Deoxycorticosterone-secreting adrenocortical carcinoma

A case of DOC-secreting adrenocortical carcinoma in a 66-year-old man is reported. He had hypertension, hypokalemia, suppressed PRA, and excessive serum levels of DOC. His serum aldosterone level was normal. The resected adrenal mass weighed 230 g. Histologically, the tumor was mainly composed of compact cells associated with necrosis and atypical mitoses. Invasion of venous structure, sinusoids, and capsule was also present. Immunohistochemically, P450 C21 (21 -hydroxylase) was positive in many tumor cells, and P450 C17(17 α-hydroxylase) was intensely positive in a relatively small number of tumor cells. The patient died 9 months after operation due to rupture of metastatic liver tumor.Endocr Pathol 4:165–168, 1993.     

Use of the genomic subtractive hybridization technique to develop a real-time PCR assay for quantitative detection of Prevotella spp. in oral biofilm samples

Genomic subtractive hybridization was used to design Prevotella nigrescens-specific primers and TaqMan probes. Based on this technique, a TaqMan real-time PCR assay was developed for quantifying four oral black-pigmented Prevotella species. The combination of real-time PCR and genomic subtractive hybridization is useful for preparing species-specific primer-probe sets for closely related species.     

Immunocytochemical localization of secretogranin III in the endocrine pancreas of male rats

Secretogranin III (SgIII), a member of the granin protein family, is expressed specifically in neuronal and endocrine cells. To examine the precise localization of SgIII in the endocrine pancreas, pancreatic tissues of rats were analyzed immunocytochemically with a polyclonal anti-serum raised against rat SgIII. By light microscopy of semithin sections, the immunoreactivity for SgIII was readily detected in pancreatic A- and B-cells, faintly so in D-cells, and not at all in the exocrine pancreas. By immunoelectron microscopy, immunogold particles indicative of SgIII were observed in the peripheral regions of secretory granules, and universally in the pancreatic endocrine cells. Morphometrical analyses indicated that SgIII is most preferentially localized in the periphery of the secretory granule among granins. These findings suggest that SgIII is closely associated with the secretory granule membrane, serving to anchor the aggregates of other soluble constituents to the membrane.     

Lamivudine and IFN-beta sequential therapy in HBe antigen-positive patients with chronic hepatitis B virus genotype C infection.

Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response.     

Attenuation of retinal photooxidative damage in thioredoxin transgenic mice

Thioredoxin (TRX) is an endogenous redox (reduction/oxidation) regulator that has cytoprotective effects against various types of oxidative stresses. Exposure to excessive levels of white light induces retinal photoreceptor damage. To test the cytoprotective effect of overexpressed TRX against retinal photooxidative damage, both TRX transgenic (trx-tg) mice and C57BL/6 (wild type) mice were exposed to intense white fluorescent light. The amounts of oxidized and tyrosine-phosphorylated proteins decreased in the neural retinas of the trx-tg mice compared to the wild type mice after light exposure. The electroretinographic amplitudes were higher and the formation of oxidized DNA was lower in trx-tg mice compared to wild type mice after light exposure. These results suggest that overexpression of TRX suppresses retinal photooxidative damage. TRX intensification may be a useful therapeutic strategy to prevent retinal photic injury.     

Polo-like kinase 1 expression in medullary carcinoma of the thyroid: its relationship with clinicopathological features.

OBJECTIVE: Polo-like kinase 1 (PLK1) is one of the serine-threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. In this study, we investigated PLK1 expression in medullary thyroid carcinoma by means of immunohistochemistry. METHODS: We immunohistochemically investigated PLK1 expression in 67 cases of medullary thyroid carcinoma. RESULTS: The PLK1 expression level was elevated in 43 of the 67 cases (64.1%). Furthermore, the expression level was directly linked to lymph node metastasis, advanced stage and male sex. All patients who were negative for PLK1 expression are currently alive without tumor recurrence, while 6 of the 43 PLK1-positive patients showed recurrence and 3 have already died of this disease. CONCLUSIONS: These findings suggest that PLK1 expression significantly reflects aggressive characteristics of medullary thyroid carcinoma.     

CD69-null mice protected from arthritis induced with anti-type II collagen antibodies

CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response when injected with anti-type II collagen antibodies. Cell transfer experiments with neutrophils, but not T cells or spleen cells, from wild-type mice into CD69-null mice restored the induction of arthritis. These results indicate a critical role for CD69 in neutrophil function in arthritis induction during the effector phase. Thus, CD69 would be a possible therapeutic target for arthritis in human patients.     

An improved method for recovery of F-defective Sendai virus expressing foreign genes from cloned cDNA

An improved system is described to recover non-transmissible Sendai virus that lack the envelope fusion (F) gene from cloned cDNA. The system (1) used plasmids that expressed the F and the HN viral envelope proteins, as well as the plasmids that expressed the viral NP, P, and L proteins as helper plasmids for recovery, and (2) overlaid packaging cells that expressed the F protein. With this improved system, we have succeeded in recovery of F-defective Sendai virus expressing two foreign proteins, and expression vectors that do not contain the EGFP reporter gene. This system may provide the basis for constructing recombinant F-defective Sendai virus for preventing and treating human diseases in the form of vaccines and vectors for gene therapy.     

Airway responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo

BACKGROUND: Chronic exposure to fenoterol (FEN), a beta(2)-adrenergic receptor (beta(2)-AR) agonist, was shown to induce both airway hyperresponsiveness and airway remodeling in experimental animals. OBJECTIVE: We wanted to know the effects of chronic exposure to procaterol (PRO), a beta(2)-AR agonist, on airway function and structure, because this agent is widely used as a bronchodilator in Japan. For comparison, the effects of FEN were also examined. METHODS: Aerosolized PRO (0.1 or 1 mg/ml), FEN (1 mg/ml) or vehicle (0.9% NaCl) was given to guinea pigs 3 times a day for 6 weeks. Sublaryngeal deposition of these agents was calculated using radioisotopes. At 72 h after the last inhalation of PRO, FEN or vehicle, the dose-response relationship between lung resistance (R(L)) and intravenously administered acetylcholine (ACh) was measured. After measuring R(L), histological changes in noncartilaginous airway dimensions were evaluated. RESULTS: The amount of sublaryngeal deposition of 0.1 mg/ml PRO in the present study was speculated to be 100 times larger than that of therapeutic dose. ACh concentrations causing 2-fold, 10-fold and maximal increases in R(L) were not different in 4 groups tested. In the smaller membranous airways (<0.4 mm in diameter), but not the larger ones, thickening of adventitial areas was significantly greater in animals treated with beta(2)-AR agonists than in control animals (23 and 25, and 96% higher in animals treated with 0.1 and 1 mg/ml PRO or 1 mg/ml FEN, respectively). The degree of the increase was significantly less in PRO-treated animals than in FEN-treated animals (p < 0.01). CONCLUSION: Our results did not provide any evidence that regular inhalation of PRO at the therapeutic dose might induce bronchial hyperresponsiveness. In addition, huge amounts of PRO only caused a mild thickening of the adventitial areas, suggesting that PRO may be a weak inducer of airway remodeling compared with FEN.