Challenges in creating a vaccine to prevent hepatitis E

Recombinant hepatitis E virus capsid protein (HEV CP) assembles orally immunogenic virus-like particles (VLP) when expressed in an insect cell system. We used plant expression cassettes, pHEV101 and pHEV110, for transformation of potato to express HEV CP, and 10 independent transgenic lines of HEV101 and 6 lines of HEV110 were obtained. ELISA for HEV CP was performed on tuber extracts. Accumulation of HEV CP in tubers varied from about 5 to 30 microg/g fresh tuber depending on the transgenic plant line. We further compared the expression levels with the yield of tubers for each line. Tuber yield varied less than expression levels, and ranged from about 600 to 1000 g per pot. Although Western blot showed that apparently intact HEV CP accumulated, we observed very limited assembly of virus-like particles in potato tubers. Oral immunization of mice with transgenic potatoes failed to elicit detectable anti-CP antibody response in serum, suggesting that VLP assembly is a key factor in orally delivered HEV CP vaccines.     

Insulin-induced lipohypertrophy: report of a case with histopathology

An 82-year-old woman with type 2 diabetes had been treated with recombinant human insulin for 16 years. She developed large swellings in both sides of her lower abdomen. The masses were soft, painless, and located around her insulin injection sites. Based on the history and clinical features, a diagnosis of insulin-induced lipohypertrophy was made. Total resection revealed that the lesions were composed entirely of fatty tissue. Microscopic examination showed nests of mature adipocytes expanding toward the dermal reticular layer. The hypertrophic adipocytes were twice as large as those from normal subcutaneous areas and contained numerous small lipid droplets. Electron microscopic analysis also revealed a minor population of small adipocytes, suggesting active differentiation or proliferation. Thus, the possible in vivo effects of insulin on adipocytes were clearly observed in this case of insulin-induced lipohypertrophy. To our knowledge, this is the first report of insulin-induced lipohypertrophy with detailed histological examinations.     

Adrenocorticotropic hormone is produced in the ventricle of patients with essential hypertension

OBJECTIVE: Aldosterone is produced in the ventricle of patients with hypertension. The present study was designed to examine whether adrenocorticotropic hormone (ACTH) and cortisol are also produced from the heart in patients with essential hypertension. METHODS: The study population consisted of 57 patients with essential hypertension and 28 control subjects. Plasma levels of ACTH, aldosterone, and cortisol were measured in the aortic root, the anterior interventricular vein and the coronary sinus during cardiac catheterization. RESULTS: The plasma levels of ACTH were significantly higher at the anterior interventricular vein and coronary sinus than at the aortic root (12.7 +/- 1.0 versus 10.7 +/- 0.9 pmol/l, P < 0.001; and 12.3 +/- 1.0 versus 10.7 +/- 0.9 pmol/l, P < 0.001, respectively) in the hypertension group, whereas there were no significant differences in the levels among these sites in the control group. The plasma levels of aldosterone were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root (261.7 +/- 16.4 versus 239.1 +/- 15.1 pmol/l, P < 0.001; and 258.8 +/- 17.0 versus 239.1 +/- 15.1 pmol/l, P < 0.01, respectively) in the hypertension group, whereas there were no significant differences in the levels among these sites in the control group. CONCLUSIONS: ACTH as well as aldosterone is produced, but cortisol is not produced, from the ventricle of patients with essential hypertension.     

A case of hepatocellular carcinoma initially treated by carbon ions, followed by protons for marginal recurrence with portal thrombus

We report a case of hepatocellular carcinoma (HCC), initially treated by carbon ions, then subsequently by protons for marginal recurrence. A 52-year-old man with stage II HCC was enrolled in the clinical study for carbon ion therapy. A total dose of 52.5 GyE in 8 fractions was delivered through a right lateral port for 13 days. Dynamic CT performed 7 months after the initiation of carbon ion therapy showed a decrease in the size of the tumor. Dynamic CT performed 12 months after the therapy revealed marginal recurrence of HCC accompanied with portal vein tumor thrombus (PVTT). Proton therapy of 66 GyE in 22 fractions was delivered through posterior and right lateral ports for 33 days. Dynamic CT performed 3 months after the initiation of proton therapy showed a regression of the recurrent tumor and disappearance of the PVTT. No serious adverse effects were observed during or after these two treatments. He was free from further recurrence 27 months after the initiation of the first carbon ion therapy. Both carbon ions and protons were effective with minimal side effects.