Internal Medicine Commons^™

Translational Regulation Of Nuclear Gene Cox4 Expression By Mitochondrial Content Of Phosphatidylglycerol And Cardiolipin In Saccharomyces Cerevisiae, Xuefeng Su, William Dowhan

Faculty, Staff and Student Publications

Previous results indicated that translation of four mitochondrion-encoded genes and one nucleus-encoded gene (COX4) is repressed in mutants (pgs1Delta) of Saccharomyces cerevisiae lacking phosphatidylglycerol and cardiolipin. COX4 translation was studied here using a mitochondrially targeted green fluorescence protein (mtGFP) fused to the COX4 promoter and its 5' and 3' untranslated regions (UTRs). Lack of mtGFP expression independent of carbon source and strain background was established to be at the translational level. The translational defect was not due to deficiency of mitochondrial respiratory function but was rather caused directly by the lack of phosphatidylglycerol and cardiolipin in mitochondrial membranes. Reintroduction of …

Physiological Effects On Demography: A Long‐Term Experimental Study Of Testosterone’S Effects On Fitness, W. Reed, M. Clark, P. Parker, S. Raouf, N. Arguedas, D. Monk, E. Snajdr, V. Nolan, E. Ketterson

Biology Department Faculty Works

Understanding physiological and behavioral mechanisms underlying the diversity of observed life‐history strategies is challenging because of difficulties in obtaining long‐term measures of fitness and in relating fitness to these mechanisms. We evaluated effects of experimentally elevated testosterone on male fitness in a population of dark‐eyed juncos studied over nine breeding seasons using a demographic modeling approach. Elevated levels of testosterone decreased survival rates but increased success of producing extra‐pair offspring. Higher overall fitness for testosterone‐treated males was unexpected and led us to consider indirect effects of testosterone on offspring and females. Nest success was similar for testosterone‐treated and control males, …

Spectrum Of Neurological Involvement In Adult Patients With Bacterial Endocarditis, Faisal Wasim Ismail, Muhammad Tariq, Mahboob Alam, Raymond A Smego

Section of Internal Medicine

Objective: To describe the spectrum of neurological involvement, and document in-hospital mortality in adult patients with bacterial endocarditis.
Design: Descriptive, non-interventional.
Place and duration of study: Department of Gastroenterology, The Aga Khan University Hospital, Karachi from November 1999 to October 2002.
Patients and methods: Patients were enrolled from the emergency and outpatient departments, using purposive, non-probability sampling, provided they fulfilled pre-defined inclusion and exclusion criteria. Case records of patients admitted to hospital with a diagnosis of bacterial endocarditis were prospectively analyzed. Data was entered and analyzed on SPSS 11. Frequency, Mean, Mode and Percentage were calculated.
Results: Neurological complications were …

The Earliest Dipodomyine Heteromyid In North America And The Phylogenetic Relationships Of Geomorph Rodent, Steven J Norris

Faculty, Staff and Student Publications

The proteome of the spirochete bacterium Borrelia burgdorferi, the tick-borne agent of Lyme disease, has been characterized by two different approaches using mass spectrometry, providing a launching point for future studies on the dramatic changes in protein expression that occur during transmission of the bacterium between ticks and mammals.

Construction Of Improved Temperature-Sensitive And Mobilizable Vectors And Their Use For Constructing Mutations In The Adhesin-Encoding Acm Gene Of Poorly Transformable Clinical Enterococcus Faecium Strains, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator …

Chronic Exposure To Mdma (Ecstasy) Elicits Behavioral Sensitization In Rats But Fails To Induce Cross-Sensitization To Other Psychostimulants, Gunjan M Modi, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

BACKGROUND: The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA.

METHODS: The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 …

Dose-Response Characteristics Of Methylphenidate On Locomotor Behavior And On Sensory Evoked Potentials Recorded From The Vta, Nac, And Pfc In Freely Behaving Rats, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

BACKGROUND: Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC).

METHODS: The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto …

Spectrum And Outcome Of Infections In Systemic Lupus Erythematosus Patients, Bushra Jamil, Sobia Rafi, Hammad Hussain, Khizar Hameed

Department of Medicine

No abstract provided.

Stress Levels, Psychological Symptoms, And C-Reactive Protein Levels In Covid-19: A Cross-Sectional Study, Jian Zhang, Wei Li, Hideo Hoshi, Stephen L Mills, Stephen C Massey

Faculty, Staff and Student Publications

The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF alpha ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF alpha ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, …

Cart: An Hrs/Actinin-4/Berp/Myosin V Protein Complex Required For Efficient Receptor Recycling, Qing Yan, Wei Sun, Pekka Kujala, Yasmin Lotfi, Thomas A Vida, Andrew J Bean

Faculty, Staff and Student Publications

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The …

Improving Clinical Practice Using Clinical Decision Support Systems: A Systematic Review Of Trials To Identify Features Critical To Success, Kensaku Kawamoto, Caitlin A. Houlihan, E. Andrew Balas, David F. Lobach

School of Medical Diagnostics & Translational Sciences Publications

Objective To identify features of clinical decision support systems critical for improving clinical practice. Design Systematic review of randomised controlled trials.
Data sources Literature searches via Medline, CINAHL, and the Cochrane Controlled Trials Register up to 2003; and searches of reference lists of included studies and relevant reviews.
Study selection Studies had to evaluate the ability of decision support systems to improve clinical practice.
Data extraction Studies were assessed for statistically and clinically significant improvement in clinical practice and for the presence of 15 decision support system features whose importance had been repeatedly suggested in the literature.
Results Seventy studies …

Genetic Networks Controlling Retinal Injury, Felix R Vazquez-Chona, Amna N Khan, Chun K Chan, Anthony N Moore, Pramod K Dash, M Rosario Hernandez, Lu Lu, Elissa J Chesler, Kenneth F Manly, Robert W Williams, Eldon E Geisert

Faculty, Staff and Student Publications

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.

METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.

RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription …

Characteristics Of Patients With Guillain Barre Syndrome At A Tertiary Care Centre In Pakistan, 1995-2003, Mohammad Yawar Yakoob, Aisha Rahman, Bushra Jamil, Nadir Ali Syed

Department of Medicine

Objective: To study the clinical presentation, hospital course and outcome of patients admitted with Guillain Barre Syndrome (GBS) to a tertiary care hospital in Karachi, Pakistan.
Methods: The charts of patients conforming to International Classification of Diseases (ICD) code 9.0, for GBS, from September 1995 to January 2003 were reviewed. Clinical data was recorded on a standardized questionnaire, which included patients' age, sex, antecedent events, neurological signs and symptoms and ventilation requirement. The hospital course was analyzed, including nosocomial infections, therapy given and the functional status of patients, using the Rankin scale (0-6). Standard SPSS 11.5 software (Windows) …

Survival Of Patients Treated With Intra-Aortic Balloon Counterpulsation At A Tertiary Care Center In Pakistan - Patient Characteristics And Predictors Of In-Hospital Mortality., Fahim H. Jafary, Sohail A. Khan, Haresh Kumar, Numaan F. Malik, K. Kazmi, Sajid Dhakam, Azam Shafquat, Aamir Hameed, Javed Tai, Najaf Nadeem

Department of Medicine

BACKGROUND: Intra-aortic balloon counterpulsation (IABC) has an established role in the treatment of patients presenting with critical cardiac illnesses, including cardiogenic shock, refractory ischemia and for prophylaxis and treatment of complications of percutaneous coronary interventions (PCI). Patients requiring IABC represent a high-risk subset with an expected high mortality. There are virtually no data on usage patterns as well as outcomes of patients in the Indo-Pakistan subcontinent who require IABC. This is the first report on a sizeable experience with IABC from Pakistan.

METHODS: Hospital charts of 95 patients (mean age 58.8 (+/- 10.4) years; 78.9% male) undergoing IABC between 2000-2002 …

Methods And Apparatus For In Vivo Identification And Characterization Of Vulnerable Atherosclerotic Plaques, Pedro Moreno, Robert A. Lodder, William O'Connor, James E. Muller

Internal Medicine Faculty Patents

Methods and apparatus for analyzing the chemical composition of vulnerable plaques with an intravascular catheter having a near-infrared light source, a fiber-optic probe, a mechanism for directing the light from the light source into a blood vessel, and detectors for detecting light reflected or scattered by the tissue. The light source may be a tunable laser, and may transmit an incident beam having a wavelength ranging from 1400 to 4100 nm. A computer may be included to receive and process the spectral data in the analysis of the vulnerable plaques. A catheter system may be configured to provide near-IR spectrometric …

Wilson's Disease: A Review, A Hassan, F Masood

Section of Internal Medicine

No abstract provided.

Excess Stroke In Mexican Americans Compared With Non-Hispanic Whites: The Brain Attack Surveillance In Corpus Christi Project, Lewis B Morgenstern, Melinda A Smith, Lynda D Lisabeth, Jan M H Risser, Ken Uchino, Nelda Garcia, Paxton J Longwell, David A Mcfarling, Olubumi Akuwumi, Areej Al-Wabil, Fahmi Al-Senani, Devin L Brown, Lemuel A Moyé

Faculty, Staff and Student Publications

Mexican Americans are the largest subgroup of Hispanics, the largest minority population in the United States. Stroke is the leading cause of disability and third leading cause of death. The authors compared stroke incidence among Mexican Americans and non-Hispanic Whites in a population-based study. Stroke cases were ascertained in Nueces County, Texas, utilizing concomitant active and passive surveillance. Cases were validated on the basis of source documentation by board-certified neurologists masked to subjects' ethnicity. From January 2000 to December 2002, 2,350 cerebrovascular events occurred. Of the completed strokes, 53% were in Mexican Americans. The crude cumulative incidence was 168/10,000 in …

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Internal Medicine Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …

Banti's Syndrome: Case Report And Review Of Literature, S. N. Waqar, S. Jindhani, N. S. Baig, M. A. Waqar, Faisal Wasim Ismail, Muhammad Tariq

Section of Internal Medicine

No abstract provided.

Flexible Recording/High Energy Electrode Catheter With Anchor For Ablation Of Atrial Flutter By Radio Frequency Energy, Chien-Suu Kuo, John G. Gurley

Internal Medicine Faculty Patents

An electrode catheter is provided having a predetermined flexibility throughout the entire length or at least at the contact portion, such as the electrode region, to allow for the molding of the contact portion such that it conforms to the shape of the heart at a preselected desired target area, such as the isthmus between the inlet of inferior vena cava and posterior tricuspid annulus. The catheter also includes a guiding sheath that is preferably semirigid and may be pre-shaped with at least one bend or angulation to assist in molding to ensure that the electrode region overlies the desired …

Plasma Total Homocysteine And The Effect Of B-Group Vitmains. Current Knowledge And Future Directions In Assessment For Cardiovascular Diseases Among U.S. Cardiovascular Specialists, Salam F. Sunna

All-Inclusive List of Electronic Theses and Dissertations

Cardiovascular disease remains the major cause of morbidity and mortality in the United States claiming the lives of over 40% of the nearly 2.4 million Americans who die each year. Recent studies have shown that elevated homocysteine in the blood is related to a higher risk of coronary heart disease, peripheral vascular disease and stroke independent of other classical cardiovascular disease risk factors. The aim of this study is to determine the general awareness and acceptance of U.S. cardiovascular specialists of the homocysteine theory, the criteria used for ordering a homocysteine test, the frequency physicians refer patients to dietitians for …

Abscesses In The Liver: Amoebic Or Pyogenic?, Bushra Jamil, Saeed Hamid

Department of Medicine

No abstract provided.

Combination Anti-Leukimic Therapy By Utilizing Suramin And Biologic Response Modifiers, Michael A. Doukas

Internal Medicine Faculty Patents

A method of treating leukemia which includes administering an effective amount of composition comprising suramin and a biological response modifier, wherein the suramin and the biological response modifier show synergistic or additive anti-leukemic activity. A pharmaceutical composition is also disclosed.

Bacterial Isolates From Neutropenic Febrile Pediatric Patients And Their Sensitivity Patterns To Antibiotics, F N. Bhatti, I A. Burney, M I. Moid, T Siddiqui

Section of Internal Medicine

Patients on cytotoxic therapy often develop neutropenia and fever. Our interest was to identify the common pathogens isolated from such patients and to study the sensitivity patterns of these organisms to the antibiotics used in their treatment. Thus, guidelines can be established by hospitals to identify which antibiotics can be used in the treatment of these patients when the results of cultures and sensitivities are not available. We conducted a retrospective study of neutropenic pediatrics presenting to AKUH from July, 1990 to June, 1996. A total of 153 isolates in 35 different patients were studied. Samples for culture were taken …

The Association Of Hla-Drb Genes And The Shared Epitope With Rheumatoid Arthritis In Pakistan, K Hameed, S Bowman, E Kondeatis, R Vaughan, T Gibson

Section of Internal Medicine

The association of particular HLA-DR alleles and the shared epitope with rheumatoid arthritis (RA) is now well established. The strength of these links varies between races. Furthermore, the proposition that the presence of the shared epitope is indicative of severe disease has been more difficult to sustain in non-Europeans. This study examines the frequency of HLA-DR and HLA-DRB1 amongst Pakistanis for the first time. Using the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (PCR-SSOP) and primers (PCR-SSP), HLA-DR phenotype and genotype frequencies were ascertained in 86 RA hospital out-patients and 79 healthy controls matched for age, gender and ethnicity. …

Metabolically Inactive Insulin Analog Prevents Type I Diabetes In Prediabetic Nod Mice, Dennis G. Karounos, J. Scott Bryson, D. A. Cohen

Internal Medicine Faculty Publications

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected …

Ultrastructure Of The May-Hegglin Anomaly, T Siddiqui

Section of Internal Medicine

Ultrastructural features of the leucocytes in two patients suffering from the May-Hegglin anomaly were studied using electron microscopy. In both the cases, electron dense material parallel to the long axis of the inclusions were noted. Platelet ultrastructure was normal. A review of the literature indicates that the May-Hegglin anomaly is a heterogeneous condition both ultrastructurally and clinically.

An Epidemic Of Dengue Fever In Karachi--Associated Clinical Manifestations, J A. Qureshi, N J. Notta, N Salahuddin, V Zaman, J A. Khan

Section of Internal Medicine

Dengue is a mosquito borne disease with worldwide distribution. Depending on virulence factors and host immune status, infection can manifest as a severe but non fatal viral syndrome or a rapidly progressive and a frequently fatal haemorrhagic fever. During the course of an outbreak of viral fever in Karachi, Pakistan from June, 1994 to September, 1995, we studied 145 cases admitted at the Aga Khan University Hospital. 43% of the cases were between the age group of 20-30 years, majority of these being male (75%). Amongst the clinical signs and symptoms, the most frequent findings were fever, vomiting and abdominal …

Chemotherapy-Induced Non-Hodgkin's Lymphoma In A Patient With Hodgkin's Disease--A Case Report, I A. Burney, I A. Malik

Section of Internal Medicine

Modern chemotherapy and radiation treatment of Hodgkin’s disease has resulted in overall cure rates in excess of 60%1 . However, the greatly improved survival rates have also led to increasing incidence of long-term side-effects of these treatment modalities2 . The most serious consequence is the occurrence of second cancer3 . We report a case of non-Hodgkin’s lymphoma occurring in a patient who was previously treated for Hodgkin’s disease.

Pneumonia Caused By Nocardia Caviae In A Healthy Neonate, Perween Mufti, Bushra Jamil

Department of Medicine

Nocardia infections have been associated with patients of Aids, chronic granulomatous disease, recipient of organ transplant and malignancy Pulmonary nocardiosis in neo­nates is an unusual infection. A case of neonatal pulmonary nocardiosis mimicking miliaiy tuberculosis has been reported in the past. We report another case of pulmonary nocardiosis in a neonate presenting as consolidation with pleural effusion and cavitation.