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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 19 recordsLinked to original sources
PubMed2026

Genome-targeted enrichment and sequencing of human-infecting Cryptosporidium spp.

Cryptosporidium spp. are parasites that cause severe illness in vulnerable human populations. Obtaining pure and sufficient Cryptosporidium DNA from clinical and environmental samples is a challenging task. Oocysts shed in available fecal samples can be limited in quantity, require purification (biased towards dominant strains), and yield limited DNA (&#x2009;<&#x2009;40 fg/oocyst). Here, we use updated genomic sequences from a broad diversity of Cryptosporidium species that have been found to infect humans (C. cuniculus, C. hominis, C. meleagridis, C. parvum, C. tyzzeri, and C. viatorum) to develop and validate a set of 100,000 RNA baits (CryptoCap_100k) with the aim of enriching Cryptosporidium DNA from varied samples. Compared to unenriched libraries, CryptoCap_100k increases the percentage of reads mapping to target genome sequences, increases the depth and breadth of genome coverage, and facilitates analyses of genetic variants in many samples, while decreasing overall costs.

Cryptosporidium↗
PubMed2025

GENOME TARGETED ENRICHMENT AND SEQUENCING OF HUMAN-INFECTING CRYPTOSPORIDIUM spp.

Cryptosporidium spp. are parasites that cause severe illness in vulnerable human populations. Obtaining pure and sufficient Cryptosporidium DNA from clinical and environmental samples is a challenging task. Oocysts shed in available fecal samples can be limited in quantity, require purification (biased towards dominant strains), and yield limited DNA (<40 fg/oocyst). Here, we use updated genomic sequences from a broad diversity of human-infecting Cryptosporidium species ( C. cuniculus , C. hominis , C. meleagridis , C. parvum , C. tyzzeri , and C. viatorum ) to develop and validate a set of 100,000 RNA baits (CryptoCap_100k) with the aim of enriching Cryptosporidium spp. DNA from varied samples. Compared to unenriched libraries, CryptoCap_100k increases the percentage of reads mapping to target genome sequences, increases the depth and breadth of genome coverage and the reliability of detecting species and mixed infections within a sample, and allows assessment of genetic variation via SNP calling, while decreasing costs.

Journal Article↗
PubMed2024

WHOLE GENOME TARGETED ENRICHMENT AND SEQUENCING OF HUMAN-INFECTING CRYPTOSPORIDIUM spp.

Cryptosporidium spp. are protozoan parasites that cause severe illness in vulnerable human populations. Obtaining pure Cryptosporidium DNA from clinical and environmental samples is challenging because the oocysts shed in contaminated feces are limited in quantity, difficult to purify efficiently, may derive from multiple species, and yield limited DNA (<40 fg/oocyst). Here, we develop and validate a set of 100,000 RNA baits (CryptoCap_100k) based on six human-infecting Cryptosporidium spp. (C. cuniculus, C. hominis, C. meleagridis, C. parvum, C. tyzzeri, and C. viatorum) to enrich Cryptosporidium spp. DNA from a wide array of samples. We demonstrate that CryptoCap_100k increases the percentage of reads mapping to target Cryptosporidium references in a wide variety of scenarios, increasing the depth and breadth of genome coverage, facilitating increased accuracy of detecting and analyzing species within a given sample, while simultaneously decreasing costs, thereby opening new opportunities to understand the complex biology of these important pathogens.

Journal Article↗
PubMed2024

Phylogenomic reconstruction of Cryptosporidium spp. captured directly from clinical samples reveals extensive genetic diversity.

Cryptosporidium is a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twenty Cryptosporidium species infect humans, of which C. parvum and C. hominis are the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnose Cryptosporidium. Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understand Cryptosporidium global population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ~92% of the genome of C. parvum. CES-Seq is sensitive and successfully sequenced Cryptosporidium genomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species of Cryptosporidium directly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.

Cryptosporidium↗
PubMed1992

KiS1--a novel monoclonal antibody which recognizes proliferating cells: evaluation of its relationship to prognosis in mammary carcinoma.

Immunohistochemical staining with a novel monoclonal antibody, KiS1, which recognizes a cell cycle-associated antigen, was investigated in 142 cases of stage I and II invasive breast carcinoma. KiS1 staining indices were compared with disease-free interval, overall survival, and post-relapse survival. Using a semi-quantitative method of assessment, we found that tumours with a high level of staining (34/142, 24 per cent) had a significantly worse prognosis than those with a low level of staining (108/142, 76 per cent). Significant correlations were found between KiS1 staining and disease-free interval (P < 0.001), overall survival (P < 0.001), and post-relapse survival (P = 0.008). A more time-consuming, quantitative method of assessment gave similar results. Cox multivariate analysis showed these results to be independent of nodal status, histological type, and grade of tumour (P = 0.01). We conclude that KiS1 is a valuable new antibody which affords useful prognostic information in breast carcinoma. As it can be used in formalin-fixed, paraffin-embedded material, it may be of particular use in the study of small lesions such as those identified in the Breast Cancer Screening Programme.

Adult↗
PubMed1992

Serious complications of vascular catheter-related Staphylococcus aureus bacteremia in cancer patients.

Over the period 1986 to 1989, 53 cancer patients were identified with catheter-related Staphylococcus aureus bacteremia at the University of Texas M.D. Anderson Cancer Center. Septic thrombosis was diagnosed in 12 (23%) patients and was suspected in another 3 (6%). Of the 12 patients, five developed deep-seated infections (septic emboli, endocarditis, meningitis, abscess), compared with 2 of the 38 other patients with no septic thrombosis (p < 0.01). Fever persisted for more than three days after antibiotic initiation in 52% of the patients with complications (septic thrombosis and/or deep-seated infections), compared with 19% of those without complications (p < 0.02). Of the three patients with complications who were treated for 14 days with intravenous antistaphylococcal antibiotics, two relapsed; in contrast, all of the nine patients with complications who were treated for more than 14 days (mean 4 weeks) were cured, and none relapsed (p < 0.05). Of the nine patients with complications who were treated with a long course of therapy, only one required surgery. The possibility of septic thrombosis and/or deep-seated infections should be considered in all cancer patients with catheter-related Staphylococcus aureus bacteremia, and if present, the condition should be treated with appropriate intravenous antibiotics for at least four weeks.

Adult↗
PubMed1992

Effect of dietary fish oil supplementation on the antigen-induced late-phase response in the skin.

We have studied the effect of dietary fish oil supplementation (3.2 gm/day of eicosapentaenoic acid and 2.2 gm/day of docosahexaenoic acid) for 10 weeks on the antigen-induced, cutaneous late-phase response (LPR) in 16 atopic individuals. All subjects developed an LPR to intradermal allergen injection. The mean +/- SEM area of induration at 6 hours was 1840 +/- 472 mm2. A biopsy was performed at the LPR site at 6 hours. Subjects were then randomized to receive fish oil or placebo olive oil in a double-blind, parallel fashion, for 10 weeks. After the diet, there were no significant differences between fish oil and placebo treatment in the size of the immediate wheal-and-flare response or the extent of induration at 4 and 6 hours, as compared with prediet values in each group. Histologically, at 6 hours, there was a significant infiltrate into the allergen site compared with that of the control diluent site of total inflammatory cells (p less than 0.002) as well as of eosinophils (p less than 0.001). However, there were no significant differences when pre- and postdiet values were compared. Hence, we conclude that dietary fish oil supplementation does not inhibit the cutaneous LPR clinically or histologically.

Adult↗
PubMed1992

Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia.

OBJECTIVE: To determine the impact of catheter management on the acute and long-term outcome of catheter-related coagulase-negative staphylococcal bacteremia. DESIGN: Retrospective surveillance of catheter-related sepsis using quantitative blood and catheter cultures. SETTING: University-affiliated tertiary cancer center. PATIENTS AND METHODS: Seventy patients with catheter-related coagulase-negative staphylococcal bacteremia were studied by retrospective chart review. The clinical characteristics of the patients and the management of the bacteremias were determined. The impact of immunosuppressive risk factors, antibiotic therapy, and catheter management on the recurrence of the bacteremia was investigated. RESULTS: Acute sepsis-related morbidity and mortality were not related to catheter management. However, during a 12-week followup period, the bacteremia recurred in 20% of the patients whose catheters remained in place, compared with only 3% of those whose catheters were removed (p less than .05). By multivariate analysis, patients whose catheters remained in place were 2.9 times more likely to experience a recurrence than those whose catheters were removed (odds ratio = 2.9, 95% confidence interval = 1.2-8.8, p = .03). All other potential risk factors were equally distributed between patients, with and without a recurrence. CONCLUSIONS: Although patients with catheter-related coagulase-negative staphylococcal bacteremia could be treated successfully while the catheter remains in place with the majority remaining free of recurrence, catheter retention results in a significantly higher risk for the recurrence of the bacteremia.

Adolescent↗
PubMed1992

Pulmonary scintigraphy in elastase-induced emphysema in pigs. Correlation with high-resolution computed tomography and histology.

OBJECTIVES: The objective of this study is to evaluate the mild physiologic changes of elastase-induced pulmonary emphysema in the pig by radionuclide scintigraphy and to correlate these findings with high-resolution computed tomography (HRCT) and histologic examination. METHODS: Eight 7- to 12-week-old Yorkshire pigs were studied. Perfusion and ventilation studies were performed in six pigs at 1- or 2-week intervals after elastase instillation. HRCT was simultaneously performed for correlation with radionuclide scintigraphy. For the perfusion scans, technetium 99m (99mTc) macroaggregated albumin (MAA) was used, and both planar and single-photon emission CT (SPECT) images were obtained. Ventilation studies were performed with xenon-133 gas with dynamic sequential imaging. RESULTS: Histopathologic findings demonstrated dilatation and destruction of the alveoli and were similar to those previously reported by the authors. The SPECT perfusion images showed significantly impaired perfusion of the involved segment of the lung, corresponding to the region where elastase was instilled. The planar xenon-133 ventilation scintigraphy did not show abnormal air trapping. The mild emphysema induced with elastase manifested as decreased and impaired perfusion with no detectable ventilation abnormalities. The sensitivity of SPECT perfusion studies for the detection of the mild changes of elastase-induced pulmonary emphysema were higher than that of HRCT. CONCLUSIONS: The perfusion studies reflect functional or physiologic changes in contrast to structural changes seen on HRCT. This pig model was valuable to study the scintigraphic manifestation of elastase-induced pulmonary emphysema.

Animals↗
PubMed1992

Experimental pulmonary infarction in a pig model.

RATIONALE AND OBJECTIVES: The authors sought to develop a reliable animal model for experimental pulmonary infarction, to evaluate it with radiologic-pathologic correlation, and to determine the use of high-resolution computed tomography (HRCT) in monitoring parenchymal lung damage due to infarction. METHODS: Selective left lower lobe pulmonary artery occlusion was performed in seven Yorkshire pigs with transcatheter silicone elastomer injection. After occlusion, 99m technetium (99mTc) macroaggregated albumin perfusion lung scans and sequential in vivo HRCT lung scans were obtained from days 0 to 46. The in vivo radiologic findings were correlated with specimen radiography, specimen HRCT, and histologic findings. RESULTS: A complete and permanent arterial occlusion was achieved, involving up to three orders of branching distal to the catheter. An anatomically defined perfusion defect was seen on 99mTc lung scans corresponding to the occluded area. HRCT changes consisted of confluent densities progressing to mixed alveolar and interstitial opacities within the first week after embolization. In the follow-up period, marked parenchymal clearing was observed. In all cases after pulmonary artery occlusion, the histologic findings were characteristic of pulmonary infarction and demonstrated alveolar edema, hemorrhage, limited alveolar wall damage, and septal thickening followed by residual fibrosis. CONCLUSION: Using this model, it is feasible to produce pulmonary infarction in the pig which may potentially be useful to study the pathophysiologic and radiologic changes of pulmonary infarction.

Animals↗
PubMed1992

Phyllodes tumours: a clinicopathological review of 30 cases.

Thirty cases of phyllodes tumour (cystosarcoma phyllodes) of the breast that presented to the Clinical Oncology Unit at Guy's Hospital were reviewed. Tumours were classified as benign, malignant or borderline according to the following histological criteria: mitotic rate, nuclear pleomorphism, stromal overgrowth and tumour margins. In 14 (46.5%) cases the tumours were considered histologically benign, in 11 (36.5%) malignant, and in five (17%) borderline. Recurrence was seen in a similar proportion of patients with tumours classified as benign (21%) and malignant (18%) according to histological criteria. Malignant lesions tended to recur earlier. Infiltrating tumour margins were noted in all patients and stromal overgrowth in all but one in whom recurrence was observed. Risk of recurrence also appeared to be related to tumour size. Only one patient developed distant metastases and died of her disease. Because of treatment variation no conclusion can be made regarding optimal therapy but the importance of adequate clearance, either through wide excision or mastectomy, is emphasized for all phyllodes tumours irrespective of histological features.

Adult↗
PubMed1992

Glucocorticoid increases glucose cycling and inhibits insulin release in pancreatic islets of ob/ob mice.

Normoglycemic ob/ob mice were treated for 24 or 48 h with either 25 micrograms/day of dexamethasone or saline. After an overnight fast, the animals were killed and pancreatic islets were incubated with 3H2O or [U-14C]glucose or [5-3H]glucose at 5.5 and 16.7 mM glucose. Incorporation of 3H from 3H2O into carbon 2 of medium glucose and the yield of 14CO2 from [U-14C]glucose and 3H2O from [5-3H]glucose were measured. Dexamethasone treatment for 48 h significantly increased the rate of dephosphorylation of glucose in islets both at 5.5 mM (24 vs. 16%) and 16.7 mM (56 vs. 36%) glucose, whereas glucose oxidation and utilization were unaffected. Dexamethasone treatment also inhibited insulin release by approximately 60% at 5.5 and 16.7 mM glucose, either in the presence or absence of 10 mM arginine, but had no effect when insulin release was stimulated by 1 mM 3-isobutyl-1-methylxanthine. Moreover, 24-h treatment with dexamethasone significantly increased glucose cycling at low and high glucose concentrations in the medium and inhibited insulin responsiveness to glucose and arginine. In conclusion, short-term dexamethasone treatment increases glucose flux through glucose-6-phosphatase in islets from ob/ob mice. This effect may contribute to the decreased insulin response to glucose and arginine found in animals treated with dexamethasone.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Tidal breath flow-volume curves in obstructive sleep apnea.

Because of the gravitational position during sleep and the associated relaxed state, we hypothesized that passive expiration in the supine position might reflect upper airway pathophysiology in obstructive sleep apnea (OSA). We prospectively enrolled and tested 92 subjects with several clinical conditions. Maximal comfort and relaxation during expiration was achieved by connecting subjects to a ventilator via a mouthpiece. An initial respiratory rate of 16 breaths/min and tidal volume of 10 ml/kg were selected. Fine adjustments were then made to achieve maximal subject relaxation. Using this method, we obtained reproducible tidal breath flow-volume curves (TBFVC). Testing was performed in both sitting and supine positions. Standard pulmonary function tests, including spirometry and lung volume measurements, were also obtained in both sitting and supine positions. Of 86 patients who could be evaluated, 12 (60%) of 20 subjects with documented OSA (respiratory disturbance index: mean, 64.8; range, 10 to 120.5) demonstrated a positional change in the terminal portion of the TBFVC; 10 (32%) of 31 with a history of snoring also tested positive, but only three (9%) of 35 subjects with no OSA, by polysomnography (n = 8) or questionnaire (n = 27), demonstrated such a positional change. This positional change in TBFVC, which was significantly more frequent in subjects with OSA, could not be attributed to any measurable pulmonary function abnormality or body mass index. We believe this positional change in TBFVC reflects upper airway functional narrowing induced by assumption of supine position and decreasing airflow rates.

Female↗
PubMed1992

Surgical stabilization of cervical spinal fractures using methyl methacrylate. Technical considerations and long-term results in 52 patients.

This study analyzes the long-term outcome of 52 consecutively treated patients with acute cervical spinal fracture/dislocation who underwent posterior surgical stabilization using methyl methacrylate in the absence of bone grafting. The patients ranged in age from 15 to 93 years. In 40 patients the injury was located in the lower cervical spine; for these a previously described surgical format was employed. In 12 patients the fracture involved C-1 or C-2, and the modification used for these injuries is presented. The postoperative period of evaluation ranged from 6 months to 12 years. There was one case of infection, which eventually required removal of the acrylic, but there were no instances of new neurological injury or of operative mortality. Failure of stabilization occurred in two previously reported patients treated early in the series. Comparison of the patient outcome in this study with that of certain other reports suggests that at least four technical factors are important for the success of methyl methacrylate stabilization: 1) the acrylic inlay must be provided with an anchor to bone; 2) the anchor must be of a type that does not easily erode through bone; 3) the inclusion of wire must be done in a manner that allows each strand to be completely encased in the acrylic; and 4) the cross-sectional area of the inlay is critical.

Adolescent↗
PubMed1992

Naked megakaryocyte nuclei as an indicator of human immunodeficiency virus infection.

Compact, lobulated megakaryocyte nuclei, apparently denuded of cytoplasm (naked nuclei), have been reported to be markedly increased in the bone marrow of persons infected with human immunodeficiency virus (HIV). We have confirmed this observation and have developed a useful diagnostic index, the naked nucleus ratio, to characterize the bone marrow of individuals who are infected with HIV. The naked nucleus ratio, calculated as the average number of naked nuclei per high-power field divided by the average number of intact megakaryocytes per high-power field, has a sensitivity of 97.9% and a specificity of 96.4% for patients with HIV infection. In our patients with a 62.6% prevalence of HIV infection, the predictive value of a positive test was 97.9% and the predictive value of a negative test was 96.4%. An increase in the naked nucleus ratio above 10%, without specific changes in the bone marrow, should raise or may confirm the suspicion of HIV infection.

Biopsy↗