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.     

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.     

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.