Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2′-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-¹⁰B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-¹⁰B (BPA), the tumors were irradiated with neutrons, or those without ¹⁰B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).Results: Without ¹⁰B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With ¹⁰B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.Conclusion: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.     

Expression of apoptosis-related proteins in adenomyotic uteri treated with danazol and GnRH agonists.

The biologic properties of adenomyosis and the effects of therapeutic agents on adenomyosis were evaluated with immunohistochemistry, terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, transmission electron microscopy, and analysis of genomic abnormality. In the adenomyotic endometrium, estrogen receptor (ER) expression was more intense than in the eutopic endometrium during the secretory phase, and bcl-2 was constantly expressed throughout the menstrual cycle. The expression of ER and bcl-2 was weaker in the adenomyotic endometrium treated with danazol than in that treated with gonadotro-pin-releasing hormone agonist (GnRHa), whereas bcl-2 phosphorylated on serine-87 was more intensely expressed in danazol-treated adenomyotic endometrium than in the GnRHa-treated one. The number of TUNEL-positive cells increased in the adenomyotic endometrium treated with danazol or GnRHa. Ultrastructurally, most of the adenomyotic endometrial cells treated with danazol underwent postapoptotic necrosis and formed a cluster of dead cells. In contrast, cells treated with GnRHa underwent typical apoptosis and were sparsely distributed in the adenomyotic endometrium. Analysis of several cancer-related genes showed no microsatellite instability or loss of heterozygosity in adenomyotic tissues. Therefore, we conclude that the occurrence of adenomyosis is correlated to bcl-2 expression regulated by estrogen and ER rather than genetic mutation.     

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: Value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.     

Anatomical status of the human musculus uvulae and its functional implications

In our ongoing series of anatomical studies to determine the three‐dimensional architecture of the human velar muscles, we have previously reported on the palatopharyngeus. The present study deals with the musculus uvulae (MU), in which the positional relationships of its origin to the posterior nasal spine and the palatine aponeurosis, as well as the interrelation between its anatomical status and functions, have yet to be clarified. Macroscopic and microscopic examinations were performed on 25 and 2 cadavers, respectively. In the former, bilateral MUs and their adjacent structures were exposed mainly from the nasal aspect. In the latter, the soft palates embedded in paraffin were cut into frontal and sagittal sections and alternately processed with HE and Azan stains. The left and right MUs adjacent to each other were found to run longitudinally along the midline beneath the nasal aspect of velum. It was overlaid by glandular tissue that increased in amount as it coursed distally. After originating from the oral surface of palatine aponeurosis, it ran backward to cross above the sling formed by the levator veli palatini muscles of both sides and reached the tip of uvula with its muscle fibers intermingled with glandular tissue. Past studies have proposed three functions of MU to enhance the efficiency of velopharyngeal closure: space occupier, stiffness modifier, and velar extensor. All of the above‐described anatomical characteristics of MU could be explained as being adapted for these functions. This implies that MU is actively responsible for maintaining the velopharyngeal closure efficiency. Clin. Anat. 27:1009–1015, 2014. © 2014 Wiley Periodicals, Inc.     

Silencing of homeobox A5 gene in the stratum corneum of psoriasis

Analysis of psoriatic parakeratotic cells is helpful for understanding the pathogenesis of psoriasis. Methylation analysis can be performed on psoriatic scales, but it is unclear whether genes can be silenced by DNA methylation in psoriatic stratum corneum. The present study was conducted to detect genes silenced in psoriatic stratum corneum. Methylation array analysis with 485 577 probes, quantitative real‐time methylation‐specific PCR (RT‐MSP) and bisulphite sequencing were performed for 30 psoriatic scale samples, 6 fully developed psoriatic skin samples and 12 normal skin samples. Immunohistochemical staining of HOXA5 was performed for 29 psoriatic epidermal samples and 13 normal epidermal samples. The genome‐wide methylation array detected two CpG sites within CpG islands (CGIs) located in promoter regions of HOXA5 and LIAS that had methylation levels of >0.6 in at least one of the three psoriatic scale samples and of <0.2 in all three normal skin tissue samples (methylation rate range, 0.0‐1.0). RT‐MSP for HOXA5CGI, in which the primers were successfully developed, revealed that the average methylation level of 27 psoriasis scales (60.2%) is significantly higher than that of 9 normal skin samples (34.6%) (P=.013). Immunohistochemical staining revealed that HOXA5 protein was not expressed in the stratum corneum of fully developed psoriatic epidermis, but the protein was expressed in the stratum corneum of incompletely developed epidermis and normal epidermis. In conclusion, HOXA5 can be silenced in the stratum corneum of psoriasis. The silenced gene was identified by non‐invasive methylation analysis of psoriatic scales.     

Association of Eating Alone With Depression Among Older Adults Living Alone: Role of Poor Social Networks

ObjectivesEating alone is associated with an increased risk of depression symptoms. This association may be confounded by poor social networks. The present study aimed to determine the role of poor social networks in the association of eating alone with depression symptoms, focusing on cohabitation status.MethodsSeven hundred and ten community-dwelling older adults were categorized according to their eating style and social network size, evaluated using an abbreviated version of the Lubben Social Network Scale, with poor social network size (defined as the lowest quartile). Living arrangements and depression symptoms, detected using the Zung Self-Rating Depression Scale, were also assessed.ResultsA mixed-design two-way analysis of covariance (eating style and social network size factors) for the depression scale score, adjusted by covariates, yielded significant effects of social network size and eating style without interaction. Greater depression scores were observed in eating alone and poor social network size. Analysis of participants living with others showed the same results. However, among older adults living alone, only a significant main effect of social network size was observed; poor social network size resulted in greater depression scores irrespective of eating style.ConclusionsPoor social network size, and not eating alone, was associated with greater depression symptoms among older adults living alone, whereas both factors may increase depression symptoms among older adults living with others. Poor social network size may show a stronger influence on depression than eating alone in older adults living alone; thus, social network size is an important health indicator.Key words: eating alone, social network, living alone, depression, older adults