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Biomedical subjects

K Shah

Publications and source records attributed to K Shah.

At least 73 records · Page 4Linked to original sources
PubMed1998

Aerobic and anaerobic bacteriology of otorrhea associated with tympanostomy tubes in children.

The microbiology of in 55 ear aspirates obtained from 34 children with chronic otorrhea was studied. Aspiration of the middle ear exudate was done immediately following removal of tympanostomy tube (TT). The middle ear aspirates and swab specimens of the external auditory canals were cultured for aerobic and anaerobic bacteria. Sixty-five isolates were recovered only from the middle ears, 73 only from the external ear canals, and 73 were present at both sites. Analysis of the 138 middle ear isolates demonstrated the recovery of aerobic bacteria only in 28 patients (50%), anaerobes only in seven (13%), and both aerobes and anaerobes in 20 (36%). There were 77 aerobic and 61 anaerobic isolates. Commonly recovered aerobes were Pseudomonas aeruginosa (17 isolates), Staphylococcus aureus (11), Proteus sp. (7), Moraxella catarrhalis (6), Klebsiella pneumoniae (5) and non-typable Haemophilus influenzae (5). Commonly isolated anaerobes were Peptostreptococcus sp. (25 isolates), Prevotella sp. (10), Bacteroides sp. (8) and Fusobacterium sp. (6). Pseudomonas aeruginosa and S. aureus were more often isolated in children older then 6 years. These findings demonstrate the polymicrobial bacteriology of TT-related otorrhea in children. Specimens collected from the external auditory canals can be misleading. Reliable information can be obtained from the ear exudes when collected through the TT or through the open perforation after their removal.

Bacteria, Aerobic↗
PubMed1998

Detection of genital human papillomavirus and associated cytological abnormalities among college women.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is strongly implicated in the etiology of cervical neoplasia; however, the frequency, rate, and predictors of neoplastic progression are unknown. GOAL: To measure the type-specific prevalence of cervical HPV and the rate of development of cytological abnormalities among a cohort of college women and to elucidate factors associated with acquisition of HPV DNA and progression to cytological abnormalities. STUDY DESIGN: Women 18 to 40 years of age seeking routine gynecologic care at a university health center were enrolled in a cross-sectional study with prospective, longitudinal follow-up of a subset of women. Demographic and behavioral data were collected using a written questionnaire. HPV DNA was detected in cervical scrapes by polymerase chain reaction using L1 consensus primers and a generic and 25 type-specific probes, and cervical cytological abnormalities were identified by Papanicolaou's (Pap) smear. RESULTS: HPV DNA was detected in 35% of the 414 women in the cross-sectional study; 66% of infections were with intermediate or high cancer risk HPV types. Multiple lifetime sex partners was an independent predictor of prevalent infection. Longitudinal analysis of 205 women showed that detection was transient (HPV DNA absent at follow-up) in 38% of the 84 women who were HPV-positive at enrollment. Persistent detection of the same HPV type at > or = 2 visits occurred in 14% of women and was significantly more common when intermediate or high cancer risk types were present. After 16 months of observation, 9% of HPV-infected women developed low-grade squamous intraepithelial lesions (SIL) and 5% developed high-grade SIL; the risk of incident SIL was 7.8-fold higher among women who had persistent HPV detection with the same type. CONCLUSIONS: It was concluded that cervical HPV infection is highly prevalent among college women. Although most infections are caused by intermediate of high cancer risk types, few women (5%) developed high-grade SIL during 16 months of observation.

Adolescent↗
PubMed1998

Primary carcinoma of the fallopian tube: comparative genomic hybridization reveals high genetic instability and a specific, recurring pattern of chromosomal aberrations.

Primary fallopian tube carcinoma (PFTC) is a rare and highly aggressive tumor. Twelve cases of PFTC (stages IA to IV) were analyzed by comparative genomic hybridization. The most consistent DNA gain was mapped to chromosome arm 3q in 11 of 12 cases. In six cases, the gain of 3q was present as a high level copy number increase (amplification) with a consensus region mapped to 3q26.2-qter. In the 12 cases, other frequent gains were located on chromosome arms 1q (in 11 cases), 2q (in 10), 7q (in 9), 8q (in 9), 5p (in 8), 6p (in 7), 12p (in 7), and 14q (in 6). Frequent copy number losses occurred on chromosome arms 16q (in 8 cases), 22q (in7), 6q (in 6). 8p (in 6), 18q (in 6), Xq (in 6), 1p (in 5), and 17p (in 5). All chromosomes were involved in chromosomal aberrations and the average number of copy alterations per case was 19.7. None of the 12 carcinomas revealed the presence of human papillomavirus (HPV) genomes. All of the cases exhibited crude aneuploidy. Strong p53 immunoreactivity could be observed in 10 of 12 cases while p21/WAF1 expression was low or undetectable. These results indicate that PFTC is a genomically highly unstable cancer, an observation that is in agreement with the poor prognosis associated with this tumor. A high frequency of 3q-gains has also been observed in HPV-related carcinomas of the uterine cervix. However, none of the PFTC was HPV related, suggesting that the 3q-gain is independent from HPV DNA.

Aged↗
PubMed1998

[Detection of human papillomavirus DNA by PCR in high-risk women. Validation of a protocol].

OBJECTIVE: To validate a protocol for HPV DNA detection using PCR (polymerase chain reaction). METHOD: HPV was investigated in cervical exfoliative specimens from 93 women at high risk for HPV infection Blind comparisons of HPV DNA detection using two PCR protocols were carried out in our laboratory and a widely accepted reference laboratory. RESULTS: HPV DNA prevalence varied according to the different protocols. A good agreement with the reference protocol was reached when a reduction of the cellular amount for DNA extraction was carried out. The prevalence of HPV DNA in this population was 50.5%. All cases with dysplasia were HPV DNA positive. The HPV type distribution was as follows: 29.8% HPV 16, 17% HPV 33, 12.7% HPV 11/6, 12.7%, HPV 18, 23.4% HPV 31, 3.6% HPV 39 y 4.3% HPV 51. An underestimation of the prevalence of HPV 51 was detected by our procedure in relation to the reference laboratory. CONCLUSIONS: HPV DNA detection by PCR may increase with simple protocol modifications. Regular validation studies are important to reach good sensitivity levels.

Adult↗
PubMed1997

Loss of FHIT expression in cervical carcinoma cell lines and primary tumors.

Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.

Acid Anhydride Hydrolases↗
PubMed1997

Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo.

The voltage activated K+ channel (Kv1.3) has recently been identified as the molecule that sets the resting membrane potential of peripheral human T lymphoid cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell activation, suggesting that Kv1.3 may be a target for immunosuppression. However, despite the in vitro evidence, there has been no in vivo demonstration that blockade of Kv1.3 will attenuate an immune response. The difficulty is due to species differences, as the channel does not set the membrane potential in rodent peripheral T cells. In this study, we show that the channel is present on peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin, we demonstrate that Kv1.3 also regulates the resting membrane potential, and that blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge. In addition, prolonged Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic development of T cell subsets. These results provide in vivo evidence that Kv1.3 is a novel target for immunomodulation.

Animals↗
PubMed1997

Engineering unnatural nucleotide specificity for Rous sarcoma virus tyrosine kinase to uniquely label its direct substrates.

Protein phosphorylation plays a central role in controlling many diverse signal transduction pathways in all cells. Novel protein kinases are identified at a rapid rate using homology cloning methods and genetic screens or selections; however identification of the direct substrates of kinases has proven elusive to genetic methods because of the tremendous redundancy and overlapping of substrate specificities among protein kinases. We describe the development of a protein engineering-based method to identify the direct substrates of the prototypical protein tyrosine kinase v-Src, which controls fibroblast transformation by the Rous sarcoma virus. To differentiate the substrates of v-Src from all other kinase substrates, we mutated the ATP binding site of v-Src such that the engineered v-Src uniquely accepted an ATP analog. We show that the engineered v-Src kinase displayed catalytic efficiency with the ATP analog, N(6)-(cyclopentyl) ATP, which is similar to the wild-type kinase catalytic efficiency with ATP itself. However, the N(6)-(cyclopentyl) ATP analog was not accepted by the wild-type kinase. Furthermore, the engineered v-Src exhibited the same protein target specificity as wild-type v-Src despite the proximity of the reengineered nucleotide binding site to the phosphoacceptor binding site. The successful engineering of v-Src's active site to accept a unique nucleotide analog provides a unique handle by which the direct substrates of one kinase (v-Src) can be traced in the presence of any number of cellular kinases.

Amino Acid Sequence↗
PubMed1997

A recurrent pattern of chromosomal aberrations and immunophenotypic appearance defines anal squamous cell carcinomas.

Squamous cell carcinomas of the anus are rare neoplasias that account for about 3% of large bowel tumours. Infections with human papillomaviruses are frequently detected in these cancers, suggesting that pathogenic pathways in anal carcinomas and in carcinomas of the uterine cervix are similar. Little is known regarding recurrent chromosomal aberrations in this subgroup of squamous cell carcinomas. We have applied comparative genomic hybridization to identify chromosomal gains and losses in 23 cases of anal carcinomas. A non-random copy number increase of chromosomes 17 and 19, and chromosome arm 3q was observed. Consistent losses were mapped to chromosome arms 4p, 11q, 13q and 18q. A majority of the tumours were aneuploid, and most of them showed increased proliferative activity as determined by staining for Ki-67 antigen. p53 expression was low or undetectable, and expression of p21/WAF-1 was increased in most tumours. Sixteen cancers were satisfactorily tested for the presence of HPV by consensus L1-primer polymerase chain reaction; nine were HPV positive, of which eight were positive for HPV 16.

Adult↗
PubMed1997

Arterial embolization is a rapid and effective technique for controlling pelvic fracture hemorrhage.

OBJECTIVE: To review the success rate of embolization in stopping hemorrhage for unstable patients with severe pelvic fractures, to calculate the time to achieve embolization, and to determine the yield from angiography. DESIGN: Retrospective review of patients admitted to a Level I trauma center with pelvic fractures during a 5-year period. MATERIALS AND METHODS: Charts were reviewed for Injury Severity Score, age, blood pressure, prothrombin time/partial thromboplastin time, pelvic fracture type, mortality, time to reach the angiography suite, time to achieve embolization, and mechanism of injury. MEASUREMENTS AND MAIN RESULTS: Of 806 patients admitted with pelvic fractures, 35 underwent pelvic angiography, and 15 (1.9%) required embolization. Embolization was successful for all patients. No deaths resulted from ongoing hemorrhage. Angiography yield in initially unstable patients was 64%. The mean age and initial hemodynamic instability were significantly greater in nonsurvivors. The time from arrival in the trauma bay to arrival in the angiography suite ranged from 50 to 1,140 minutes, and the time spent in the angiography suite performing embolization ranged from 50 to 140 minutes, with an average time of 90 minutes. Patients who were embolized within 3 hours of arrival had a significantly greater survival rate. CONCLUSION: Only a small percentage of patients with pelvic fractures require embolization, but when it is used, embolization can be 100% effective. Age, time to achieve embolization, and initial hemodynamic instability appear to be important factors in survival.

Adolescent↗
PubMed1997

Bioethical aspects of HIV infection in children.

The care of HIV-infected children is fraught with many bioethical conflicts and dilemmas that require careful attention if care is to be provided appropriately. Understanding of the interplay of such general principles as autonomy, nonmaleficence, confidentiality, and veracity helps to clarify the nature of specific conflicts. This article addresses both general principles and their specific applications to pediatric patients with HIV infection. It addresses these matters from the points of view both of patients and parents. It shows why conflict is practically inevitable, and it points the way toward prevention and resolution of conflict. Practical guidelines are provided in relation to the critical problem of disclosure of diagnosis to the patient.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q.

We have analyzed 30 cases of advanced-stage cervical squamous cell carcinoma (stages IIb-IV) by comparative genomic hybridization (CGH). The most consistent chromosomal gain in the aneuploid tumors was mapped to chromosome arm 3q in 77% of the cases. Acquisition of genetic material also occurred frequently on Iq (47%), 5p (30%), 6p (27%), and 20 (23%). Recurrent losses were mapped on 2q (33%), 3p (50%), 4 (33%), 8p (23%), and 13q (27%). High-level copy number increases were mapped to chromosome 8, chromosome arms 3q, 5p, 8q, 12p, 14q, 17q, 19q, 20p, and 20q, and chromosomal bands 3q26-27, 9p23-24, 11q22-23, and 12p13. In the majority of the cases, the presence of high-risk human papilloma virus genomes was detected. High proliferative activity was accompanied by crude aneuploidy. Increased p21/WAF-I activity, but low or undetectable expression of TP53 were representative for the immunophenotype. This study confirms the importance of a gain of chromosome arm 3q in cervical carcinogenesis and identifies additional, recurrent chromosomal aberrations that are required for progression from stage I tumors to advanced-stage carcinomas.

Adult↗
PubMed1997

Social differences in sexual behaviour and cervical cancer.

In this chapter we first describe the variation of cervical cancer in relation to social class. Thereafter we examine the causes for the occurrence of socioeconomic differences in invasive cervical cancer, using data from two case-control studies carried out in Colombia and Spain. Cervical cancer is the most common cancer in developing countries and the sixth most common in developed countries. In all areas, it is more frequent among women of low socioeconomic status, it is associated with multiple sexual partners and early age at first sexual intercourse, and both incidence and mortality are reduced by screening. According to population-based surveys in industrialized countries, men of low socioeconomic status report fewer sexual partners than men of high socioeconomic status but there is no clear indication that the same is true of women of low socioeconomic status. In the case-control studies in Spain and Colombia, the human papillomavirus and all other sexually transmitted diseases were more prevalent among women in low socioeconomic strata. Number of sexual partners and particularly contacts with prostitutes were higher among husbands of women of low socioeconomic status. Other potential risk factors for the disease, such as smoking and oral contraceptive use, and also cervical cancer screening (Pap smears), were more common in women of high social strata. Women with no schooling had a threefold higher risk in Spain and a fivefold higher risk in Colombia of having cervical cancer compared with women who had achieved a higher educational level. After adjustment for sexual behaviour, HPV DNA status, history of Pap smears and husband's contact with prostitutes, this association was considerably reduced. These results are indicative that socioeconomic differences in the incidence of cervical cancer can be partly explained by differences in the prevalence of HPV DNA. Men's sexual behaviour and particularly contacts with prostitutes might be a major contributor to the higher prevalence of HPV DNA among the poor.

Adolescent↗
PubMed1996

Cloning of a cysteine protease required for the molting of Onchocerca volvulus third stage larvae.

We have investigated the involvement of a cysteine protease in the development of Onchocerca volvulus fourth stage larvae (L4) by testing the effect of cysteine protease inhibitors on the survival of third stage larvae (L3), and the molting of L3 to L4 in vitro. When larvae were cultured in the presence of specific inhibitors, the peptidyl monofluoromethylketones, viability of either L3 or L4 was not affected. However, the inhibitors reduced the number of L3 that molted to L4 in vitro in a time- and dose-dependent manner. Molting was completely inhibited in the presence of 50-250 microM inhibitor. Ultrastructural examination of L3 that did not molt in the presence of inhibitors indicated that new L4 cuticle was synthesized, but there was no separation between the L3 and the L4 cuticles. The endogenous cysteine protease was detected in molting larvae after binding to labeled inhibitors, and by antibodies directed against a recombinant O. volvulus L3 cysteine protease that was cloned and expressed. The enzyme was detected in cuticle regions where the separation between the cuticles occurs in molting larvae. These studies suggest that molting and successful development of L4 depends on the expression and release of a cysteine protease.

Amino Acid Sequence↗
PubMed1996

Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix.

We have chosen tumors of the uterine cervix as a model system to identify chromosomal aberrations that occur during carcinogenesis. A phenotype/genotype correlation was established in defined regions of archived, formalin-fixed, and hematoxylin/eosin-stained tissue sections that were dissected from normal cervical epithelium (n = 3), from mild (n = 4), moderate (n = 6), and severe dysplasias/carcinomas in situ (CIS) (n = 13), and from invasive carcinomas (n = 10) and investigated by comparative genomic hybridization. The same tissues were analyzed for DNA ploidy, proliferative activity, and the presence of human papillomavirus (HPV) sequences. The results show that an increase in proliferative activity and tetraploidization had occurred already in mildly dysplastic lesions. No recurrent chromosomal aberrations were observed in DNA extracted from normal epithelium or from mild and moderate dysplasias, indicating that the tetraploidization precedes the loss or gain of specific chromosomes. A gain of chromosome 3q became visible in one of the severe dysplasias/CIS. Notably, chromosome 3q was overrepresented in 90% of the carcinomas and was also found to have undergone a high-level copy-number increase (amplification). We therefore conclude that the gain of chromosome 3q that occurs in HPV16-infected, aneuploid cells represents a pivotal genetic aberration at the transition from severe dysplasia/CIS to invasive cervical carcinoma.

Aneuploidy↗
PubMed1996

Identification and mapping of a putative bombesin receptor gene on human chromosome 17q21.3+.

A mouse bombesin receptor cDNA was used as a probe to screen a human P1 genomic library. Clone HBR1 was isolated and used to localize a putative human bombesin receptor gene (HBRKS) on human chromosome 17q21.3 by fluorescent in situ hybridization (FISH). HBRKS was identified and mapped by polymerase chain reaction (PCR) amplification from a Yeast artificial chromosome (YAC) contig spanning 17q21-q23. In addition, a few candidate genes were found by exon-trapping from HBR1.

Animals↗
PubMed1996

Chimeric synthetic peptides as antigens for detection of antibodies to HIV-1 and HIV-2.

Two chimeric peptides incorporating immunodominant sequences from both HIV-1 (LGIWGCSGKLICTT) and HIV-2 (LNSWGCAFRQVCHT) were synthesized. Peptides KS1-KS2 and KS2-KS1 represented sequences from the two viruses in both possible orders, separated by two glycine residues as spacers. These peptides were evaluated as antigens in an ELISA using a panel of specimens derived from HIV-1 (n = 25) and HIV-2 (n = 25) infected individuals and seronegative people (n = 38). The results were compared to plates coated with individual peptides KS1 and KS2 and to plates coated with two peptides (KS1 and KS2) together. Data demonstrated that individually, KS1 and KS2, are good antigens and can detect antibodies to their respective viruses quite efficiently. However, when coated together, their ability to detect antibodies to both HIV-1 and HIV-2 was reduced, as evidenced by a decrease in OD values obtained. The chimeric peptides KS1-KS2 and KS2-KS1 detected antibodies to HIV-1 and HIV-2; however, their sensitivity of detection was variable and dependent upon the order of their sequence. For both peptides, antibodies directed to the C-terminal portion were detected with higher sensitivity than those directed to the N-terminal part of the peptides. This may be related to peptide adsorption to the solid surface and epitope accessibility to the antibodies. Such chimeric antigens may be very useful for simultaneous detection of antibodies to HIV-1 and HIV-2.

AIDS Serodiagnosis↗