High-mobility Group Box Protein-1, Matrix Metalloproteinases, and Vitamin D in Keloids and Hypertrophic Scars.

Keloids and hypertrophic scars represent excessive wound healing involving high production of collagen by skin fibroblasts. This review focuses on the role of high-mobility group box protein-1 (HMGB-1), matrix metalloproteinases (MMPs), and vitamin D in these conditions. Although the role of HMGB-1 in keloids and hypertrophic scars is unclear, the effect of HMGB-1 on fibroblasts suggests a profibrotic role and a potential contribution to excessive scarring. MMPs contribute extensively to wound healing and characteristically degrade the extracellular matrix. MMP-1 is decreased in keloids and hypertrophic scars. However, other MMPs, including MMP-2, have been found to be increased and are thought to possibly contribute to keloid expansion through peripheral extracellular matrix catabolism. Many novel therapeutic approaches to keloids and hypertrophic scars target MMPs and aim to increase their levels and catabolic activity. The higher prevalence of keloids in darker skin types may partially be due to a tendency for lower vitamin D levels. The physiologically active form of vitamin D, 1,25(OH)2D3, inhibits the proliferation of keloid fibroblasts, and correlations between vitamin D receptor polymorphisms, such as the TaqI CC genotype, and keloid formation have been reported. Additionally, vitamin D may exert an antifibrotic effect partially mediated by MMPs. Here, we critically discuss whether keloid and hypertrophic scar formation could be predicted based on vitamin D status and vitamin D receptor polymorphisms. Specifically, the findings identified HMGB-1, MMPs, and vitamin D as potential avenues for further clinical investigation and potentially novel therapeutic approaches to prevent the development of keloids and hypertrophic scars.

Study of two-neutron radioactivity in the decay of 26O.

A new technique was developed to measure the lifetimes of neutron unbound nuclei in the picosecond range. The decay of 26O→24O+n+n was examined as it had been predicted to have an appreciable lifetime due to the unique structure of the neutron-rich oxygen isotopes. The half-life of 26O was extracted as 4.5(-1.5)(+1.1)(stat)±3(syst) ps. This corresponds to 26O having a finite lifetime at an 82% confidence level and, thus, suggests the possibility of two-neutron radioactivity.

Evidence for the ground-state resonance of 26O.

Evidence for the ground state of the neutron-unbound nucleus (26)O was observed for the first time in the single proton-knockout reaction from a 82 MeV/u (27)F beam. Neutrons were measured in coincidence with (24)O fragments. (26)O was determined to be unbound by 150(-150)(+50) keV from the observation of low-energy neutrons. This result agrees with recent shell-model calculations based on microscopic two- and three-nucleon forces.

Exploring the low-Z shore of the island of inversion at n=19.

The technique of invariant mass spectroscopy has been used to measure, for the first time, the ground state energy of neutron-unbound (28)F, determined to be a resonance in the (27)F+n continuum at 220(50) keV. States in (28)F were populated by the reactions of a 62 MeV/u (29)Ne beam impinging on a 288 mg/cm(2) beryllium target. The measured (28)F ground state energy is in good agreement with USDA/USDB shell model predictions, indicating that pf shell intruder configurations play only a small role in the ground state structure of (28)F and establishing a low-Z boundary of the island of inversion for N=19 isotones.

Surgical management of acquired (cicatricial) buried penis in an adult patient.

The pathological entity of the buried penis occurs most commonly in children and is usually managed by urologists. Its presentation in the adult population may invoke plastic surgery expertise. The pathophysiology of buried penis in the adult is entirely distinct from that in children, and management principles may be complicated. Many plastic surgeons are unaware of the entity, even though they may be called to assist urology specialists in the management of complications in an adult patient. Not surprisingly, precious little information is available in the plastic surgical literature to provide management guidelines for this condition. This report highlights evaluation and management principles in an unusual case of adult (acquired, cicatricial) buried penis, and helps define the role of the plastic surgeon in such cases.

Reactivation of herpes simplex virus from latently infected mice after administration of cadmium is mouse-strain-dependent.

It was previously reported that administration of cadmium (Cd) to CBA mice latently infected with herpes simplex virus (HSV) results in a high incidence of virus reactivation in vivo. In the present study, Cd-inducible reactivation was used to compare CBA with four other laboratory mouse strains. HSV reactivation, as measured by the recovery of infectious particles from latently infected trigeminal ganglia following Cd treatment, occurred predominantly in the CBA strain and was almost entirely absent from other strains tested. There was no correlation of strain-dependent Cd toxicity with the recovery of infectious virus. In situ examination of Cd-treated ganglia from latently infected CBA and BALB/c mice revealed that viral antigens were expressed exclusively in CBA specimens, but that viral replicative transcripts were expressed in both strains, although more strongly in CBA than in BALB/c specimens. We conclude that Cd treatment had induced reactivation of HSV from both mouse strains, and that the reactivation process was completed in CBA but not in BALB/c mice.

Screening for specific inhibitors of phagocytosis of thioglycollate-elicited macrophages.

Phagocytosis is one of the basic and characteristic properties of macrophages. We screened metabolites of Actinomyces for low molecular weight substances that selectively inhibited phagocytosis of dried yeast but not pinocytosis of neutral red by thioglycollate-elicited peritoneal macrophages. Inhibitors of actin filament organization, protein kinases, respiration, and lipid synthesis selectively inhibited phagocytosis, and blockers of proton gradients selectively inhibited pinocytosis. This suggests that these functions are differently regulated. We applied this system to screening of metabolites of Actinomyces, and identified mycotrienin, piericidin, and genistein as selective inhibitors of phagocytosis.

An HSV LAT null mutant reactivates slowly from latent infection and makes small plaques on CV-1 monolayers.

A Herpes simplex virus type I (HSV-I) strain 17 mutant deleted between the NotI and HpaI restriction sites of the latency associated transcript (LAT) region has been constructed. The mutant, therefore, contains a deletion of the putative LAT promoter and is called 17N/H. The 17N/H isolate established latent infections in mice nearly as efficiently as its wildtype parent. However, like other LAT null mutants, 17N/H reactivates from explanted ganglia with much slower kinetics than its LAT competent parent. In tissue culture, although 17N/H produces as much virus per cell as its strain 17 parent, it produces small plaques. The small plaque phenotype appears to be due to the inability of the virus to be released from the infected cell into the medium, following low but not high multiplicities of infection (m.o.i.). The mutant was also shown to produce an aberrant LAT homologous transcript of 1.1 kb as well as overproduce an approximately 29,000-Da HSV-specific polypeptide, which is barely detectable in wildtype infected cells. Rescuants of the 17N/H defect were constructed using a 10-kb restriction fragment containing viral sequences spanning the deletion, make large plaques, and have reactivation patterns and infected cell gene product profiles indistinguishable from the 17 parent. This shows that the phenotypes observed in 17N/H are reversed when the deletion, or at most sequences within 5 kb of each side of the deletion, is corrected. The possibilities that the defect in viral egress from infected cell, the small LAT homologous transcript, and the accumulation of the 29,000 Da polypeptide are related to the delayed reactivation kinetics are discussed.