK randomized trial of HRT should be feasible and has now been planned. Successful implementation necessitates the provision of information about HRT and the estrogen deficiency side effects of breast cancer therapy to health professionals and women with breast cancer.

Adult↗

A study of craniofacial growth in infant heart transplant recipients receiving cyclosporine.

BACKGROUND: Cyclosporine is an effective immunosuppressive drug that has found widespread application in organ transplantation. However, a few studies have implicated cyclosporine as adversely affecting craniofacial growth in the pediatric population. The purpose of this study was to evaluate the possible untoward effects of cyclosporine long-term on craniofacial growth in a group of infant heart transplantation recipients. METHODS: A prospective group (n = 28) of 18 Caucasian (white) children (9 female and 9 male, ages 4-10 years) and 10 Hispanic children (3 female and 7 male, ages 4-10 years) were evaluated. No attempt was made for either study group to delineate on individuals specific country of origin. None of the subjects had undergone orthodontic therapy. All subjects had heart transplantations before 6 months of age and followed the Loma Linda University International Pediatric Heart Transplantation Immunosuppression protocol. The primary immunosuppression agent was cyclosporine with azathioprine or methotrexate. Rescue therapy for graft rejection consisted of glucocorticoid and/or polyclonal antibody therapy. None of the subjects received the immunosuppressant tacrolimus (FK506). Using lateral cephalometric radiography, seven skeletal angular measurements (SNA, SNB, ANB, GoGn-SN, NA-Pog, ArGoMe, NPog-AB) were examined and compared to contemporary growth standards. Hand/wrist radiographs were evaluated for bone age. Also, longitudinal height, weight, and head circumference data was obtained and compared to standardized growth and development curves. RESULTS: Descriptive statistics were used to summarize the data. Cephalometrically, 86% (N = 24), showed minor deviation from mean normative values. Four of the subjects (14%) exhibited cephalometric measures indicative of individuals with a vertical growth pattern. Analysis of the hand/wrist radiographs showed all but one subject to have normal bone age. Height, weight, and head circumference data revealed a wide range of growth percentiles for the entire group with mean percentiles in the range of 25% to 50%. CONCLUSIONS: The findings of this pilot study indicated that, in general, skeletal growth of the craniofacial complex as well as axial skeletal growth was not statistically significantly altered by the immunosuppressive regimen of cyclosporine over the time period evaluated. Further longitudinal data of this study's subjects may shed more light on the possible adverse effects of cyclosporine on craniofacial growth and development in spite of the fact that no untoward correlation was found over the time period studied.

Animals↗

Genetic variation among populations of the Hessian fly Mayetiola destructor (Diptera: Cecidomyiidae) in Morocco and Syria.

The RAPD-PCR technique was used to study genetic variation within and among geographical populations of the Hessian fly, Mayetiola destructor (Say), from Morocco and Syria, associated with the fly's ability to overcome resistance in three wheat cultivars containing H5, H13 and H22 resistance genes. Variation was detected both for the level of susceptibility of the cultivars and RAPD profiles of M. destructor populations. By the use of RAPD-PCR, high genetic variability was detected among individuals and populations of M. destructor within and between areas separated geographically. The DNA fingerprints of populations of M. destructor were area-specific with Nei's measures of genetic distance ranging from 0.156 (between Abda and Beni Mellal, Morocco) to 1.977 (between Marchouch, Morocco and Lattakia, Syria). Cluster analysis of the genetic distances among the populations, identified the Syrian population as an outlier. A highly significant correlation (r = 0.81) observed between the genetic and geographic distances among the populations, provided genetic support for dispersal of the fly from its presumed origin in West Asia to Morocco.

Animals↗

Renal citrate metabolism and urinary citrate excretion in the infant rat.

BACKGROUND: Although hypercalciuria has the same prevalence in children as adults, children rarely develop renal stones. This may be explained by a greater urinary citrate excretion in infants compared with adults. The present study examines the renal excretion of citrate and renal cortical citrate metabolism in infant and adult rats. METHODS: Adult male and newly weaned infant rats were acclimated to metabolic cages and fed synthetic diets. Urine was collected after two days, and renal cortical citrate metabolism was assayed. RESULTS: Infant rats had a lower plasma [HCO3-] and higher plasma [K+] and had a fourfold higher urinary citrate:creatinine ratio and a twofold higher concentration of citrate in their urine compared with adult rats. This higher urinary citrate excretion was not due to a difference in renal proximal tubular Na/citrate cotransporter activity, nor renal cortical citrate synthase or ATP citrate lyase activities in infants as compared with adults. However, infant rat kidneys had significantly lower mitochondrial aconitase (m-aconitase) activity. Renal cortical citrate concentrations were comparable in infant and adult rats. Manipulation of plasma [K+] to adult levels did not affect the higher urinary citrate excretion in infant rats. CONCLUSIONS: Urinary citrate excretion in infant rats is greater than in adults but does not parallel tissue [citrate]. Thus, this higher urinary citrate is likely due to maturational differences in the proximal tubule, other than Na/citrate cotransport, that directly affect citrate transport.

Aging↗

End-tidal carbon monoxide measurements in women with pregnancy-induced hypertension and preeclampsia.

OBJECTIVE: We sought to compare the end-tidal carbon monoxide breath levels in pregnant women with and without pregnancy-induced hypertension and preeclampsia. STUDY DESIGN: We prospectively performed end-tidal carbon monoxide measurements corrected for ambient carbon monoxide in nonsmoking women during late gestation (>31 weeks). The study group included 22 women with pregnancy-induced hypertension or symptoms of preeclampsia and a control group of 20 normotensive pregnant women. RESULTS: The carbon monoxide measurements corrected for ambient carbon monoxide (mean +/- SD) were significantly lower (P <.01) in the hypertensive group than in the control group (1.17 +/- 0.35 vs 1.70 +/- 0.54 ppm). The study group had a significantly higher number of low (<1.2 ppm) end-tidal carbon monoxide measurements corrected for ambient carbon monoxide (13 [59.1%] vs 1 [5.0%]; P <.001). The end-tidal carbon monoxide measurements corrected for ambient carbon monoxide remained significantly lower in comparison with those found in the control group when the study group was divided into women with pregnancy-induced hypertension only (n = 11) and those with preeclampsia (n = 11) (1.19 +/- 0.37 ppm; P <.01; and 1.15 +/- 0.41 ppm; P <.01; respectively). CONCLUSIONS: Our findings suggest that carbon monoxide formation may be significantly lower in women with pregnancy-induced hypertension and preeclampsia. These data suggest that carbon monoxide could have a contributory role in the apparent paradox of the seemingly protective effect of smoking to decrease the risk of preeclampsia.

Adult↗

Fission yeast homologs of human CENP-B have redundant functions affecting cell growth and chromosome segregation.

Two functionally important DNA sequence elements in centromeres of the fission yeast Schizosaccharomyces pombe are the centromeric central core and the K-type repeat. Both of these DNA elements show internal functional redundancy that is not correlated with a conserved DNA sequence. Specific, but degenerate, sequences in these elements are bound in vitro by the S. pombe DNA-binding proteins Abp1p (also called Cbp1p) and Cbhp, which are related to the mammalian centromere DNA-binding protein CENP-B. In this study, we determined that Abp1p binds to at least one of its target sequences within S. pombe centromere II central core (cc2) DNA with an affinity (K(s) = 7 x 10(9) M(-1)) higher than those of other known centromere DNA-binding proteins for their cognate targets. In vivo, epitope-tagged Cbhp associated with centromeric K repeat chromatin, as well as with noncentromeric regions. Like abp1(+)/cbp1(+), we found that cbh(+) is not essential in fission yeast, but a strain carrying deletions of both genes (Deltaabp1 Deltacbh) is extremely compromised in growth rate and morphology and missegregates chromosomes at very high frequency. The synergism between the two null mutations suggests that these proteins perform redundant functions in S. pombe chromosome segregation. In vitro assays with cell extracts with these proteins depleted allowed the specific assignments of several binding sites for them within cc2 and the K-type repeat. Redundancy observed at the centromere DNA level appears to be reflected at the protein level, as no single member of the CENP-B-related protein family is essential for proper chromosome segregation in fission yeast. The relevance of these findings to mammalian centromeres is discussed.

Autoantigens↗

Maturation of proximal straight tubule NaCl transport: role of thyroid hormone.

We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across the apical membrane is via parallel Na(+)/H(+) and Cl(-)/OH(-) exchangers, which increases in activity with maturation. The present in vitro microperfusion study examined whether thyroid hormone plays a role in the maturational increase in PST NaCl transport. Neonatal and adult PST were perfused with a high-chloride-low bicarbonate solution without organic solutes, simulating late proximal tubule fluid. Thyroid hormone-treated neonates had a higher rate of PST total and passive NaCl transport. In 8-wk-old animals that were hypothyroid since birth, the maturational increase in total and passive NaCl transport was prevented. Thyroid treatment for 4 days in hypothyroid 8-wk-old rabbits increased the rate of both total and passive NaCl transport. The maturational increases in both Na(+)/H(+) and Cl(-)/OH(-) exchange activities were blunted in 8-wk-old hypothyroid animals and increased to control levels with thyroid treatment. This study demonstrates that thyroid hormone is a factor responsible for the maturational increase in both active and passive PST NaCl transport.

Aging↗

Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport.

The kidney has the highest abundance of cytochrome P-450 of all extrahepatic organs. Within the kidney, the highest concentration of cytochrome P-450 is found in the proximal tubule. Whether 20- or 19(S)-hydroxyeicosatetraenoic acid (HETE), the major P-450 metabolites of arachidonic acid in the proximal tubule, affect transport in this segment has not been previously investigated. We examined the direct effects of 20- and 19(S)-HETE on volume absorption (J(v)) in the rabbit proximal straight tubule (PST). Production of 20-HETE by rabbit PST was demonstrated by incubating microdissected tubules with [(3)H]arachidonic acid and separating the lipid extract by HPLC. There was significant conversion of [(3)H]arachidonic acid to 20-HETE in control tubules that was inhibited by 10(-5) M N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). Addition of exogenous 20-HETE had no effect on PST volume transport. However, inhibition of endogenous production of 20-HETE using DDMS stimulated transport. In the presence of DDMS, 20-HETE inhibited PST J(v). 19(S)-HETE in the bathing solution stimulated PST J(v) alone and in the presence of DDMS. Thus omega- and omega-1-hydroxylase products of arachidonic acid have direct effects on PST transport. Endogenous production of 20-HETE may play a role in tonic suppression of transport and may therefore be an endogenous regulator of transport in the proximal tubule.

Amides↗

Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule.

The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na(+)/H(+) exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known to be present on the apical membrane of the PCT. Here we examined apical membrane PCT sodium-dependent proton secretion of wild-type (NHE3(+/+)/NHE2(+/+)), NHE3(-/-), NHE2(-/-), and double-knockout NHE3(-/-)/NHE2(-/-) mice to determine their relative contribution to luminal proton secretion. NHE2(-/-) and wild-type mice had comparable rates of sodium-dependent proton secretion. Sodium-dependent proton secretion in NHE3(-/-) mice was approximately 50% that of wild-type mice. The residual sodium-dependent proton secretion was inhibited by 100 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA). Luminal sodium-dependent proton secretion was the same in NHE3(-/-)/NHE2(-/-) as in NHE3(-/-) mice. These data point to a previously unrecognized Na(+)-dependent EIPA-sensitive proton secretory mechanism in the proximal tubule that may play an important role in acid-base homeostasis.

Amiloride↗

Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules.

Neonates have a lower serum bicarbonate level than adults, which is caused by a lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption occurs in the proximal tubule, in which proton secretion is predominantly mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that there is a maturational increase in apical membrane rabbit proximal convoluted tubule Na+/H+ antiporter activity. However, in rat brush border membrane vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter activity was assayed as the proton secretory rate on luminal sodium removal. Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8 +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next examined whether the increase in Na+/H+ antiporter activity was associated with changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In summary, this study demonstrates that there is a maturational increase in rat apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush border membrane vesicle NHE3 protein abundance.

Aging↗

Symptomatic and asymptomatic chlamydial non-gonococcal urethritis in Jamaica: the potential for HIV transmission.

To determine the contribution of Chlamydia trachomatis to non-gonococcal urethritis (NGU) in men attending sexually transmitted disease (STD) clinics in Jamaica we studied men with NGU (n=339), and control groups including asymptomatic men who were STD contacts (n=61), asymptomatic men who were not STD contacts (n=32) and men with gonococcal urethritis (GU) (n=61). Urethral specimens were examined for C. trachomatis and Neisseria gonorrhoeae. Serological tests for syphilis (STS) and HIV-1 infection were also performed. C. trachomatis accounted for 63% of cases of NGU but high prevalences were also found in asymptomatic STD contacts (59%), asymptomatic STD non-contacts (78%) and men with GU (48%). The prevalence of C. trachomatis in men with GU differed significantly from that in men with NGU and asymptomatic STD non-contacts (P<0.05). C. trachomatis infection in men with NGU was associated with multiple sex partners (71% vs 58%; chi2=4.78; odds ratio (OR)=1.76; P<0.05) and previous history of gonococcal infection (83% vs 42%; chi2=59.8; OR=6.8; P<0.0001). Concomitant infection with HIV-1 occurred in 5.2% of cases of NGU and 50% and 90%, respectively, of the HIV-positive men had chlamydia or reactive STS. As a cost effective strategy in the control of STD and HIV we recommend presumptive treatment for C. trachomatis in men seeking STD treatment in Jamaica.

Case-Control Studies↗