Role of proliferative marker index and KBTBD4 mutation in the pathological diagnosis of pineal parenchymal tumors

Brain Tumor Pathology - Pineal parenchymal tumors (PPTs) are clinically rare and a biopsy is often required for a definitive diagnosis. To improve the accuracy of histological assessment of PPTs,...     

K-13, a novel inhibitor of angiotensin I converting enzyme produced by Micromonospora halophytica subsp. exilisia. II. Structure determination

The structure of K-13, a potent inhibitor of angiotensin I converting enzyme (ACE), was determined to be a cyclic dipeptide composed of tyrosine and an unusual diamino dicarboxylic acid, isodityrosine, by spectral and chemical studies of K-13 and its derivatives.     

The configuration of mitiromycin and its derivation from mitomycin B

The configuration of mitiromycin (2) was first determined by NMR experiments including the NOE technique. The absolute structure of 2 was related to mitomycin B (3) because 2 was derived from 3 under basic conditions. The ketonic form 4 was presumed to be involved in the generation of 2.     

Prolonged cerebral salt wasting following craniopharyngioma surgery and posterior reversible encephalopathy syndrome: a case report]

A 9-year-old boy was admitted to our hospital with daytime urinary incontinence for the past one year. MRI showed craniopharyngioma occupying the third ventricle. The tumor was excised by interhemispheric approach. Because hyponatremia and polyuria with high renal loss of sodium were observed on postoperative day 3, hydrocortisone and DDAVP were replaced. On postoperative day 24, successive general convulsions and hyponatremia recurred, and MRI FLAIR imaging showed marked brain edema in the bilateral parieto-occipital lobes. This finding disappeared late in the course of treatment, and the case was diagnosed as posterior reversible encephalopathy syndrome. The pathophysiology of cerebral salt wasting and posterior reversible encephalopathy syndrome in a craniopharyngioma patient are also discussed in the article.     

Carotid sinus nerve terminals which are tyrosine hydroxylase immunoreactive are found in the commissural nucleus of the tractus solitarius

Summary Tyrosine hydroxylase immunoreactive sensory neurons in the petrosal ganglion selectively innervate the carotid body via the carotid sinus nerve. Central projections of the carotid sinus nerve were traced with horseradish peroxidase. The commissural nucleus of the tractus solitarius was examined by dual labelling light and electron microscopy. Dense bilateral labelling with horseradish peroxidase was found in the tractus solitarius and commissural nucleus of the tractus solitarius. Horseradish peroxidase was found in unmyelinated axons, myelinated axons, and nerve terminals. About 88% of horseradish peroxidaselabelled carotid sinus nerve axons were unmyelinated. Tyrosine hydroxylase immunoreactivity was identified in unmyelinated axons, myelinated axons, dendrites, perikarya, and nerve terminals. Most tyrosine hydroxylase immunoreactive axons (93%) in the commissural nucleus of the tractus solitarius were unmyelinated. Tyrosine hydroxylase immunoreactivity was simultaneously identified in carotid sinus nerve unmyelinated axons, myelinated axons, and nerve terminals. These double-labelled terminals comprised 28% of the number of tyrosine hydroxylase immunoreactive terminals in the commissural nucleus of the tractus solitarius, and 55% of transganglionically-labelled terminals. Therefore, there are both central and peripheral sources of tyrosine hydroxylase immunoreactive nerve terminals in the commissural nucleus of the tractus solitarius. These data support the hypothesis that peripheral tyrosine hydroxylase immunoreactive neurons are involved in the origination of the chemoreceptor reflex. Axo-axonic synapses between peripheral carotid sinus nerve afferent terminals and central terminals containing tyrosine hydroxylase immunoreactivity were observed in 22% of the axo-axonic synapses observed. Thus, central tyrosine hydroxylase immunoreactivity neurons are involved in the modulation of the chemo- and/or baroreceptor reflexes. Synaptic contacts were not observed between carotid sinus nerve afferents and tyrosine hydroxylase immunoreactive perikarya of dendrites. Catecholaminergic neurons are thus unlikely to be the second order neurons of either the chemo- or baroreceptor reflex in the commissural nucleus of the tractus solitarius.     

Single-phased luminescent mesoporous nanoparticles for simultaneous cell imaging and anticancer drug delivery

Multifunctional materials for biological use have mostly been designed with composite or hybrid nanostructures in which two or more components are incorporated. The present work reports on a multifunctional biomaterial based on single-phased luminescent mesoporous lanthanide oxide nanoparticles that combine simultaneous drug delivery and cell imaging. A simple strategy based on solid-state-chemistry thermal decomposition process was employed to fabricate the spherical mesoporous Gd(2)O(3):Eu nanoparticles with homogeneous size distribution. The porous nanoparticles developed by this strategy possess well-defined mesopores, large pore size and volume, and high specific surface area. The mesoporous features of nanoparticles impart the material with capabilities of loading and releasing the drug with a relatively high loading efficiency and a sustained release behavior of drugs. The DOX-loaded porous Gd(2)O(3) nanoparticles are able to kill the cancer cells efficiently upon incubation with the human cervical carcinoma (HeLa) cells, indicating the potential for treatment of cancer cells. Meanwhile, the intrinsic luminescence of Gd(2)O(3):Eu nanoparticles gives the function of optical imaging. Therefore, the drug release activity and effect of drugs on the cells can be effectively monitored via luminescence of nanoparticles themselves, realizing multifunctionality of simultaneous cell imaging and anticancer drug delivery in a single-phased nanoparticle.     

Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII–FS) in patients with haemophilia A: a long-term, multicentre clinical study in Japan

The recombinant full-length FVIII product Kogenate has been reformulated using sucrose (rFVIII-FS) instead of human serum albumin as a stabiliser in purification and formulation. The in vivo recovery, haemostatic efficacy, and safety of rFVIII-FS were investigated in 20 previously treated patients with severe or moderate haemophilia A for > or = 24 weeks. In vivo recoveries of 73.5 +/- 16.3%, 78.4 +/- 16.1%, and 82.8 +/- 23.9% after the initial infusion of 50 IU kg(-1) rFVIII-FS and at weeks 12 and 24, respectively, showed no significant changes over time. A total of 1115 infusions (mean dose 24.1 +/- 8.4 IU kg(-1)) were included in the analysis of haemostatic efficacy. One (80.5%) or two (8.2%) infusions achieved adequate haemostasis in 88.7% of all bleeding episodes, and haemostatic efficacy was judged 'excellent' or 'good' in 749 of 764 episodes (98.0%). The haemostatic efficacy was judged as 'excellent' or 'good' in 924 of 1115 (82.9%) infusions. Twenty-one adverse events were observed in 12 patients in the total 1541 infusions included in the safety analysis. Causality with respect to rFVIII-FS could not be ruled out in three events in one HIV-negative patient: elevated CD4(%), decreased CD8(%), and elevated CD4/CD8 ratio. No FVIII inhibitor development was observed in any patient. ELISA assay testing for antibodies to rFVIII, baby hamster kidney cell (BHK) protein, and murine IgG were all negative. These results show that rFVIII-FS is a safe and effective for long-term treatment of patients with haemophilia A.