Inhibition of homotypic adhesion of T-cells: secondary structure of an ICAM-1-derived cyclic peptide

The objective of this study was to elucidate the solution conformation of cyclo-(1, 12) Pen1-Pro2-Ser3-Lys4-Val5-Ile6-Leu7-Pro8-Arg9-Gly10-Gly11-Cys12 (1) derived from the intercellular adhesion molecule-1 (ICAM-1). Cyclic peptide 1 inhibits homotypic adhesion of T-cells (Molt-3) mediated by ICAM-1 and the leukocyte function-associated antigen-1 (LFA-1) on the surface of T-cells. Cyclic peptide 1 is more potent than is the linear peptide Pen1-Pro2-Ser3-Lys4-Val5-Ile6-Leu7-Pro8-Arg9-Gly10-Gly11-Cys12 (2) in inhibiting homotypic adhesion. The difference in biological activity of peptides 1 and 2 may be due to the more stable conformation of cyclic peptide 1 compared to linear peptide 2 or because cyclization prevents the peptide from adopting non-productive conformation. Therefore, conformational studies of cyclic peptide 1 will give a better understanding of its biological active conformation. The conformational studies of cyclic peptide 1 were done by NMR, CD and molecular dynamics simulations. NMR studies indicated that the major conformation of cyclic peptide 1 contained trans-configuration at both X-Pro peptide bonds. Type I β-turns at Lys4-Val5-Ile6-Leu7 and Leu7-Pro8-Arg9-Gly10 were found in cyclic peptide 1. The C- and N-terminal regions of this peptide were stabilized by antiparallel β-sheet-like structure with the presence of intramolecular hydrogen bonds. The overall structure of this peptide exposed the hydrophobic side chains on one face of the molecule and the hydrophilic side chains on the other.     

Host response and tumour biological behaviour in the two histological types of gastric carcinoma

It appears that there is validity in categorizing gastric carcinoma into two histologic types, intestinal and diffuse. The local host tissue response in 92.5% of cases of the intestinal type of gastric carcinoma was of an exudative nature. Diffuse gastric carcinoma in 70% of cases incited a dense productive fibrosis. Pools of mucin and large number of 'signet-ring' cells were mostly encountered in the intestinal type of carcinoma. Applying Dukes' parameters the tumour was found to be more than three times more invasive in cases of diffuse carcinoma. The prognostic bearing of the two histologic types, different host tissue response, behaviour of the tumour in terms of mucous production and local extension are discussed and it is suggested that diffuse gastric carcinoma carries a worse prognosis than the intestinal type. Study of a larger series of cases and longer follow-up with controlled treatment is essential to confirm this assessment.     

Effect of Varying Atrial Sensitivity, AV Interval, and Detection Algorithm on Automatic Mode Switching

Automatic mode switching (AMS) is absolutely dependent on atrial tachyarrhythmia detection. The effects of programming several features that could influence tachyarrhythmia detection were assessed in 18 patients (six women; mean age 64 years) with pacemakers having AMS capability. The atrial electrogram amplitude in sinus rhythm at implant (SR-EGM), last measured atrial sensing threshold prior to tachycardia (A-SENS), and atrial sensing threshold for effective AMS during atrial tachyarrhythmia (AMS-SENS) were obtained. Additionally, ten patients had AV intervals increased from 60 to 200 ms, while seven patients had detection algorithms made more stringent from 5 beats at 150 beats/min to 11 beats at 200 beats/min to assess their effects on AMS efficacy. Results: Sensitivities: Mean SR-EGM = 3.55 mV; mean A-SENS = 2.06 mV; and mean AMS-SENS = 1.46 mV. Fourteen patients developed atrial fibrillation and four atrial flutter. Thirteen of 14 patients who developed atrial fibrillation sensed adequately at ≥ 1.0 mV in normal sinus rhythm (NSR), but only six patients had effective AMS at these settings in atrial fibrillation. Three of four patients who developed atrial flutter had effective AMS at ≥ 2.0 mV. AV Interval: AMS was effective in eight of ten patients at AV intervals up to 200 ms. One patient lost AMS at an AV interval of 120 ms. Algorithm: In two of seven patients, AMS was not effective if the detection algorithm was more stringent than five beats at 150 beats/min. Conclusions: (1) In atrial fibrillation, effective AMS requires more sensitive atrial settings than in NSR: (2) AV intervals as short as 120 ms can interfere with AMS function; and (3) More stringent detection algorithms may be inappropriate for effective AMS function.     

EPIDEMIOLOGY OF UPPER AERODIGESTIVE CANCERS AMONG ARMED FORCES PERSONNEL AND THEIR FAMILIES

Cancers of the oral cavity, pharynx, and esophagus are now suspected to have common etiologic factors and have been grouped together as “upper aerodigestive” cancers. Since this grouping is of relatively recent origin there have been no epidemiological studies on this group among Armed Forces personnel. 114 cases of upper aerodigestive cancers and an equal number of controls were studied. The largest number of cases were in the age group of 40–49 years with male preponderance. Lower level of education, smoking, quid chewing, and alcohol use were found to be the major risk factors for these cancers. A dose response relationship was observed for smoking, quid chewing and alcohol intake.KEY WORDS: Neoplasms, Smoking, Quid chewing, Alcohol     

Characterization of Conduction in the Ventricles of Normal and Heterozygous Cx43 Knockout Mice Using Optical Mapping

INTRODUCTION: Gap junction channels are important determinants of conduction in the heart and may play a central role in the development of lethal cardiac arrhythmias. The recent development of a Cx43-deficient mouse has raised fundamental questions about the role of specific connexin isoforms in intercellular communication in the heart. Although a homozygous null mutation of the Cx43 gene (Cx43-/-) is lethal, the heterozygous (Cx43+/-) animals survive to adulthood. Reports on the cardiac electrophysiologic phenotype of the Cx43+/- mice are contradictory. Thus, the effects of a null mutation of a single Cx43 allele require reevaluation. METHODS AND RESULTS: High-resolution video mapping techniques were used to study propagation in hearts from Cx43+/- and littermate control (Cx43+/+) mice. Local conduction velocities (CVs) and conduction patterns were quantitatively measured by determining conduction vectors. We undertook the characterization of ECG parameters and epicardial CVs of normal and Cx43+/- mouse hearts. ECG measurements obtained from 12 Cx43+/+ and 6 Cx43+/- age matched mice did not show differences in any parameter, including QRS duration (14.5 +/- 0.9 and 15.7 +/- 2.3 msec for Cx43+/+ and Cx43+/-, respectively). In addition, using a sensitive method of detecting changes in local CV, video images of epicardial wave propagation revealed similar activation patterns and velocities in both groups of mice. CONCLUSION: A sensitive method that accurately measures local CVs throughout the ventricles revealed no changes in Cx43+/- mice, which is consistent with the demonstration that ECG parameter values in the heterozygous mice are the same as those in wild-type mice.     

Histocompatibility Antigens (HL–A) in Leprosy

HL–A antigens of 70 leprosy patients and 40 normal healthy individuals were determined by the standard microlymphocytotoxicity test. Both lepromatous and non-lepromatous leprosy patients were tested for the presence of 11 HL–A antigens, and the frequency of each specificity was compared with that in a normal population of the same ethnic group. Although the statistical significance of HL–A8 specificity was found to be marginal in lepromatous leprosy patients, when using ordinary 2x2 statistics, there did seem to be a decreased frequency of HL–A9 among the non-lepromatous type. Other antigens tested did not reveal any significant differences between the two groups of subjects.