Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3-/- mice.

Identifying versatile inhibitors of metastasis that operate in multiple sites against distinct cancer cell types is important for designing novel therapeutics for metastasis. We show that multiple tissues of timp-3-/- mice are more susceptible to metastatic colonization. Overall, a 5-14-fold increase in liver and kidney colonization occurred by EL-4 lymphoma cells, and a twofold increase upon targeting B16F10 melanoma cells to the bone or lung of timp-3-/- mice. There was a general lack of macrophage or neutrophil localization to metastases in the liver, kidney and lung, and of osteoclasts to bone in both genotypes. Analysis of lung showed that proliferation or angiogenesis were unaltered within the metastatic colonies. Lung-trap assays revealed that initial tumor cell trapping was similar in the lung vasculature of timp-3-/- and wild-type mice. However, more tumor cells were found in timp-3-/- lungs at 48 and 96 h after tumor cell injection indicating more efficient extravasation and initial proliferation. Activation of pro-MMP-2 was greater in timp-3-/- lungs at these time points. These data demonstrate TIMP-3 functions to inhibit metastatic dissemination of diverse cancer cells to multiple organs. TIMP-3 regulates MMP-2 activation to limit tumor cell extravasation and subsequent colonization of the lung, without augmenting inflammatory cell response.

Effect of the menstrual cycle on endothelium-dependent vasodilation of the brachial artery in normal young women.

In normal young women, endothelium-dependent, flow-mediated vasodilation is enhanced when serum estradiol levels are elevated and unopposed by elevated levels of progesterone.

Characterization of muscarinic receptors of bovine adrenal chromaffin cells: binding, secretion and anti-microtubule drug effects.

1. Binding of [3H]QNB to adrenal membranes is saturable, specific and to a single class of receptors. 2. Tubulozole, and not other microtubule drugs, inhibits [3H]QNB binding. 3. Pretreating cultured chromaffin cells with oxotremorine, a muscarinic receptor agonist, has no effect on either basal, nicotine (10 microM) or K(+)-stimulated catecholamine release and failed to enhance secretion of submaximal concentrations of nicotine (3-5 microM). 4. These results confirm that binding of [3H]QNB is associated with muscarinic receptors on bovine adrenal medullary tissue. 5. These studies also demonstrate that although bovine adrenal chromaffin cells possess muscarinic receptors, these receptors do not appear to be coupled to secretory processes.

Zinc status in children and young adults with sickle cell disease.

Previous studies have suggested an association of zinc deficiency and short stature in some children and adults with sickle cell disease (SCD). As a result, zinc supplementation has been recommended for these patients. The mechanism for zinc deficiency in certain patients with SCD is unknown, although renal loss of zinc has been suggested as a contributing factor. The zinc status of 29 subjects with SCD and 18 black controls was studied. No evidence of zinc deficiency in our population with SCD was found when plasma and cellular zinc levels were measured. Likewise, levels of two zinc-dependent enzymes, alkaline phosphatase and delta-aminolevulinic acid dehydratase, were normal in these subjects with SCD. Although adolescent subjects with SCD tended to be shorter than control subjects, there was no correlation between the height-forage z score and plasma zinc levels (r = -.31). It was concluded that zinc deficiency was not present in our population with SCD, and that there was no correlation between plasma zinc levels and the height-for-age z score in growing adolescent patients with SCD. These findings suggested that zinc supplementation may not be necessary in all patients with SCD.

Plasma and serum zinc concentrations: effect of time between collection and separation.

The effect of time between collection and separation of blood samples obtained from 9 subjects was examined with respect to plasma and serum zinc concentrations. There was a linear increase of 6% in zinc concentrations for the first 2 h that was similar for plasma and serum. Plasma zinc continued to increase linearly over the next 2 h, but increase in serum zinc concentrations was less for the second 2 h. It is concluded that differences between heparinized plasma and serum zinc concentration observed previously in this laboratory and elsewhere are attributable primarily to differences in time between collection and separation.

Blepharoplasty. Avoiding plastic eyelids.

The goal of a facial plastic surgeon should be to correct the undesirable conditions for which he has been consulted and to avoid leaving his mark on the patient. By embracing the concept that prevention is better than cure, it is generally possible to avoid the "operated-on look" following cosmetic surgery. We describe a number of safeguards we use to preserve natural-looking eyes following lower lid blepharoplasty in men and women. The most common, permanent complication described following conventional lower lid blepharoplasty is the round eye. The condition is readily identified by an increase in scleral show between the limbus and lower lash margin. Closer evaluation will reveal inferomedial displacement of the lateral commissure, increased slope of the lateral third of each eyelid, a flattened, unanimated, pretarsal component, and an unnatural infralash crease produced by the healed incisional scar. These findings are one step short of ectropion; therefore, the methods herein described should help reduce the incidence of this more dreaded and serious complication of blepharoplasty.

A new twist in nasal tip surgery. An alternative to the Goldman tip for the wide or bulbous lobule.

When the cartilaginous framework in the tip of the nose fails to provide adequate support and definition, the rhinoplastic surgeon must create strength and refinement. To achieve these results, we advocate a new twist of an old concept that can be used to create a stronger, more triangular lobule in the wide, bulbous, or bifid tip. Morselizing, incising, and suturing alar cartilages have long been recognized as adjunctive procedures in tip rhinoplasty; however, the specific method described herein can provide results comparable to the classic Goldman tip while guarding against the possibility of cartilage displacement and mucous membrane entrapment.

Functional evaluation of the spinal accessory nerve after neck dissection.

The pain and dysfunction associated with a loss of innervation by the spinal accessory nerve has motivated surgeons to modify the classic radical neck dissection. A prospective study of 109 patients who underwent either a radical neck dissection or a modification of it with preservation of the spinal accessory nerve revealed that those patients in whom the nerve, muscle, and vein were preserved had less dysfunction (30 percent) than those with nerve preservation only (50 percent) or classic radical neck dissection (60 percent). In addition, even when the functional disability was the same, there was less associated pain with nerve-sparing procedures. Furthermore, a large group of patients (40 percent) who underwent classic radical neck dissection had minimal disability. Given these results, a prospective study of recurrence data in these patients is indicated.