Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor.

Involvement of nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation of multiple myeloma has been well established. In this study we observed that NF-kappaB is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. In addition, we found the phosphorylation of p65 subunit of NF-kappaB in addition to the phosphorylation of IkappaBalpha and the activation of NF-kappaB DNA binding and that various target genes of NF-kappaB including bcl-x(L), XIAP, c-IAP1, cyclin D1, and IL-6 are up-regulated. We then examined the effect of a novel IkappaB kinase inhibitor, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP). When myeloma cells were treated with ACHP, the cell growth was efficiently inhibited with IC(50) values ranging from 18 to 35 mumol/L concomitantly with inhibition of the phosphorylation of IkappaBalpha/p65 and NF-kappaB DNA-binding, down-regulation of the NF-kappaB target genes, and induction of apoptosis. In addition, we observed the treatment of ACHP augmented the cytotoxic effects of vincristine and melphalan (l-phenylalanine mustard), conventional antimyeloma drugs. These findings indicate that IkappaB kinase inhibitors such as ACHP can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of NF-kappaB.     

A case of anaphylaxic shock due to latex glove used on internal examination and on the probe of intrauterine echogram

A 15 year old female with uterus bicornis bicollis was admitted for operation. She had a history of atopic dermatitis and allergy to buckwheat, raw egg and latex. Two months previously she had developed whole body flushing during dental treatment, and latex glove used by the dentist had been suspected as the cause. Prior to the operation she underwent internal examination and intrauterine echogram in which a latex glove was carelessly used by another gynecologist who had not confirmed her past history. After 30 minutes, dyspnea and urticaria without itching, appeared suddenly. Blood pressure decreased to 80/50 mmHg and heart rate increased to 120 beats.min-1. She was then transferred to our ICU. Methylprednisolone was administered intravenously for dyspnea and circulatory collapse. After 3 hours, the patient made an uneventful recovery. The increased plasma latex protein-specific IgE levels confirmed anaphylaxis to latex. The increasing incidence of potentially life-threatening allergic reactions to latex has caused mounting concern over recent years. We may suspect latex allergy when an anaphylaxic reaction or shock of unknown origin occurs. In hospitals, latex free products must be prepared for use with latex allergic patients and for protection of medical staff with this allergy.     

Japanese standard for clinical stabilometry assessment: Current status and future directions

Stabilometry is a useful tool for examining patients with functional disorders of the vestibular system. However, measurement techniques and devices vary by country. Therefore, international standardization of stabilometry is mandatory to validate the exchange of important findings. This was advocated at the 1983 Posturography Meeting in Kyoto but has not been adopted worldwide, and each country has continued to use unique regional measurement methods. In Japan, stabilometry has widespread application in medical practice in conjunction with research into its applications. With a goal of international standardization, we present details of stabilometry measurement methods and their application in Japan, together with a brief history and potential future directions of stabilometry.     

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.     

Anthropometric characteristics and comorbidities in Japanese patients with neurofibromatosis type 1: A single institutional case–control study

Neurofibromatosis type 1 (NF1) is a well‐known genetic disorder characterized by café‐au‐lait spots and neurofibromas, but many other clinical characteristics and associated comorbidities also have been reported. This study aimed to characterize NF1 further by investigating its association with anthropometric characteristics and other diseases. We performed a case–control study of 227 NF1 patients (101 male, 126 female) and a randomly selected age‐ and sex‐matched control group of 681 non‐NF1 patients (303 male, 378 female) who visited our institution in Japan. We examined adult (≥20 years) height and body mass index (BMI), and, in the total sample, allergic diseases (bronchial asthma [BA], atopic dermatitis [AD] and allergic rhinitis) and other respiratory cardiovascular and psychiatric disorders. In adults, the mean BMI was lower in the NF1 group than in the control group, and was significantly statistically different among men (P = 0.0238). In the whole sample, the prevalences of BA (P = 0.0184), AD (P = 0.0144) and valvular heart disease (P = 0.0166) were significantly greater in the NF1 group than in the control group. To date, no similar research on the BMI or the prevalence of allergic disease in NF1 patients has been reported. Our results suggest that NF1 patients tend to have lower BMI and may have alterations in specific metabolic pathways and altered allergic immunity.     

Inactivation of mitogen‐activated protein kinase is neither necessary nor sufficient for the onset of pronuclear formation in mouse oocytes

Mammalian oocytes are arrested at metaphase II due to high MAP kinase activity. After fertilization, oocytes resume meiosis, leading to female chromosome segregation, polar body emission and pronuclear (PN) formation. Previous biochemical studies showed that MAP kinase activity remained high for several hours after fertilization and began to decrease in parallel with PN formation. It has been thought that MAP kinase activity is incompatible with PN formation, and its inactivation is required for the initiation of PN formation in mammalian oocytes. In this study, we revisited this hypothesis by examining MAP kinase activity and PN formation in individual mouse oocytes using cytological analysis. We showed that MAP kinase activity in oocytes could be evaluated using phospho‐ERK1/2 immunofluorescent staining. Co‐immunofluorescent staining of phospho‐ERK1/2 and nuclear pore components showed that PN formation preceded MAP kinase inactivation and could be initiated while MAP kinase activity was still high. Moreover, artificial inactivation of MAP kinase or its downstream target, ribosomal S6 kinase, accelerated but did not rapidly induce PN formation. Our results show that although the MAP kinase pathway negatively regulates PN formation, its inactivation is neither necessary nor sufficient for PN formation. These results suggest the involvement of other essential factor(s) in this process.