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Biomedical subjects

M Baum

Publications and source records attributed to M Baum.

At least 127 records · Page 7Linked to original sources
PubMed1998

Wheat cytoplasmic arginine tRNA isoacceptor with a U*CG anticodon is an efficient UGA suppressor in vitro.

Many RNA viruses express part of their genomic information by read-through over internal termination codons. We have recently characterized tobacco cytoplasmic (cyt) and chloroplast (chl) tRNACmCATrp and tRNAGCACys as natural suppressor tRNAs that are able to read the leaky UGA codon in RNA-1 of tobacco rattle virus, albeit with different efficiencies. Here we have identified a third natural UGA suppressor in plants. We have purified and sequenced four cyt tRNAArg isoacceptors with ICG, CCG, U*CG and CCU anticodons from wheat germ. With the exception of tRNAICGArg, these are the first sequences of plant tRNAsArg. In order to study the potential suppressor activity of wheat tRNAsArg we have used in vitro synthesized mRNA transcripts in which different viral read-through regions had been placed. In vitro translation was carried out in a homologous wheat germ extract. We found that tRNAU*CGArg is an efficient UGA suppressor in vitro, whereas the other three tRNAArg isoacceptors exhibit no or very low suppressor activity. Interaction of tRNAU*CGArg with the UGA codon requires a G:U base pair at the third anticodon position. This is the first time that an arginine-accepting tRNA has been characterized as a natural UGA suppressor. A remarkable feature of cyt tRNAU*CGArg is its ability to misread the UGA at the end of the coat protein cistron in RNA-1 of pea enation mosaic virus, which is not accomplished by cyt tRNACmCATrp or cyt tRNAGCACys, due to an unfavourable codon context.

Anticodon↗
PubMed1998

The Fanconi syndrome of cystinosis: insights into the pathophysiology.

Cystinosis is a lysosomal storage disease which is the most-common inherited cause of the Fanconi syndrome. Insights into the pathophysiology of the proximal tubular defect have come from in vitro studies of the cystine-loaded tubule. Proximal tubules loaded with cystine have a generalized proximal tubule transport defect characteristic of the Fanconi syndrome. The decrease in proximal tubular transport with cystine loading is not due to an increase in paracellular permeability with backflux of solute transport from the blood to the tubular lumen, but due to a decrease in active transport. The Na-K-ATPase activity is intact under Vmax conditions in cystine-loaded tubules; however, the production of ATP is severely compromised. The cystine-loaded tubule has a lower intracellular phosphate concentration than that of control tubules. This low intracellular phosphate concentration in cystine-loaded tubules likely plays a critical role in the decrease in intracellular ATP. Preservation of intracellular phosphate at control levels prevents the decrease in intracellular ATP and the proximal tubule respiratory dysfunction with cystine loading. The clinical significance and future directions for investigation are discussed.

Cystinosis↗
PubMed1998

Campaign strategy and tactics for clinical trials in surgical oncology.

The strategic planning of the campaign against cancer and the employment of clinical trials on a national and supranational basis could be improved. Lessons and principles derived from other spheres of ordered activity might be usefully applied to the realm of clinical trials. Principles taught by military strategists may find practical applications in the development and prosecution of successful clinical trials of cancer therapy. In this paper we reflect upon the parallels and divergences between the principles of campaign strategy needed for the successful prosecution of military objectives and the efficient and effective prosecution of major clinical trials.

Clinical Trials as Topic↗
PubMed1998

Tamoxifen--the treatment of choice. Why look for alternatives?

Tamoxifen is currently established as the endocrine treatment of choice in breast cancer. In advanced breast cancer, response rates of up to 60% in women with oestrogen receptor (ER)-positive tumours have been reported. In early breast cancer, tamoxifen can produce significant benefits, both statistically and clinically, in terms of reduction in relative risk of relapse or death in all patient subgroups (i.e. ER status, aged < or > 50 years) except premenopausal women with ER-negative tumours. The major benefit, however, is seen in women over 50 years old with ER-positive tumours. The results of randomized trials suggest that the optimum duration of tamoxifen therapy is at least 5 years. Two large pragmatic trials (aTTom and ATLAS) are under way to determine whether additional benefit can be gained from continuing tamoxifen treatment beyond 5 years. Recent data also suggest possible synergism between tamoxifen and chemotherapy in the treatment of early breast cancer in post-menopausal women. Other benefits of tamoxifen treatment include reduction in the risk of developing contralateral breast cancer. Included among the non-breast cancer benefits of tamoxifen are reduced risk of cardiovascular disease and protection against bone loss in post-menopausal women. These benefits must be weighed against the possible increased incidence of endometrial cancer. Notwithstanding its undoubted success, there is a need for agents to improve upon tamoxifen. Newer agents, such as the luteinizing hormone-releasing hormone analogue goserelin and the new-generation aromatase inhibitors, such as anastrozole, will add new life to the search for an improved endocrine therapy for early breast cancer.

Aged↗
PubMed1998

Inhibition of proximal convoluted tubule transport by dopamine.

BACKGROUND: Dopamine can produce a natriuresis and diuresis independent of changes in renal hemodynamics. However, previous studies have failed to demonstrate an inhibition of transport by dopamine in intact proximal convoluted tubules. METHODS: Rabbit proximal convoluted tubules were perfused in vitro with an ultrafiltrate-like solution and bathed in a serum-like albumin solution. RESULTS: In the present study, the addition of 10-5 M dopamine to the lumen or bath of proximal convoluted tubules perfused in vitro had no effect on transport. In proximal convoluted tubules, addition of 10-6 M bath norepinephrine increased the rate of volume absorption from 0.65 +/- 0.08 to 0.93 +/- 0.08 nl/mm. min (P < 0.01). Addition of 10-5 M luminal dopamine in the presence of bath norepinephrine inhibited the rate of volume absorption to 0.72 +/- 0.10 nl/mm. min (P = 0.01). The inhibition in the rate of volume absorption by luminal dopamine in the presence of bath norepinephrine was completely blocked by the DA1 antagonist, SCH 23390. The DA1 agonist luminal 10-5 M fenoldopam also inhibited volume absorption in the presence of bath norepinephrine, but the DA2 agonist luminal 10-5 M quinpirole was without effect. Bath 10-5 M dopamine had no effect on volume absorption in the presence of bath norepinephrine. CONCLUSION: Dopamine has no direct epithelial action on the proximal convoluted tubule. However, luminal dopamine antagonizes the stimulation in transport produced by norepinephrine. These studies suggest that luminal dopamine may play a role to modulate sodium transport in the presence of renal nerve activity.

Animals↗
PubMed1998

Effects of thyroid hormone on the neonatal renal cortical Na+/H+ antiporter.

The neonatal proximal tubule has a lower rate of bicarbonate absorption than that of adults. This is due, in part, to a lower rate of apical membrane Na+/H+ antiporter activity. The purpose of these studies was to examine if thyroid hormone could be a factor in the maturational increase in Na+/H+ antiporter activity. Hypothyroid (0.01% propylthiouracil in drinking water starting at day 14 gestation and throughout the postnatal period), euthyroid, and hyperthyroid (intraperitoneal triiodothyronine, 10 micrograms/100 g body wt, once daily on days 17 to 20 of postnatal life) rats were all studied at 21 days of life. Renal cortical brush border Na+/H+ antiporter activity was 453 +/- 24, 527 +/- 30 and 608 +/- 25 pmol/mg protein in the hypothyroid, euthyroid and hyperthyroid groups, respectively (P < 0.001). Hyperthyroid neonates had approximately twofold greater renal cortical NHE-3 mRNA abundance than euthyroid and hypothyroid neonates (P < 0.05). Brush border membrane NHE-3 protein abundance in hypothyroid and hyperthyroid neonates was one-third and twofold that of euthyroid 21-day-old rats, respectively (P < 0.001). These data are consistent with a potential role of thyroid hormone in the postnatal increase in Na+/H+ antiporter activity.

Animals↗
PubMed1998

Self-reported infectious mononucleosis and 6 cancers: a population-based, case-control study.

A study was undertaken to estimate the magnitude of association between self-reported infectious mononucleosis (IM) and 6 types of cancer, including Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal cancer, nasal cancer, primary liver cancer, and sarcoma. Cases were male, aged 15-39 y in 1968, who lived in 8 cancer registry areas. Controls were men selected by random-digit telephone dialing. Cases included 1511 persons with non-Hodgkin's lymphoma, 343 with Hodgkin's disease, 386 with sarcoma and 168, 113 and 70 with primary liver, nasopharyngeal and nasal cancers, respectively. There were 1910 controls. For the 6 cancers combined, the overall odds ratio for IM occurring < 5 and > or = 5 y of the reference date were 5.40 [95% (Confidence Interval (CI) = 1.61, 18.09] and 1.08 (0.84, 1.40), respectively. Analogous values were 4.59 (1.25, 16.85) and 1.07 (0.78, 1.48) for non-Hodgkin's lymphoma and 7.49 (1.52, 36.92) and 1.35 (0.87, 2.09) for Hodgkin's disease. There was the suggestion of a protective association with IM occurring > or = 5 y before cancer onset for the 4 non-lymphomatous cancers. Strongly positive associations between self-reported IM and 6 types of cancer were observed for IM occurring < 5 y before the onset of cancer. There was a suggestion, which is noted with extreme caution, that IM earlier in life might have had a protective association with the 4 non-lymphomatous cancers.

Adolescent↗
PubMed1998

Human herpesvirus 8 as a potential sexually transmitted agent in Honduras.

The seroprevalence of human herpesvirus 8 (HHV-8) was studied in 326 human immunodeficiency virus (HIV)-positive and -negative persons from Honduras; women constituted 77% (n = 251) of the subjects. Sera were tested for lytic HHV-8 antibodies by an IFA, and positive samples were confirmed by a radioimmunoprecipitation assay. Of the 326 persons tested, 58 (17.8%) had HHV-8 antibodies. Among the HIV-infected women, 22.7% were seropositive; 11.3% of the HIV-negative women were seropositive. HHV-8 seroprevalence was almost four times higher in HIV-positive female commercial sex workers (36%) than in HIV-negative female non-commercial sex workers (9.9%; odds ratio = 3.8, 95% confidence interval = 1.1-13; P = 0.01), suggesting that commercial sex work is a risk factor for HHV-8 infection. In the men studied, the overall HHV-8 seroprevalence was 22.6%, with a seropositivity rate of 28% for HIV-positive men compared with 12% for HIV-negative men.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effect of supplemental beta-carotene on plasma concentrations of carotenoids, retinol, and alpha-tocopherol in humans.

High doses of beta-carotene, a lipid-soluble nutrient, may affect the plasma concentrations of other lipid-soluble nutrients. The purpose of this study was to assess the effects of long-term daily supplementation with beta-carotene (50 mg/d) on circulating concentrations of other carotenoids, retinol, and alpha-tocopherol over time. Data were available from 259 men and women participating in the Carotene Prevention Trial, a 2-center chemoprevention trial designed to determine whether supplemental beta-carotene can prevent second malignant tumors in patients cured of an early stage cancer of the oral cavity, pharynx, or larynx. Up to 2 blood samples were obtained before the intervention (before and after a 1-mo placebo run-in), with postrandomization samples obtained at 3, 12, 24, 36, 48, and 60 mo. Supplementation with beta-carotene produced a persistent 9- to 10-fold increase in median plasma beta-carotene concentrations (225 nmol/L at baseline to 2255 nmol/L at 3 mo) and a persistent 2-fold increase in median plasma alpha-carotene concentrations (45 nmol/L at baseline to 95 nmol/L at 3 mo). Concentrations of retinol, alpha-tocopherol, lycopene, and lutein/zeaxanthin were not affected by supplemental beta-carotene. Up to 5 y of daily supplementation with beta-carotene increased circulating concentrations of alpha- and beta-carotene, but did not alter concentrations of lycopene, lutein/zeaxanthin, retinol, or alpha-tocopherol.

Adult↗
PubMed1998

Maturation of rabbit proximal straight tubule chloride/base exchange.

The present in vitro microperfusion study compared the mechanism and rates of NaCl transport in neonatal and adult rabbit proximal straight tubules. In proximal straight tubules perfused with a late proximal tubular fluid and bathed in a serumlike albumin solution, the rate of volume absorption (JV) was 0.54 +/- 0.10 and 0.12 +/- 0.05 nl.mm-1.min-1 in adults and neonates, respectively (P < 0.05). With the addition of 10(-5) M bath ouabain, JV decreased to 0.27 +/- 0.07 and -0.03 +/- 0.04 nl.mm-1.min-1 in adult and neonatal tubules, respectively (P < 0.05), consistent with lower rates of active and passive NaCl transport in the neonatal proximal straight tubule. The effect of luminal sodium and chloride removal on intracellular pH was used to assess the relative rates of Na+/H+ and Cl-/base exchange. The rates of Na+/H+ and Cl-/base exchange were approximately fivefold less in neonatal proximal straight tubules than adult tubules. In both neonatal and adult proximal straight tubules, the rate of Cl-/base exchange was not affected by formate, bicarbonate, or cyanide and acetazolamide, consistent with Cl-/OH- exchange. These data demonstrate an increase in proximal straight tubule NaCl transport during postnatal renal development.

Aging↗
PubMed1998

Endogenous angiotensin II modulates rat proximal tubule transport with acute changes in extracellular volume.

In the present study, we examined whether the effect of endogenously produced angiotensin II on proximal tubule transport in the male Sprague-Dawley rat is regulated by acute changes in extracellular volume. We measured the magnitude of endogenous angiotensin II-mediated stimulation of transport by sequentially perfusing proximal tubules in vivo, first with an ultrafiltrate-like solution, then by reperfusion of the same tubule with an ultrafiltrate-like solution containing 10(-8) M losartan (angiotensin II receptor antagonist). During volume contraction, 10(-8) M losartan decreased volume reabsorption from 4.20 +/- 0.50 to 1.70 +/- 0.30 nl . mm-1 . min-1 (P < 0.05), a decrease of 58.0 +/- 7.0%. In contrast, after acute volume expansion, 10(-8) M losartan decreased volume reabsorption from 1.84 +/- 0.20 to 1.31 +/- 0.20 nl . mm-1 . min-1 (P < 0.05), a decrease of 29.6 +/- 9.0%. In hydropenic rats, addition of exogenous luminal angiotensin II had no effect on transport. However, in volume-expanded rats, addition of 10(-8) M angiotensin II increased volume reabsorption from 2.10 +/- 0.34 to 4. 38 +/- 0.59 nl . mm-1 . min-1 (P < 0.005). These data are consistent with endogenously produced angiotensin II augmenting proximal tubule transport to a greater degree during volume contraction than after volume expansion.

Absorption↗
PubMed1998

Mild cognitive impairment and risk of mortality in HIV-1 infection.

HIV-1-associated cognitive impairment has only been preliminarily investigated for associations with mortality. The authors examined 119 HIV-1-positive homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th percentile in response speeds and in long-term memory retrieval accuracy were at 6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively, of those at the 75th percentile--independent of baseline CDC clinical stage, CD4 cell count, hemoglobin level, antiretroviral and prophylactic medication use, and sociodemographics. Cognitive impairment should be identified early--for maximization of both functional status and survival time.

AIDS Dementia Complex↗
PubMed1998

Clinical prognostic and predictive factors for primary chemotherapy in operable breast cancer.

PURPOSE: This study aimed to identify clinical factors that are of prognostic significance or that predict for subsequent treatment outcome in patients with large operable breast cancer treated with primary chemotherapy (PCT) at our institution. METHODS: One hundred eighty-five patients received the following regimens: CMF or MMM (76 patients), ECF (75 patients), AC or FEC (34 patients), followed by surgery, with radiotherapy (RT) given to those with breast conservation. A number of common clinical variables were assessed in relation to local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Clinical responders had improved DFS (P = .009) and OS (P = .08) compared with nonresponders. There was no association between clinical or pathologic complete remission (CR) and survival. Pretreatment clinical axillary node positivity was a significant predictor of worsened DFS (P = .0001), OS (P = .0001), and LRFS (P = .03). Patients remaining clinically node-positive postchemotherapy had an inferior outcome compared with those becoming node-negative (DFS, P = .03; OS, P = .03) but pathologic axillary node status was not shown to predict for survival. Twenty-nine patients in clinical CR following PCT who electively did not have surgery and were treated with RT alone had significantly increased local recurrence rate compared with partial responders having surgery and RT (P = .02). There were no differences in DFS or OS between these groups. On multivariate analysis, clinical axillary node status was the only independent predictor of OS and DFS, and LRFS. CONCLUSION: Pretreatment and posttreatment clinical axillary node status is a major predictor of outcome following PCT. Complete clinical response does not define a more favorable subgroup compared with those not obtaining CR.

Adult↗
PubMed1998

Bone mineral density in children with myelomeningocele.

BACKGROUND: Difficulties with ambulation in patients with myelomeningocele often lead to physical inactivity, osteoporosis, and subsequent development of pathologic fractures. OBJECTIVE: The purpose of this study was to examine bone mineral density and biochemical markers of bone metabolism in patients with myelomeningocele. DESIGN AND METHODS: A total of 35 patients between 6 and 19 years of age with myelomeningocele (ambulatory and nonambulatory) were randomly chosen at the Texas Scottish Rite Hospital for Children. We measured bone mineral density of the distal radius in these patients using single photon absorptiometry and measured the biochemical markers of bone metabolism including parathyroid hormone, 1,25 vitamin D, osteocalcin, urinary pyridinolines/deoxypyridinolines, and urinary calcium excretion. RESULTS: Bone mineral density of the distal radius in the patients with myelomeningocele was approximately 1 to 2 standard deviation units below the mean of the normal population. There were no significant differences between ambulators and nonambulators. However, bone mineral density of the 8 patients who suffered multiple fractures (19) was significantly lower than that for those remaining patients without fractures. Elevated urinary pyridinoline levels, which indicate elevated bone reabsorption, were found more frequently in both non- and limited ambulators than in full-time ambulators. Urinary calcium excretion also was greater than twofold higher in nonambulatory patients versus ambulatory patients. There were no other differences in the biochemical markers of bone metabolism (osteocalcin, parathyroid hormone, 1,25 vitamin D, and urinary deoxypyridinolines) between ambulators and nonambulators. Bone mineral density rises in normal growing children 6 to 19 years of age. When the boys and girls were considered separately, bone mineral density rises with age in boys, but not in girls. CONCLUSION: Patients with myelomeningocele have decreased bone mineral density and are at risk of suffering pathologic bone fractures. The measurement of bone mineral density may help to identify those patients at greatest risk of suffering multiple fractures. The urinary calcium excretion of nonambulators was higher than that of ambulators and likely contributes to their decreased bone mineral density. Bone mineral density increases with age in boys, but not in girls.

Adolescent↗