[The causes of death in patients with non-MDR pulmonary tuberculosis in our hospital].

We studied the causes of death in 295 patients (mean (+/- SD) age 70.5 +/- 13.2 y.o.) with active non-MDR pulmonary tuberculosis who died in our hospital between 1991 and 1999. A hundred and twenty eight patients (43.4%, group A) died of tuberculosis, while 167 patients (56.6%) of other accompanying diseases. In 46 patients of the latter (15.6%, group B), pulmonary tuberculosis gave an unfavorable impact on their clinical course. In these patients the extent of pulmonary tuberculosis on chest roentgenograph was similar with the remaining 121 patients who also died of the accompanying diseases (41.0%, group C) and was less severe than those of the group A patients. Their nutritional conditions measured by serum albumin and choline-esterase level on admission, however, were as low as those of the group A patients and distinctly worse than those of the group C patients. Most patients of groups A and B died within 3 months after admission, while less than half patients of group C died during the same period. The age frequency distribution of the patients in groups B and C had a single peak in the age group 70 to 89, while that in group A showed two peaks, one similar peak as in groups B and C, and another peak in the age group 50 to 59. The numbers of homeless patients, of the patients with extensive cavitary lesions, and of the patients who died of ARDS (Adult Respiratory Distress Syndrome) or severe pneumothorax in group A were the most also in the age group 50 to 59, indicating that the patients' delay in admitting to hospitals was the major cause of high motality in this age group. As to detailed causes of death in group A, patients died of respiratory failure (32 cases), emaciation (28 cases), progression of pulmonary tuberculosis (20 cases), ARDS (15 cases), tuberculosis-related diseases such as pneumothorax, hemoptysis, and DIC (24 cases). In groups B and C patients died of organ failure (36 cases), infectious diseases (33 cases) and malignancy (30 cases). The total number of died patients has increased, and the proportion of cases dying of ARDS and infectious diseases has increased statistically significantly recently.

Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity.

All disulfide analogs (types I, II and III) of protegrin (PG)-1, an 18-residue antimicrobial peptide having two intramolecular disulfide bonds, were synthesized using regioselective disulfide bond formation. Random air-oxidation of the fully reduced PG-1 formed the type III PG-1. In addition, a type III analog containing an amidated carboxy-terminal residue was also prepared. Each analog showed significant and different antibacterial and anti-human immunodeficiency virus (HIV) activity. Deletion of two disulfide bridges caused a significant decrease in activity.

Solution-phase synthesis of an anti-human immunodeficiency virus peptide, T22 ([Tyr5,12,Lys7]-polyphemusin II), and the modification of Trp by the p-methoxybenzyl group of Cys during trimethylsilyl trifluoromethanesulfonate deprotection.

T22 ([Tyr5,12,Lys7]-polyphemusin II) was previously synthesized by a solid-phase method and was found to have a strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3'-dideoxy-thymidine (AZT). In the present study, the solution-phase synthesis of T22 was attempted in order to produce this peptide on a large scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragments and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf) in trifluoroacetic acid followed by air-oxidation. During this deprotection, a significant by-product derived from the transfer of the p-methoxybenzyl (MBzI) group from the sulfhydryl group of the cysteine residue to the side chain of the tryptophan residue was formed. This side reaction was found to be efficiently suppressed by adopting a two-step deprotection procedure using silver trifluoromethanesulfonate (AgOTf)-TMSOTf or trimethylsilyl bromide (TMSBr)-TMSOTf.

Structure-activity relationships of an anti-HIV peptide, T22.

T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have a strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). We studied the structure-anti-HIV activity relationships of T22 and determined the following information. The number of Arg residues in the N-terminal and C-terminal regions of T22 is closely related with anti-HIV activity. Disulfide rings, especially the major disulfide ring, are indispensable for anti-HIV activity and maintenance of the secondary structure. Between two repeats of Tyr-Arg-Lys, which are a characteristic structure contained in T22, Tyr-Arg-Lys in the N-terminal portion is more closely related with anti-HIV activity. We found some compounds having a higher selectivity index (50% cytotoxic concentration/50% effective concentration) than that of T22.