Ablation and mutation of nonmuscle myosin heavy chain II-B results in a defect in cardiac myocyte cytokinesis

We have identified a novel form of cardiac myocyte enlargement in nonmuscle myosin heavy chain II-B (NMHC II-B) ablated mice, based on a partial failure in cytokinesis. In contrast to most cells, cardiac myocytes lack NMHC II-A, and ablation of NMHC II-B results in a heart with 70% fewer myocytes at embryonic day 14.5 (E14.5) than control mice (B+/B- and B+/B+). In addition, B-/B- cardiac myocytes show a marked increase in binucleation at E12.5, reflecting the occurrence of karyokinesis in the absence of cytokinesis. An increase in binucleation and cell size is also found in hypomorphic, homozygous mice harboring a single amino acid mutation (R709C) in the gene encoding NMHC II-B. The nonmyocytes in B-/B- hearts and homozygous mutant hearts, all of which contain NMHC II-A, do not show either of these abnormalities. B-/B- cardiac myocytes at E14.5 show a decreased bromodeoxyuridine (BrdU) labeling index compared with controls, consistent with the decrease in myocyte proliferation. This decreased BrdU labeling is not seen in nonmyocyte cells in the heart. In addition to these changes, both B-/B- mice as well as homozygous mutated mice show an increase in cyclin D2 and D3 reflecting an abnormality in earlier steps in the cell cycle. Whereas cardiac myocytes completely ablated for NMHC II-B show enlargement and binucleation, mice expressing as little as 6% of the normal amount of wild-type NMHC II-B in the heart do not show these abnormalities.     

Distinct usages of phospholipase C gamma and Shc in intracellular signaling stimulated by neurotrophins

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of the neurotrophin family, bind to and activate TrkA, TrkB and TrkC, respectively, members of the Trk receptor tyrosine kinase family, to exert various effects including promotion of differentiation and survival, and regulation of synaptic plasticity in neuronal cells. Many reports have suggested that different neurotrophins show distinct biological functions, although molecular mechanisms by which neurotrophins exert their different functions remain unclear. In the present study, we found distinct usages of phospholipase Cgamma (PLCgamma) and Shc in intracellular signaling stimulated by neurotrophins. BDNF stimulated much stronger interactions of PLCgamma with Trk than NGF and NT-3 in PC12 cells stably expressing TrkB and cultured cerebral cortical neurons, respectively, although BDNF, NGF and NT-3 induced similar levels of tyrosine phosphorylation of Trk. Furthermore, the cultured cortical neurons showed large PLCgamma-dependent increases in intracellular Ca(2+) levels in response to BDNF compared with NT-3. In Shc signaling, NGF, but not BDNF, displayed interactions between Trk and Shc in a phenylarsine oxide (PAO; an inhibitor of tyrosine phosphatase)-dependent manner in TrkB-expressing PC12 cells. These results indicated that neurotrophins stimulate distinct kinds of interactions between Trk and PLCgamma and between Trk and Shc. These differences may lead to the distinct biological functions of neurotrophins.     

Quantification of L-type fatty acid binding protein in the urine of preterm neonates

We measured urinary excretion of L-type fatty acid binding protein (L-FABP) in preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels (expressed as the ratio to creatinine) in preterm neonates were considerably higher than those of healthy adults. They did not change significantly during the study period. Urinary L-FABP levels showed significant positive correlation with those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L-FABP is expressed in the neonatal kidney. Our results may also point to potential effects of proximal tubular damage and oxidative stress on urinary excretion of L-FABP.     

Anomic alexia of kanji in a patient with anomic aphasia

The ability to read aloud kanji (logogram) words and to comprehend their meaning was systematically examined to clarify the underlying mechanism of kanji alexia in a patient with anomic aphasia. Confrontation naming, reading aloud and reading comprehension tasks were performed using 110 words from 11 semantic categories written in kanji or kana. Performance in oral reading of kanji words was significantly worse than oral reading of the same words transcribed into kana words. In addition, for kanji words reading aloud was much worse than reading comprehension. Oral reading of kanji words had a significant correlation with naming pictures corresponding to the words, but no correlation with comprehension of kanji words. Qualitative analyses demonstrated that errors in oral reading and naming tasks had many features in common. Our results indicated that some common mechanisms underlie both naming and oral reading of kanji words. We propose calling this type of alexia "anomic alexia of kanji", which should be distinguished from kanji alexia with difficulty in both reading aloud and comprehension. Lesions in our patient were located in the middle part of the left middle temporal gyrus and its subcortical area, which could be important for access to the phonological lexicon from semantics.     

Low prevalence of HPV infection and its natural history in normal oral mucosa among volunteers on Miyako Island, Japan

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) infection in normal oral mucosa, and to observe the natural history in the oral cavity in oral swab samples collected from healthy volunteers on Miyako Island, Okinawa, Japan. STUDY DESIGN: The prevalence of HPV infection in oral buccal mucosa cell scrapes collected between 2000 and 2002 from a cohort of 668 healthy volunteers was determined. HPV DNA was detected by consensus polymerase chain reaction (PCR) using MY09/MY11 primers followed by direct cycle sequencing. Just over 2 years later the HPV-positive participants were reevaluated. RESULTS: Of the 668 subjects, 662 samples were analyzed for HPV. HPV DNA was detected in 4 (0.6%) specimens. HPV type 16 (HPV16), HPV53, and HPV71, mucosal types, and HPV12, a cutaneous type, were all identified by direct sequencing. In the follow-up survey, the HPV71- and HPV12-positive participants again tested positive, while HPV DNA was not detected in the HPV16- and HPV53-positive participants. CONCLUSION: The results of this study among healthy individuals from Miyako Island suggest that oral HPV infection is uncommon. In this cohort, HPV71 and HPV12 were persistent, while HPV16 and HPV53 were transient in normal oral mucosa.     

Anti-atherogenic effects of an egg yolk-enriched garlic supplement

It has been suggested that oxidation of low-density lipoprotein (LDL) plays an important role in the initiation and progression of atherosclerosis. In the present study, we determined the anti-atherogenic effects of egg yolk-enriched garlic powder (EGP), which has been used as a traditional health-promoting food in southern Japan since ancient times, on LDL oxidation and oxidant stress-induced cell injury models. We confirmed that EGP inhibits copper-induced LDL oxidation in a dose-dependent manner. We also observed that pretreatment of EGP significantly suppressed the production of peroxides in HL60 cells and protected endothelial cells from hydrogen peroxide-induced cell injury. These findings might, in part, be ascribed to the biodistribution of garlic compounds and egg yolk interaction, and suggest that EGP might be useful in the prevention of atherosclerosis.     

Nursing discharge summaries of deceased patients with respiratory diseases

To explore how nurses feel about deceased patients and end-of-life care, the nursing discharge summaries of 115 sequential patients who died in the respiratory division of a Japanese university hospital were reviewed. When compared to discharge summaries of patients with non-malignant illness, a significantly higher percentage of discharge summaries of those with malignant illnesses documented support from family members (P = 0.0166), patient's hope for cure (P = 0.0206), and patient anxiety (P = 0.0258). As difficult situations stay with nurses as memories, it is important for both new graduates and skilled nurses to document their feelings in difficult clinical situations.     

Preventive effects of oren-gedoku-to on mucositis caused by anticancer agents in patients with acute leukemia

Most anticancer agents frequently cause mucositis, such as stomatitis and gastrointestinal mucosal injury, which is closely associated with decrease in quality of life, infections and discontinuation of chemotherapy in patients with malignancy. We retrospectively evaluated the preventive effect of oral administration of oren-gedoku-to on stomatitis and diarrhea induced by cytotoxic drugs in 40 patients with acute leukemia. Incidence of stomatitis was 27.9% in the group given oren-gedoku-to, which was significantly lower compared with 71.6% in those who received a gargle consisting of allopurinol, sodium gualenate, and povidone-iodine. Drug-induced diarrhea was observed in 9.3% of the oren-gedoku-to group compared with 31.7% of the control group. These observations indicate a significant preventive effect of oren-gedoku-to on mucositis caused by anticancer agents.