Pemphigoid Nodularis: A Case with 230 kDa Hemidesmosomes Antigen Associated with Bullous Pemphigoid Antigen

We report a 73-year-old woman with typical clinical, histological and immunofluorescence features of pemphigoid nodularis. Direct immunofluorescence studies of prurigo nodularis-like lesions and peribullous skin showed the linear deposition of IgG and C3 at the basement membrane zone. Circulating IgG against the basement membrane was also detected by indirect immunofluorescence. The serum from the patient was shown to contain the autoantibody against 230 kDa hemidesmosomal antigen associated with bullous pemphigoid antigen.     

Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP₂) and Ca²⁺ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP₂. Activated μ-calpain and PIP₂ were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca²⁺ mobilization with increased PIP₂ immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca²⁺ and PIP₂ breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.     

Pseudopodia of capillary endothelium in ocular tissues

The frequencies of pseudopodia projecting from capillaries of various parts of the eye were observed in 16 human eyes with a transmission electron microscope. The pseudopodia were found mainly projecting from the choriocapillaris and rarely seen in the retina, iris or ciliary body. The frequencies of pseudopodia from the choriocapillaris were not correlated with the localization in the fundus (macular area or peripheral fundus), age, sex, time elapsed between death or enucleation and fixation. The significance of pseudopodia from the choriocapillaris is unknown. However, there is the possibility that pseudopodia are related to choroidal neovascularization or have other physiological functions.     

A new experimental trial using repeated heating every 24 hours for local hyperthermic therapy with bleomycinin vivo

This report presents the effect of repeated heating every 24 hrs using bleomycin (BLM) which, although seemingly contrary to the usual agreement that hyperthermia should be carried out with a long interval due to thermotolerance, holds many possibilities. FM3A cells on the foot pad of C3H mouse were immersed in a heated water bath at 43 and 44°C for 30 min. The effect of repeated heating was appreciated by an improved growth curve and 50 day survival compared to mice which received heating twice with a 96-hr interval. Repeated heating every 24 hrs 5 times with BLM suppressed tumor growth significantly as compared to heating twice with a 96-hr interval without BLM. The longest survival time was obtained by the repeated heating with BLM among all protocols. There is therefore a good possibility that more effective results could be obtained clinically by repeated heating over a short period.     

Surgical results of performing R4 gastrectomy for gastric cancer located in the upper third of the stomach

Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.     

Gadolinium-enhanced breath-hold three-dimensional time-of-flight MR angiography of the abdominal and pelvic vessels: The value of ultrafast MP-RAGE sequences

MR angiography (MRA) was performed in 50 consecutive subjects (mean age, 59 years), who had been referred for abdominal MRA, on a 1.5-T superconductive unit that used a body phased-array coil. Three breath-hold three-dimensional sequences were evaluated both in phantom and clinical studies: (a) standard fast three-dimensional gradient-echo sequence (TR = 15, TE = 6; imaging time, 32 seconds), (b) ultrafast three-dimensional gradient-echo sequence (TR = 8.2, TE = 3; imaging time, 18 seconds), and (c) ultrafast magnetization-prepared (MP) rapid acquisition gradient echo (RAGE) (TR = 5.8, TE = 2.9, inversion time [TI] = 20; imaging time, 15 seconds). The initial 30 patients were randomized into three groups by three separate sequences. For the remaining 20 patients, ultrafast-gradient-echo and ultrafast MP-RAGE sequences were performed. Conventional angiography was performed on 36 patients. Signal measurements of the phantom and clinical images of the aorta, visceral branches of the aorta, iliac arteries, inferior vena cavae, and portal veins were performed. The overall image quality and background fatty tissue contrast of the vessels were rated subjectively. Comparison of images between MRA and conventional angiography also was performed. The contrast between the vessels and background fatty tissue was significantly higher in the ultrafast MP-RAGE sequence in both quantitative and qualitative analysis, and image-quality ultrafast MP-RAGE was superior to the other two sequences (P < .01). The aorta and iliac arteries could be visualized in all pulse sequences, and abnormalities of these vessels were diagnosed correctly. The renal artery was visualized more clearly with the two ultrafast sequences.     

Cerebrovascular reserve capacity in ischemia due to occlusion of a major arterial trunk: studies by Xe-CT and the acetazolamide test.

Classifications based on clinical and radiographic criteria have proved to be inadequate predictors of the course of cerebral ischemia or its response to therapy. In this study the cerebrovascular reserve capacity (CRC) of 46 patients with symptomatic cerebrovascular ischemia was studied by stable xenon-enhanced CT (Xe-CT) combined with the acetazolamide test. Fifteen patients had internal carotid artery (ICA) occlusion, 10 had ICA stenosis, 10 had middle cerebral artery (MCA) occlusion, and 11 had MCA stenosis. In the patients with chronic cerebral ischemia due to occlusive lesions of the ICA and MCA, the CRC was reduced most in those with MCA occlusion, followed, in descending order, by those with ICA stenosis, MCA stenosis, and ICA occlusion. Our results indicate that measurement of the CRC elucidates cerebral hemodynamic factors that cannot be detected by angiography in patients with chronic cerebral ischemia and that Xe-CT combined with the acetazolamide test is useful for this purpose.     

Effects of beta-adrenoceptor-related agents on hypoxic pulmonary vasoconstriction and relation with cyclic AMP and prostaglandins]

Effects of a beta-agonist (isoproterenol) and beta-antagonists (propranolol and pindolol) on hypoxic pulmonary vasoconstriction (HPV) and on changes in some chemical mediators were compared between HPV-responsive lobes and non-responsive lobes in which HPV was induced by aspirin DL-lysine (ASA groups). Hypoxic ventilation (4 min) was repeated in 56 of isolated, blood-perfused dog lung lobes. Each drug was administrated in a bolus dose of 0.2 mg in the intermittent period between hypoxia. In HPV-responsive lobes, the first hypoxia increased pulmonary vascular resistance by 33% or more in all groups. Both isoproterenol and pindolol inhibited the elicitation of HPV completely, but propranolol induced almost the same degree of HPV as control. In ASA groups, HPV was completely inhibited by isoproterenol, but was not influenced by propranolol. However, pindolol's inhibitory effect on HPV was less than that in HPV-responsive lobes. Isoproterenol significantly increased cyclic AMP from 17.0 to 76.7 pmol/ml in HPV-responsive lobes (n = 7). Pindolol increased prostaglandin E2 from 87.0 to 1015.4 pg/ml in HPV-responsive lobes (n = 7), and from 93.4 to 361.3 pg/ml when ASA was treated. Propranolol did not show the different results from the control group whether ASA was present or not. The different mechanisms among beta-adrenoceptor-related agents in HPV and pulmonary circulation were investigated.     

Phorbol ester, not growth hormone releasing factor, consistently stimulates growth hormone release from somatotroph adenomas in culture

In order to study the mechanism of GH secretion from somatotroph adenoma cells, we have compared the effect of 12–O-tetradecanoyl phorboi-13-acetate (TPA) with that of growth hormone releasing factor (GRF) on GH secretion from human somatotroph adenoma cells cultured in monolayer. Pituitary adenoma cells were obtained from 13 patients with acromegaly undergoing surgery. On the 7th day of culture, the cells were exposed for 2 h to secretagogues. All 13 adenoma cell cultures (100%) responded to TPA (1·6–16·0 nmol/I) with a two- to six-fold increase in GH release (240·37% Increase of control: mean±SE). The response was detectable within 10 min, and was maximal at 2 h. Phosphollpase C (7·7 mmol/I) also stimulated a two-to ten-fold Increase In GH release in all four adenomas examined (100%). GH release was stimulated by GRF (2·0 nmol/I) in eight out of 12 adenoma cells (67%), but the magnitude of the responses to GRF (60·18% Increase of control: mean ± SE) were much smaller than that of TPA. Five out of 13 adenomas secreted detectable amount of PRL Into the medium and these five adenomas (100%) responded to TPA (16·0 nmol/I) with a two- to six-fold Increase. These observations indicate that the activation of protein kinase C is the consistent stimulator in GH and PRL secretion In human somatotroph adenoma cells. However, It is not determined whether the protein kinase C     

Carinal resection and reconstruction for recurrent lung cancer

A patient with a recurrent tumor in the trachea adjacent to the right main bronchus was treated by surgical resection 19 months after undergoing surgery for the primary cancer. The patient had previously undergone right upper lobectomy for T1N0M0 stage I squamous cell carcinoma. A carinal resection was performed which included 4 rings of the trachea, 2 rings of the righ main bronchus, and 1 ring of the left main bronchus. Reconstruction consisted of an end-to-end anastomosis of the trachea and left main bronchus, and an end-to-side anastomosis of the right and left main bronchi. The postoperative course was uneventful, and at present the patient is healthy 12 months following reoperation.