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Biomedical subjects

J S Isenberg

Publications and source records attributed to J S Isenberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

The role of oxidative stress in chemical carcinogenesis.

Oxidative stress results when the balance between the production of reactive oxygen species (ROS) overrides the antioxidant capability of the target cell; oxidative damage from the interaction of reactive oxygen with critical cellular macromolecules may occur. ROS may interact with and modify cellular protein, lipid, and DNA, which results in altered target cell function. The accumulation of oxidative damage has been implicated in both acute and chronic cell injury including possible participation in the formation of cancer. Acute oxidative injury may produce selective cell death and a compensatory increase in cell proliferation. This stimulus may result in the formation of newly initiated preneoplastic cells and/or enhance the selective clonal expansion of latent initiated preneoplastic cells. Similarly, sublethal acute oxidative injury may produce unrepaired DNA damage and result in the formation of new mutations and, potentially, new initiated cells. In contrast, sustained chronic oxidative injury may lead to a nonlethal modification of normal cellular growth control mechanisms. Cellular oxidative stress can modify intercellular communication, protein kinase activity, membrane structure and function, and gene expression, and result in modulation of cell growth. We examined the role of oxidative stress as a possible mechanism by which nongenotoxic carcinogens may function. In studies with the selective mouse liver carcinogen dieldrin, a species-specific and dose-dependent decrease in liver antioxidant concentrations with a concomitant increase in ROS formation and oxidative damage was seen. This increase in oxidative stress correlated with an increase in hepatocyte DNA synthesis. Antioxidant supplementation prevented the dieldrin-induced cellular changes. Our findings suggest that the effect of nongenotoxic carcinogens (if they function through oxidative mechanisms) may be amplified in rodents but not in primates because of rodents' greater sensitivity to ROS. These results and findings reported by others support a potential role for oxidative-induced injury in the cancer process specifically during the promotion stage.

Animals↗
PubMed1997

The tetratricopeptide repeat containing Tg737 gene is a liver neoplasia tumor suppressor gene.

The Tg737 gene was investigated for gross alterations in a series of rodent/human liver tumors and human tumorigenic cell lines. The Tg737 gene was found to be altered in approximately 40% of the rodent chemically-induced liver tumors, 40% of the human liver tumors, and in liver, kidney and pancreatic human tumor cell lines. Ectopic re-expression of the Tg737 gene in a Tg737 deleted mouse liver tumor cell line resulted in suppression of tumorigenic growth, without altering in vitro cell culture growth. Treatment of mice which are either homozygous normal or heterozygous deleted at the Tg737 locus with the carcinogen diethylnitrosamine resulted in an increase in preneoplastic foci formation in the Tg737 heterozygous deleted mice. Ectopic expression of the Tg737 gene results in multinucleated cells, loss of Tg737 gene expression results in the proliferation of liver stem cells (oval cells) without concomitant differentiation, and reexpression of the Tg737 gene reestablished responsiveness to external differentiation factors. We believe this is the first report demonstrating tumor suppression activity for a tetratricopeptide repeat gene family member and provides insights into the function of this family of genes in mammalian cells.

Animals↗
PubMed1997

Quantitative evaluation of the effects of gravity and dependency on microvascular tissue transfer to the lower limb, with clinical applications.

The authors have attempted quantitatively to evaluate the effects of gravity and dependency on free-tissue transfers to the lower limb, particularly in the immediate postoperative period, using the diagnostic modalities of Doppler ultrasonography and interstitial compartment pressure measurements. Results of these quantitative evaluations promoted a change in postoperative management among patients undergoing lower-limb tissue transfer. The experience in two patient cohorts is presented.

Adult↗
PubMed1997

Inhibition of WY-14,643 induced hepatic lesion growth in mice by rotenone.

The effect of rotenone treatment on [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (WY-14,643) hepatic lesion growth in male B6C3F1 mice was investigated. Following induction of hepatic focal lesions by diethylnitrosamine (DEN) 35 mg/kg twice a week for 8 weeks, mice were placed into one of the four treatment groups: group I, control NIH-07 diet (control diet), group II, rotenone (600 mg/kg diet), group III NIH-07 diet containing WY-14,643 (1000 mg/kg diet), and group IV, NIH-07 diet containing WY-14,643 (1000 mg/kg diet) and rotenone (600 mg/ kg diet). Mice were killed after 30 and 60 days of dietary treatment. The effect of treatment with WY-14,643 and rotenone on hepatic lesion growth was examined by estimating the number of focal lesions per liver and the relative volume of focal lesions. WY-14,643 (group III) increased both the number and the volume of focal lesions. In particular, an increase in number and volume of basophilic lesions was seen. Co-treatment with WY-14,643 and rotenone (group IV) decreased both the number and the volume of the total number of focal lesions and basophilic foci compared with WY-14,643 treatment alone (group II). Alterations in the growth of hepatic focal lesions was further investigated by examining DNA synthesis and apoptosis within individual lesions. WY-14,643 (group III) treatment increased the DNA synthetic labeling index in all foci. Co-treatment of rotenone and WY-14,643 (group IV) decreased focal DNA synthesis and mitosis and increased the incidence of apoptotic hepatocytes. These data suggest that rotenone's ability to inhibit WY-14,643-induced hepatic focal lesion growth was mediated through a decrease in hepatic focal proliferation and an increase in focal apoptosis.

Adenoma↗
PubMed1997

What you see is what you get: lack of significant postoperative contour change in muscle transplants to the lower leg.

A widely held tenet in the reconstructive surgery literature is that muscle transplants undergo significant postoperative atrophy, contributing to progressive improvement in appearance of the reconstruction. In contrast, it has been our experience that muscle transplants retain the majority of their bulk following inset, and undergo minimal postoperative atrophy. Prospective evaluation of 20 patients undergoing muscle transplant reconstruction of Gustillo type IIIB lower limb wounds found minimal decrease in limb circumference at 6-month follow-up, as measured at the point of maximum transplant projection.

Adult↗
PubMed1997

Rectus abdominis muscle transplant in lower limb salvage: a recent series of 25 patients.

A recent series of 25 patients who underwent reconstruction of Gustilo IIIB lower extremity wounds with rectus abdominis muscle transplants is presented. Complications include one flap loss and one donor site skin incision dehiscence. At follow-up, a majority of patients were ambulatory and a third employed in some fashion. Comparison with a historical group of patients demonstrates continued improvement in surgical results.

Adolescent↗
PubMed1997

Timing, magnitude, and utility of surgical delay in the TRAM flap: I. Animal studies.

Surgical delay is an effective technique, but the precise timing of the delay effect and the required extent of the delay procedure are uncertain. We endeavored to study flap survival as a function of the duration of the delay period in a rat transverse rectus abdominis myocutaneous (TRAM) flap model. Two specific delay procedures (limited and extensive) were utilized, and flap survival was assessed after delay periods of 3, 7, 10, 14, 21, and 30 days (n > or = 7, all groups). A delay of 7 days or greater resulted in statistically significant improvement in flap survival in all groups. The delay effect appeared to be maximal at 14 days, and in the extensive delay group, a 14-day delay resulted in statistically greater flap survival than a 7-day delay. Improvement in flap survival was greater when an extensive delay procedure was used. Although the model system has limitations, the rat TRAM flap appears to be a suitable model for the study of the delay phenomenon. Possible clinical correlations are addressed in part II.

Analysis of Variance↗
PubMed1996

The limited value of preoperative angiography in microsurgical reconstruction of the lower limb.

Biplanar angiography has been a prerequisite in microvascular reconstruction of the lower extremity. While defining arterial anatomy, the procedure is not without morbidity. More important, angiography does not determine the acceptability of arterial blood flow through a particular recipient vessel. The purpose of this study was to evaluate the safety of microvascular tissue transplantation for reconstruction of complex lower-limb wounds, without preoperative angiography. A consecutive series of 48 patients undergoing tissue transplantation for complex wound reconstruction during a recent 8-month period is presented. Sixty percent of patients had soft-tissue wounds classified as Gustilo IIIB preoperatively, although 89 percent of wounds ultimately arose from trauma. Preoperative and intraoperative clinical assessment of recipient vessels allowed successful reconstruction in all but one case. The only loss of a transplant arose as a result of venous outflow obstruction, a situation not to be improved by preoperative angiography. In no instance was a patient explored and reconstruction deferred due to inadequate recipient vasculature. The results of this study support microvascular tissue transplantation to lower-limb wounds without preparatory angiography in almost all circumstances. Adequate clinical parameters are presented for determining recipient pedicle status, both preoperatively and intraoperatively.

Adolescent↗
PubMed1996

Zone of injury: a valid concept in microvascular reconstruction of the traumatized lower limb?

Microvascular reconstruction at the lower extremity for complex composite wounds has traditionally been predicated upon performance of the microanastamosis beyond the so-called "zone of injury." Failure to do so was believed to account for increased rates of vessel thrombosis and transplant loss. Extensive vessel dissection and vein grafts were often employed in efforts to avoid the zone of injury. To further analyze the validity of this concept, we conducted a prospective evaluation of all patients undergoing microvascular reconstruction of composite lower limb wounds during a 5-month period at Los Angeles County Medical Center. There were 28 patients in this cohort. Twenty-six (93%) were judged Gustilo IIIB or worse preoperatively. Distance from the microanastamosis to the proximal bony osteotomy (zone of injury) averaged 45.7 mm. In no case was a vein graft required. All transplants healed uneventfully without any loss. A reassessment of the concept of zone of injury is urged with analysis of the quality of the recipient vessels and not their location being clinically important.

Adult↗
PubMed1996

Microvascular transplantation in the salvage of lower extremity trauma in the elderly.

Successful salvage of Gustilo IIIB tibial fractures with microvascular transplantation has been documented in the young. Similar results from the application of these techniques to the elderly has not been demonstrated. An 8-year review located 12 patients 60 years or older who underwent soft tissue reconstruction of IIIB tibial fractures with microvascular transplants. Ten patients were available for long-term follow-up (average 43 months). To date, 80% remain ambulating with no secondary amputations or late infections reported.

Activities of Daily Living↗
PubMed1996

Permanent lip augmentation using autologous breast implant capsule.

Permanent augmentation of lip volume can be achieved either with autologous or nonautologous implants. The constant risk of infectious complications remains the disadvantage of nonautologous implants. Likewise, autologous implants of dermis, fat, or fascia are prone to reabsorption and require an additional donor incision. In several patients undergoing revisional aesthetic breast augmentation, grafts of scar capsule were utilized for lip augmentation. Results at 10 months demonstrate persistent volume enhancement.

Adult↗