Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits

The dynamic characteristics of the baroreflex neural arc from pressure input to efferent sympathetic nerve activity (SNA) reveal derivative characteristics in the frequency range of 0.01 to 0.8 Hz (i.e., the baroreflex gain augments with increasing frequency) and high-cut characteristics in the frequency range above 0.8 Hz (i.e., the baroreflex gain decreases with increasing frequency) in rabbits. The derivative characteristics accelerate the arterial pressure regulation via the baroreflex. The high-cut characteristics preserve the baroreflex gain against pulsatile pressure by attenuating the high-frequency components less necessary for arterial pressure regulation. However, to what extent the carotid sinus baroreceptor transduction from pressure input to afferent baroreceptor nerve activity (BNA) contributes to these characteristics remains unanswered. To test the hypothesis that the carotid sinus pressure-BNA transduction partly explains the derivative characteristics but not the highcut characteristics, we examined the dynamic BNA response to pressure input in the frequency range from 0.01 to 3 Hz by using a white noise analysis in 7 anesthetized rabbits. The transfer function from pressure input to BNA showed slight derivative characteristics in the frequency range from 0.01 to 0.3 Hz with approximately a 1.7-fold increase in dynamic gain, but it showed no high-cut characteristics. In conclusion, the carotid sinus baroreceptor transduction partly explained the derivative characteristics but not the high-cut characteristics of the baroreflex neural arc. The present results suggest the importance of the central processing from BNA to efferent SNA to account for the overall dynamic characteristics of the baroreflex neural arc.     

Effect of phospholipase A2 inhibitor ONO-RS-082 on substance P-induced histamine release from rat peritoneal mast cells.

Rat peritoneal mast cells purified on a Percoll gradient were challenged with substance P (SP) and the effect of phospholipase A2 inhibitor ONO-RS-082 on SP-induced histamine release from the cells was investigated. 10(-5) mol/l SP caused a significant histamine release and the amount of histamine release reached maximum at 1 min after the challenge. ONO-RS-082 inhibited the SP-induced histamine release in a concentration-dependent manner at the concentration from 10(-6) to 10(-4) mol/l, suggesting possible involvement of phospholipase A2 in SP-induced histamine release from rat peritoneal mast cells.     

p53 protein overexpression and K-rascodon 12 mutation in pancreatic ductal carcinoma: Correlation with histologic factors

The correlation of p53 protein overexpression and the K-ras codon 12 mutatlon wlth histologlc type, grade of cytologic atypla, depth of lnvasion and other histologlc prognostic factors was studied In paraffin sectlons from 43 ductectatic-and 70 solid-type pancreatic ductal carcinomas. Overexpression of p53 was found in 23.3% (10143) of ductectatic carcinomas (17.2% of intraductal and 35.7% of lnvaslve carclnomas) and in 61.4% (43/70) of solid carcinomas. In ductectatic cancers, p53 overexpression was detected In 14.8% (4/27) of carcinomas wlth lowgrade atypla (CAL), 50.0% (5110) of carcinomas wlth high-grade atypla (CAH) and in 16.7% (In) of mixed low- and hlgh-grade cancers. In the last group, expression was restricted to an area of CAH. In solld cancers, p53 overexpression did not dlffer by histologic type or grade. Overexpresslon of p53 and K-ras mutatlons did not correlate with histologlc prognostic factors (lymphatic, venous and perineural Invasion, and lymph node metastasls) in ductectatlc and solld cancers or depth of invasion of solld carclnomas. Our data suggest that p53 alteratlon occurs at an early intraductal stage of solld carcinoma, irrespectlve of cellular atypla, but Is low in ductectatic CAL and becomes hlgher In ductectatlc CAH. K-ras mutatlon, present In a high percentage of tumors of all groups and not correlating with the factors above, showed no changes In frequency with tumor progression.     

Effects of body and head positions on bilateral difference in tympanic temperatures

Summary We have examined the nonparallel changes in tampanic membrane temperatures (T _ty) from the two ears in response to various changes in body and head positions. Upon assuming a lateral recumbent position, the T _ty on the lower side increased while that on the upper side decreased. Pressure application over a wide area of the lateral chest only caused inconsistent and obscure asymmetric changes in T _ty. A lateral flexion of the head with the subject sitting upright and a rotation of the head to the side in a supine position induced an increase in the T _ty on the lower side compared to that on the upper side. The temperature and blood flow of the forehead often decreased on the lower side and increased on the upper side, although such responses were not always concomitant with the asymmetric changes in T _ty. A dorsal flexion of the head with the subject in a reclining position caused a slight increase in the T _ty, whereas raising the head upright induced a slight decrease in them. Two additional experiments were carried out with single photon emission computed tomography using ^99mTc-hexamethylpropyleneamine oxime as tracer, and a slight, relative decrease in counts was noted in the right hemisphere during rotation of the head to the right. These results would strongly suggest that unilateral increases and decreases in T _ty could have been caused by one-sided decreases and increases, respectively, in blood flow to the brain and/or the tympanic membrane, induced by a vasomotor reflex involving vestibular stimulation.     

Epidermoid Cyst Derived from an Accessory Spleen in the Pancreas

A rare case of splenic epidermoid cyst (SEC) of the pancreas discovered in a 32-year-old Japanese female is reported. The lesion, 5x6cm in size including caseous material and serous fluid in the lumen, was discovered by ultrasonography and computed tomography at the tail of the pancreas and was easily removed. Histopathologically, the cystic wall consisted of three components: the inside was lined by mature squamous epithelium with keratinization, the middle layer consisted of splenic pulp with a sinus structure, and the peripheral layer was dense fibrous connective tissue in which some involutional pancreatic ducts and islets were recognized. The literature about SEC of the pancreas is discussed in comparison with other types of epidermoid cyst including lymphoepithelial cyst and dermoid cyst in the pancreas. Acta Pathol Jpn 41: 916 921, 1991.     

Atypical Glomus Tumor in the Mediastinum: A Case Report with Immunohistochemical and Ultrastructural Studies

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small “glo-moid” cells arranged in organoid and hemangiopericytoma-like patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.     

Long‐term observation of a Japanese mucolipidosis IV patient with a novel homozygous p.F313del variant of MCOLN1

Mucolipidosis type IV (MLIV) is an autosomal recessively inherited lysosomal storage disorder characterized by progressive psychomotor delay and retinal degeneration that is associated with biallelic variants in the MCOLN1 gene. The gene, which is expressed in late endosomes and lysosomes of various tissue cells, encodes the transient receptor potential channel mucolipin 1 consisting of six transmembrane domains. Here, we described 14‐year follow‐up observation of a 4‐year‐old Japanese male MLIV patient with a novel homozygous in‐frame deletion variant p.(F313del), which was identified by whole‐exome sequencing analysis. Neurological examination revealed progressive psychomotor delay, and atrophy of the corpus callosum and cerebellum was observed on brain magnetic resonance images. Ophthalmologically, corneal clouding has remained unchanged during the follow‐up period, whereas optic nerve pallor and retinal degenerative changes exhibited progressive disease courses. Light‐adapted electroretinography was non‐recordable. Transmission electron microscopy of granulocytes revealed characteristic concentric multiple lamellar structures and an electron‐dense inclusion in lysosomes. The in‐frame deletion variant was located within the second transmembrane domain, which is of putative functional importance for channel properties.     

Terbutaline-induced triphasic changes in volume of rat alveolar type II cells: the role of cAMP

Changes in the volume of rat alveolar type II cells (AT-II cells) induced by terbutaline, a beta(2)-agonist, were measured using video-enhanced contrast microscopy. The changes consisted of three phases: initial cell shrinkage, cell swelling, and gradual cell shrinkage. The initial cell shrinkage was Ca(2+)-dependent and was inhibited by quinine (a K+ channel blocker). The subsequent cell swelling was cAMP-dependent and was inhibited by amiloride (a Na+ channel blocker). The final cell shrinkage was cAMP-dependent and was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, a Cl- channel blocker). Thus, terbutaline-induced cell volume changes were regulated by both Ca2+ and cAMP. Accumulation of cAMP alone, however, induced the Ca2+ -dependent cell shrinkage of AT-II cells and H-89 (a PKA inhibitor) inhibited terbutaline-induced cell volume changes. This suggests that cAMP accumulation stimulates the Ca2+ signal during terbutaline stimulation. In conclusion, terbutaline stimulates not only Na+ influx, but also K+ and Cl- release mediated via cAMP accumulation in rat AT-II cells, which induces the triphasic cell volume changes.     

Dosimetric properties of radiophotoluminescent glass rod detector in high-energy photon beams from a linear accelerator and cyber-knife

A fully automatic radiophotoluminescent glass rod dosimeter (GRD) system has recently become commercially available. This article discusses the dosimetric properties of the GRD including uniformity and reproducibility of signal, dose linearity, and energy and directional dependence in high-energy photon beams. In addition, energy response is measured in electron beams. The uniformity and reproducibility of the signal from 50 GRDs using a 60Co beam are both +/- 1.1% (one standard deviation). Good dose linearity of the GRD is maintained for doses ranging from 0.5 to 30 Gy, the lower and upper limits of this study, respectively. The GRD response is found to show little energy dependence in photon energies of a 60Co beam, 4 MV (TPR20(10)=0.617) and 10 MV (TPR(20)10=0.744) x-ray beams. However, the GRD responses for 9 MeV (mean energy, Ez = 3.6 MeV) and 16 MeV (Ez = 10.4 MeV) electron beams are 4%-5% lower than that for a 60Co beam in the beam quality dependence. The measured angular dependence of GRD, ranging from 0 degrees (along the long axis of GRD) to 120 degrees is within 1.5% for a 4 MV x-ray beam. As applications, a linear accelerator-based radiosurgery system and Cyber-Knife output factors are measured by a GRD and compared with those from various detectors including a p-type silicon diode detector, a diamond detector, and an ion chamber. It is found that the GRD is a very useful detector for small field dosimetry, in particular, below 10 mm circular fields.