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Biomedical subjects

A Baron

Publications and source records attributed to A Baron.

At least 55 records · Page 3Linked to original sources
PubMed1999

The FHIT gene is expressed in pancreatic ductular cells and is altered in pancreatic cancers.

We examined 2 normal pancreata, 21 primary pancreatic ductal cancers, and 19 pancreatic cancer cell lines for Fhit expression and FHIT gene status. The normal pancreas expressed Fhit protein in the cytoplasm of ductular cells, whereas interlobular and larger ducts, acini, and insulae of Langerhans were negative. Fhit protein was detected by immunoblot assay in 11 pancreatic cancer cell lines; of the 8 cell lines lacking Fhit protein, 7 lacked FHIT mRNA and 1 showed an abnormally sized transcript. DNA from five of these eight cell lines showed homozygous loss of FHIT exon 5. In 8 of the 21 primary cancers, Fhit expression was detected by immunohistochemistry. Reverse transcription-PCR analysis of 6 of the 13 cases lacking Fhit showed normal-sized FHIT product in 3 cases and a mixture of normal and abnormal products in the other 3. Sequencing showed that abnormal bands were missing variable numbers of exons. Loss of microsatellite DNA markers internal to the FHIT gene was observed in 10 of 13 primary cancers lacking Fhit protein (homozygous in two cases) and in only 1 of the 8 cancers expressing Fhit protein. In nine primary cancers, four expressing and five lacking Fhit protein, it was possible to obtain pure cancer DNA by microdissection. Three of the five microdissected cases lacking Fhit protein exhibited homozygous deletion of FHIT exon 5. In conclusion, the lack of Fhit protein in pancreatic cancers correlated with absence or alteration of FHIT mRNA and was often associated with FHIT gene anomalies.

Acid Anhydride Hydrolases↗
PubMed1999

Descriptive anatomic study of the fourth perforating artery of the femoral system.

The existence of the fourth perforating artery of Paturet [7], a collateral branch of the superficial femoral artery in its lower third, is the subject of much debate. This artery has so far only been the subject of radio-anatomic descriptions based on arteriographies carried out within the context of arteriopathy of the lower limbs. We present a descriptive anatomic study of this artery based on 14 observations on 32 dissections. Three types of approach were carried out: exposure of the artery of the femoral quadriceps muscle up to its ending in the vastus lateralis; a lateral "orthopaedic" approach to the lower third of the femur; and a "vascular" approach by a medial incision to the femoro-popliteal axis in the lower third of the thigh. Its main relations are described, passing in front of the superficial femoral vein and then behind the femur before ending at the vastus lateralis muscle. These relations explain the possibility of anastomoses with collateral or terminal branches of the deep femoral artery (vastus lateralis artery, third perforating artery). The fourth perforating artery of Paturet [7] must be protected in traumatologic and vascular surgery. It is the main collector of vascular anastomoses between the deep femoral artery and the femoro-popliteal axis in the event of proximal occlusion of the superficial femoral artery. Its removal, in such a case, can aggravate an underlying arteriopathy.

Aged↗
PubMed1999

Indicators of nutritional risk in a rural elderly Hispanic and non-Hispanic white population: San Luis Valley Health and Aging Study.

OBJECTIVE: To describe the prevalence of nutritional risk factors among elderly residents in a rural Hispanic and non-Hispanic white population. DESIGN: A geographically based survey of community-dwelling elderly adults. SUBJECTS/SETTING: From July 1993 to July 1995, all Hispanic persons older than 65 years and an age-stratified, random sample of 69% of non-Hispanic white persons, from 2 Colorado counties, were invited to participate in a study of functional impairment and disability (81% responded). After exclusion of 184 respondents who required a surrogate respondent and 8 with missing diet data, the study consisted of 1,006 subjects. Interviews included questions similar to the Nutrition screening Initiative checklist, a 21-item food frequency questionnaire, and anthropometric measures. STATISTICAL ANALYSES PERFORMED: Gender- and ethnicity-specific, age-adjusted prevalence for each risk factor was estimated by use of logistic regression. RESULTS: Hispanic participants were more likely than non-Hispanic whites to report inadequate intake of vegetables, problems with teeth or dentures that limited the kinds and amounts of food eaten, difficulty preparing meals, and lack of money needed to buy food. Hispanic women reported nutritional risk factors more often than Hispanic men, although anthropometric markers indicated that Hispanic men may be at higher risk of nutritional deficiency. APPLICATIONS/CONCLUSIONS: Hispanic men and women had a higher prevalence of nutritional risk factors than non-Hispanic whites. Intervention programs targeting rural, elderly Hispanics should aim to ensure that basic nutrition needs (access to food, help preparing meals, and adequate dental care) are being met. Community programs to increase activity levels and consumption of nutrient-dense foods are recommended.

Aged↗
PubMed1999

Purification of large quantities of human salivary cystatins S, SA and SN: their interactions with the model cysteine protease papain in a non-inhibitory mode.

OBJECTIVES: Our aim was to purify large quantities of human salivary cystatins S, SA and SN in order to determine whether these salivary cystatins have a stable interaction with cysteine proteases at a second binding site, other than the protease active site. This property may affect their availability to act as cysteine protease inhibitors within the oral environment. METHODS: Salivary cystatins S, SA and SN were purified from human submandibular sublingual saliva to homo- geneity by column chromatography. Formation of stable complexes between the model cysteine protease papain in the absence of reductant was assessed by SDS-PAGE and probing Western blots with antibody to human salivary cystatin SN. Proteolytic activity of the complex was determined in the gel after electrophoresis. RESULTS AND CONCLUSIONS: Only cystatin SN (14.3 kD) was found to form a stable complex with papain (22 kD) that could be separated by SDS-PAGE producing a Coomassie stained band at (37 kD). After western transfer this same band (37 kD) cross-reacted with antibody to SN. In the presence of E64, an active site inhibitor of cysteine proteases, the same complex was formed, suggesting that SN is able to bind to papain at a site other than the active site. Activity staining of the gel confirmed that this complex (-E64) retained proteolytic activity. Such complex formation between cystatin SN and cysteine proteases in a non-inhibitory mode may reduce its availability to act as an effective cysteine protease inhibitor in the oral environment.

Blotting, Western↗
PubMed1999

Functional aspects of the human salivary cystatins in the oral environment.

OBJECTIVES: The aim of this study was to investigate the cysteine protease inhibitory properties of the human salivary cystatins S, SA and SN in order to identify potential in vivo target cysteine proteases which may include those involved in periodontal tissue destruction. In addition, the potential role of the salivary cystatins with respect to the tooth mineral balance and pellicle formation was also investigated. METHODS: Salivary cystatins S major, S minor, SA, SAT (a truncated form of SA) and SN were purified from human submandibular sublingual saliva. Sensitive fluorometric assays were used to test the inhibitory action of each purified form of salivary cystatin against a variety of cysteine proteases and to determine whether pH affected their inhibitory activity towards the well-characterized cysteine protease papain. Their potential role in the mineral balance of the tooth was assessed by the measurement of calcium binding and the rate of binding to carbonated apatite (CAP). RESULTS AND CONCLUSIONS: Salivary cystatin SN was found to inhibit the human lysosomal cathepsins B, H and L and salivary cystatin SA was found to inhibit human lysosomal cathepsin L in vitro. These proteases are involved in periodontal tissue destruction and these data suggest that salivary cystatins SA and SN are involved in the control of the proteolytic events in vivo. Salivary cystatin S was not an inhibitor of the cysteine proteases tested suggesting that its primary role is not as a cysteine protease inhibitor. However, S was able to bind more calcium and bind more rapidly to CAP than SA or SN, suggesting that its primary role in the oral environment is likely to be the involvement with the mineral balance of the tooth.

Amino Acid Sequence↗
PubMed1998

Molecular pathogenesis of sporadic duodenal cancer.

Whether duodenal adenocarcinoma should be considered as a gastrointestinal or as a peripancreatic cancer is a matter of debate, as is the opportunity and type of treatment. We investigated 12 such cancers for the genetic anomalies involved in the pathogenesis of gastrointestinal malignancies, including (a) those occurring in common-type cancers - allelic losses at chromosomes 3p, 5q, 17p and 18q, and Ki-ras and p53 alterations; and (b) those characteristic of mutator-phenotype cancers - microsatellite instability and TGF-betaRII gene mutations. We found Ki-ras and p53 mutations in five (42%) and eight cancers (67%), respectively; chromosome 3p, 5q, 17p and 18q allelic losses in two of nine (22%), six of ten (60%), six of nine (67%) and three of ten (30%) informative cancers, respectively. Finally, three cancers (25%) showed widespread microsatellite instability and two of them had a TGF-betaRII gene mutation. Our data suggest that duodenal cancers may arise from either of the two known pathogenetic molecular pathways of gastric and colorectal cancers. The majority of our cases were highly aggressive cancers with frequent chromosomal changes and p53 mutations as observed in the common-type gastrointestinal malignancies, while widespread subtle alterations characteristic of mutator-phenotype cancers occurred in a minority, which also showed a favourable long-term outcome.

Adult↗
PubMed1998

Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.

During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium.

Adenoma↗
PubMed1998

Incidence and progression of diabetic retinopathy in Hispanics and non-Hispanic whites with type 2 diabetes. San Luis Valley Diabetes Study, Colorado.

OBJECTIVE: To learn if Hispanic people with type 2 diabetes have excess incidence and/or progression of diabetic retinopathy and to explore the association of risk factors with diabetic retinopathy. RESEARCH DESIGN AND METHODS: There were 244 subjects with type 2 diabetes (65.3% Hispanic) with at least one follow-up visit between 1984 and 1992 examined for the development of retinopathy over a median of 4.8 years (range 2.0-6.6 years). Stereo fundus photos were graded by the University of Wisconsin Reading Center. RESULTS: Of the 169 subjects without retinopathy at baseline, 47 developed some retinopathy, an incidence rate of 63.7 per 1,000 person-years (PY), or a 4-year cumulative incidence of 22.5%. The Hispanic incidence rate was 58.3/1,000 PY (95% CI: 39.4-83.3), which was lower than among non-Hispanic whites, 76.1/1,000 PY (44.3-121.9). Progression occurred in 24 of the 75 subjects with retinopathy at baseline, a 4-year cumulative rate of 24.1%. Logistic regression showed that insulin treatment was associated with higher risk of any retinopathy (odds ratio [OR] = 8.45, 2.65-26.97), and both systolic blood pressure (odds ratio [OR] = 1.58, 0.99-2.52) and total GHb (OR = 1.46, 0.99-2.17) nearly attained statistical significance. After adjustment for multiple potential risk factors, the Hispanic/non-Hispanic white OR was 0.66 (0.28-1.57). CONCLUSIONS: No excess risk for incident retinopathy was found among Hispanic compared with non-Hispanic white subjects in this population. These results are consistent with our previously reported prevalence data from the same population but differ from reports of excess prevalence among Texas Hispanics. No other Hispanic incidence data are available to assist in reconciling this difference.

Blood Pressure↗
PubMed1997

Sec-independent protein translocation by the maize Hcf106 protein.

The bacterial Sec and signal recognition particle (ffh-dependent) protein translocation mechanisms are conserved between prokaryotes and higher plant chloroplasts. A third translocation mechanism in chloroplasts [the proton concentration difference (DeltapH) pathway] was previously thought to be unique. The hcf106 mutation of maize disrupts the localization of proteins transported through this DeltapH pathway in isolated chloroplasts. The Hcf106 gene encodes a receptor-like thylakoid membrane protein, which shows homology to open reading frames from all completely sequenced bacterial genomes, which suggests that the DeltapH pathway has been conserved since the endosymbiotic origin of chloroplasts. Thus, the third protein translocation pathway, of which HCF106 is a component, is found in both bacteria and plants.

Amino Acid Sequence↗
PubMed1997

Simultaneous antiandrogen withdrawal and treatment with ketoconazole and hydrocortisone in patients with advanced prostate carcinoma.

BACKGROUND: Although antiandrogen withdrawal has moderate efficacy in patients with hormone refractory prostate carcinoma (HRPC), the effect of the simultaneous suppression of adrenal androgens with ketoconazole at the time of antiandrogen withdrawal is not known. METHODS: Twenty consecutive patients with HRPC who had developed progressive disease despite combined androgen blockade were treated with antiandrogen withdrawal and simultaneous ketoconazole as a means of inhibiting adrenal steroid production. Prostate specific antigen (PSA) response was defined as a > 50% fall in PSA from baseline that was maintained for at least 8 weeks. RESULTS: Ten patients had established metastatic disease, 2 had high PSAs and no imaging studies (PSA of 70 and 160 ng/mL, respectively), 3 had microscopically positive lymph nodes and serologic progression, and 5 had serologic progression alone. Overall, of 20 evaluable patients, 11 (55%) had a > 50% fall in PSA (95% confidence interval [CI], 31.5-76.9%). The median PSA response duration was 8.5 months (95% CI, 7-17 months). The median survival was 19 months. Toxicity was mild, with Grade 1 and 2 nausea and emesis in 15% of patients, Grade 1 fatigue in 10% of patients, and reversible Grade 1 or 2 hepatotoxicity in 10% of patients. Mild skin toxicity was observed in 20% of patients. CONCLUSIONS: The addition of ketoconazole and hydrocortisone to antiandrogen withdrawal appears to increase the PSA response proportion observed with antiandrogen withdrawal alone. Toxicity is mild.

Adrenal Cortex Hormones↗
PubMed1997

Epoxyeicosatrienoic acids activate a high-conductance, Ca(2+)-dependent K + channel on pig coronary artery endothelial cells.

1. Epoxyeicosatrienoic acids (EETs) have been described as endothelium-derived hyperpolarizing factors (EDHFs), based on their stimulatory effects on smooth muscle K+ channels. In order to reveal a putative autocrine effect of EETs on endothelial channels, we have studied the effects of the four EET regioisomers (5,6-EET, 8,9-EET, 11,12-EET and 14,15-EET) on the high-conductance, Ca(2+)-dependent K+ (BKCa) channel recorded in inside-out patches of primary cultured pig coronary artery endothelial cells. Currents were recorded in the presence of either 500 nm or 1 microM free Ca2+ on the cytosolic side of the membrane. 2. In 81% of experiments, EETs at < 156 nM, applied on the cytosolic side of the membrane, transiently increased BKCa channel open state probability (PO) without affecting its unitary conductance, thus providing evidence for direct action of EETs, without involvement of a cytosolic transduction pathway. 3. The four EET regioisomers appeared to be equally active, multiplying the BKCa channel PO by a mean factor of 4.3 +/- 0.6 (n = 15), and involving an increase in the number and duration of openings. 4. The EET-induced increase in BKCa channel activity was more pronounced with low initial PO. When the BKCa channel was activated by 500 nM Ca2+, application of EETs increased the initial PO value of below 0.1 by a factor of 5. When the channel was activated by 1 microM Ca2+, application of EETs increased the initial PO value by a factor of 3. 5. Our results show that EETs potentiate endothelial BKCa channel activation by Ca2+. The autocrine action of EETs on endothelial cells, which occurs in the same concentration range as their action on muscle cells, should therefore fully participate in the vasoactive effects of EETs, and thus be taken into account when considering their putative EDHF function.

8,11,14-Eicosatrienoic Acid↗
PubMed1997

Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice.

Human complement receptors type 1 (hCR1;CD35) and type 2 (hCR2;CD21) are expressed on B lymphocytes at specific stages during differentiation and activation. These receptors play critical roles in the immune response to T-dependent Ags in addition to germinal center formation. Expression of both hCR2 and hCR1 is decreased on B lymphocytes of patients with systemic lupus erythematosus (SLE). We have studied the expression of mouse CR2 and CR1 on normal populations of mouse B lymphocytes in BALB/c mice. Our results demonstrate that expression of these receptors in the normal state closely parallels that of hCR2. During bone marrow development, expression is first detected on low B220/high IgM cells, demonstrating that complement receptors appear after central tolerance mechanisms are completed. In the splenic microenvironment the highest levels of receptor expression are found on marginal zone B lymphocytes. Mouse CR2 and CR1 are also found on peritoneal B1a and B1b cells in addition to IgA+ Peyer's patch B cells. Activation of splenic B cells under Th2 conditions results in a marked decrease in receptor expression. To determine whether the patterns of receptor expression also parallel those found in human disease, we studied the MRL lpr/lpr (MRL/lpr) model of SLE. Interestingly, we found an early decrease in complement receptor expression that is progressive and first detectable before major clinical manifestations of nephritis. We hypothesize that the early decrease in complement receptor expression such as that demonstrated by MRL/lpr mice plays an important role in the pathogenesis of murine and perhaps human SLE.

Animals↗
PubMed1997

Dynamic MR colpocystorectography assessing pelvic-floor descent.

Magnetic resonance colpocystorectography (MR-CCRG) is presented in the evaluation of patients with pelvic-floor disorders. Five healthy volunteers and 44 female patients with isolated or combined visceral descent underwent dynamic MRI and dynamic fluoroscopy (DF). MR-CCRG was performed with the patient in a supine position using a True FISP sequence (1 image/1.2 s; in-plane resolution 1.02 mm) during pelvic floor contraction, relaxation, and straining maneuvers. Relevant organs, such as urethra, bladder, vagina, and rectum, were opacified by using a saline solution, Magnevist (Schering AG, Berlin, Germany), and sonography gel, respectively. The clinical evaluation and the intraoperative results (30 cases) were used as reference. MR-CCRG and DF were non-diagnostic in 3 cases each. Most patients had a combined type of visceral prolapse, the most frequent combination being a vaginal vault prolapse and a cystocele. The points of reference were sufficiently outlined by DF and MR-CCRG. In comparison with the clinical and intraoperative results, MR-CCRG proved to be especially beneficial in the diagnosis of different types of enteroceles including a uterovaginal prolapse. MR-CCRG showed an equal or higher sensitivity and specificity for all individual sites when compared with DF. Also, predominant herniation obscuring other concomitant prolapse could be verified in 8 cases. MR-CCRG is superior to DF and accurately depicts pelvic-floor descent and prolapse in women. The possibility of dynamic presentation (see enclosed CD-ROM) allows for a better understanding of the organ movements within a given topographic reference setting.

Contrast Media↗
PubMed1996

Ca(2+)-dependent non-selective cation and potassium channels activated by bradykinin in pig coronary artery endothelial cells.

1. Using the cell-attached and inside-out modes of the patch-clamp technique, we studied the Ca(2+)-dependent ionic channels activated by bradykinin in cultured pig coronary artery endothelial cells to further understand electrophysiological events underlying cellular activation. 2. In the cell-attached mode, bradykinin (94 nM) activated two types of Ca(2+)-dependent channels: a high conductance K+ channel (285 pS in high symmetrical K+), whose open state probability was increased by depolarization, and a lower conductance inwardly rectifying non-selective cation channel (44 pS in high symmetrical K+). 3. The 285 pS K+ channel was half-maximally activated by cytosolic Ca2+ levels of 1.6 and 4.5 microM at +10 and -30 mV, respectively. Such local concentrations should be reached in the presence of bradykinin, which induces a mean maximal cytosolic Ca2+ rise of 1.3 microM. 4. The 285 pS K+ channel was inhibited by d-tubocurarine, which acted by reducing the mean open time duration (flickering pattern), finally reducing the channel conductance. 5. Divalent cations such as Ca2+ could flow through the 44 pS non-selective cation channel, with nearly the same permeability (P) as monovalent cations (PK: PNa: PCa = 1:1:0.7). 6. The cation channel appeared to be more sensitive to Ca2+ than the K+ channel, with a half-maximal open probability induced by 0.7 microM Ca2+ on the intracellular side of the membrane. 7. In contrast to the K+ channel, the cation channel mean open time was clearly increased by bradykinin. This effect was delayed compared with the increase in the channel open state probability and was rapidly lost in the inside-out configuration. Caffeine also activated the cation channel but more transiently than bradykinin and without any effect on the open duration. 8. In the absence of extracellular Ca2+, the bradykinin-induced increase in cytosolic free Ca2+ was shortened temporally by 52% and reduced in amplitude by 88%, whereas the bradykinin-induced hyperpolarization was not significantly reduced in amplitude but was shortened by 70%, thus illustrating the major role of Ca2+ influx in endothelial cell activation by bradykinin. 9. We conclude that bradykinin activates two types of Ca(2+)-dependent channels in coronary endothelial cells: a high conductance K+ channel regulated by membrane potential, and an inwardly rectifying cation channel allowing Ca2+ entry, the cation channel being about 6 times more sensitive to Ca2+ than the K+ channel. The increase in cation channel open state probability involves an increase in open number, like the K+ channel, but also involves a rise in channel open duration. Ca2+ entry via cation channels could contribute to increase the cytoplasmic Ca2+ level, activate Ca(2+)-dependent K+ channels, thus triggering membrane hyperpolarization when the endothelial cell is stimulated by a vasoactive agonist such as bradykinin.

Animals↗