Clinicopathological study on the relationship between serum-CEA and tissue-CEA of resected lung cancer cases

The clinicopathological correlation between serum-CEA (s-CEA) and immunohistological tissue-CEA (t-CEA) was studies on 63 cases of operated lung cancers. T-CEA was examined by peroxidase anti-peroxidase (PAP) method. T-CEAs were detected in 36/39 cases (92.3%) of adenocarcinoma, 16/16 cases (100%) of epidermoid carcinoma, 2/5 cases (40%) of large cell carcinoma, and 1/3 case (33.3%) of small cell carcinoma. T-CEAs in adenocarcinoma and large cell carcinoma with mucin exhibited moderate to strong reactivity with diffuse distribution, and also s-CEA of these cases indicated high levels. On the contrary, in epidermoid carcinoma t-CEAs showed a weak reactivity with focal distribution, and s-CEAs also demonstrated low levels. In adenocarcinoma it was suggested that the more cancers were differentiated, the more t-CEA and s-CEA were increased, and about two third of cases showed a balance between t-CEA and mucin content in cancer tissue. S-CEAs were not correlated with the size of the primary lesion or the extent of lymph node metastasis, but with the histological types, i.e. high levels of s-CEA in adenocarcinoma and large cell carcinoma with mucin.     

Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection

In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.     

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.     

Autographa californica M nucleopolyhedrovirus ProV-CATH is activated during infected cell death

V-CATH, a cathepsin L-like cysteine protease encoded by the baculovirus Autographa californica M nucleopolyhedrovirus, has been shown to play an essential role in host liquefaction. Similar to cellular cathepsin L, V-CATH is synthesized as an inactive proenzyme and is activated by cleavage of the propeptide. Previous studies indicated that removal of the propeptide was rapid, occurring as soon as the protein could be detected by Western blot, 22 h postinfection. We found, however, that these results reflected artifactual processing of the proenzyme. When the protease inhibitor E-64 was used to prevent this aberration, we found that proV-CATH accumulated in infected cells and activation did not begin until the onset of cell death, at approximately 80 h postinfection. Western blot analysis of fractions of live and dead cells isolated by fluorescence-activated cell sorting revealed that mature V-CATH was found only in dead cells. The regulation of activation of proV-CATH, therefore, was quite different from that of cellular cathepsins. Acridine orange staining revealed that lysosome integrity was lost in dead cells, an occurrence that could lead to the activation of proV-CATH by lysosomal proteases.     

Pharmacokinetics of flosequinan in elderly patients with chronic congestive heart failure

Summary We have investigated the pharmacokinetics of the direct vasodilator flosequinan in elderly patients with congestive heart failure. Eight patients received a single dose of 50 mg, and 8 patients received once-daily treatment with 25 mg for two weeks.In the single dose study, the t_max of flosequinan was 2.5 h, C_max was 1.17 g · ml^–1 and t_1/2 was 5.63 h. The t_max of the metabolite BTS 53554 was 20.3 h, C_max was 1.44 g · ml^–1 and t_1/2 was 62.0 h.BTS 53554 accumulated gradually in the 14-day repeated dose study and steady-state was reached after approximately 2 weeks. Flosequinan was not found to accumulate.Adverse reactions were not observed in either the single or repeated dose study.It is advisable to consider renal function and body weight when flosequinan is to be administered to elderly patients with congestive heart failure. The initial dose should be 25 mg.     

Radiofrequency capacitive hyperthermia combined with irradiation or chemotherapy for patients with invasive bladder-cancer

The immediate therapeutic clinical efficacy and long-term outcome of hyperthermia in combination with irradiation or chemotherapeutic agent was evaluated in 46 patients with invasive bladder cancer. Radiohyperthermia was performed in 19 cases and chemohyperthermia in 27 cases. Complete response (CR) was obtained in 5 and partial response (PR) in 15 of the 46 cases. Five-year survival rates by the Kaplan-Meier method were 43.8% in the CR/PR group and 18.3% in the no change (NC)/progressive disease (PD) group, showing no difference of survival rate between the CR/PR group and the NC/PD group. The overall median survival period for the CR/PR group without metastasis was 61.6 months compared to 32.3 months for the NC/PD group without metastasis (P<0.05).     

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.     

Immunohistochemical and ultrastructural analysis of dysplastic epithelium of human ocular surface: basement membrane and intermediate filament.

PURPOSE: The dysplastic corneal epithelium is characterized by the abnormal proliferation of epithelial cells. The phenotypes of these cells have not been elucidated. We investigated whether such epithelium expresses the phenotypes of corneal or conjunctival epithelial cells. METHODS: The corneas and conjunctivae from four normal subjects and from one patient with epithelial dysplasia of the central cornea were immunostained for IV and VII collagens and for cytokeratins. Monoclonal antibodies against collagen IV reacted to the [alpha1(IV)]2alpha2(IV) or alpha5(IV) molecule. Anti-cytokeratin antibodies were used to define epithelial cell types. The ultrastructure of the basement membrane (BM) of each specimen also was examined. RESULTS: Type VII collagen immunoreactivity was detected in all the specimens of epithelial BM. The anti-collagen IV [alpha1(IV)]2alpha2(IV) antibody labeled the conjunctival BMs, not the BMs of the corneal epithelia, of each subject. The normal corneal epithelial BM, not the BM of the conjunctival or dysplastic corneal epithelium, was immunolabeled with anti-alpha5(IV) antibody. The pattern of cytokeratin expression in the corneal epithelial dysplasia resembled that seen in the normal conjunctivae. Small breaks in the BM of dysplastic corneal epithelium were ultrastructurally revealed. The number of hemidesmosomes in the dysplastic corneal epithelium was decreased as compared with that in the normal BM. CONCLUSION: The composition of collagen types within the BM and the cellular phenotype of the dysplastic epithelium in the cornea resembled those of conjunctival epithelium, not of the cornea.     

Cerebral atrophy in multiple system atrophy by MRI

Cranial magnetic resonance images (MRI) of the cerebral areas of 40 patients with multiple system atrophy (MSA) and of 61 age-matched controls were analyzed. The cerebral area of MSA patients was 131. 95+/-15.89 cm(2) (mean+/-S.D.), which was significantly smaller than that of normal controls at 149.01+/-10.93 cm(2) (P<0.0001). All 23 MSA cases subjected to the MRI study over a 1-year period showed progressive cerebral atrophy, and the atrophy rate was 2.46+/-1. 66%/year. There were no significant differences within the MSA subtypes or between gender. The progression of cerebral atrophy in MSA correlated more with duration (r=-0.634) than age (r=-0.421). We conclude that MRI findings throughout the course of MSA suggest progressive cerebral atrophy, which is common in all subtypes and reflects duration of the disease rather than age.