Carbohydrate expression profile of colorectal cancer cells is relevant to metastatic pattern and prognosis

Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-Lewis^X (LEX-2), anti-sialyl Lewis^a (NS19-9), and anti-sialyl-dimeric Lewis^X (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.     

The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells

Peroxisome proliferator activator-receptor (PPAR)-gamma ligand induces growth arrest of cancer cells through apoptosis. In this study, we examined the effects of PPAR-gamma inhibitors on cell proliferation in renal cell carcinoma (RCC), bladder tumor (BT), and prostatic carcinoma (PC) cell lines. We investigated the inhibitory effect of PPAR-gamma ligands, troglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) on RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. PPAR-gamma ligands (troglitazone and 15dPGJ2) induced the reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT, and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, clearly showed marked inhibition of cell proliferation using troglitazone and 15dPGJ2. All PPAR-gamma inhibitors stopped the growth of all RCC, BT and PC cells. Cells treated with PPAR-gamma inhibitors showed chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies), and cytoplasmic condensation. These cellular changes were typically redundant characteristics of apoptosis. PPAR-gamma ligands may mediate potent antiproliferative effects against RCC, BT and PC cells through differentiation. Thus, PPAR-gamma may become a new target in treatment of urological tumors.     

Expression of gastrin-releasing peptide (GRP) in the bovine uterus during the estrous cycle

Gastrin-releasing peptide (GRP) has been proposed as a novel regulatory peptide in the reproductive tract. We previously demonstrated that GRP immunoreactivities are found predominantly in the uterine gland epithelial cells of nonpregnant and pregnant cows. The present study focused on the distribution of GRP immunoreactivity and the expression of GRP mRNA in the bovine endometrium during the estrous cycle. Tissues were collected from 21 uterine horns and bodies during the estrous cycle. RT-PCR showed the expected GRP mRNA fragments (284 bp) in the tissues from all stages of the cycle. In situ hybridization results ascertained the expression of the GRP mRNA in the uterine gland epithelial cells and superficial epithelial cells of the endometrium. Positive staining of GRP immunoreactivity in the uterine gland epithelial cells was detected in both the uterine horn and body from all stages of the cycle. In metestrus and diestrus stages, GRP was also detected in the superficial epithelial cells of horn, but not in the body. The degrees of GRP mRNA expression and intensities of GRP immunoreactivity in the endometrium increased from proestrus to diestrus stages. These findings suggest that GRP may be important both in the endometrial remodeling during the estrous cycle and in the implantation and development of blastocysts.     

Hypersegmentation of inflammatory cells in Langerhans cell granulomatosis

Langerhans cell granulomatosis (LCG) is characterized by a mixture of Langerhans cells and eosinophils in varying proportions. The characteristic morphology of Langerhans cells have already been described in many articles, but little attention has been paid to inflammatory cells. We examined six cases of Langerhans cell granulomatosis, which had originally been diagnosed as eosinophilic granuloma. Inflammatory cells present in LCG showed hypersegmentation. Twenty percent to 70% of eosinophils had three or more segmented nuclei, and 10-25% of neutrophils had five or more segmented nuclei. Such findings have never been described, and we believe hypersegmentation to be a feature of LCG. Furthermore, we emphasize that eosinophils in LCG mimic neutrophils in ethanol-fixed preparations, and thus may be a pitfall in making a diagnosis in cytology and intraoperative consultation.     

Mechanomyography of the human quadriceps muscle during incremental cycle ergometry

The mechanical activity of the human quadriceps muscle during maximal incremental cycle ergometry was investigated by mechanomyography (MMG). MMG and surface electromyography (EMG) recordings of vastus lateralis muscle activity were obtained from nine males. Cycle ergometry was performed at 60?rev/min and work load was incremented step wise by 20?W (3.2?Nm) every minute until volitional fatigue. The mean amplitudes of MMG (mMMG) and EMG (mEMG) during the contraction phase were calculated from the last six contractions in each load. The duration, load and work rate of exercise at exhaustion were 13.3 (1.6)?min, 44.1 (5.5)?Nm, 276.7 (34.7)?W, respectively. A linear relationship between mMMG and load was evident in each subject (r?=?0.868–0.995), while mEMG seemed to dissociate as the load became greater. In the grouped mean data, mMMG was linearly related to load whether aligned to the absolute (r?=?0.995) or maximal (r?=?0.995) load. Involvement of the noise component was further investigated by studying passive cycling by four subjects. Pedals were rotated passively for the first half of each stage (PAS) and the subject then pushed the pedals for the second half (ACT). In the lighter load region, the mMMG of ACT was as small as that of PAS. However, the change in the mMMG of PAS was very small compared with that of ACT. In conclusion, this study demonstrates a linear relationship between the mMMG of the quadriceps muscle and work load during maximal incremental cycle ergometry. The effect of movement noise was thought to be small and stable.     

Glomerulonephritis with fibrillary deposition in a transgenic mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse)

Glomerulonephritis was observed in a 34-week-old transgenic CB6F1 mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse) from a medium-term carcinogenicity study of N-methyl-N-nitrosourea (MNU). Lesions were characterized by severe diffuse enlargement and prominent hyalinization of glomeruli. The hyaline material was positive for periodic acid-Schiff but negative for amyloid by the Congo red method. Immunohistochemically, affected glomeruli were positive for polyclonal anti-mouse IgG. Ultrastructurally, there were characteristic subendothelial and mesangial deposits composed of fibrils showing a fingerprint pattern. Lamellae were 7.5-14.3 nm in diameter and formed multilayered structures. In addition to the renal lesions, a lymphoma was observed in the thymus, with metastasis to the spleen and some lymph nodes. However, there was no glomerulonephritis in 32 other mice bearing thymic lymphomas and in more than 40 males and females given MNU in the same study. Thus, the lesions in this mouse may have been spontaneous. Glomerulonephritis was not found in more than 120 other male and female rasH2 mice in our facility. This is the first report of glomerulonephritis in a rasH2 mouse, a promising candidate for medium-term carcinogenicity risk assessment.     

Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis.

A review of the case histories of 19 Japanese patients with enzymatically proven glycogen storage disease (GSD) III who developed muscular symptoms at various ages illustrates the phenotypic variability of this disease. There seem to be 4 subgroups of GSD III with muscle involvement according to the clinical symptoms. The first group of patients is characterized by the childhood onset of muscle weakness and hepatic disorders. The second group of patients develops muscular symptoms in adult years while the liver symptoms start in childhood. The third group includes the patients whose muscle weakness started in adult years long after liver symptoms in childhood had disappeared. The fourth group shows only muscular symptoms as adults without any sign or history of liver dysfunction since childhood. The prognosis for each subgroup seems to be different; however, none of them appears to be better than that for GSD I, as has been suggested previously.     

Immunohistochemical evaluation of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons of young adult mice using dopamine and tyrosine hydroxylase antibodies

The recovery of dopamine (DA) neurons in young adult mice from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damage was analyzed at various times after MPTP treatment with DA and tyrosine hydroxylase (TH) immunohistochemistry and also by chemical DA assay. A remarkable discrepancy in the recovery rate of DA and TH reactivities of the nigral neurons was observed: the TH immunoreactivities of both cell bodies in the substantia nigra and terminals in the neostriatum were markedly reduced 4 days after MPTP. However, these reactivities progressively improved and almost fully recovered after 25 days, while the DA immunoreactivities were maximally depleted 10 days after, and the depletion continued even through the 25th day. The alteration of DA levels was correlated with that of DA immunoreactivity. These findings suggest that a major effect of MPTP on the DA neurons of young adult mice is a transient neurotoxicity, and that the TH content improves more promptly than that of DA.     

Can Mycobacterium tuberculosis infection prevent asthma and other allergic disorders?

It is generally considered that tuberculosis (TB) is a disease which upregulates Th1 cell function. There is a hypothesis that infection of Mycobacterium tuberculosis may prevent allergic disorders such as bronchial asthma. However, our clinical experience of patients with TB somewhat conflicts this hypothesis. Hence, we investigated Th1/Th2 balance in the peripheral blood of patients with active TB by measuring serum levels of IgE antibody and by intracellular cytokine assay. We found that serum levels of IgE in the patients with active TB were significantly higher than in those with lung cancer or with COPD. In the TB patients, titers of IgE tended to correlate with disease severity. Intracellular cytokine assay demonstrated that IFN-gamma-positive cells were significantly decreased in the patients with active TB compared to normal controls. The ratio of IFN-gamma-positive (Th1-like)/IL-4-positive (Th2-like) cells was remarkably reduced in the TB patients (p < 0.0001). This ratio showed a significant negative correlation with erythrocyte sedimentation rate and with C-reactive protein. Therapy against TB for 2-3 months did not result in significant changes of the Th1/Th2 ratio. These findings suggest that infection of M. tuberculosis does not systematically upregulate Th1 cells in some patients, and is unlikely to prevent allergic disorders like asthma.