We have investigated the relationships between the minimum inhibitory concentrations (MICs) of eight beta-lactams and their binding affinities of penicillin binding proteins in low- and high-level methicillin-resistant Staphylococcus aureus (MRSA). For high-level MRSA (H-MRSA), a significant correlation was found between IC50 for PBP2A and MIC, whilst no clear relationship was apparent for low-level MRSA (L-MRSA). However, the product of the IC50s for PBP2A and PBP4 significantly correlated with the MIC in L-MRSA. Since PBP4 is thought to mediate secondary cross-linking of the staphylococcal cell wall, we analyzed the effect on cell wall cross-linking of L- and H-MRSA of two representative drugs (cefoselis and flomoxef). Interestingly, the decrease in cell wall cross-linking, which was clearly observed in L-MRSA, was diminished with H-MRSA. It is concluded that for L-MRSA, a reduction in cell wall cross-linking caused by inhibiton of PBP4 may contribute to the antimicrobial activity of beta-lactam antibiotics, while for H-MRSA, inhibition of PBP2A mainly determines the antimicrobial activity. Since neither alteration of expression nor binding affinity of PBP4 were observed in these studies, unknown factors must operate to diminish the effect of PBP4 inhibition and contribute to the mechanism of high level resistance of MRSA.

Anti-Bacterial Agents↗

PubMedDate not supplied

Quantitative morphology of renal cortical structures during compensatory hypertrophy.

The compensatory hypertrophy in different renal cortical structures was studied in rats 10 and 21 days after unilateral nephrectomy (UNX). Quantitative morphological/stereological analysis revealed significant increases in total renal cortical volume--33% on day 10 and 48% on day 21--after UNX. These changes were paralleled by significant increments in the volumes of proximal convoluted tubule (PCT, 55%), distal convoluted tubule (DCT, 114%), and cortical collecting duct (CCD, 106%) segments on day 10. The corresponding changes on day 21 were 76, 122, and 212%, respectively. These alterations were accompanied by increases in segment length; 3% PCT, 23% DCT, and 50% CCD on day 10 and 9% PCT, 30% DCT, and 142% CCD on day 21 after UNX. The total luminal and basolateral cell membrane surface areas also exhibited a time-dependent increase after UNX. The increments in both luminal and basolateral membrane domains in PCT and DCT after 10 days were not significant, but reached significance after 21 days (PCT: luminal membrane 21%, basolateral membrane 63%; DCT: luminal membrane 98%, basolateral membrane 63%). In contrast, CCD membrane areas had increased substantially already 10 days after UNX (luminal membrane 92%, basolateral membrane 71%). It declined subsequently by day 21 (luminal membrane 57%, basolateral membrane 32%). The cell rubidium concentration after a 30-second rubidium infusion, an index of Na-K-ATPase activity, as well as sodium concentrations were unaltered in cells of all nephron segments investigated. Altogether the stereological analysis shows that the compensatory increase in organ volume can be attributed primarily to an increase in nephron epithelial volume. The PCT responds with 'radial' hypertrophy (thickening of the tubular epithelial wall), while the DCT undergoes 'length' hypertrophy (increase of tubular length without thickening of the tubular wall and without an increase in number of cells). This type of hypertrophy is especially prominent on day 21 after UNX for the CCD which doubles in length. Only on day 10 does the CCD seem to respond with hyperplasia. Adaptive changes in response to UNX develop gradually. Only a few of the morphological parameters studied had completed their change by 10 days, the majority required longer.

Adaptation, Physiological↗

PubMedDate not supplied

Intraoperative squash and touch cytology of chondroid chordoma of the skull base. Report of a case with immunocytochemical and immunohistochemical studies.

BACKGROUND: Chondroid chordoma is a rare variant of chordoma and is usually located in the sphenooccipital region. This tumor shows clinical and histologic features common to both conventional chordoma and low grade chondrosarcoma and has a better prognosis than either of those lesions. To our knowledge, there has been no English language report describing its cytologic features. CASE: The cytologic features of skull base chondroid chordoma observed in intraoperative crush and touch preparations from a 33-year-old female are reported. Touch cytology revealed round or stellate cells distributed in a mucoid background without a typical epithelial cordlike arrangement. The cells had variably vacuolated cytoplasm and round or oval nuclei and showed slight cellular pleomorphism. May-Giemsa staining was superior to Papanicolaou staining in demonstrating the mucoid matrix and vacuolated cytoplasm of the tumor cells. Additionally, crush preparations were effective in demonstrating well-differentiated chondroid elements. Immunocytochemistry with positivity for S-100 protein and cytokeratins was an essential adjunct in the cytologic diagnosis of chordoma and helped in distinguishing it from other chondrogenic tumors. CONCLUSION: It is possible and advantageous to diagnose chondroid chordoma with a combination of cytologic and immunocytochemical studies of intraoperative crush and touch preparations in conjunction with clinical and radiographic information.

Adult↗

PubMedDate not supplied

GPI-anchored molecule-like protein (GML) expression in non-small cell lung cancer (NSCLC).

BACKGROUND: GPI-anchored molecule-like protein (GML) has been identified as a new target molecule of p53. In esophageal cancer cell lines, expression of GML mRNA, which was found to be significantly correlated with in vitro anti-cancer drug sensitivity, was observed only in the presence of wild-type p53. MATERIALS AND METHODS: The relationship between expression of GML mRNA and p53 gene status in 24 non-small cell lung cancer (NSCLC) cell lines was examined using RT-PCR and PCR-SSCP followed by direct DNA sequencing. RESULTS: Expression of GML mRNA was observed in only 3 of 24 cell lines. In contrast to previous studies showing p53-dependent GML expression, of the 3 cell lines expressing GML mRNA, one had a p53 gene mutation (codon 245: Gly to Cys). CONCLUSION: These findings suggest that the expression of GML mRNA is infrequent and regulated in a p53-independent manner in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMedDate not supplied

Prognostic significance of telomeric repeat length alterations in pathological stage I-IIIA non-small cell lung cancer.

This study was performed to evaluate the prognostic significance of alteration in telomere length in pathological stage (p-stage) I-IIIA non-small cell lung cancer (NSCLC). Paired cancer and normal lung tissues were obtained from 72 patients with histologically confirmed p-stage I-IIIA NSCLC. Terminal restriction fragment (TRF) length, which indicates telomere length, was measured by Southern blot analysis. Tumor telomerase activity was also assayed by non-radioactive PCR-ELISA in 55 patients. TRF length (mean +/- SD) in normal tissue was 6.2 +/- 1.1 Kb. Therefore, upper and lower limits of normal range in TRF length was set at 8.4 (mean + 2SD) Kb and 4.0 (mean-2SD) Kb, respectively. A tumor showing TRF length over normal range was defined as positive for the alteration. In 72 patients, 25 (34.7%) with alteration in TRF length had significantly shorter survival durations than those of the others. Telomerase activity did not correlate with survival duration. In multivariate analysis, alteration in TRF length (P = 0.0033) was second to p-stage (P = 0.0004) in importance among the various parameters.

Adult↗

PubMedDate not supplied

Dermatomyositis associated with Sjögren's syndrome: VEGF involvement in vasculitis.

Two patients with dermatomyositis complicated with Sjögren's syndrome (SjS), are reported. Both patients exhibited sensory-dominant polyneuropathy, compatible with neurologic involvement in SjS. Vascular endothelial growth factor (VEGF) levels were increased in their plasma. Histological examination demonstrated vasculitic changes in biopsied specimens of muscle and salivary glands from the patients, and VEGF was overexpressed in the vasculitic lesions. These findings suggest that VEGF overexpression was associated with the development of vasculopathy in skeletal muscle and salivary glands and possibly in the peripheral nervous system.

Dermatomyositis↗

PubMedDate not supplied

Magnetic resonance imaging in chronic liver disease evaluated in relation to hepatic fibrosis--clinical and experimental results.

In 21 patients with chronic liver disease, the ratio of liver to muscle signal intensity on T1-weighted images was negatively correlated with the progression of hepatic fibrosis defined according to findings by laparoscopy and liver biopsy, and differentiated six patients with early chronic hepatitis from eight with liver cirrhosis. On T2-weighted images, the number of low intensity nodules comparable in size to regenerating nodules surrounded by connective tissues showed a positive correlation with stage. When hepatic fibrosis with no necrosis or fat infiltration was induced in rats, T2 values were positively correlated with hepatic hydroxyproline content, though there was no such correlation for T1 values. These results suggest that MR imaging may be useful for determining the progression of hepatic fibrosis in chronic liver disease. T2 values may directly reflect hepatic fibrosis.

Adult↗

PubMedDate not supplied

Computed tomography density of gallbladder stones may aid in predicting the rate of stone fragmentation with extracorporeal lithotripsy.

Thirty-six patients with gallbladder stone(s), 21 with solitary stone and 15 with multiple stones up to five in number, were treated by a single session of extracorporeal shock wave lithotripsy. In eight patients (group A), stones were gradually fragmented from the surface, producing fine powderlike fragments which made residual stones invisible, leading to reduced therapeutic efficacy. In 13 patients (group B), residual stones remained visible up to 2,400 shocks, though they showed similar fragments. Such fragments did not appear throughout treatment in 14 patients (group C). Computed tomography (CT) attenuation number, when the region of interest was settled on the whole stone, increased in the order of group A, B, and C. When the distribution of CT density on stones was analyzed, the density was diffusely lower than 50 HU in all patients in group A, higher than 50 HU only on the surface in all patients except for two in group B, and diffusely higher than 50 HU in all patients except for one in group C. CT findings may be useful for predicting the fragmentation mode of gallbladder stones by extracorporeal shock wave lithotripsy.

Adult↗