Pathological study of mice with total deficiency of sphingolipid activator proteins (SAP knockout mice)

Sphingolipid activator proteins (SAPs) A to D are lysosomal factors required in degradation of sphingolipids with short hydrophilic head groups and are derived from a precursor protein. Sap-B deficiency causes a variant of metachromatic leukodystrophy and sap-C deficiency causes a variant of Gaucher disease. Human total SAP deficiency has been reported in two patients in a single family. In these cases, various inclusions were described in the liver, skin, muscle and peripheral nerves ultrastructurally, but there was no report on the pathological study of the central nervous system (CNS). With targeted disruption of the precursor protein gene, we have generated mice with total SAP deficiency. These mice developed progressive neurological symptoms around day 20 and could not survive beyond day 40. Their cardinal pathology is extensive neurovisceral storage. Neuronal storage was already detected in the dorsal root ganglia as early as postnatal day 1 and diffuse neuronal storage was detected in the CNS after day 10. This storage was immunoreactive with anti-ubiquitin antibody and ultrastructurally appeared as inclusions consisting of numerous concentric lamellar and dense granular structures in the perikarya as well as in dendrites and axons. Axonal spheroids containing electron-dense concentric lamellar bodies and neurofilaments were also conspicuous. The extent of neuronal storage, numbers of storage neurons and axonal spheroids increased with age, accompanied with hypomyelination, astrogliosis and increase of macrophages. After day 30, argyrophilic tangle-like structures, which were immunoreactive with an antibody to phosphorylated neurofilaments, were found in the perikarya of many spinal and some neocortical neurons. Inclusions with various ultrastructural features were also noted in the glial cells, choroid plexus epithelial cells, vascular endothelial cells, Schwann cells, macrophages, fibroblasts, hepatocytes, and renal tubular epithelial cells. Some inclusions in the visceral organs were closely similar to those described in human cases of total SAP deficiency. The ultrastructural features of these inclusions in SAP knockout mice appeared unique and were different from those of other known sphingolipidoses. Received: 4 November 1997 / Accepted: 10 December 1997     

Mitral valve replacement through right thoracotomy after previous coronary artery bypass grafting

The Usefulness of Brachial Artery Cannulation, Perfused Ventricular Fibrillation with Moderate Hypothermia, and Minimal Dissection Techniques It has been reported by several authors that a right thoracotomy for mitral valve surgery can be useful after previous coronary aortery bypass grafting (CABG). A 76-year-old man with mitral valve regurgitation after previous CABG underwent mitral valve replacement with some modified techniques. Cardiopulmonary bypass was established with right brachial artery cannulation and right femoral venous cannulation with the aid of vacuum-assisted venous drainage. Ventricular fibrillation (VF) was induced by rapid pacing of the ventricle, and mitral valve replacement was performed under perfused VF with moderate hypothermia. The patient’s postoperative course was uneventful. This method appears to be a safe and easy alternative mitral valve surgery for complicated cases of this type.     

Hermansky-Pudlak综合征1型（HPS1）在日本白化病患者中频发和HPS1突变蛋白的功能分析

H erm ansky-Pudlak综合征(H PS)是一种常染色体隐性遗传病,具有眼皮肤白化病(OCA)、出血素质和蜡样物质溶酶体内沉积等特征。目前已知人类有7种遗传学上不同的H PS亚型;多数见于波多黎各地区。本文中,作者报道了对24例日本OCA患者的H PS1基因分析———这些患者缺乏已知的引起     

MRI abnormalities of the oculomotor nerve in a case of ophthalmoplegic migraine]

A 15-year-old girl presented with headache in the left retro-orbital area associated with double vision. She had a history of migraine headaches since the age of 9, and her mother also had suffered from migraine. The patient had experienced a similar episode at the age of 13, which resolved without any treatment in a day. On examination, two days after the onset of diplopia the patient had left ptosis and paresis of inwards and downwards in the left eye. Her pupils were isocoric, and the light reflex was prompt. MRI of the brain showed thickening and enhancement of the left third nerve through the cistern portion, especially at the oculomotor midbrain exit. No cavernous sinus involvement was noted. Results of the hemogram, ESR, and CSF were normal. The oculomotor palsy resolved spontaneously within six days. A follow-up MRI two months later demonstrated a marked lessening of enhancement at the oculomotor nerve but did not completely disappeared. These serial MRI abnormalities are thought to be important and typical findings seen in the patients of ophthalmoplegic migraine.     

Biologically active gangliosides from echinoderms

This review will summarize the authors’ studies on the structure and the biological activities of the gangliosides from echinoderms. Over 40 gangliosides have been obtained and characterized from 13 kinds of echinoderms, namely, Acanthaster planci, Asterina pectinifera, Asterias amurensis versicolor, Astropecten latespinosus, Luidia maculata, Linckia laevigata (starfish), Cucumaria echinata, Holothuria pervicax, H. leucospilota, Stichopus japonicus, S. chloronotus (sea cucumber), Comanthus japonica (feather star) and Ophiocoma scolopendrina (brittle star). The structural feature of the echinoderms gangliosides was their unique carbohydrate moieties. The biological property of the gangliosides from echinoderms, taking up in this review, was mainly neuritogenic activity.     

Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies

Although macroprolactinemia due to antiprolactin (anti-PRL) autoantibodies is not uncommon among hyperprolactinemic patients, the pathogenesis of such macroprolactinemia is still unknown. We examined IgG subclasses of anti-PRL autoantibodies by enzyme immunoassay, and PRL phosphorylation and isoforms by Western blotting, mass spectrometry, and two-dimensional electrophoresis in six patients with anti-PRL autoantibodies and in 29 controls. PRL-specific IgG subclasses in patients with anti-PRL autoantibodies were heterogeneous, but five of six patients showed IgG4 predominance, which is known to be produced by chronic antigen stimulation. Western blot and mass spectrometric analyses revealed that human pituitary PRL was phosphorylated at serine 194 and serine 163, whereas serine 163 in serum PRL was dephosphorylated. On two-dimensional electrophoresis, serum PRL mainly consisted of isoform with isoelectric point (pI) 6.58 in control hyperprolactinemic patients, whereas acidic isoforms (pIs 6.43 and 6.29) were also observed in patients with anti-PRL autoantibodies. Our data first demonstrate that human pituitary PRL is serine phosphorylated and partially dephosphorylated in serum, and suggest that the acidic isoforms may give rise to chronic antigen stimulation in patients with anti-PRL autoantibodies.     

Horizontal canal benign paroxysmal positional vertigo--its affected side and horizontal semicircular canal function

We report horizontal canal BPPV (HC-BPPV) targeting its pathophysiology, the affected side, and the function of the horizontal semicircular canal, together with a review of the literature. Subjects were 13 patients with HC-BPPV visiting our vertigo outpatient clinic at Nara medical university hospital and a related hospital in the 2.5 years from January 2000 to June 2002. Subjects were classified into 7 with canalolithiasis and 6 patients of cupulolithiasis after a neurotological examination. CP was positive in 54% of all patients, 71% of those with canalolithiasis, and 33% of those with cupulolithiasis. To determine the affected side in HC-BPPV, we used the affected side by using the law of Ewald in canalolithaisis patients and the detection of a neutral diminishing nystagmus in cupulolithiasis patients. CP positive in caloric testing indicated insignificant dysfunction of the horizontal semicircular canal in canalolithiasis patients compared to that in cupulolithasis patients. The mechanism behind caloric nystagmus was thought to be a convection of endolymphatic fluid interrupted consequently by an otolith in the semicircular canal in canalolithiasis patients. In contrast, CP was positive in cupulolithiasis patients regarded as having no convection of endolymphatic fluid. The mechanism causing a difference in caloric test results between canalolithiasis and cupulolithiasis patients thus requires a larger patient population and further examination to be conclusive.