Biomedical subjects

S Qualman

Publications and source records attributed to S Qualman.

11 recordsLinked to original sources

PubMed2000

Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study.

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Only 11 embryonal rhabdomyosarcomas (E-RMS) have previously been subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 12 E-RMS specimens from 10 patients entered into Intergroup Rhabdomyosarcoma Study (IRS) I-IV and two local patients were analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (50%), 7 (42%), 8 (67%), 11 (42%), 12 (58%), 13q21 (33%), and 20 (33%) and losses of 1p35-36.3 (42%), 6 (33%), 9q22 (33%), 14q21-32 (25%), and 17 (25%) were most prominent. Chromosomal regions 1p35-36.3 and 9q22 represent novel regions of loss. Importantly, loss of 9q22 corresponds to the locus of a putative tumor suppressor gene (PTCH), which has been shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome. Loss of 1p36 corresponds to the locus for PAX7, a paired box containing gene characteristically altered in alveolar rhabdomyosarcoma. Moreover, loss of 1p36 is prominent in another common pediatric soft tissue tumor, neuroblastoma. Gains of 2, 7, 8, 12, and 13 and loss of 14 were seen in the sole prior E-RMS CGH series; thus, these data provide important confirmatory results. In contrast to this previous study, however loss, not gain, of chromosome 17 was observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss of 17p (TP53) in E-RMS. In summary, CGH and FISH analyses of 12 E-RMS specimens revealed novel genomic imbalances that may be useful in directing further molecular studies for the determination of E-RMS critically involved genes.

Adolescent↗

PubMed2000

Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass.

Rhabdomyosarcomas are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology, it is often difficult to distinguish between the distinct subtypes of rhabdomyosarcomas. By using cryosections of tumor specimens and immunohistochemistry, in the present study we show that strong expression of myogenin in rhabdomyosarcoma is associated with alveolar histology (P = <0.0001, Fisher's exact test). Although staining for myogenin was observed in 22 of 26 rhabdomyosarcomas, all alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for myogenin, as defined by the frequency and intensity of staining of the tumor cells. The staining pattern suggests that the tumor cells are clonally derived from myogenin-positive progenitor cells. In contrast, most embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for myogenin. In these tumors a larger proportion of tumor cells were distinctly negative for myogenin. Six of seven alveolar rhabdomyosarcomas that strongly stained for myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/reverse transcriptase-polymerase chain reaction. One of two embryonal rhabdomyosarcomas that strongly stained for myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for myogenin by Western blotting using a smaller subset of rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P = 0.01, Pearson Correlation), although the former technique was more sensitive for detecting tumors with low levels of the protein. On average, alveolar rhabdomyosarcomas expressed at least threefold more myogenin than embryonal rhabdomyosarcomas. Our data show that staining for myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and embryonal rhabdomyosarcomas. We propose that embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of myogenin. In contrast, we propose that alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of myogenin) or that the pathological mechanisms involved in these neoplasms also induce strong expression of this protein.

Antibodies, Monoclonal↗

PubMed1998

Providing human tissues for research: how to establish a program.

The Cooperative Human Tissue Network is a group composed of cooperating academic institutions that supply human tissues to researchers studying a wide range of neoplastic and other diseases. The experience of the Cooperative Human Tissue Network in establishing methods of prospective tissue collection and in developing tumor banks is discussed to aid institutions in establishing tissue resources for their local investigators, who may wish to use human tissues in current or future research projects. The advantages to pathology departments and to associated medical institutions of establishing an organized tissue resource include ensuring proper institutional review board approval of research projects using human tissues, protecting diagnostic specimens, creating new opportunities for extramural research, increasing the speed of diagnostic specimen transport to surgical pathology, and providing educational and research opportunities for pathologists and pathology residents. Methods of tissue collection, processing, storage, data collection, and supply are outlined. Also, resources necessary to begin organized tissue collection, including personnel, space, equipment, and supplies, are discussed.

Female↗

PubMed1997

Can the histologic changes of cystic fibrosis-associated hepatobiliary disease be predicted by clinical criteria?

BACKGROUND: Correlation between clinical parameters and histology changes in cystic fibrosis liver disease has not been documented. The purpose of this study was to determine the histologic spectrum of cystic fibrosis liver disease and the degree to which a clinical scoring system can identify subjects with significant histologic abnormalities. METHODS: We reviewed the predictive value of physical examination, biochemical parameters, and a clinical liver score, incorporating physical examination and biochemical parameters, in predicting significant abnormalities of liver histology in 43 cystic fibrosis patients who underwent hepatic biopsy. Biopsies were scored by two masked pathologists for fibrosis, inflammation, inspissation, fatty infiltration, and congestion. RESULTS: Significant histologic disease was present in 56% of patients despite little biochemical or physical examination evidence of disease. No single parameter used in the scoring system predicted the type or degree of the liver disease. The clinical liver score had a sensitivity of 85% and a specificity of 82% in predicting significant histologic changes, yet it was unable to predict the specific lesion. CONCLUSIONS: Significant histologic liver disease is common in cystic fibrosis, although the exact nature of the lesion cannot be predicted without liver biopsy. A clinical liver score that was developed for this may be useful in determining which patients require more definitive evaluation.

Adolescent↗

PubMed1994

Absent intestinal musculature: anatomic evidence of an embryonic origin of the lesion.

Absent intestinal musculature is a rare entity of uncertain etiology. The diagnosis is confirmed histologically by segmental absence of the intestinal muscularis. The remaining layers of the bowel wall are completely intact, and notably absent are significant inflammation and hemorrhage. The authors report two cases of segmental absence of intestinal musculature presenting as perforations. There was gross or microscopic evidence of diverticula formation at sites of perforation and absent muscle. Based on the anatomic evidence in these specimens and a review of the surgical literature, we propose that the etiology is based on embryologic diverticuli.

Child, Preschool↗

PubMed1993

Homozygous inactivation of WT1 in a Wilms' tumor associated with the WAGR syndrome.

Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator.

Adolescent↗

PubMed1990

Necrotizing tracheobronchitis following high frequency ventilation: effect of hydrocortisone.

A piglet model of acute respiratory failure was used to determine whether necrotizing tracheobronchitis (NTB) produced during high-frequency pneumatic flow interrupter (HFFI) ventilation could be attenuated by prior administration of 2 mg/kg hydrocortisone IV. Fourteen piglets (means age 3.6 days, means wt 1.4 kg) were anesthetized and paralyzed before saline lung lavage. The animals were randomly assigned to either placebo (P) or hydrocortisone (H) group. Continuous HFFI (10 Hz) was interrupted five times per minute by a 1-second deflationary pause. All animals were kept on 1.0 FI02 with ventilators adjusted to maintain adequate arterial blood gases. Airway pressures were similar for both groups. After 8 hours of ventilation the animals were sacrificed and their lungs inflated with formalin to 40 cm H2O. Sections were obtained from trachea, carina, main stem, and peripheral bronchi. A total airway injury (TAIS) was calculated by a pathologist unaware of treatment assignment. There was a significant difference (p less than 0.01, Wilcoxon rank sum) in TAIS scores between P (means 21.3) and H (means 7.8). In five out of seven P animals and in one out of seven H animals, NTB was severe and extended to the hilar bronchi. Although NTB is multifactorial in origin, the prior use of hydrocortisone may decrease the severity and extent of lesions by modifying the inflammatory response to this specific airway injury.

Animals↗

PubMed1988

Necrotizing tracheobronchitis following high-frequency ventilation: effect of lung deflation.

A piglet model of acute respiratory failure was used to determine whether necrotizing tracheobronchitis (NTB) reported during high-frequency pneumatic flow interrupter (HFFI) ventilation could be minimized by a different ventilatory strategy. Twenty-one piglets (mean age 3.8 days, average weight 1.4 kg) were anesthetized with ketamine and given Pavulon prior to saline lung lavage. Femoral vessels were cannulated for measurements of blood pressures, arterial blood gases (ABG), and fluid administration. Airway pressures were measured 5 mm above the endotracheal tube tip. To allow for lung deflation, HFFI (10 Hz) was programmed to pause for 1 sec either 5 (HFFI5) or 12 times per min (HFFI12). Seven animals were assigned to each of the treatment groups and to a conventional mechanical ventilation (CMV) control. All animals were kept on 1.0 FIO2 with ventilators adjusted to maintain ABG (pO2 = 50-100 mmHg and pCO2 = 30-40 mmHg). After 6 h of ventilation, the animals were sacrificed and their lungs inflated with formalin to 40 cm H2O. Sections were obtained from trachea, carina, mainstem, and hilar bronchi. An airway injury score (AIS) was calculated after "blinded" microscopic evaluation. There was no difference in total AIS between CMV (2.4) and HFFI12 (8.6) but a statistically significant difference (p less than 0.05) existed between CMV and HFFI5 (14.1). NTB was limited to the trachea during HFFI12 but extended down to the hilar bronchi during HFFI5. More frequent lung deflations reduce the severity and distribution of NTB during HFFI ventilation.

Animals↗

PubMed1987

Malignant peripheral primitive neuroectodermal tumor of the uterus.

Peripheral primitive neuroectodermal tumor (PPNET) is rare, occurring most often in young adults. Approximately 50 cases have been reported, with only four cases involving the female genital tract. We report the fifth patient. The term "PPNET" should be used only for tumors with neuroectodermal elements exclusively that occur at sites outside the central and sympathetic nervous system. The pathologic differential diagnoses include rhabdomyosarcoma, immature malignant teratoma, small cell carcinoma of the cervix, and ganglioneuroma. Therapy for this tumor has varied, and no effective regimen has been established.

Adolescent↗

PubMedDate not supplied

Necrotizing tracheobronchitis (NTB) following high frequency ventilation: role of an angiotensin converting enzyme inhibitor.

The purpose of this investigation was to study the effect of an angiotensin converting enzyme inhibitor (enalaprilat) on the morphologic manifestations of experimentally induced necrotizing tracheobronchitis (NTB). Twenty piglets were anesthetized before saline lung lavage. High frequency flow interrupter (HFFI) ventilation was used with a strategy known to produce NTB. Animals were randomly assigned to receive IV enalaprilat 0.1 mg/kg (ENP-Hi), enalaprilat 0.01 mg/kg (ENP-Lo), or saline (C). After 8 hours of ventilation, the piglets were sacrificed. Total airway injury scores (mean +/- S.D.) were 1.2 +/- 0.7 for ENP-Hi, 0.2 +/- 0.2 for ENP-Lo, and 21.3 +/- 16 for group C. Enalaprilat minimizes NTB lesions in neonatal piglets exposed to high frequency oscillatory ventilation. Although the origin of NTB is multifactorial, airway mucosa ischemia may play an important role. Enalaprilat may compensate for the reduction of mucosal blood flow by limiting formation of angiotensin II and/or preventing degradation of bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Ectopic pancreas and the islet cell dysmaturational syndrome.

Two cases of ectopic pancreas are described in the setting of the islet cell dysmaturational syndrome. Microscopic and immunostaining studies revealed both lesions to be composed of primarily (80 percent to 90 percent) islet tissue with nuclear hyperchromasia and probable depletion of immunoreactive insulin in one case. Persistent hyperinsulinemic hypoglycemia required a second laparotomy with resection of ectopic pancreas in one case. Awareness of the phenomenon led to successful identification and resection of ectopic islet tissue on first surgery in a subsequent case. Ectopic pancreas is a relatively common developmental pancreatic anomaly, and knowledge of its potential contribution to life-threatening hypoglycemia may obviate the need for multiple surgeries in some cases of islet cell dysmaturational syndrome.

Choristoma↗