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Biomedical subjects

T Margolis

Publications and source records attributed to T Margolis.

10 recordsLinked to original sources

Evidence for a bidirectional element located downstream from the herpes simplex virus type 1 latency-associated promoter that increases its activity during latency.

Herpes simplex virus type 1 (HSV-1) latent infection in vivo is characterized by the constitutive expression of the latency-associated transcripts (LAT), which originate from the LAT promoter (LAP). In an attempt to determine the functional parts of LAP, we previously demonstrated that viruses harboring a DNA fragment 3' of the LAT promoter itself were able to maintain detectable promoter expression throughout latency whereas viruses not containing this element could not (J. R. Lokensgard, H. Berthomme, and L. T. Feldman, J. Virol. 71:6714-6719, 1997). This element was therefore called a long-term expression element (LTE). To further study the role of the LTE, we constructed plasmids containing a DNA fragment encompassing the LTE inserted into a synthetic intron between the reporter lacZ gene and either the LAT or the HSV-1 thymidine kinase promoter. Transient-expression experiments with both neuronal and nonneuronal cell lines showed that the LTE locus has an enhancer activity that does not activate the cytomegalovirus enhancer but does activate the promoters such as the LAT promoter and the thymidine kinase promoter. The enhancement of these two promoters occurs in both neuronal and nonneuronal cell lines. Recombinant viruses containing enhancer constructs were constructed, and these demonstrated that the enhancer functioned when present in the context of the viral DNA, both for in vitro infections of cells in culture and for in vivo infections of neurons in mouse dorsal root ganglia. In the infections of mouse dorsal root ganglia, there was a very high level of promoter activity in neurons infected with viruses bearing the LAT promoter-enhancer, but this decreased after the first 2 or 3 weeks. By 18 days postinfection, neurons harboring latent virus without the enhancer showed no beta-galactosidase (beta-gal) staining whereas those harboring latent virus containing the enhancer continued to show beta-gal staining for long periods, extending to at least 6 months postinfection, the longest time examined.

Animals↗

Vesicovaginal fistula.

Vesicovaginal fistulas are often the result of obstetric trauma in third world countries and gynecologic surgery in developed countries. Improvement in obstetric care and the increased use of cesarean section has resulted in a decrease in the incidence of obstetric fistulas in the United States. However, the incidence of fistulas as a result of surgery has remained relatively unchanged for years. Most postoperative fistulas occur under very normal operative circumstances. The keys to prevention of postoperative fistulas are wide dissection of the bladder from the cervix and vagina in the correct plane during surgery and recognition of bladder damage intraoperatively with appropriate repair. More than 90 percent of vesicovaginal fistulas can and should be repaired vaginally. The procedures available for repair are the flap splitting and Latzko techniques. On occasion an abdominal approach is indicated, particularly for vesicouterine fistulas. Requirements for successful repair include adequate surgical exposure, wide mobilization of the vagina, nonexcision of the fistula tract, tension-free closure of the bladder, and grafting when indicated.

Female↗

Full-thickness Martius grafts to preserve vaginal depth as an adjunct in the repair of large obstetric fistulas.

We performed a modified bulbocavernosus full-thickness pedicle graft procedure on four patients with large obstetric fistulas in Ghana, West Africa. The bulbocavernosus fat pad was harvested in the usual manner, and the full-thickness skin patch was taken from the medial thigh. All grafts showed 100% take by the tenth postoperative day. Adequate vaginal depth and caliber were obtained in all patients. Sexual function resumed in all patients except one, who suffered a recurrent vesicovaginal fistula. This method of vaginoplasty may be useful in patients who have massive vaginal-wall destruction of either gynecologic or obstetric origin.

Adult↗

Acute retinal necrosis syndrome presenting with papillitis and arcuate neuroretinitis.

Acute retinal necrosis (ARN) syndrome is a diffuse uveitis characterized by a peripheral necrotizing retinitis and retinal vasculitis. The authors document and discuss a case of ARN syndrome that initially presented with remarkable changes in the peripapillary retinal nerve fiber layer that they have termed arcuate neuroretinitis. These changes consisted of a well-defined arcuate band of retinitis paralleling the course of a parafoveal nerve fiber bundle. Evaluation of serial serum antibody titers suggests HSV-2 as a possible causative agent in this unique presentation of ARN syndrome.

Acute Disease↗

Use of intravenous acyclovir for treatment of herpes zoster ophthalmicus in patients at risk for AIDS.

Patients who are homosexual, intravenous drug abusers, or have received multiple blood transfusions are at greater risk to contract the immunosuppressive disorders of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). These persons also have a greater chance of developing serious neurologic complications after an episode of Herpes zoster. We present two cases which emphasize the serious complications of Herpes zoster ophthalmicus in such patients. Since systemically administered acyclovir may shorten the disease course and reduce the complications of Herpes zoster in immunocompromised individuals, the authors favor treatment of all such patients who have Herpes zoster ophthalmicus with a seven-day course of high-dose (30 mg/kg/day) intravenous acyclovir. To minimize serious neurologic complications in such patients, treatment should be instituted immediately before the results of human immunodeficiency virus (HIV) testing are known.

AIDS-Related Complex↗

Identifying HSV infected neurons after ocular inoculation.

ICR mice were inoculated intracamerally with McKrae strain herpes simplex virus (HSV) followed by intraperitoneal injection with 3H-thymidine. Infected mice were sacrificed after 3 or 4 days and the eyes, trigeminal ganglia (TG) and superior cervical ganglia (SCG) were embedded in glycol methacrylate, sectioned, and dipped for autoradiography. Light microscopy revealed silver grain labeling over neurons in the ipsilateral retina, TG and SCG of infected animals. No labeling of neurons was noted in the contralateral TG or SCG. Since the DNA of mature neurons does not replicate, we interpret these labeled neurons to represent cells with active replication of HSV. This technique allows the study of HSV infection of the nervous system with excellent tissue preservation. Furthermore, it may be used to distinguish those neurons with intrinsic viral synthesis from those harboring virus synthesized at a distant site with subsequent intracellular spread.

Animals↗

Sinus node dysfunction in a healthy pediatric population.

ECG recordings of 624 healthy children (age range 6 to 12 years) from a rural population were analyzed for evidence of sinus node dysfunction. Twelve children were found to have the disorder and they underwent further assessment in order to establish any etiological factors or anatomical abnormalities. All the children were asymptomatic and physical examination was completely normal. Standard ECG taken during 24-h monitoring demonstrated that the most common finding, seen in 10 of 12 patients, was that of sinus arrest. Second-degree sinoatrial exit block, Mobitz type I, occurred in four children and Mobitz type II was seen in three. Two of the children were found to have holosystolic mitral valve prolapse, which was in the normal frequency range for a population of healthy children. After a 2-year follow-up and reassessment, there was no change in the symptomatology, the ECG tracings or the physical findings of any of the children.

Arrhythmia, Sinus↗

Regional distribution of the MB isoenzyme of creatine kinase in the human heart.

Human myocardial tissue obtained at autopsy from ten patients was examined for content of the MB isoenzyme of creatine kinase (CK-MB). We wished to determine whether this isoenzyme is distributed homogeneously throughout the heart. In eight cases, there was no history or pathological evidence of heart disease. Two had a history of previous myocardial infarction; in these, tissue was obtained from sites distant from the scar. Difference was found between the CK-MB content of the right atrium and the left atrium, and between the right ventricle and left ventricle. In all cases, the CK-MB content of the right side of the heart significantly exceeded that of the left side of the heart. Statistically significant differences were also found between the CK-MB content of the anterior interventricular septum and that of the posterior septum. These topographical variations in CK-MB content may be related to differences in the density of contractile elements in various parts of the heart and, moreover, are not taken into account in the enzymatic estimation of infarct size.

Creatine Kinase↗