Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes

A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368–376. Both peptides contain consensus motifs of HLA-A2 binding peptides.     

Microalbuminuria and nerve conduction velocity in type-I diabetics during conventional therapy and during continuous I.V. insulin infusion

Summary The objective of this study was to follow the development of microalbuminuria and nerve conduction velocity under continuous i.v. insulin therapy over a limited period of 4 months. For this purpose, 8 labile type I diabetics were selected (age 33±8 years, duration of diabetes 16±9 years) and treated conventionally with two insulin injections daily over 4 months. Afterwards, the same patients were treated with continuous i.v. insulin infusion and finally again with two injections daily over 4 months each. This procedure allowed each diabetic to serve as his own control. HbA₁, microalbuminuria, nerve conduction velocity and relative refractory period of the ulnar nerve were checked at montly intervals. During the continuous i.v. infusion over 4 months, blood sugar values were significantly lower, glucosuria had disappeared almost completely and the glycosylated hemoglobin had fallen to near normal values. The mean rate of albumin excretion was 16±5 μg/min at rest and 76±26 μg/min during exercise (normal: 3.9±0.4 and 4.8±1.2 μg/min, respectively) and did not change significantly. Nerve conduction velocity in the ulnar nerve rose significantly under i.v. insulin therapy from 47.9±0.6 m/sec to 52±0.6 m/sec. Similarly, the relative refractory period of the same nerve fell significantly from 3.7±0.2 to 1.9±0.1 msec (i.e. to within normal range). It is concluded that functional disturbances of peripheral nerve can regress by improved blood sugar control with continuous i.v. insulin infusion over 4 months. On the other hand, incipient microangiopathy measured as microalbuminuria remains unchanged over the same period of time. If an improvement is at all possible, considerably longer periods of euglycemia are likely to be necessary. Supported by Grant No. 3.964-0.80 from the Swiss National Science Foundation.     

Posterior chamber IOL implantation during keratoplasty for aphakic or pseudophakic corneal edema

Because of their many advantages, posterior chamber (PC) intraocular lenses (IOLs) were sutured to the posterior iris (in the absence of a lens capsule) in combination with penetrating keratoplasty for aphakic and pseudophakic corneal edema in 53 cases. Secondary PC IOL implantations were performed in aphakic corneal edema (nine cases), and IOLs were exchanged for PC IOLs in pseudophakic corneal edema (44 cases). Ninety-six percent of the grafts remained clear. Forty-three percent of the eyes had 20/40 or better visual acuity, 38% between 20/50 and 20/200, and 19% worse than 20/200, with an average follow-up time of 6.4 (range 3-13) months. The most common cause of poor vision was cystoid macular edema present preoperatively in 20 eyes and postoperatively in 22 eyes. Other causes of persistent visual impairment included macular degeneration (five cases), retinal detachment (two cases), preoperative glaucoma damage (one case), severe postoperative glaucoma damage (one case), endophthalmitis (one case), and graft rejection (one case). Our short-term results indicate that this procedure may be a viable alternative to the use of secondary anterior chamber IOL implantation during penetrating keratoplasty.     

Herovici's picropolychromium. Application to the identification of type I and III collagens

A staining technique differentiating two colorimetric types of connective fibers had been proposed by Herovici previously to the identification of collagen types. This technique has been applied to skin, lung and liver specimens and the results have been compared with immunotyping and literature data on collagen types I, III and IV. The conclusions are focused on the ability of the technique to identify at a first approach collagen types I and III, which are known to be of crucial importance in mechanical tissular properties.     

One-stage phalloplasty in transsexuals

Until now, phalloplasty in transsexuals has been done with cutaneous and musculocutaneous flaps from the abdomen or the thigh in multiple procedures over a long period. We report a one-stage phalloplasty in female transsexuals with a modified Chinese forearm flap, including the cutaneous nerves anastomosed to the genital branches of the ilioinguinal and iliohypogastric nerves and the perineal branches of the pudendal nerve to obtain true genital sensibility. Immediate hysterectomy and vaginal closure are performed, providing vaginal skin to complete the neoscrotum built up with the labia and to cover the glans. A vaginal flap draped around the catheter provides the urethra, which is stripped through the dermal tube of the forearm flap acting as a corpus spongiosum. Autogenous costal cartilage is used as a stent for reinforcement, substituting for the corpora cavernosa. The donor forearm area is covered with split skin.     

Structure-activity relationship of macrocyclic and linear gadolinium chelates: Investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme

Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylene-triamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC₅₀ = .016 ± .006 mmol/1) and Gd-DTPA (IC₅₀ = .350 ± .034 mmol/1). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn²⁺ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: 67 ± 9% versus baseline; and Gd-DTPA-BMA: 73 ± 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd³⁺ release) in the case of linear Gd chelate may have deleterious biologic consequences.     

An analysis of the association of trauma centers with per capita hospitalizations and death rates from injury.

OBJECTIVE: This study used population-based data bases to assess the association of trauma centers with per capita county hospitalization and trauma death rates in the State of North Carolina. SUMMARY BACKGROUND DATA: The current study extended previous work using two North Carolina data bases to assess the association of the presence of a trauma center with per capita county trauma death rates. METHODS: Data on per capita county trauma hospitalizations and deaths were obtained from the state hospital discharge data base and the North Carolina Medical Examiner's data base. Bivariate and multivariate analysis techniques were used. The dependent variables of interest were prehospital, hospital, and total trauma death rates and hospitalization rates for injury. RESULTS: Bivariate analysis identified a number of factors associated with per capita county hospitalizations and trauma death rates. These included the per cent unemployment, racial distribution, county alcohol tax receipts, and advanced life support certified emergency medical services providers. The per capita trauma death rates were significantly lower in counties with trauma centers compared with those without trauma centers (4.0 +/- 0.5 and 5.0 +/- 1.1 deaths per 10,000 population, p = 0.0001, respectively). The per capita hospitalizations for trauma were also lower in counties with trauma centers. Multivariate modeling showed that the presence of a trauma center and advanced life support providers were the best predictors of decreased per capita county trauma death rates. CONCLUSIONS: The study showed that the presence of a trauma center and advanced life support training were the two medical system factors that were the best predictors of the per capita county prehospital and total trauma death rates. These findings are consistent with the hypothesis that trauma centers are associated with a decrease in trauma death rates.     

Normal and regenerating optic fibers in goldfish tectum: HRP-EM evidence for rapid synaptogenesis and optic fiber-fiber affinity

The distribution of normal and regenerating retinal fibers and synapses was studied on tectum in goldfish by light (LM) and electron microscopy (EM). Since labeling of the early regenerating fibers was previously reported to be difficult, a new 'cold-fill' HRP labeling protocol was developed, which labeled regenerating optic fibers and terminals on tectum as early as 14 days after nerve crush when they first arrive on tectum. In order to characterize the laminar distribution of optic afferents in normal fish and in fish regenerating for 14-240 days, EM photomontages of areas 14 microns wide by 160 microns deep through the HRP-labeled primary optic innervation layer (S-SO-SFGS) were constructed. The time points in regeneration that were examined spanned the period in which others have shown that an initially diffuse retinotopic map becomes spatially restricted. At the LM level regenerating optic fibers were restricted to the optic lamina. They reinnervated tectum in an anterior to posterior sequence as previously seen with autoradiography. In addition, at 14 days, some "pioneer" optic fascicles were found to have already grown to posterior tectum where they gave rise to branches with boutonlike terminations and growth-cone-like processes. Form the ultrastructural analysis it was clear that optic fibers and terminals observed strict laminar boundaries as they partitioned themselves in the optic laminae (S, SO and SFGS) in both normal and regenerating fish. The behavior of optic fibers was lamina specific with respect to synapse formation and the orientation of fiber outgrowth. As early as 14 days regeneration, optic fibers made synapses onto the four types of postsynaptic profiles observed in normal fish. Numerous optic terminals were labeled at 14 days, and there appeared to be no waiting period between fiber ingrowth to the SO and synapse formation in the S and SFGS. At 14-60 days, atypical synaptic contacts which appear to be nascent synapses were made by labeled optic fibers in fascicles and by growth-cone-like processes. By 21-30 days, the density of optic terminals was high and there were many more fasciculated optic fibers in the SFGS than normal as late as 350 days. These findings suggest that optic fiber lamination is highly constrained by tectal cues, that fibers rapidly regenerate many synaptic terminals before retinotopic map refinement is complete, and that fibers have a strong affinity for each other.