The biological characteristics and chemosensitivity of anaplastic thyroid carcinoma transplanted into nude mice

Three xenografts established from three patients with anaplastic thyroid carcinoma were investigated for their biological characteristics and chemosensitivity. The histological and immunohistochemical findings of these tumors were almost the same as those of the original tumors. Although the growth rate of each xenograft was constant, the tumor doubling time varied from 4.8 per 9.0 days, and the labeling indexes, determined using bromodeoxyuridine pulse labeling, varied from 11.4 to 25.1 per cent. The chemosensitivity tests were performed according to the Battelle Columbus Laboratories Protocol, with adriamycin, cyclophosphamide, cisplatin, mitomycin C and tegafur administered intraperitoneally to tumor-bearing nude mice in maximum tolerable doses. Tumors with slower growth rates tended to be sensitive to more drugs. Furthermore, cyclophosphamide showed antitumor effects against all the tumors tested. Although previous treatments of the original tumors may have affected the results, our results suggest that a more suitable chemotherapy for anaplastic thyroid carcinoma could be developed.     

Comparison of ascorbic acid and ascorbic acid 2-O-alpha-glucoside on the cytotoxicity and bioavailability to low density cultures of fibroblasts.

Ascorbic acid 2-O-alpha-glucoside (AA-2G) is a stable ascorbate derivative which has vitamin C activity in vivo and in vitro. We studied whether AA-2G exerts a prooxidant action in cultured fibroblasts from chick embryo and human skin, as does ascorbic acid. At concentrations of 0.1-1.0 mM, ascorbic acid markedly reduced the viable cell number of low density cultures within 24 hr, whereas AA-2G had no such effect. The ascorbate cytotoxicity was dependent on the cell density at the time of its addition and it was characteristic of low density cultures. This cytotoxicity was completely prevented by catalase and partially by an Fe3+ ion chelator, desferrioxamine. In the early culture stage at which a morphological change in the fibroblasts began to occur, intracellular ascorbate concentrations in low density cultures after addition of ascorbic acid were much higher than in high density cultures. However, at the same concentrations, AA-2G did not cause an elevation even in low density cultures and it was also effective on collagen synthesis at high and medium densities. These results suggest that the abnormally accumulated ascorbic acid in the cells cultured at low density possibly amplifies the generation of oxygen radicals through the reduction of Fe3+ ions and subsequent oxidative reactions, leading to cell death. Therefore, it is concluded that AA-2G which supplies an adequate amount of ascorbic acid during culture period is a bioavailable ascorbate source without cytotoxicity.     

Mirror foot: treatment of three cases and review of the literature

Purpose  To describe three cases of mirror foot and to develop a new classification of the mirror feet with an emphasis on their treatment. Methods  Surgical treatment was performed on three patients with mirror foot. Mirror feet in the English literature were surveyed and cases found in PubMed as well as our three cases were classified according to a new classification that was an analogy of the mirror hand classification proposed by Al-Qattan et al. (J Hand Surg Br 23:534–536, 1998). Results  All three cases obtained satisfactory outcome after the treatment. In addition to these cases, 28 mirror feet were well described in the English literature, among which only seven cases have been documented for their treatment. All of the cases could be assigned to one of the categories of the proposed classification. Conclusion  Mirror foot is a very rare congenital deformity of the foot. We successfully treated three novel cases of mirror feet. A classification of the mirror feet proposed in this article was useful in order to understand its nature and obtain a guideline for its treatment.     

Antibody Response to Bacterial Antigens: Characteristics of Antibody Response to Somatic Antigens of Salmonella typhimurium

The character of the antibody response in the rabbit to Salmonella typhimurium somatic (O) antigen was similar to the response to each of several serotypes of Shigella flexneri O antigens, namely a predominance of production of immunoglobulin M (IgM) antibody. Lipopolysaccharide protein (LPSP) and lipopolysaccharide (LPS) fractions of Salmonella O antigen differed significantly in both quantitative and qualitative aspects of their immunogenicity. LPSP elicited high levels of agglutinins and also induced the production of a significant amount of immunoglobulin G (IgG) antibody at a late period. LPS antigen elicited low levels of agglutinins which were exclusively IgM antibody. These results suggested that the chemical nature of the antigen is one important factor in the determination of the character of the antibody response. Further, it is suggested that the protein moiety of the O antigen complex is a carrier active in allowing induction of early IgM and of late IgG antibodies; in contrast, the lipid moiety may compete with this action of the carrier protein, thereby suppressing IgG antibody in the primary stage of the antibody-forming process.     

Three-dimensional organization of the hepatic microvasculature in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic fibrovascular dysplasia. Although hepatic vascular shunts are often observed in HHT, the responsible pathological mechanism is unknown. This issue was addressed by performing a 3-dimensional reconstruction study of the hepatic microvasculature of an HHT-involved liver in a 79-year-old woman. Clinical observation revealed high-output congestive heart failure and hepatic encephalopathy due to arteriovenous and portovenous shunts, respectively. Angiography revealed tortuous dilation of hepatic arterial branches and intrahepatic arteriovenous shunts. The 3-dimensional analysis of the autopsy liver revealed focal sinusoidal ectasia, arteriovenous shunts through abnormal direct communications between arterioles and ectatic sinusoids, and portovenous shunts due to frequent and large communications between portal veins and ectatic sinusoids. Type 1 HHT was suggested by the lack of endoglin immunoreactivity in the liver. The 3-dimensional reconstruction study of hepatic microvasculature was successful in identifying the pathological changes responsible for the intrahepatic shunts in HHT.     

Development of early apopotosis and changes in lymphocyte subsets in lymphoid organs of mice orally inoculated with nivalenol

Development of early apoptosis and changes in lymphocyte subsets were examined in lymphoid organs of female BALB/c mice after oral administration of 15 mg/kg b.w. of nivalenol (NIV), the major type B trichothecene mycotoxin, by FACS analysis. Judging from the results of viable cell count and apoptotic cell index, NIV attacked Peyer's patches first and thymus most severely. In thymus, selective damage in CD4(+)CD8(+) cells was observed at 12 and 24 h after inoculation (HAI), following the peak of apoptosis at 9 HAI. CD4(+) cells were clearly suppressed at 3 HAI in Peyer's patches, at and after 9 HAI in mesenteric lymph nodes, and 3 to 12 HAI in spleen, respectively. CD8(+) cells were also suppressed at 24 HAI in mesenteric lymph nodes and at 12 HAI in spleen, respectively. As to changes in B cell subsets, IgG(+) cells significantly decreased from 3 to 12 HAI and all B cell subsets at 24 HAI in mesenteric lymph nodes. In spleen, IgM(+) cells were suppressed at 9 HAI. On the other hand, in Peyer's patches, following clear decrease in the numbers of pan-T and pan-B cells and viable cells at 3 HAI, all B cell subsets, especially IgA(+) cells, showed a significant increase in their numbers at 9 HAI, and the numbers of IgA(+) and IgM(+) cells remained higher values than controls thereafter. Taken together, in the course of recovery from NIV-induced prominent damage in Peyer's patches at 3 HAI, interaction of NIV with Peyer's patches might result in in vivo stimulation of interleukin production at this site and result in increased proliferation and differentiation of IgA-secreting B cells at and after 9 HAI.     

Morphometric analysis of the development of sexual dimorphism of the mouse pelvis

Sex differences in the innominate bone of C57BL/Tw mice were studied morphometrically from the day of birth to 120 days of age. In neonatal male and female mice, a small cartilaginous spine was found on the basal part of ischium. This process disappeared in males within 24 hours after birth, whereas in females it remained until at least 30 days. Other sexual differences in the pubis and the ischium appeared at 30 and 120 days, respectively. The pubis in female mice was longer and thinner than that in the males, and the ischium in male mice was shorter and thicker than that in the females. Thirty-day-old female mice treated neonatally with testosterone or 5 alpha-dihydrotestosterone possessed pubic bones shorter and thicker than those of the age-matched untreated females. Pubes in male mice castrated at the day of birth were thinner than those in intact males. These findings suggest that the shape of the innominate bone is transformed to the male type under the influence of early postnatal androgen.     

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II,randomized, double-blind,placebo-controlled clinical study

Clinical and Experimental Nephrology - The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be...     

Long-term outcome of coronary events in hemodialysis patients younger and older than 65 years of age

BACKGROUND AND AIM: It has been reported that a coronary event is the leading cause of mortality in HD patients. The aim of this study was to examine and compare prospectively the effect of aging in relation to the in-hospital and the long-term outcome in HD patients with or without revascularization therapy who had experienced a coronary event. STUDY PATIENTS AND METHODS: Seventy consecutive HD patients with coronary events (9 AMI, 48 AP, and 13 CHF) were registered in this study and 69 patients underwent CAG. Patients were classified into elderly (> or = 65, n = 33) and younger (< 65, n = 37) groups based on their ages at the time of the events. Forty-six patients (21 vs 25) underwent initial coronary revascularization therapy. We followed 70 HD patients with coronary events for a mean period of 31 +/- 21 months (range: 1 day to 77 months). RESULTS: A level of 64% of the elderly group and 41% of the younger group experienced coronary events within the first year of HD. The diseased vessels (2.2 vs 1.9 per patient) and stenotic lesions (2.8 vs 2.5 pre patients) were not significantly different between the two groups. The 70-month survival rate was significantly lower (21% vs 65%, p = 0.0423) in the elderly group than in the younger group. The complicated rate of stroke after a major event was significantly higher (14 vs 4, p = 0.0025) in the elderly group than in the younger group. Moreover 21 elderly patients (11 cardiac death, 5 stroke, 4 cancer) and 9 younger patients (8 cardiac death, 1 stroke) died during the 70-month follow-up period. CONCLUSIONS: Coronary events were most frequent in the first year of HD. Long-term survival rate was significantly lower in elderly patients than in younger patients. Cardiac death was the most common cause of death in both groups regardless of performing coronary revascularization. Death due to stroke and cancer was also more common in elderly patients.