Corneal amyloidosis complicated by trichiasis. Immunohistochemical identification of the amyloid light chain protein

Purpose: To identify the amyloid protein of the corneal amyloidosis complicated by trichiasis.Methods: The two patients were 41-year-old and 38-year-old women with trichiasis. They had gelatinous drop-like corneal change in the hemilateral eye. The lesion was excised and examined by light and electron microscopy. Additionally, we performed an immunohistochemical study with immunofluorescence techniques using cryosections.Results: The amyloid deposits were confirmed with light and electron microscopy. Congo red positive staining was not reduced following pretreatment with potassium permanganate. Immunohistochemically, amyloid deposits in the cornea stained positively with serum human light chain kappa and lambda. Pretreatment of the section with 0.05% Tween-20 did not decrease the staining with fluorescence. The deposits stained negatively with serum prealbumin and keratin antibodies.Conclusions: These findings indicate the protein of the corneal amyloidosis complicating trichiasis to be an amyloid light chain (AL) protein that has never been identified in this kind of corneal amyloidosis.     

Role of somatosensory feedback from tools in realizing movements by patients with ideomotor apraxia

In order to investigate the underlying mechanism of ideomotor apraxia, we studied 9 patients who could not mime using tools despite the ability to manipulate actual tools normally. In all the mime tasks, visually presented tools or model gestures by examiners were fundamentally ineffectual in improving the patients' performances. Even the remarkable improvement demonstrated when using actual tools disappeared immediately after the subjects took their hands off them. In a further experiment, 4 of the 9 patients were required to pretend to use tools while holding a stick, resulting in significant improvements or normal miming. These findings suggest that the somatosensory feedback continuously supplied from a handheld tool is a crucial component in enabling patients with ideomotor apraxia to actually use tools.     

Unique medical education programs at Nippon Medical School

In an attempt to improve the content of the educational programs offered by Nippon Medical School and to better prepare our students to work in the rapidly changing world of medicine, the school has recently revamped its teaching methodology. Particular emphasis has been placed on 1) simulator-based education involving the evaluation of students and residents in a new clinical simulation laboratory; 2) improving communication skills with the extensive help of simulated patients; 3) improving medical English education; 4) providing early clinical exposure with a one-week clinical nursing program for the first year students to increase student motivation at an early stage in their studies; 5) a new program called Novel Medical Science, which aims to introduce first-year students to the schools fundamental educational philosophy and thereby increase their motivation to become ideal physicians. The programs have been designed in line with 2006 guidelines issued by the Ministry of Education, Culture, Sports, Science and Technology to allow flexibility for students to take part in education outside their own departments and year groups as part of the Ministry's program to encourage distinctive education at Japanese universities.     

High levels of immunoreactive endothelin-1 in human follicular fluids

Follicular fluids were obtained from 180 follicles of 15 womenundergoing follicular aspiration for in-vitro fertilization.Follicular development was induced by a combination of buserelinacetate and human menopausal gonadotrophin. Endothelin-1 (ET-1)concentrations in human follicular fluids were determined byspecific radioimmunoassay. ET-1-like immunoreactivity (ET-1-LI)ranged from 338 to 928 pg/ml. ET-1-LI concentrations in follicularfluids obtained from immature (< 15 mm) follicles were significantlyhigher than those from mature (15–25 mm) and post-mature(25 mm) follicles. No correlation was found between the concentrationof ET-1-LI, on the one hand, and that of oestradiol, progesterone,testosterone, prolactin, luteinizing hormone, insulin-like growthfactor-I, prostaglandin E₂ or platelet activating factor onthe other, in follicular fluids. However, a significant positivecorrelation was observed between ET-1-LI concentration and folliclestimulating hormone and IGF-II concentrations, respectively.These data suggest that the high concentration of ET-1 foundin follicular fluids may play some physiological role in folliculardevelopment.     

Immunohistochemical localization of tenascin and ki-67 nuclear antigen in human endometrium throughout the normal menstrual cycle

To elucidate the possible regulation of endometrial growth, we investigated the expression of tenascin, an extracellular matrix protein associated with cell proliferation and morphogenetic events, in relation to the mitotic marker ki-67 antigen in human endometrium throughout the menstrual cycle. The endometrial tissue was obtained from women with regular menstruation undergoing hysterectomy due to benign uterine disease. Cryostat sections were subjected to double immunohistochemistry to detect both tenascin and ki-67. During the proliferative phase, an intense deposition of tenascin fibrils occurred in the extracellular matrix of the stroma immediately subjacent to the uterine epithelium that showed the highest proportion of ki-67 positive cells. In the secretory phase, the amount of tenascin expression and the proliferative index of the epithelium were markedly reduced. The topological immunoreactivity of tenascin, however, was clearly related to ki-67 localization close to the tortuous endometrial gland and spiral artery. Expression of tenascin, showing changes depending on the menstrual phase, appears to be influenced by ovarian steroid hormones, and it might play a role in regulating human endometrial development by interaction with mitotic cells.     

Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration.

AIMS: The present study examines the relationship between markers of endothelial dysfunction and diabetic neuropathy or consequent neuropathic foot ulceration in patients with Type 2 diabetes mellitus. METHODS: We studied 65 Type 2 diabetic patients including 25 diabetic patients without neuropathy, 27 with neuropathy but no history of foot ulceration, and 13 with neuropathic ulceration. Plasma concentrations of von Willebrand factor (vWF) and soluble thrombomodulin (TM), measures of endothelial dysfunction, were determined by enzyme immunoassays. We performed various tests quantifying aspects of diabetic neuropathy including vibration perception threshold (VPT; for sensory neuropathy), coefficient of variation of R-R intervals (CVR-R; for cardiac autonomic neuropathy), and cold-induced vasodilation in the great toe for peripheral sympathetic neuropathy. RESULTS: CVR-R and cold-induced vasodilation were significantly diminished in patients with neuropathic foot ulceration compared with patients with neuropathy but no history of foot ulceration. Plasma vWF concentrations were positively correlated with VPT and cold-induced vasodilation test, and were inversely correlated with CVR-R. Multivariate analysis disclosed that VPT and percentage vasodilation were independent factors for plasma vWF. Plasma vWF was significantly elevated in patients with foot ulceration compared with patients without neuropathy or those with neuropathy but not foot ulceration. However, plasma TM concentrations did not differ between the three groups. CONCLUSIONS: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.     

Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

Adrenomedullin (AM) is a novel vasorelaxant peptide, isolated from human pheochromocytoma. Although AM may be involved in the regulation of the cardiovascular system, a number of other mechanisms are also involved. The present study was undertaken to confirm the presence of AM in human maternal circulation and in placental function during pregnancy. Immunoreactive (ir) AM concentrations in maternal plasma were 3.4+/-0.7fmol/ml (mean+/-s.e. m.) in the first trimester, 3.3+/-1.1fmol/ml in the second trimester, 7.3+/-2.8fmol/ml in the third trimester, 4.1+/-1.9fmol/ml in early puerperium and 3.0+/-0.4fmol/ml in non-pregnant periods; the concentration in the third trimester was significantly greater than those in other periods. Plasma concentrations of estradiol (E(2)), progesterone, human placental lactogen (hPL) and human chorionic gonadotropin (hCG) were also measured, using RIA kits. Significant correlations have been demonstrated between the concentrations of irAM and those of E(2), progesterone and hPL. We therefore examined the expression of AM within the placental tissues using immunohistochemistry and northern blot analysis in order to demonstrate a correlation between the presence of AM in the placenta and maternal plasma. Using immunohistochemistry, we detected AM in the amnion at term and the expression of AM mRNA in human placental tissues using cloned human (h) AM complementary DNA as a probe. This study demonstrates the immunoreactivity of human hAM in maternal plasma during pregnancy, and suggests that hAM in maternal plasma is generated partly from placental tissue.