Sexual violence in patients with psychiatric conditions: Factors for consideration in case management.

Patients with underlying psychiatric conditions are vulnerable to the experience of sexual violence. Barriers and facilitators to disclosure exist, at the level of the individual, healthcare system, legal system and society in general. Management requires a trauma-informed approach with a focus on avoidance of stigma, optimisation of pre-existing psychiatric conditions and appropriate treatment of psychological sequalae. Preventive strategies by the patient, practitioner and healthcare system, may assist to reduce the risk of future sexual violence.

Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series.

BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.

Smear layer removal efficacy of different irrigating solutions: a comparative scanning electron microscope evaluation.

AIMS: Comparative evaluation of cleaning efficacy of smear layer removal by different irrigating solutions such as 2.5% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA) with 2.5% NaOCl, 10% citric acid with 2.5% NaOCl and 1% tetracycline Hydrochloride (HCl) with 2.5% NaOCl for smear layer removal in the apical third of root canal. SETTINGS AND DESIGN: In vitro material science study. MATERIALS AND METHODS: Seventy-five single rooted permanent maxillary central incisor teeth were subjected to standardized root canal instrumentation (crown down technique). The teeth were randomly divided into five groups with 15 teeth in each groups: (1) Normal saline (n = 15) (2) 2.5% NaOCl (n = 15) (3) 17% EDTA + 2.5% NaOCl (n = 15) (4) 10% citric acid + 2.5% NaOCl (n = 15) (5) 1.0% tetracycline HCL + 2.5% NaOCl (n = 15). After final irrigation, the teeth were prepared for scanning electron microscope analysis to evaluate the cleaning of apical third of radicular dentine to determine the presence or absence of smear layer. STATISTICAL ANALYSIS USED: The results were analyzed by nonparametric statistical analysis techniques. Kruskal-Wallis test, Mann-Whitney test and Chi-square tests were carried out. RESULTS: There was no significant statistical difference in the efficacy of smear layer removal when 2.5% NaOCl was compared with 17% EDTA with 2.5% NaOCl, 10% citric acid with 2.5% NaOCl and 1% tetracycline HCl with 2.5% NaOCl in apical third of root canals. CONCLUSIONS: The present study suggests that irrigating agents, citric acid and tetracycline HCl can be used as an alternative to EDTA for the removal of smear layer in endodontics.

Comparative evaluation of microleakage of silorane-based composite and nanohybrid composite with or without polyethylene fiber inserts in class II restorations: an in vitro study.

AIM: To evaluate microleakage between nanocomposite and silorane composite in class II restorations with or without a polyethylene fiber insert. METHODOLOGY: Standardized class II cavities were prepared on extracted molars and randomly divided into 4 groups (n=20 each): group 1, Ceram X mono; group 2, Ceram X mono + Ribbond; group 3, Filtek P90; and Group 4, Filtek P90 + Ribbond. All specimens were subjected to a thermocycling regime, immersed in 2% methylene blue dye for 24 hours, sectioned longitudinally, and examined under a stereomicroscope to assess dye penetration on a six-point scale. The score data were subjected to statistical analysis whereby Kruskal-Wallis analysis of variance was used for multiple group comparisons and the Mann-Whitney test for groupwise comparisons at a significance level of p≤0.05. RESULTS: A statistically significant decrease in microleakage was found when Ribbond fiber was used with nanoceramic and silorane composite. A highly significant decrease in microleakage scores was found in silorane composite when compared to nanoceramic composite. CONCLUSION: Use of polyethylene fiber and silorane composite reduces microleakage in class II composite restorations with gingival margins below the cemento-enamel junction.

Islet-specific microRNAs in pancreas development, regeneration and diabetes.

Diabetes is a chronic and slowly progressive disease that is presently reaching epidemic proportions in several parts of the world. Multiple aspects including genetic and lifestyle changes have been identified as the key factors leading to the development of type 1 and type 2 diabetes. Although molecular mechanisms underlying the pathogenesis of diabetes remain unclear, recent discoveries in understanding post-transcriptional gene regulation by microRNAs (miRNAs) has opened a new area of research. MicroRNAs have been implicated as new players in pathogenesis as well as complications of diabetes. MiRNAs have been shown to be necessary not only during embryonic development of insulin-producing cells, transcription of (pro-)insulin gene and insulin secretion, but also in development of insulin resistance and diabetes. The present review summarizes the findings related to understanding the role of miRNAs in endocrine pancreas development, pancreas regeneration, islet function and diabetes.

Taurine supports preservation of proendocrine cell types in human umbilical cord blood-derived mononuclear cells during cryostorage.

BACKGROUND: We demonstrated earlier that a subset of human umbilical cord-blood (hUCB)-derived mononuclear cells (MNCs) express proendocrine transcription factors and exhibit potential to differentiate into endocrine pancreatic lineage. The growing interest in the use of MNCs for diabetes has promoted cryopreservation of these cells for future use in translational research. Development of optimal cryopreservation media is critical to the success of translational research. METHODS: We explored protective effects of taurine in cryopreservation of hUCB-derived MNCs. MNCs were isolated using Histopaque and 3 million viable cells were cryofrozen using 10% dimethyl sulfoxide (v/v) in fetal bovine serum or supplemented with taurine (0.3/3.0 mmol/L). Cryopreservation conditions were assessed based on their viability, growth, and ability to retain endocrine pancreatic transcription factor expressing cells. RESULTS: UCB-derived MNCs adhered and grew as mesenchymal-like cells in culture following revival from various cryopreservation conditions. Interestingly, MNCs expressed threefold more ngn3, 2-fold more nkx6.1, and 15-fold more isl1 transcripts in taurine-supplemented cryo-medium compared to the conventional cryomix. CONCLUSION: The present study demonstrates that taurine supplementation to cryopreservation media improved retention of endocrine pancreatic transcription factor-expressing MNCs.

Invariant natural killer T cells: innate-like T cells with potent immunomodulatory activities.

Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that react with glycolipid antigens presented by the major histocompatibility complex class I-related glycoprotein CD1d. Although iNKT cells express an antigen-specific receptor of the adaptive immune system, they behave more like cells of the innate immune system. A hallmark of iNKT cells is their capacity to produce copious amounts of immunoregulatory cytokines quickly after activation. The cytokines produced by iNKT cells can influence the level of activation of many cell types of the innate and adaptive immune systems as well as the quality of an adaptive immune response. As such, iNKT cells have emerged as important regulators of immune responses, playing a role in microbial immunity, autoimmunity, tumor immunity, and a variety of inflammatory conditions. Although several endogenous and exogenous glycolipid antigens of iNKT cells have been identified, how these glycolipids orchestrate iNKT-cell functions remains poorly understood. Nevertheless, iNKT cells hold substantial promise as targets for development of vaccine adjuvants and immunotherapies. These properties of iNKT cells have been investigated most extensively in mouse models of human disease using the marine sponge-derived agent alpha-galactosylceramide (alpha-GalCer) and related iNKT-cell antigens. While these preclinical studies have raised enthusiasm for developing iNKT-cell-based immunotherapies, they also showed potential health risks associated with iNKT cell activation. Although alpha-GalCer treatment in humans was shown to be safe in the short term, further studies are needed to develop safe and effective iNKT-cell-based therapies.

Administration of 5-androstenediol to mice: pharmacokinetics and cytokine gene expression.

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in military and civilian populations associated with possible exposure to ionizing radiation. Previous studies in mice have shown that a single subcutaneous (sc) injection of the natural steroid androst-5-ene-3beta,17beta-diol (5-androstenediol, 5-AED), 24-48 h prior to a lethal dose of whole-body (60)Co gamma radiation, stimulated hematopoiesis and enhanced survival. These effects are consistent with our previous observation of 5-AED-induced elevations in circulating G-CSF in normal and irradiated mice. The purpose of this study was to obtain data on the pharmacokinetics of 5-AED after sc and buccal administration to mice, and to determine whether cytokine genes are induced by sc 5-AED in hematopoietic tissues (bone marrow, spleen). We studied effects on serum cytokines and chemokines, and also analyzed the pharmacokinetics of 5-AED after sc administration and compared it with buccal delivery. 5-AED was administered 24 h before irradiation or sham-irradiation. Cytokine mRNAs were quantified by quantitative real-time PCR (QRT-PCR), and cytokine levels in serum by multiplex Luminex. 5-AED administration was associated with elevation of message for GM-CSF, IL-2, IL-3, IL-6, and IL-10 in spleen, and GM-CSF and IL-2 in bone marrow. Irradiation enhanced G-CSF, GM-CSF, IFN-gamma, TPO, IL-2, IL-3, IL-6, IL-10, and IL-12 in spleen, and GM-CSF, IFN-gamma, TPO, IL-3, and IL-10 in bone marrow. Serum levels of G-CSF were significantly elevated in 5-AED-treated mice 4 h after irradiation or sham-irradiation. Serum macrophage inflammatory protein-1gamma (MIP-1gamma) was significantly elevated 4 h after irradiation in 5-AED-treated mice. Plasma 5-AED peaked 2 h after sc injection (30 mg/kg), and remained significantly above control after 4 days, but not 8 days. The time course of plasma 5-AED after buccal delivery (60 mg/kg) was similar, but levels were significantly lower compared to sc delivery. Plasma 5-AED 24 h after administration was not significantly different between sc and buccal delivery. However, in contrast to many studies showing enhanced survival after sc administration of 5-AED, we found no effect on survival of buccal 5-AED. The results suggest that radioprotection is not dependent on the 5-AED concentration at the time of irradiation, but rather on events triggered during the first few hours after administration. The current results suggest that further studies are warranted to directly test the roles of cytokines in the radioprotective effects of 5-AED.

Altered expression and activity of G-proteins, mitogen activated protein kinases, and tyrosine kinases in aging kidney cortex.

BACKGROUND: Renal function declines with age and this may be related to changes in the expression or activity of various signal transduction proteins in the kidney. METHODS: The present study compared the expression and activity of G alpha i(1-3) and G alpha s phosphorylation of mitogen activated protein kinases (MAP-K) (44 and 42 kd) and the activity of tyrosine kinase in renal cortical homogenates of young (4-month-old) and aging (14-month-old) rats. RESULTS: The GTP/(GTP + GDP) binding ratio of G alpha s was significantly decreased in the kidney cortex of aging rats compared to young rats, while the GTP/(GTP + GDP) binding ratio of G alpha i(1-3) increased significantly in kidney cortex of aging rats. Tyrosine kinase activity and phosphorylation of MAP-K (44 and 42 kd) were also reduced in the kidney cortex of aging rats compared to young rats. CONCLUSIONS: These results suggest that diminished phosphorylation of MAP-K and tyrosine kinase activity as well as changes in the binding of GTP/(GTP + GDP) to G alpha i(1-3) and G alpha s may contribute to the age-related decline in renal tubular and vascular function seen in aging animals.

Role of tyrosine kinase, ODC, and p34cdc2 kinase and cyclin B-associated cdc2 in jejunal enterocyte proliferation, maturation, and exfoliation in diabetic and DFMO-treated rats.

BACKGROUND: Several signal transduction pathways involved in rapidly proliferating cells of the intestine are currently not well understood. In the jejunum, crypt enterocytes are constantly replicating, lower villi are maturing, and upper villi are constantly shed. Type I diabetes is associated with jejunal mucosal hyperplasia, and administration of diflouromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), causes hypoplasia. Phosphorylation of proteins controls cellular proliferation and/or exfoliation. Cell division cycle kinase (p34cdc2) and cyclin B-associated p34cdc2 kinase regulate the cell cycle during the transition from G2-M phase. Our aims were to: 1) investigate the activities of tyrosine kinase, ODC, total p34cdc2 kinase, and cyclin B-associated p34cdc2 kinase and 2) phosphorylate proteins at tyrosine residues in jejunal upper villi, lower villi, and crypt enterocytes of DFMO-treated control and diabetic rats. METHODS: Diabetes was induced by streptozotocin. DFMO was administered in drinking water in both control and diabetic groups for 10 days after the induction of diabetes. Jejunal enterocytes were isolated and kept frozen at -70 degrees C until ready to process. RESULTS: Diabetic rats showed jejunal mucosal hyperplasia as indicated by increases in the jejunal mucosal weight/cm and DNA content compared to control rats. Diabetic crypt enterocytes showed significant increases in activities of tyrosine kinase, ODC, total p34cdc2 kinase, and cyclin B-associated cdc2 as well as increased phosphorylation of proteins at tyrosine residues compared to control rats. DFMO prevented diabetes-induced jejunal hyperplasia, and decreased the activities of these enzymes and phosphorylation of proteins at tyrosine residues in both diabetic and control rats. Phosphorylation of a 14 kd protein became prominent in crypt, upper villi, and lower villi enterocytes of DFMO-treated diabetic and control groups. CONCLUSION: Diabetic jejunal mucosal hyperplasia appears to involve activation of complex signal transduction pathways such as tyrosine kinase, ODC, p34cdc2 kinase, and cyclin B. These enzymes are involved in proliferation and/or exfoliation of jejunal enterocytes. Our results also suggest that tyrosine phosphorylation of a 14 kd protein may be involved in cell exfoliation and that jejunal mucosal hypoplasia may be a synergistic effect caused by down regulation of the above enzymes.

Effects of diabetes and difluoromethylornithine treatment on hyperplasia, activity of MAP-kinase, and activity and association with cyclin B of p34cdc2 kinase in rat jejunal mucosa.

BACKGROUND: The different signal transduction pathways of rapidly proliferating cells of the intestine are not clearly understood. We report here a possible signaling pathway that involves regulation of activity of two closely related kinases, MAP-K (mitogen-activated protein kinase) and p34cdc2 kinase, during hyperplasia of diabetic jejunal mucosa. Our aim was to investigate the activity and phosphorylation of MAP-K and activity and association of p34cdc2 kinase with cyclin B during diabetes-induced jejunal mucosal hyperplasia in vivo. METHODS: We studied untreated and difluoromethylornithine (DFMO) treated control rats and rats with streptozotocin-induced type I diabetes. Assays were done 10 days after the induction of diabetes. In diabetic rats there was jejunal hyperplasia as indicated by increases in the jejunal mucosal weight/cm and DNA content as well as increased activities of MAP-K and p34cdc2 kinase and association of the latter with cyclin B as compared to corresponding values in control rats. Administration of DFMO, an irreversible inhibitor of the proliferation-associated enzyme ornithine decarboxylase (ODC), prevented diabetes-I induced jejunal hyperplasia and decreased all of the above enzymic parameters in both diabetic and control rats. In our previous in vivo study, DFMO administration also blocked diabetic jejunal hyperplasia and in addition decreased ornithine decarboxylase and tyrosine kinase activities jejunal and tyrosine phosphorylation of proteins. CONCLUSION: Thus the jejunal mucosal hyperplasia found in diabetes appears to involve activation of signal transduction pathways involving tyrosine kinases, MAP-K, p34cdc2 kinase, and cyclin B.

Evidence of sex-specific differences in masticatory jaw movement patterns.

The complexity of human oral functional movements has not been studied in detail quantitatively, and only recently have studies begun to evaluate whether such movements contain sex-specific characteristics. Therefore, the purposes of this study were: (1) to quantify in detail the jaw movements and associated masticatory electromyographic activity occurring during gum chewing, and (2) to explore these data for evidence of sex specificity. Fourteen male and 17 female subjects participated in the study. Approximately 11 right- and 11 left-sided chewing cycles and associated masticatory electromyographic activity were sampled from each subject. The samples were quantified into 165 variables per chewing cycle, averaged to create a single multivariate vector for each subject, and then analyzed by a step-wise discriminant analysis. With a combination of 6 variables, a jackknifed cross-validation test found the probability of correct classification to be 93.5%. These findings support the hypothesis that masticatory jaw movements contain sex-specific features.

Intratracheal surfactant administration preserves airway compliance during lung reperfusion.

BACKGROUND: Decreased airway compliance after lung transplantation has been observed with severe ischemia-reperfusion injury. Further, it has been shown that the surfactant system is impaired after lung preservation and reperfusion. We hypothesized that surfactant replacement after allograft storage could preserve airway compliance during reperfusion. METHODS: Rabbit lungs were harvested after flush with 50 mL/kg of cold saline solution. Immediate control lungs were studied with an isolated ventilation/perfusion apparatus using venous rabbit blood recirculated at 40 mL/min, room-air ventilation at 20 breaths/min, and constant airway pressure (n = 8). Twenty-four-hour control lungs were preserved at 4 degrees C for 24 hours and then similarly studied (n = 7). Surfactant lungs underwent similar harvest and preservation for 24 hours, but received 1.5 mL/kg of intratracheal surfactant 5 minutes before reperfusion (n = 10). Airway pressure and flow were recorded continuously during 30 minutes of reperfusion. Tidal volume and airway compliance were calculated at 30 minutes. RESULTS: Tidal volume was 33.67 +/- 0.57, 15.75 +/- 5.72, and 29.83 +/- 1.07 mL in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.004, surfactant versus 24-hour control). Airway compliance was 1.94 +/- 0.27, 0.70 +/- 0.09, and 1.46 +/- 0.10 mL/mm Hg in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.002, surfactant versus 24-hour control). CONCLUSIONS: We conclude that surfactant administration before reperfusion after 24 hours of cold storage preserves tidal volume and airway compliance in the isolated ventilated/perfused rabbit model of lung reperfusion injury.

Relation of ornithine decarboxylase and tyrosine kinase activity in the jejunal mucosa in vivo.

Our aim was to study the relationship between jejunal mucosal activity of ornithine decarboxylase and tyrosine kinase during proliferation in adolescent rats in vivo. Their relationship in the proliferating intestinal mucosa under in vivo conditions has not been reported before. From the results of in vitro studies, it was speculated that tyrosine kinase activity modulated ornithine decarboxylase activity during colonic mucosal proliferation (Majumdar AP. Am J Physiol 259:G626-G630, 1990). Jejunal mucosal hyperplasia was induced by Type 1 diabetes and suppressed in both control and diabetic rats by administration of difluoromethylornithine. Jejunal mucosal weight and enzyme activity were determined after 3, 6, and 10 days, and tyrosine-specific phosphorylated proteins after 10 days of induction of diabetes. Difluoromethylornithine suppressed jejunal mucosal proliferation and tyrosine kinase activity after the 6- and 10- day study periods. After the 3-day study period although jejunal mucosal growth was suppressed, tyrosine kinase activity was not. Activity of tyrosine kinase and ornithine decarboxylase were highly significantly correlated at all time periods in both control and diabetic rats. Tyrosine-specific phosphorylated proteins of 34, 54, 80, and 200 kDa proteins were observed in jejunal mucosa of both control and diabetic rats. In the difluoromethylornithine-treated rats, phosphorylation of the above proteins was negligible while the phosphorylation of a 14-kDa protein was prominent. We speculate that in vivo ornithine decarboxylase activity may be modulating tyrosine kinase activity and that phosphorylation of a 14-kDa protein was associated with suppressed mucosal growth in difluoromethylornithine-treated rats.

Pulmonary function after non-heart-beating lung donation in a survival model.

BACKGROUND: Lung procurement from recently deceased cadavers has been suggested to enlarge the limited donor pool. We hypothesized that lungs harvested from non-heart-beating donors (NHBD) would function as well as those harvested from heart-beating donors. METHODS: Sixteen adult swine underwent left lung allotransplantation. Controls received lungs procured from heart-beating donors, NHBD pigs received lungs immediately harvested from donors after death from asphyxiation, and NHBD-15 and NHBD-30 pigs received lungs harvested after 15 and 30 minutes after asphyxiation. RESULTS: After 1 week of survival, mean dynamic airway compliance (mL/cm H2O +/- standard error of the mean) was 16.3 +/- 0.7 in controls, and 17.3 +/- 1.0, 16.4 +/- 6.0, and 7.3 +/- 1.6 in the NHBD, NHBD-15, and NHBD-30 groups, respectively (p = 0.02, NHBD-30 versus others combined). No significant differences were noted in the pulmonary venous partial pressure of oxygen or pulmonary vascular hemodynamics compared with controls. CONCLUSIONS: The decrease in airway compliance noted in the NHBD-30 group may reflect an exacerbation of reperfusion injury caused by 30 minutes of warm ischemia during organ retrieval. We conclude that posttransplantation lung function using an NHBD with up to 15 minutes of warm ischemia is equivalent to lung function after heart-beating harvest.

Intestinal mucosal ornithine decarboxylase and brush border membrane vesicle Na(+)-H+ exchange activities in diabetic rats.

To determine the possibility that intestinal mucosal ornithine decarboxylase activity can modulate mucosal brush border membrane Na(+)-H+ exchange activity, we studied the relationship between jejunal mucosal ornithine decarboxylase activity and mucosal brush border membrane Na(+)-H+ exchange activity in adolescent streptozotocin-diabetic and normal control rats. Diabetes was associated with enhanced intestinal mucosal ornithine decarboxylase and Na(+)-H+ exchange activities. Groups of diabetic and control rats were given difluoromethylornithine in drinking water to suppress intestinal mucosal ornithine decarboxylase activity. As expected, 10 days after induction of diabetes, intestinal mucosal weight (67.7 mg/cm vs 56.1 mg/cm), DNA (47.3 micrograms/mg protein vs 32.7 micrograms/mg protein), ornithine decarboxylase activity (1107 units/hr vs 654 units/hr), and brush border membrane vesicle Na(+)-H+ exchange activity, assessed as Vmax of 22Na+ uptake (32.5 nmol/mg protein/15 min vs 15.2 nmol/mg protein/15 min), were significantly greater in diabetic than in control rats. Treating diabetic and control rats with difluoromethylornithine suppressed jejunal mucosal growth by over 30%, ornithine decarboxylase activity by over 80%, and brush border membrane vesicle 22Na+ uptake by over 60%. Highly significant direct correlations (r > 0.900) were observed between jejunal DNA content, mucosal ornithine decarboxylase activity, and brush border membrane vesicle Na(+)-H+ exchange activity. The above findings suggest that jejunal mucosal ornithine decarboxylase activity can modulate mucosal epithelial proliferation and mucosal brush border membrane Na(+)-H+ exchange activity.

Polyamines and intestinal epithelial hyperplasia in streptozotocin-diabetic rats.

We measured specific activity of ornithine decarboxylase (ODC) and contents of putrescine and of the polyamines (spermidine and spermine) in isolated villus and crypt enterocytes from the jejunum of adolescent streptozotocin-diabetic and weight-matched control rats and diabetic and control rats treated with difluoromethyl ornithine (DFMO) 10 days after induction of diabetes. Consistent with previous observations by others of elevated ODC activity and contents of putrescine and of the polyamines in the intestinal epithelium undergoing hyperplasia, our studies showed elevated ODC activity and contents of putrescine and spermidine, but not of spermine, in the hyperplastic intestinal epithelium of diabetic rats. As in previous studies, suppression of ODC activity by DFMO prevented not only the jejunal epithelial hyperplasia in the diabetic rats, but also retarded jejunal epithelial growth in the control rats. DFMO administration lowered ODC activity by over 80% in both diabetic and control rat enterocytes and prevented the rise in enterocyte contents of putrescine and spermidine in the diabetic rat. The observation that, in both diabetic and control rats, treatment with DFMO lowered spermidine content in the crypt enterocytes but had no similar consistent effect on contents of putrescine or spermine suggested that spermidine could have been responsible for the intestinal epithelial hyperplasia in the diabetic rats and for the normal growth of the intestinal epithelium in control rats.

Superficial fascia--an appropriate anatomic boundary for excising warts on the foot.

When performing wart surgery of the foot, it is necessary to excise the lesion to the level where the superficial fascia is visible. This approach minimizes painful scar formation and ensures complete removal of the wart.

Antibody reactivity with HBLV (HHV-6) in U.S. populations.

500 sera representing healthy blood donors and a random representation of the U.S. population collected 10 years ago were screened by ELISA for antibody reactivity with purified, disrupted HBLV virions. In each group, the ELISA results were normally distributed with no evidence of bimodality. All sera were subsequently retested after preincubation of each with well-characterized preparations of disrupted HSB-2 cells or HBLV-infected HSB-2 cells. Sera showing significant levels of HBLV-specific neutralization (50% or more) were found in Minneapolis, Kansas City, and in a random population survey (81, 88 and 97% of donors, respectively). Mean ELISA test values were the same for all groups and for males and females within the same group. Sera from these normal donors reacted preferentially with viral antigens of 120 and 58 kDa by Western blot. In a hospital-based prevalence study, frequent IgM and IgG seroconversions were apparent among infants less than 1 year old, and mean ELISA test values reached the adult level before school age. Antigen preparations used in blocking experiments showed no competitive cross-reactivity with antisera against EBV, CMV, HSV, VZV, HIV, or adenovirus type 2 at levels which reduced antibody binding to HBLV by more than 90%. Antibody cross-reactivities towards HBLV and other human herpesviruses were assessed by cross-correlation of viral antibody titers against all of the viruses and by cross-absorptions of antisera against the other viruses with HBLV. In these experiments no antibody cross-reactivity between HBLV and other human herpesviruses were detected. The significance of these findings with respect to health/disease status is presently unknown. Further seroepidemiologic studies of quantitative levels of HBLV antibody reactivity to measure the age of primary infection and progressive changes in healthy and selected disease populations are needed to determine the risk of disease associated with HBLV infection.