In order to study whether hyperplasia or hypertrophy of cells is responsible for the thickening of airway muscles, 3-D morphometry of airway muscle cells was performed on resin-embedded semithin serial sections of autopsied lungs from 10 asthmatics and five control subjects. There were five Type I and five Type II asthmatic lungs, as defined in an earlier study, thickened muscles being found only in the central bronchi in Type I and distributed over the whole airway tree in Type II. The analysis was based on "unbiased" 3-D morphometry to obtain the numerical density NV of muscle cells using a "disector," a spatial probe introduced by Sterio in 1984, which we modified into a stack of serial sections. The mean number NL of cells per unit airway length and the mean volume Vc of a single muscle cell were also determined. In Type I asthmatics, the number of cells increased in the larger bronchi unaccompanied by cellular hypertrophy at any level of the airway tree. In contrast, in Type II asthmatics, hypertrophy was shown to prevail over the whole airway, but it was most remarkable in the bronchioles, whereas hyperplasia was mild and localized only in the bronchi. The two types of asthmatic lungs may therefore result from different pathogeneses.

CPT-11 is a very active agent for NSCLC with acceptable toxicities. Further trials in combination with other agents for this disease are warranted.

Under the assumption that the more hyperreactive the bronchial muscles are, the greater their work hypertrophy, we analyzed the distribution of hypertrophic smooth muscles along airways to see where in the bronchial tree asthmatic constrictions mainly occur. Autopsy lungs from 16 patients with bronchial asthma, 13 with other COPDs, and 20 controls were submitted to morphometry of the bronchial muscles. In microscopic slides, cross sections of airways were taken from the segmental bronchi to the terminal bronchioles. The perimeter length L of the basement membrane and the area S of muscles were measured, and the anatomic radius R and the muscular thickness D were calculated in a standardized circular state, in which the basement membrane was stretched into a circle without changing L or S. On bilogarithmic coordinates of D and R on which data from the asthmatics were pooled, it was shown that hypertrophy of muscles was the most pronounced in larger bronchi where constriction was most likely to occur. Closer analysis of patients, however, revealed that besides this typical pattern, which we designated Type I asthma, there was a group of patients (Type II) in whom hypertrophy involved the entire range of airways, including the bronchioles, suggesting that the site of asthmatic response varies among patients. In nonasthmatic patients with COPD, only mild hypertrophy of muscles was found in the large airways, despite the presence of obstructive lesions mainly in the small airways.

Cytochrome P450IIE1 (P450IIE1) is involved in metabolic activation of carcinogenic nitrosamines, aniline and benzene. We detected a restriction fragment length polymorphism of the human P450IIE1 gene with the restriction endonuclease Oral. The population was thus divided into three genotypes, namely, heterozygotes (CD) and two forms of homozygotes (CC and DD). The distribution of these genotypes among lung cancer patients differed front that among controls with statistical significance of P< 0.05 (x2=7.01 with 2 degrees of freedom). This result strongly suggests that host susceptibility to lung cancer is associated with the Dral polymorphism of the P450IIE1 gene.

The presence or absence of a methicillin resistance gene in 58 clinical isolates of Staphylococcus aureus was examined by the polymerase chain reaction (PCR) and Southern blot analyses. The results were analyzed in relation to those of the MIC assay of methicillin and oxacillin. PCR assay results were identical to those of Southern blot analysis of genomic DNA digested with HindIII (positive, 28 strains; negative, 30 strains). Among the 28 PCR-positive strains, 6 strains showed methicillin susceptibility by the conventional susceptibility test (MICs, less than or equal to 8 micrograms/ml). Culturing of the six strains with ceftizoxime led to an increase in the phenotypic level of resistance to methicillin and oxacillin, indicating that these strains should be classified as methicillin-resistant S. aureus (MRSA). The PCR assay was found to be a sensitive and reliable procedure for the rapid diagnosis of MRSA infection, even in cases in which the conventional MIC assay failed to detect MRSA.