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Biomedical subjects

G Singer

Publications and source records attributed to G Singer.

At least 19 recordsLinked to original sources
PubMed1998

Direct binding to nucleic acids by Vpr of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a 15kDa regulatory protein packaged in the HIV-1 virion. Although the molecular mechanism of Vpr function during viral replication remains elusive, Vpr has been found to possess interesting biological activities, including cell-cycle arrest at the G2/M check point, promotion of the HIV-1 pre-integration complex for nuclear transport, and a low but significant level of transcriptional activation of a variety of viral and cellular promoters. We now present data suggesting that HIV-1 Vpr is a nucleic-acid-binding protein. This activity of Vpr was demonstrated by DNA-cellulose chromatography, antibody co-immunoprecipitation, and gel electrophoretic mobility shift assays. By mutational analysis, the C-terminal region of Vpr, which is rich in basic amino-acid residues, was shown to be critical for Vpr binding to nucleic acids. The nucleic-acid-binding activity of Vpr is consistent with several biological activities of Vpr and may provide an important clue for understanding the molecular interactions between HIV-1 and the host cells.

Amino Acid Sequence↗
PubMed1998

[Complex differential diagnosis of diffuse fine nodular lung infiltrates].

We report the case of a 36-year-old, previously healthy male patient presenting with progressive shortness of breath and dry cough. Chest X-ray revealed a diffuse micronodular interstitial pattern and pulmonary function tests showed reduced diffusion capacity, a restrictive pattern and obstructive airflow limitation. Transbronchial biopsy disclosed lymphangiosis carcinomatosa. The primary tumor was adenocarcinoma of the stomach. Differential diagnosis and the diagnostic approach to interstitial lung diseases are discussed. History, clinical findings, radiological and functional tests, as well as blood chemistry, serve to narrow down the differential diagnosis. The main further investigative steps are bronchoscopy with broncho-alveolar lavage and transbronchial biopsies, high resolution computer tomography, and thoracoscopic biopsy.

Adenocarcinoma, Mucinous↗
PubMed1998

Transitional cell carcinoma of the vagina with pagetoid spread pattern.

A distinctive variant of a papillary noninvasive transitional cell carcinoma (TCC) of the vagina removed from a postmenopausal woman is described. The neoplasm was evaluated by immunohistochemistry. The designation of this neoplasm as a TCC is supported by its morphological features and its coexpression for cytokeratin (CK) 7 and CK 20. Its main feature is pagetoid infiltration into adjacent vaginal epithelium. This is the second reported case involving a transitional cell metaplasia (TCM) of the vagina, a possible precursor lesion of the TCC.

Adult↗
PubMed1998

Cutaneous lung tissue heterotopia.

AIMS: We describe the clinical and pathological findings of a previously unreported cutaneous lung tissue heterotopia in a child. CASE DETAILS: The 3-year-old female patient developed a 8-mm secreting papule over her left scapula. Pathological examination revealed a lesion composed of bronchioles and alveoli within the subcutis and the dermis, with bronchiolar connection to the epidermis. Alveolar type II cells indicating full pulmonary differentiation were detected with a monoclonal antibody (AMH 152). CONCLUSIONS: The described features suggest that this lesion is a unique variant of rarely observed bronchus-like entities of the skin, designated as cutaneous bronchogenic cysts or cutaneous branchial cleft cysts.

Bronchogenic Cyst↗
PubMed1998

Use of the Taguchi method for biomechanical comparison of flexor-tendon-repair techniques to allow immediate active flexion. A new method of analysis and optimization of technique to improve the quality of the repair.

The current trend toward early active flexion after repair of the flexor tendons necessitates a stronger repair than that provided by a modified Kessler technique with use of 4-0 nylon suture. The purpose of the current study was to determine, with use of the Taguchi method of analysis, the strongest and most consistent repair of the flexor tendons. Flexor tendons were obtained from fresh-frozen hands of human cadavera. Eight flexor tendons initially were repaired with the modified Kessler technique with use of 4-0 nylon core suture and 6-0 nylon epitenon suture. A test matrix was used to analyze a total of twenty variables in sixty-four tests. These variables included eight techniques for core-suture repair, four types of core suture, two sizes of core suture, four techniques for suture of the epitenon, and two distances from the repair site for placement of the core suture. After each repair, the specimens were mounted in a servohydraulic mechanical testing machine for tension-testing to failure. The optimum combination of variables was determined, with the Taguchi method, to be an augmented Becker technique with use of 3-0 Mersilene core suture, placed 0.75 centimeter from the cut edge with volar epitenon suture. The four-strand, double modified Kessler technique provided the second strongest repair. Five tendons that had been repaired with use of the optimum combination then were tested and compared with tendons that had been repaired with the standard modified Kessler technique. With the optimum combination of variables, the strength of the repair improved from a mean (and standard deviation) of 17.2 +/- 2.9 to 128 +/- 5.6 newtons, and the stiffness improved from a mean of 4.6 to 16.2 newtons per millimeter.

Biomechanical Phenomena↗
PubMed1997

Renal allograft infiltrating lymphocytes: frequency of tissue specific lymphocytes.

Acute rejection, mediated by T lymphocytes recognizing donor MHC class I and II, is a major factor influencing renal transplant survival. To define the specificity of these effector cells we examined cytolytic activity of graft infiltrating T lymphocytes (GIL) from renal biopsies of individuals undergoing acute cellular rejection. The majority of these cells recognized MHC class I on both donor kidney epithelial cells (KCL) and B-lymphoblastoid cells (LCL) suggesting these T cells recognized peptides from various tissues. However, cold target inhibition experiments demonstrated a significant proportion of GIL T cells were tissue specific. We reported previously that kidney specific CTL can be isolated from biopsies of kidney allografts undergoing acute cellular rejection. Here we extend that observation showing we were able to isolate tissue specific CTL from two additional biopsies. Greater than 10% of the clones isolated (4 of 36 and 5 of 37) from these biopsies were CTL recognizing donor KCL but not LCL targets suggesting that peptides, recognized in the context of donor MHC, were tissue specific. Repeated isolation of significant numbers of tissue specific CTL suggests these T cells play a role in allograft rejection and may be important effector cells mediating rejection in HLA matched transplants.

Adult↗
PubMed1996

p-Glycoprotein expression as a predictor of breast cancer recurrence.

BACKGROUND: Many new prognostic factors for breast cancer have been described, and yet the ability to predict patient outcomes remains poor. Overexpression of p-glycoprotein (p-gp), the multidrug resistance efflux pump, confers a worse prognosis to patients with certain leukemias and other tumors. The purpose of this study was to analyze the potential usefulness of p-gp expression as a prognostic factor in patients with breast cancer. METHODS: Paraffin blocks were obtained from 55 previously untreated patients who underwent surgery between 1987 and 1988. To determine p-gp expression, tumor cell suspensions were incubated with the p-gp-specific C219 monoclonal antibody and analyzed using an indirect immunofluorescent flow cytometric assay. RESULTS: Twenty-four (44%) of the tumors were p-gp positive and 31 (56%) were p-gp negative. Among the p-gp positive patients, 65% had recurrence of their disease, whereas only 13% of the p-gp negative patients experienced recurrence (p = 0.0001). The 5-year disease-free rate for p-gp positive patients was 39% compared with 83% for p-gp negative patients (p = 0.0001). In univariate analysis examining 10 different variables, significant predictors of recurrence were p-gp, stage, and tumor size. Multivariate analysis using Cox Proportional Hazards regression showed that only p-gp and stage were significant independent predictors of recurrence (p = 0.0002). CONCLUSIONS: p-gp is frequently expressed in patients with untreated breast cancer, with p-gp-positive patients being at significantly greater risk for disease recurrence. p-gp appears to be a useful prognostic factor in breast cancer and could potentially help guide management.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

A comparison of outpatient and inpatient anterior cruciate ligament reconstruction surgery.

The feasibility of outpatient anterior cruciate ligament (ACL) surgery has not been reported in the literature. We evaluated outpatient ACL surgery by comparing outpatient versus inpatient pain control, narcotic consumption, postoperative complications, recovery time, and cost analysis. Thirty-seven ACL reconstructions were performed in 37 patients over a 16-month period. Twenty-five of the patients had surgery performed as outpatients and 12 as inpatients. One of the outpatients required hospitalization because of excessive nausea and vomiting and another for urinary retention. Only 2 of the 25 outpatients (8%) believed that they should have been hospitalized for pain control. Based on a visual analog scale, pain severity, pain frequency, and pain relief were measured, and no statistically significant difference (P < .05) was noted between the groups, although the data suggested that the inpatients were slightly more comfortable. There were no differences in rehabilitation or in regaining full range of motion of the operated knee. Also, the only postoperative complication in both groups occurred in an inpatient who developed arthrofibrosis. Cost analysis showed that outpatient ACL reconstruction was cost effective. The average inpatient cost was $9,220 (2.4 hospital days) compared with the average outpatient cost of $3,905. This reflected a savings of 58%. These results show that outpatient ACL reconstruction surgery is possible in the appropriate patient without harm to the patient and with a significant cost savings.

Adult↗
PubMed1994

Train-versus-pedestrian injuries. Orthopaedic management.

Between February 1989 and February 1993, a retrospective review at our facility identified 30 patients who were victims of train-versus-pedestrian accidents. Although some patients suffered head, chest, and abdominal injuries, the majority of injuries sustained were musculoskeletal. The Injury Severity Score ranged from 5 to 54, with an average of 21. Of the 30 patients, 23 (77%) had significant orthopaedic injuries, with an average of 1.7 extremities involved. The foot was the most commonly injured body segment, sustaining amputation, crush, or degloving injury in 12 patients (12/23 = 52%). The most common operative procedure was debridement, which was performed largely on patients with traumatic amputation in an effort to preserve length. Nineteen lower extremity and 2 upper extremity amputations were necessary in 14 patients (an amputation rate of 14/23 = 61%). With the exception of toe and heel avulsion, nearly all crush and avulsion injuries required amputation at a segment higher than the level of injury. Although image of an unstable patient with mangled extremities, many patients survive low-velocity collisions and subsequently require vigorous orthopaedic intervention.

Accidents↗
PubMed1992

Radial glial interaction with cerebral germinal matrix capillaries in the fetal baboon.

The occurrence of intraventricular hemorrhage (IVH) is a frequent problem in premature infants delivered between 24 (60%) and 32 weeks (80%) of gestation, a time during which the germinal matrix (GM) is prominent over the head of the caudate nucleus. Most IVH arises from the GM and it has been proposed that an important factor in the pathogenesis of IVH is a weakness of GM capillary walls due to deficient support by surrounding immature glial cells. The purpose of this study was to examine the glial-capillary interaction in the GM of fetal baboons sacrificed at 100 days (54%) gestation, a stage of GM development comparable to that during which human neonatal IVH occurs. Brains from a later gestational stage (162 days, 88%), after GM involution, were also examined. At 100 days of gestational age, the GM was prominent over the head of the caudate and contained vimentin positive, but not glial fibrillary acidic protein positive, radial glial cells which formed endfeet on capillaries in the region. Ultrastructurally, all the GM capillaries examined from this gestational time had complete, continuous endothelia marked by few pinocytotic vesicles and prominent tight junctions. The endothelial cells rested upon uninterrupted basement membranes which were contacted by clearly identifiable glial endfeet. These data show that GM capillaries have morphologies typical of CNS capillaries and suggest that the capillary immaturity within the GM is not a major contributing factor to IVH.

Animals↗
PubMed1990

The effects of corticosterone implantation on schedule-induced wheelrunning and HPA function in intact rats.

Previous research has shown that Schedule-induced wheelrunning (SIW) is dependent on the function of the pituitary-adrenal axis and that the nature of pituitary-adrenal involvement is mainly through circulating corticosterone levels. In the present study it was shown that a 10-20 day period of subcutaneous implantation of exogenous corticosterone in intact rats alters HPA function but does not influence SIW. Plasma corticosterone levels in corticosterone-treated rats significantly decreased when compared with either the vehicle treated or untreated controls, and atrophy of adrenals occurred in corticosterone-treated animals, suggesting that exogenous corticosterone implantation impairs HPA function. However, the behavioural results showed that corticosterone implantation to intact rats did not affect the acquisition and development of SIW. These results raise the question of whether corticosterone exerts a permissive action or not.

Adrenal Glands↗
PubMed1990

Effect of hypophysectomy on schedule-induced wheelrunning.

Previous research has shown that adrenalectomy suppresses schedule-induced wheelrunning, and that the suppressant effect of adrenalectomy can be totally reversed by the replacement of corticosterone. The present study confirms the role of the hormones of the pituitary adrenocortical axis in the control of schedule-induced wheelrunning by means of hypophysectomy. As anticipated, hypophysectomy also suppressed schedule-induced wheelrunning. The suppressant effect of hypophysectomy on schedule-induced wheelrunning was partially, but significantly restored by the implantation of corticosterone. Present findings, in conjunction with the previous work, show that schedule-induced wheelrunning is markedly dependent on the function of the pituitary-adrenal axis, and the nature of pituitary-adrenal involvement is mainly through circulating corticosterone levels.

Animals↗
PubMed1989

The action of corticosterone on schedule-induced wheelrunning.

Previous studies have shown that schedule-induced wheelrunning is dependent on an intact pituitary-adrenal axis, and thus the presence of circulating corticosterone. In the present study, the mechanism of action of corticosterone on schedule-induced wheelrunning was explored in two ways. In the first series of studies, the effect of different levels of corticosterone on schedule-induced wheelrunning in adrenalectomized rats was investigated; the results of this study show a dose-response relationship between levels of corticosterone and schedule-induced wheelrunning. In the second study, the glucocorticoid receptor subtype involved was determined by examining the effect of dexamethasone, a synthetic glucocorticoid, on schedule-induced wheelrunning in adrenalectomized rats. A low dose of dexamethasone effectively reversed the suppressant effect of adrenalectomy, suggesting that the behavioural action of glucocorticoids is mediated through classical (Type II) glucocorticoid receptors, and not through Type I, corticosterone-preferring receptors.

Adrenalectomy↗