Medical Sciences Commons^™

Upregulation Of Heme Oxygenase-1 Combined With Increased Adiponectin Lowers Blood Pressure In Diabetic Spontaneously Hypertensive Rats Through A Reduction In Endothelial Cell Dysfunction, Apoptosis And Oxidative Stress, Jian Cao, George Drummond, Kazuyoshi Inoue, Komal Sodhi, Xiao Ying Li, Shinji Omura

Pharmaceutical Science and Research

This study was designed to investigate the effect of increased levels of HO-1 on hypertension exacerbated by diabetes. Diabetic spontaneously hypertensive rat (SHR) and WKY (control) animals were treated with streptozotocin (STZ) to induce diabetes and stannous chloride (SnCl2) to upregulate HO-1. Treatment with SnCl2 not only attenuated the increase of blood pressure (p<0.01), but also increased HO-1 protein content, HO activity and plasma adiponectin levels, decreased the levels of superoxide and 3-nitrotyrosine (NT), respectively. Reduction in oxidative stress resulted in the increased expression of Bcl-2 and AKT with a concomitant reduction in circulating endothelial cells (CEC) in the peripheral blood (p<0.005) and an improvement of femoral reactivity (response to acetylcholine). Thus induction of HO-1 accompanied with increased plasma adiponectin levels in diabetic hypertensive rats alters the phenotype through a reduction in oxidative stress, thereby permitting endothelial cells to maintain an anti-apoptotic environment and the restoration of endothelial responses thus preventing hypertension.

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Biochemistry and Microbiology

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood.

RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Suppression Of Implanted Mda-Mb 231 Human Breast Cancer Growth In Nude Mice By Dietary Walnut, W. Elaine Hardman, Gabriela Ion

Biochemistry and Microbiology

Walnuts contain components that may slow cancer growth including omega 3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin. A pilot study was performed to determine whether consumption of walnuts could affect growth of MDA-MB 231 human breast cancers implanted into nude mice. Tumor cells were injected into nude mice that were consuming an AIN-76A diet slightly modified to contain 10% corn oil. After the tumors reached 3 to 5 mm diameter, the diet of one group of mice was changed to include ground walnuts, equivalent to 56 g (2 oz) per day in humans. The tumor growth rate from Day …

Use Of Ultraviolet Light Irradiated Multiple Myeloma Cells As Immunogens To Generate Tumor Specific Cytolytic T Lymphocytes, Charles A. Gullo Phd, William Y.K. Hwang, Chye K. Poh, Melvin Au, Geraline Cow, Gerrard Teoh

Biochemistry and Microbiology

Background:

As the eradication of tumor cells in vivo is most efficiently performed by cytolytic Tlymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described.

Methods:

Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity.

Results: …

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Biochemistry and Microbiology

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

MIIR Faculty Research

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …

The Effect Of A Nurse-Respiratory Therapist Weaning Protocol On The Duration Of Mechanical Ventilation And The Incidence Of Ventilator-Associated Pneumonia, Andrea Lucas

Theses, Dissertations and Capstones

The purpose of this research study was to show the effectiveness of implementing a standardized nurse-respiratory driven weaning protocol in decreasing the time spent on mechanical ventilation and the incidence of ventilator-associated pneumonia in mechanically ventilated patients compared to using individual physician methods. Chart reviews were performed to compare the incidence of ventilator-associated pneumonia (VAP) prior to the initiation of the nurse-respiratory driven weaning protocol. Sister Callista Roy’s Adaptation theory was used as a framework for this study to show that nurses could promote adaption by using a standardized ventilator weaning protocol. The study did not show statistical significance that …

The Function And Mechanism Of Chmp1a In Tumor Development, Jing Li

Theses, Dissertations and Capstones

Chmp1A (Chromatin modifying protein 1A/Charged multivesicular protein 1A) is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport) family, which mediates trafficking via MVB (multivesicular body) formation and sorting. Our studies suggest that Chmp1A is a novel tumor suppressor, especially in the pancreas. Knockdown of Chmp1A resulted in an increase of anchorage-independent growth of HEK 293T cells. Moreover, we showed that Chmp1A depleted HEK 293T cells forms tumor in xenograft mice. Knockdown of Chmp1A in PanC-1 cells promoted cell growth. In contrast, Doxycycline induced over-expression of Chmp1A in pancreatic cancer cells (PanC-1) resulted in cell growth inhibition, tumor …

Effects Of Aging And Gender On Regulators Of Muscle Adaptation In F344/Bn Rat Model, Satyanarayana Paturi

Theses, Dissertations and Capstones

Sarcopenia is the loss of muscle mass and strength that occurs with aging. Here we examine the effects of aging and gender on the regulation of molecules believed to regulate muscle growth and adaptation in the F344/BN rat. In male animals, soleus and EDL muscle/body weight ratio declined continuously with aging while muscle atrophy in female animals plateaued at 26-months and remained constant thereafter. Aging increased the phosphorylation of protein kinase-B (Akt) and the mammalian target of rapamycin (mTOR) in the female but not male soleus muscle. This finding was associated with the attenuation of muscle atrophy observed in female …

Manganese Superoxide Dismutase Contributes To Cisplatin-Induced Cytotoxicity Rather Than All-Trans Retinoic Acid-Dependent Chemoresistance, Zina-Ann Cardozo

Theses, Dissertations and Capstones

Neuroblastoma is an extra-cranial solid tumor of the nervous system occurring predominantly in infants and children younger than five years of age. Neuroblastoma presents a challenge to therapy primarily due to a decreased responsiveness to anticancer agents like cisplatin (CDDP), leading to recurrence. Vitamin A and its derivatives, known as retinoids, are preventive against cancer and induce differentiation in some cell lines. Retinoids are now being tested clinically for the treatment of neuroblastoma. One major limitation to retinoid therapy is the development of chemoresistance. In the present study human SK-N-SH neuroblastoma cells pretreated with 10 μM all-trans retinoic acid (ATRA) …

Impaired Overload-Induced Hypertrophy In Obese Zucker Rat Slow-Twitch Skeletal Muscle, Anil Kumar Gutta

Theses, Dissertations and Capstones

How insulin resistant muscle responds to mechanical overload (MOV) is not well understood. Using immunohistochemical analysis and immunoblotting, we investigated whether Lean Zucker (LZ) and insulin resistant Obese Zucker rats (OZ) respond in a similar fashion to MOV. Five young adult (2 months old) male LZ and OZ rats were subjected to a surgical ablation of the gastrocnemius muscle and overloaded for 8 weeks. MOV-induced increases in soleus muscle mass and average fiber cross-sectional area were attenuated in OZ compared to LZ animals. This reduction in OZ muscle adaptation was associated with decreased activity / phosphorylation levels of STAT3, β-catenin …

Association Of Epstein-Barr Virus With Nasopharyngeal Carcinoma And Current Status Of Development Of Cancer-Derived Cell Lines, Charles A. Gullo Phd, Wong Kein Low, Gerrard Teoh

Biochemistry and Microbiology

It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact, …

Dietary Canola Oil Suppressed Growth Of Implanted Mda-Mb 231 Human Breast Tumors In Nude Mice, W. Elaine Hardman

Biochemistry and Microbiology

Long chain omega 3 (n-3) fatty acids, eicosapentaenoic (EPA) and/or docosahexaenoic acid (DHA), have been shown to suppress growth of most cancer cells. In vivo, alpha linolenic acid (ALA, 18:3n-3) can be converted to EPA or DHA. We hypothesized that substituting canola oil (10% ALA) for the corn oil (1% ALA) in the diet of cancer bearing mice would slow tumor growth by increasing n-3 fatty acids in the diet. Sixty nude mice received MDA-MB 231 human breast cancer cells and were fed a diet containing 8% w/w corn oil until the mean tumor volume was 60 mm ³ . …

Increased Hemorrhagic Transformation And Altered Infarct Size And Localization After Experimental Stroke In A Rat Model Type 2 Diabetes, Adviye Ergul, Mostafa M. Elgebaly, Mary-Louise Risher, Weiguo Li, Hazem Elewa, Jeffrey A. Switzer, Christiana Hall, Anna Kozak, Susan C. Fagan

Biomedical Sciences

Background: Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury.

Methods: Diabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage …

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

MIIR Faculty Research

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …

Phase I Study Of Medi-534 Of A Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus And Parainfluenza-3 Virus In Seropositive Children, Margarita Gomez, Maurice A. Mufson, Filip Dubovsky, Conor Knightly, Wen Zeng, Genevieve Losonsky

Internal Medicine

A live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine was evaluated in healthy respiratory syncytial virus/parainfluenza virus type 3 seropositive children aged 1 to 9 years. Three cohorts of 40 children were randomized 1:1 to receive 10^4, 10⁵ or 10⁶ median tissue culture infectious dose₅₀ MEDI-534 vaccine of placebo. The vaccine's safety profile was similar to placebo, no viral shedding was detected, and the vaccine was minimally immunogenic.

Identification Of A Pool Of Non-Pumping Na/K-Atpase, Man Liang, Jiang Tian, Lijun Liu, Sandrine Pierre Phd, Jiang Liu, Joseph I. Shapiro M.D., Zi-Jian Xie

Biochemistry and Microbiology

Recent studies have ascribed many non-pumping functions to the Na/K-ATPase. Here, we present experimental evidence demonstrating that over half of the plasma membrane Na/KATPase in LLC-PK1 cells is performing cellular functions other than ion pumping. This “non-pumping” pool of Na/K-ATPase, like the pumping pump, binds ouabain. Depletion of either cholesterol or caveolin-1 moves some of the “non-pumping” Na/KATPase into the pumping pool. Graded knock-down of the 1 subunit of the Na/K-ATPase eventually results in loss of this “non-pumping” pool while preserving the pumping pool. Our prior studies indicate that a loss of the non-pumping pool is associated with a loss …

Effect Of Standard Treatment Guidelines With Or Without Prescription Audit On Prescribing For Acute Respiratory Tract Infection (Ari) And Diarrhoea In Some Thana Health Complexes (Thcs) Of Bangladesh, M. O. Faruk Khan, A.K. Azad Chowdhury, M. A. Matin, K. Begum, M. A. Galib

Pharmaceutical Science and Research

Inappropriate prescribing for ARI and diarrhoea is a serious health problem in many developing countries including Bangladesh. A baseline retrospective prescribing survey for ARI and diarrhoea have been conducted in randomly selected 60 thana health complexes (THCs) of Dhaka division of Bangladesh. In the 38 of 60 THCs, the prescribers did not comply with the standard treatment guidelines (STG) for ARI. They are marked as 'unsatisfactory performers'. In these THCs unnecessary antibiotics were prescribed in more than 50% of the encounters. The study further revealed that in 26 THCs, comprising 41.6% of the 38 THCs, the situation was even worse …

Mlck/Actin Interaction In The Contracting A7r5 Cell And Vascular Smooth Muscle, Sean Eric Thatcher

Theses, Dissertations and Capstones

Myosin light chain kinase (MLCK) is an enzyme that phosphorylates the serine-19 residue on myosin regulatory light chains (MLCs) which serves to activate the Mg2+-ATPase of myosin. This catalytic activity is thought to be the primary role of MLCK; however, it has recently been suggested that MLCK’s actin binding and bundling properties may also be of importance in smooth muscle contraction. In the absence of calcium and calmodulin (CaM), MLCK will bundle actin filaments with its N-terminus. During calcium influx and subsequent CaM activation, MLCK binding to actin decreases resulting in unbundling of actin filaments and allows myosin and actin …

Shear Stress Induced Mtor Signaling In Cultured A7r5 Aortic Smooth Muscle Cell Line, Sriram Prasad Mupparaju

Theses, Dissertations and Capstones

Vascular intervention procedures such as balloon angioplasty and stent implantation lead to denudation of endothelium exposing the underlying smooth muscle layer to effects of blood shear stress. The effect of shear stress on smooth muscle cell signaling has not been studied in depth. In this study, we examined time dependent changes in activation of Akt, mTOR and p70S6k related signaling in response to orbital shear stress on cultured A7r5 cells. A7r5 cells cultured to subconfluence on 150mm culture dishes were subjected to orbital shear of 9.8dynes/cm 2 for zero, 5 min, 15 min, 30 min, 1h, 4h and 24h. The …

Chronic Acetaminophen Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fisher 344 X Brown Norway Rat Aorta, Sarath Meduru

Theses, Dissertations and Capstones

We have previously reported that aging in the Fisher 344 X Brown Norway (FBN) rat aorta is characterized by increased levels of ROS and alterations in cell signaling. Acetaminophen was found to scavenge free radicals in recent ischemia-reperfusion studies. Here we examined if chronic treatment with a therapeutic dose of acetaminophen attenuates age-associated increase in aortic ROS accumulation and signaling. FBN rats (27 month old; n=8) were subjected to 6 months of treatment with a therapeutic dose of acetaminophen (30mg/kg/day), with age-matched untreated FBN rats as controls. Protein oxidation levels were altered in control and treated aortae compared to aortae …

The Expression And Function Of Ppar And Hif-1 In Human Melanoma, Caroline Mills

Theses, Dissertations and Capstones

The first part of my dissertation focuses on the expression and function of PPARs in human melanoma. I found that the A375 cells were significantly growth inhibited in response to _PGJ2 and troglitazone treatment. HEMn-LP showed significant growth inhibition in response to troglitazone. I found that PPARγ and PPARδ mRNA is present in both the SK-Mel 28 and A375 cells. The relative level of PPARα mRNA expression is highest in SK-Mel 28 cells, ~3 fold higher relative to both the normal human melanocytes and A375 cells. PPARγ protein was ~50% higher in both SK-Mel 28 and A375 cells relative to …

Aging Influences Multiple Indices Of Oxidative Stress In The Heart Of The Fischer 344/Nnia X Brown Norway/Binia Rat, Shinichi Asano

Theses, Dissertations and Capstones

Here we report the influence of aging on multiple markers of oxidativenitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36- month) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Compared to 6 month old rat hearts, indices of oxidative (superoxide anion (–O2 ·), 4-hyrdoxy-2- nonenal (4-HNE)) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r>0.669; r>0.710 and p<0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.

Lean And Obese Zucker Rats Exhibit Different Patterns Of P70s6kinase Regulation In The Tibialis Anterior Muscle In Response To High Force Muscle Contraction, Anjaiah Katta

Theses, Dissertations and Capstones

Increased muscle loading results in phosphorylation of the 70 kDa ribosomal S6 kinase (p70s6k) signaling pathway and this event strongly correlates with degree of muscle adaptation following resistance exercise. Here, we compared the basal and contraction- induced phosphorylation of p70s6k, Akt and mTOR in tibialis anterior muscles of lean and obese Zucker rats. Immunoblotting demonstrated differences in level of basal p70S6k phosphorylation (Thr 389) in the normal and diabetic TA. HFES had an increase in p70S6k (Thr389) phosphorylation at 0-, 1- and 3-hr in lean TA and only at 3-hr in obese TA. mTOR (Ser 2448) Phosphorylation was elevated in …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

MIIR Faculty Research

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …

Association Of Smooth Muscle Myosin And Its Carboxyl Isoforms With Actin Isoforms In Aorta Smooth Muscle, Jason Edward Black

Theses, Dissertations and Capstones

The contraction mechanism of smooth muscle is not fully understood. The primary interaction that leads to the formation of tension, the myosin-actin crossbridge, has been studied extensively. However, even this aspect of the contraction has proven not to be as simple as it might seem. There are several isoforms of smooth muscle myosin and actin, and the differences in the activities of these isoforms and their interactions during the contractile process are largely unknown. The studies to be discussed are directed at the determination of the interaction of these isoforms during the contraction of rat aortic smooth muscle. Chapter II …

Age-Related Dgc Structure And Function In The F344/N X Bn Rat Heart, Sunil K. Kakarla

Theses, Dissertations and Capstones

Recent data has suggested that disruption of the dystrophin-glycoprotein complex (DGC) may be involved in mediating the progression of cardiac hypertrophy and failure. Here we examined the regulation of DGC proteins in the hearts of adult (6 months), aged (30 months), and very aged (36 months) F344/N X BN rats . Compared to adult animals, the content of α- and β-dystroglycan were 6.93 ± 5.16% and 58.36 ± 3.64% higher, respectively (P < 0.05) in very aged animals. Immunoblotting and immunhistochemical analysis suggested that aging appeared to diminish alpha-sarcoglycan, beta-sarcoglycan and delta-sarcoglycan content by 13.89 ± 3.1%,15.8 ± 2.8% and 18.63 ± 3.04%, respectively (P < 0.05). These alterations in the DGC occurred coincident with age- associated alterations in cytoplasmic anti-rat IgG immunoreactivity, TUNEL positive nuclei, alpha-fodrin cleavage, indices of caspase-3 activation and diminished AKT phosphoryation (Ser 308). Taken together, these data suggest that aging alters cardiac DGC structure and function.

Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other …

Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough

MIIR Faculty Research

Background

Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading.

Methods

Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and …

Numerical Distribution Of Lymphoid Nodules In The Human Sigmoid Colon, Rectosigmoidal Junction, Rectum, And Anal Canal, Ivan L. Cameron, James E. Kent, Ron Philo, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

There is little information on the numerical distribution of lymphoid nodules (LN) in distal segments of the human large bowel. A novel approach was therefore developed to assess the number of LN in the sigmoid colon, the rectosigmoid segment, the rectum, and the anal canal in humans. The distal large bowel from five cadavers was selected for quantitative study. The number of LN was scored macroscopically from the proximal sigmoid colon to the distal anal canal. A numerical distribution, previously unreported, consisting of two circular bands of LN was observed in each of the five cadavers. One band was located …