Crystal structures of two tropinone reductases: Different reaction stereospecificities in the same protein fold

A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-Å resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.     

An XXX female with essential thrombocythemia

We describe an XXX female patient accompanied with essential thrombocythemia. To our knowledge this is the first case ever to have been reported. The patient was asymptomatic, but her platelet count had increased to 111.2 x 10(4)/microliter, and she was diagnosed as having essential thrombocythemia based on the diagnostic criteria of the Polycythemia Vera Study Group. At the same time, chromosome analysis of bone marrow cells revealed that she was an XXX female. The patient remained asymptomatic throughout the course of treatment.     

Effect of Intensive Salt‐Restriction Education on Clinic,Home, and Ambulatory Blood Pressure Levels in Treated Hypertensive Patients During a 3‐Month Education Period

The authors tested the hypothesis that low‐salt diet education by nutritionists would lower blood pressure (BP) levels in treated hypertensive patients. The amount of urinary salt excretion and clinic, home, and ambulatory BP values at baseline and at 3 months were measured in 95 patients with hypertension. After randomization to a nutritional education group (E group, n=51) or a control group (C group, n=44), the C group received conventional salt‐restriction education and the E group received intensive nutritional education aimed at salt restriction to 6 g/d by nutritionists. From baseline to the end of the study, 24‐hour urinary sodium excretion was significantly lowered in the E group compared with the C group (6.8±2.9 g/24 h vs 8.6±3.4 g/24 h, P<.01). Morning home systolic BP tended to be lowered in the E group (P=.051), and ambulatory 24‐hour systolic BP was significantly lowered in the E group (−4.5±1.3 mm Hg) compared with the C group (2.8±1.3 mm Hg, P<.001). Intensive nutritional education by nutritionists was shown to be effective in lowering BP in treated hypertensive patients.

The association between excessive salt intake and blood pressure (BP) elevation is well‐known, and some interventional studies such as the International Study of Electrolyte Excretion and Blood Pressure (INTERSALT) demonstrated that the amount of salt intake was associated with BP levels.¹ In an international study of 101,945 individuals from 17 countries, it was found that the estimated sodium intake of 3 g/d to 6 g/d was associated with lower incidences of cardiovascular events and death compared with higher or lower levels of salt intake.² In a study of a mildly hypertensive population, clinic and ambulatory BP levels were significantly lowered by low salt intake compared with those in the control group.³ In the same study, lower salt intake was associated with lower excretion of urinary albumin and a lower pulse wave velocity (a measure of arterial stiffness) compared with those in the control group. Taken together, these findings support the importance of salt restriction for the improved control of BP and protection from end‐organ damage, provided that the salt restriction is successfully performed.In the 2014 guidelines from the Japanese Society of Hypertension (JSH), salt restriction to <6 g/d is recommended for all hypertensive populations.⁴ However, this recommendation is mostly based on observational studies⁵ or interventional studies in which the diets of patients were completely controlled, sometimes under hospitalized conditions.⁶ For example, in the Dietary Approaches to Stop Hypertension (DASH) trial,⁷ a low‐salt diet was given to the patients during the study period. Few studies have examined whether intensive nutritional education in an outpatient clinic, especially education on dietary salt restriction, can lower not only clinic BP but also home and ambulatory BP levels. Thus, in the present study, we tested the hypothesis that intensive nutritional education focused on salt restriction and provided by nutritionists in an outpatient clinic lowers clinic, home, and ambulatory BP in treated hypertensive patients.     

Case Report: Adrenal Oncocytoma Associated with Markedly Increased FDG Uptake and Immunohistochemically Positive for GLUT1

Usually, benign tumors are not associated with an increased F-18 fluorodeoxyglucose (F-18 FDG) uptake on positron emission tomography (PET), although some exceptions have been reported in adrenal neoplasms. We present a rare case of adrenocortical oncocytoma associated with markedly increased FDG uptake, demonstrating a maximum standardized uptake value of 46.8. Histological examination demonstrated diffuse proliferation of tumor cells with eosinophilic and granular cytoplasm that were diffusely immunopositive for mitochondria and glucose transport protein 1, with focal and weak immunopositivity for 3β-hydroxysteroid dehydrogenase. Ultrastructural examination also revealed abundant mitochondria in the tumor cells. The tumor was diagnosed as adrenocortical oncocytoma and was considered benign according to Lin-Weiss-Bisceglia criteria. Diagnosis of adrenocortical oncocytoma can pose difficulties during both preoperative radiological and postoperative histopathological investigations.