Microbiology Commons^™

Characterization Of Pathogenic Mutations In 21-Hydroxylase Gene Of Pakistani Patients With Congenital Adrenal Hyperplasia And Their Family Members--A Preliminary Report, A H. Khan, M I. Nasir, T Moatter

Department of Pathology and Laboratory Medicine

Objective:
To characterize specific mutations within the 21-hydroxylase gene (CYP21-B) using ARMS-PCR assay in patients with congenital adrenal hyperplasia (CAH) and to compare it with that reported in other populations.
Subjects and Methods:
Five families, having an index case with CAH diagnosed on the basis of clinical and biochemical findings volunteered to give blood samples for analysis. A strategy, based on ARMS-PCR (Amplified Refractory Mutation System) was employed for the detection of mutations in 21-hydroxylase gene. The products of ARMS-PCR were resolved on agarose gels and the PCR products were visualized over ultra violet illumination.
Results:
Twenty-six specimens were analyzed …

Il-12 Plasmid Delivery By In Vivo Electroporation For The Successful Treatment Of Established Subcutaneous B16.F10 Melanoma, M. Lee Lucus, Loree Heller, Domenico Coppola, Richard Heller

Bioelectrics Publications

Interleukin-12 (IL-12) has been used in numerous immunotherapy protocols against melanoma. However, delivery of IL-12 in the form of recombinant protein can result in severe toxicity, and gene therapy has had limited success against B16.F10 murine melanoma. The purpose of this study was to examine the effectiveness of in vivo electroporation for the delivery of plasmid DNA encoding IL-12 as an antitumor agent against B16.F10 melanoma. We treated mice bearing established B16.F10 melanoma tumors with intratumoral (i.t.) or intramuscular (i.m.) injections of a plasmid encoding IL-12, followed by in vivo electroporation. For i.t. treatments, we used an applicator containing six …

Small Glutamine-Rich Protein/Viral Protein U–Binding Protein Is A Novel Cochaperone That Affects Heat Shock Protein 70 Activity, Peter C. Angeletti, Doriann Walker, Antonito T. Panganiban

Nebraska Center for Virology: Faculty Publications

Molecular chaperone complexes containing heat shock protein (Hsp) 70 and Hsp90 are regulated by cochaperones, including a subclass of regulators, such as Hsp70 interacting protein (Hip), C-terminus of Hsp70 interacting protein (CHIP), and Hsp70-Hsp90 organizing factor (Hop), that contain tetratricopeptide repeats (TPRs), where Hsp70 refers to Hsp70 and its nearly identical constitutive counterpart, Hsc70, together. These proteins interact with the Hsp70 to regulate adenosine triphosphatase (ATPase) and folding activities or to generate the chaperone complex. Here we provide evidence that small glutamine-rich protein/viral protein U–binding protein (SGT/UBP) is a cochaperone that negatively regulates Hsp70. By “Far-Western” and pull-down assays, SGT/UBP …

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Problem Based Learning In The 3rd World Context, V Zaman

Department of Pathology and Laboratory Medicine

No abstract provided.

Interactions Among Murine Cytomegalovirus Us22 Family Gene Products That Influence Viral Pathogenesis, Zaruhi Karabekian

Theses and Dissertations in Biomedical Sciences

Cytomegalovirus (CMV) is a complex, ubiquitous herpesvirus that is characterized by acute, chronic, and latent infections. Monocytes-macrophages are the key target cell type involved in pathogenesis, which is most effectively studied using the murine model of CMV infection. Previously three murine CMV (MCMV) genes (M139, M140, and M141) were identified to regulate viral expression in cultured macrophages and in mice. These genes are members of the US22 gene family with respect to HCMV homology. There is no function assigned to the proteins encoded by these genes. However, deletion of M139, M140, and M141 significantly curtails growth of MCMV in macrophages …

Histological Pattern Of Ovarian Neoplasma., Zubair Ahmad, Naila Kayani, Sheema H. Hasan, Suhail Muzaffar, Muhammad Shafiq Gill

Department of Pathology and Laboratory Medicine

Abstract

Objective: To see the morphological pattern of benign and malignant ovarian neoplasms. Method: Retrospective study of all consecutive cases of ovarian neoplasms diagnosed at Aga Khan University Hospital between 1st January 1993 and 30th September 1998. Setting: The Section of Histopathology, AKUH, Karachi. Observation: Of 855 ovarian tumours 506 (59.18%) were benign and 349(40.81%) malignant. Surface epithelial - stromal tumours comprised 63.50% of all tumours. Benign cystic teratoma was the commonest benign tumour (35.17% of all benign tumours) and serous cystadenocarcinoma was the commonest malignant tumour (33.33% of all malignant tumours). Mucinous cystadenocarcinomas are more common in our population …

Granular Cell Tumor Of The Breast: An Uncommon Lesion That Mimics Carcinoma, S Muzafar, M S. Siddiqui, Naila Kayani, I K. Lodhi, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Connexin-32 Contributes To Radiation Resistance In Thyroid Follicles, Da-Thao Dinh Tran

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to examine the role of gap junctions in the radiation resistance of thyroid follicles. The question of whether gap junctional intercellular communication plays an important role in the “contact effect”, wherein cells in direct apposition are more resistant to the damaging effects of radiation, has been debated for years. We used the Fischer rat thyroid cell line (FRTL-5) to carry out our experiments. This thesis is divided into two parts: 1) characterization of gap junctional properties in FRTL-5 cells and, 2) exposure of these cells to radiation.

We found that, unlike primary thyroid cells, …

Genetic Diversity Of Beta-Thalassemia Mutations In Pakistani Population, B Khateeb, T Moatter, A M. Shaghil, S Haroon, G N. Kakepoto

Department of Pathology and Laboratory Medicine

Background:
beta-thalassemia is one of the most common inherited single gene disorder in Pakistan. It is characterized by reduced or absent beta-globin gene expression resulting in abnormal maturation and survival of red blood cells. Due to high prevalence of this disease in the local population, it has become important for the health care providers to encourage people to utilize laboratory facilities for carrier and prenatal genetic testing.
Objective:
To study the frequency of beta-thalassemia mutations in Pakistani population.
Setting:
A tertiary care teaching hospital.
Methods:
Blood samples of 72 couples and chorionic villus (CV) biopsy specimen collected at the Aga …

Association Of Epstein Barr Virus (Ebv) With Nasopharyngeal Carcinoma (Npc), S H. Shah, I N. Soomro, S Haroon, T Moatter

Department of Pathology and Laboratory Medicine

Aim:
To observe the frequency of nasopharyngeal carcinoma (NPC) and its association with Epstein Barr Virus (EBV) infection.
Setting:
This study included consecutive cases of nasopharyngeal carcinoma, which were diagnosed in the Department of Pathology at the Aga Khan University Hospital, Karachi in the period of two years (1996-97).
Methods:
These tumors were initially evaluated on H&E stained sections. The tumors showing evidence of keratinization were excluded from the study. The Epstein Barr Virus was detected with the help of Polymerase chain reaction in formalin fixed, paraffin embedded tissue sections.
Results:
During the study period, seventeen cases of nasopharyngeal carcinoma …

Morphological Pattern Of Testicular Tumors, M S. Gill, S H. Shah, I N. Soomro, Naila Kayani, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

Objective:
To find out the mode of presentation, age distribution and the prevalence of various histological subtypes of testicular tumors.
Method:
All consecutive cases of testicular tumors diagnosed in the department of pathology, the Aga Khan University Hospital, Karachi, during the period of eight years (1991-98) were included in this study. Relevant clinical details such as age, clinical presentation and side of involvement of the testis were also recorded, where available.
Results:
During the span of eight years (1991-98), 170 cases of testicular tumors were diagnosed at the Aga Khan University Hospital, Karachi. Most of the tumors were diagnosed in …

Identification Of The Transactivation Domain Of The Transcription Factor Sox-2 And An Associated Co-Activator, Tamara K. Nowling, Lance R. Johnson, Matthew S. Wiebe, Angie Rizzino

Nebraska Center for Virology: Faculty Publications

The importance of interactions between Sox and POU transcription factors in the regulation of gene expression is becoming increasingly apparent. Recently, many examples of the involvement of Sox-POU partnerships in transcription have been discovered, including a partnership between Sox-2 and Oct-3. Little is known about the mechanisms by which these factors modulate transcription. To better understand the molecular interactions involved, we mapped the location of the transactivation do-main of Sox-2. This was done in the context of its interaction with Oct-3, as well as its ability to transactivate as a fusion protein linked to the DNA-binding domain of Gal4. Both …

Risk Of Imported Filariasis In Pakistan, M A. Beg

Department of Pathology and Laboratory Medicine

No abstract provided.

A Preclinical Model Of Ionizing Radiation And Tnf-Alpha Gene Therapy For Cancer, Jun Li

Loma Linda University Electronic Theses, Dissertations & Projects

Long term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. This study sought to determine if pretreatment with plasmid DNA expressing Tumor Necrosis Factor-α (TNF-α) could enhance the effect of ionizing radiation in an aggressive, rapidly growing glioma tumor (C6) model. Plasmid DNA is an attractive vector system for delivery of foreign genes into eukaryotic cells due to its advantages including low immunogenicity in vivo, lesser toxicity and relatively low cost. We have constructed a plasmid-based mammalian expression vector (pGL1-TNF) to secrete human TNF-α from cancer cells. Plasmid DNA was successfully transfected into C6 cells …

Arthritis And Rosai-Dorfman Disease Of The Skin: A Diagnostic Dilemma, Irshad Nabi Soomro, Kamran Hameed

Department of Pathology and Laboratory Medicine

No abstract provided.

A Study On The Effects Of The N-Terminal Amino Acid Sequence On The Activation Of Human T-Cell Leukemia Virus Type 1 Protease, Hidayah Muhammad Kendall

Chemistry & Biochemistry Theses & Dissertations

Human T-cell leukemia virus type 1 (HTL V-1) is dependent upon the enzymatic activity of its protease for maturation. Maturation of the protease is facilitated by cleavage of specific amino acid residues, followed by dimerization. The effects of the amino acid sequence located N-terminally to the cleavage site on the ability of the protease to become active were the focus of the current study. These amino acid sequences were contributed by the plasmid vector into which the protease gene was inserted.

Surface probability analyses (SPAs) of the vectors, as well as for native sequences which produce the mature protease and …

P53 And Pcna Expression In Benign, Atypical And Malignant Meningiomas, R Ahmed, I N. Soomro, S A. Aziz, S H. Hasan

Department of Pathology and Laboratory Medicine

Objective: Alterations: p53 genes are turning out to be the most common genetic alterations in human cancers. Due to long half-life of mutated p53, its detection is possible by immunohistochemistry. Proliferating cell nuclear antigen (PCNA) is expressed by dividing cells, hence has been shown to correlate with prognosis. We have used monoclonal antibodies protein DO-7 (p53) and PC10 (PCNA) to see whether their expression correlates with histological grading in meningethelial tumour.
Material and Methods: a Twenty nine meningiomas (20 benign, 7 atypical and 2 malignant) were selected from the records of our laboratory. p53 and PCNA expression was sought by …

Spinal Cord Compression Caused By Metastatic Epithelial Myoepithelial Carcinoma Of The Parotid Gland, I N. Soomro, A S. Hussainy, K Chishti, M H. Pui, S A. Khan, R Ahmed, S H. Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Morphological Pattern And Frequency Of Thyroid Tumors, S H. Shah, S Muzaffar, I N. Soomro, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

Objective:
The present study was done to evaluate the frequency of thyroid cancer and to find out the prevalence of histological types of thyroid tumor with respect to age and sex group.
Setting:
This study included consecutive cases of malignant tumors of thyroid gland, which were diagnosed in the Department of Pathology at the Aga Khan University Hospital, Karachi during the period of three years (1995-1997).
Methods:
These cases were evaluated on H & E stained sections from paraffin embedded 10% buffered formalin fixed tissue blocks. Special stains and immunohistochemical analysis were performed whenever required.Results: A total of 8541 malignant …

Clinico-Morphological Pattern Of Intracranial Tumors In Children, Sajid H. Shah, Irshad N. Soomro, Akbar S. Hussainy, S H. Hassan

Department of Pathology and Laboratory Medicine

Objective:
The objective of present study was to observe the histopathological pattern of intracranial tumors in children (< 15 yrs) and to correlate the site of lesion along with the histological diagnosis.
Setting:
The study included consecutive cases of intracranial tumors diagnosed in children (< 15 yrs.) in the section of histopathology at the Aga Khan University Hospital, Karachi during the period of three years.
Methods:
The initial histological evaluation of these lesions was performed on H and E stained section of paraffin embedded tissue. Special stains and immunohistochemical analysis was done whenever indicated.
Results:
During the study period, fifty-four cases of intracranial tumors were diagnosed in children. The age ranged from 1-1/2 years to 4 years with male to female ratio of 1.1:1. Astrocytoma comprised 39% of all intracranial tumors of childhood. Medulloblastoma …

Detection Of Mycobacterium Tuberculosis In Paraffin Embedded Intestinal Tissue Specimens By Polymerase Chain Reaction: Characterization Of Is6110 Element Negative Strains, Tariq Moatter, Shaper Mirza, Mohammad Shahid Siddiqui, Irshad Nabi Soomro

Department of Pathology and Laboratory Medicine

Tuberculosis is still one of the most widespread infection known to mankind. Although lung is the predominant site of disease, a sizeable population in Pakistan gets intestinal disease. Clinical presentation, radiologic and endoscopic examination provide clues to the diagnosis. However, a definitive diagnosis requires biopsy material with granulomas and/or caseation complemented by acid fast staining and culture. There are many occasions when biopsy material is scanty and even in some intestinal resection cases histologic evaluation fails to confirm or rule out tuberculosis. Therefore, an investigation was conducted to assess the efficacy of PCR in the detection of mycobacterial DNA in …

Predicting Prognosis In Lung Cancer: Use Of Proliferation Marker, Ki67 Monoclonal Antibody, I N. Soomro, J Holmes, W F. Whimster

Department of Pathology and Laboratory Medicine

An investigation was carried out to assess the prognostic significance of proliferation marker Ki67 in a group of lung cancer patients treated by surgery (limited disease). Tissue was not available for Ki67 immunostaining in inoperable group. The diagnosis is established by bronchial biopsy which does not carry enough tissue for frozen section and counting. This study is supplemented by estimating the prognostic significance of histological sub-types in the operable group and in a group of inoperable patients with extensive disease. These are usually treated by radiotherapy and/or chemotherapy. In all, 267 patients were studied including 105 treated by surgery. These …

Mucinous Cystadenoma Of The Urinary Bladder, I N. Soomro, A T. Rashid

Department of Pathology and Laboratory Medicine

No abstract provided.

Parotid Gland Lipoma: A Rare Entity, S Muzaffar, N Kayani, S H. Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

Resistance Of Blastocystis Hominis Cysts To Chlorine, M Zaki, V Zaman, N A. Sheikh

Department of Pathology and Laboratory Medicine

No abstract provided.

Subcutaneous Phaeohyphomycosis: Infection With Pigmented Fungi, I N. Soomro, A Kennedy

Department of Pathology and Laboratory Medicine

No abstract provided.

Selective Increases In Antibody Isotypes And Immunoglobulin G Subclass Responses To Secreted Antigens In Tuberculosis Patients And Healthy Household Contacts Of The Patients, R Hussain, G Dawood, N Abrar, Z Toossi, A Minai, M Dojki, J J. Ellner

Department of Pathology and Laboratory Medicine

Mycobacterium tuberculosis-specific antibodies (immunoglobulin M [IgM], IgE, IgG, and IgG subclasses) were determined in 164 tuberculosis patients (pulmonary involvement, n = 135; lymph node involvement, n = 29), 59 healthy household contacts (HC), and 51 healthy endemic donors (EC) by a quantitative enzyme-linked immunosorbent assay for reactivity with culture filtrate. Among the isotypes, significant differences between tuberculosis patient groups with either pulmonary or lymph node involvement and healthy control groups (HC and EC) were detected only for IgG (P < 0.001) and IgG1 (P < 0.001) antibodies. Pulmonary patients also showed a significant difference with IgM (P < 0.01) and IgE (P < 0.05) antibodies. HC showed elevation of only IgM antibodies compared with EC, indicating that IgM antibodies may be an indicator of recent infection with M. tuberculosis. These results suggest that the switching of IgM antibody response to IgG1 is a critical event in disease progression. Polyclonal IgG1, IgG3, and IgE antibodies also showed significant elevation (P < 0.05) in patients compared with EC. A strong correlation (rho = 0.254; P < 0.003) was observed between M. tuberculosis-specific IgG1 and polyclonal IgG1 in patients, suggesting that activations of antigen-specific and polyclonal antibodies are related events. No correlation was found between IgG1 antibodies and purified protein derivative skin test results. Since IgG1 antibody responses to culture filtrate are present only after disease establishment, IgG1 responses could provide a useful diagnostic marker of disease.

A 55 Year Old Diabetic Presenting With A Rash And Polyneuropathy, S Hyder, H Rasool, H Naqvi, Naila Kayani

Department of Pathology and Laboratory Medicine

No abstract provided.

A Model Of Cytomegalovirus Association With The Development Of Heart Graft Atherosclerosis, Evan Skowronski

Loma Linda University Electronic Theses, Dissertations & Projects

The development of graft atherosclerosis in heart transplant recipients has been associated with the development of post-transplant cytomegalovirus infection. The mechanism of this involvement, however, remains unclear. I undertook a study to determine the role of cytomegalovirus in the development of graft atherosclerosis. First, a rapid method of detecting cytomegalovirus based on capillary polymerase chain reaction and gel electrophoresis was employed to determine the presence of cytomegalovirus in a wide variety of clinical samples. Detection of cytomegalovirus is a lengthy procedure under normal conditions, and timely detection of cytomegalovirus in transplant recipients may allow intervention early enough to block the …