Dietary zinc deficiency decreases glutathione S-transferase expression in the rat olfactory epithelium

Zinc deficiency leads to olfactory and gustatory dysfunction, but little is known about the underlying molecular mechanism of this phenomenon. We examined the effect of dietary zinc deficiency on the rat olfactory epithelium. Immunoreactivities of glutathione S-transferase (GST) mu, neuron-specific enolase (NSE) and proliferating cell nuclear antigen (PCNA), and in situ hybridization of GST mu mRNA in the olfactory epithelia were examined under different dietary zinc intake conditions. Adult male rats were fed a zinc-deficient (ZD) diet (0.5 mg zinc/kg diet), whereas control rats, including pair-fed (PF) and zinc-adequate (ad libitum consumption, AL) groups, were fed a zinc-adequate diet (58 mg zinc/kg diet) for 7 wk. We also examined the effect of zinc replacement (ZR) by subsequently feeding half of the ZD group a zinc-adequate diet for 5 wk after the initial 7-wk deprivation. No significant differences in immunoreactivity for NSE in olfactory epithelial receptor cells or for PCNA in basal cells were noted among groups. Intense GST mu immunoreactivity and hybridization signals were observed in olfactory supporting cells of AL, PF and ZR groups, but very minimal or no such signal was noted in ZD rats. Our findings indicated that zinc deficiency reduces GST mu expression in the supporting cells of rat olfactory epithelia but does not affect receptor cell proliferation or maintenance.     

The effect of interleukin-6 on enhancing the invasiveness of head and neck cancer cells in vitro

Patients with head and neck cancers that produce a high concentration of granulocyte colony-stimulating factor (G-CSF) or patients with esophageal squamous cell carcinomas who have elevated serum interleukin-6 (IL-6) concentrations have been found previously to be at significant risk for tumor invasion to adjacent organs as well as frequent metastases. This suggests that G-CSF and Il-6 enhance the invasiveness and metastatic potential of cancer cells. We studied the in vitro invasiveness of head and neck cancer cell lines with and without recombinant human G-CSF (rhG-CSF) and human IL-6 (hIL-6) in an extracellular matrix membrane system. The degree of invasiveness was affected by incubating cells with hIL-6, but not by pre-incubating the cell-matrix with hIL-6. The maximum concentration of hIL-6 for enhanced invasiveness was approximately 5,000 u/ml. In addition, rhG-CSF enhanced the invasiveness of tumor cells that produced large amounts of G-CSF. The present study also suggests that tumor cells tend to invade and metastasize in an environment rich in hIL-6. Received: 3 November 1997 / Accepted: 1 April 1998     

Footwear exchange has no influence on the incidence of febrile neutropenia in patients undergoing chemotherapy for hematologic malignancies.

OBJECTIVE: To determine whether footwear exchange affects the incidence of febrile neutropenia among patients undergoing chemotherapy for hematologic malignancies. DESIGN: Open trial with historical comparison. SETTING: The 12-bed high-efficiency particulate air-filtered hematology unit at Osaka University Hospital, Suita, Japan. PATIENTS: Those with hematologic malignancies who underwent chemotherapy from January 1997 through January 2003. Footwear exchange was discontinued in January 2000. METHODS: The surveillance system was based on the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention. Rates of febrile neutropenia were calculated for neutropenic patient-days (ie, days with neutropenia < 500/microL). RESULTS: From January 1997 through December 1999 and from February 2000 through January 2003, 58 and 54 patients endured 237 and 184 neutropenic periods following chemotherapy, and their total neutropenic days were 3,123 and 2,503, respectively. They showed episodes of febrile neutropenia 89 and 68 times, respectively. Infection rates were 28.5 and 27.2 per 1,000 neutropenic patient-days (P = .83), respectively. CONCLUSION: The incidence of febrile neutropenia was not affected by footwear exchange. In hematology units, changing shoes does not appear to affect the rate of infections during neutropenic periods.     

根据日本乡村绝经后妇女腰椎骨密度的随访研究制定骨质疏松的护理卫生方针

为了检测妇女绝经后发生骨量减少的相关指标进而倡导依据生活方式的特点对绝经后妇女骨质疏松的发生采取相应的预防和护理方针，我们对日本乡村的绝经后妇女（末次月经后六个月或更长时间算起）进行了为期4a的随访。我们运用双能X线骨密度仪（DXA）对腰椎骨密度（BMD）进行检测并对各种变量，包括年龄、绝经时的年龄、骨折史、日常摄奶量以及吸烟习惯进行多元分析，结果表明这些因素对于腰椎骨密度（BMD）的恢复是不相关联的。 在这些变量中，骨折史被证明对于相关人群是最具危险性的，这些对象有高比例的骨量减少（6．6％），其次是不规律的摄奶（13．6％）和吸烟（9．3％）。在护理中使用的作用于足跟骨的检测骨密度的设备被证实与作用于腰椎的DXA设备可以相互替代。依据这些结果，针对居住在日本乡村的绝经后妇女制订了相应的预防骨质疏松的方针。这些卫生指导方针依据特定区域的生活方式而制定并可适用于其他的人群和区域。在本文中，作者列出了不同的有助于预防绝经后妇女出现骨质疏松的方法并进行了调查。     

Functional analysis of dog multidrug resistance-associated protein 2 (Mrp2) in comparison with rat Mrp2.

We investigated whether the species difference in the biliary excretion activity of some Mrp2 substrates was attributable to the intrinsic transport potential or the expression level of Mrp2, especially in rat and dog. Dog Mrp2 cDNA was isolated from beagle dog liver, and a vesicle transport study was performed using recombinant rat and dog Mrp2 expressed in insect Sf9 cells. The ATP-dependent transport of 17beta-estradiol 17-(beta-D-glucuronide) ([3H]E(2)17betaG) and leukotriene C4 ([3H]LTC4), normalized by the absolute protein expression level, was similar in both Mrp2s. The Mrp2 protein expression in dog liver was only 10% of that in rat liver and was comparable with the reported difference in the biliary excretion clearance of temocaprilat as Mrp2 substrate. In contrast to LTC4, unique transport kinetics for E(2)17betaG were evident in dog Mrp2. In addition to the high-affinity site with a K(m) value of 3.25 +/- 0.10 microM, which is similar to that in rat Mrp2 (4.81 +/- 1.21 microM), dog Mrp2 has an additional low-affinity site (>75 microM), which makes a major contribution to the transport of E(2)17betaG (65% of the total transport capacity at tracer concentration). In summary, the difference in the biliary excretion activity of Mrp2 substrates between rat and dog depends on the Mrp2 protein expression level rather than the intrinsic transport activity of the transporter molecules. The unique transport properties of glucuronide conjugates by dog Mrp2 may lead to the species difference involving the drug-drug interaction or drug-induced hyperbilirubinemia on the bile canalicular membrane.     

Gamma-rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells

Adeno-associated virus (AAV) vector has several unique properties suited for gene therapy applications. However, relatively low efficiency of transgene expression, which is mainly due to a limited second-strand synthesis from the single-stranded AAV genome, can be a problem in some applications that require potent gene expression such as antitumor applications. Recently, gamma-ray irradiation has been reported to enhance the second-strand synthesis of the AAV genome, and consequently transgene expression. We demonstrate here that an AAV vector harboring the herpes simplex virus type-1 thymidine kinase (HSVtk) is able to kill cancer cells more efficiently when used in combination with gamma-ray irradiation. A human maxillary sinus cancer cell line, NKO-1, was efficiently killed in combination with HSVtk transduction and ganciclovir (GCV), as expected. More importantly, gamma-ray irradiation of practical dosages augmented the cytocidal effect of the HSVtk/GCV system. Southern analysis indicated that gamma-rays enhanced the double-strand synthesis of the rAAV genome in NKO-1 cells. These findings suggest that the combination of rAAVtk/GCV suicide gene therapy with radiotherapy has synergistic effects in the treatment of cancers and may lead to a reduction of the potential toxicity of both rAAVtk/GCV and gamma-ray irradiation.     

Resection of Gastric Cancer Remitted Anti-signal Recognition Particle Myopathy

A 72-year-old woman presented with gradually-worsening myalgia and muscle weakness of the proximal lower limbs as well as elevated serum creatine kinase level. Based on a clinicoseropathological examination including a muscle biopsy, she was diagnosed with anti-signal recognition particle (SRP) myopathy. Although the myopathy relapsed two times in two years under oral prednisolone and intravenous immunoglobulin therapy, the myopathy remained in remission for more than three years after resection of gastric cancer. Although the anti-SRP myopathy is not considered to be cancer-associated in general, we should note that some cases of anti-SRP myopathy may be ameliorated with appropriate cancer treatment.     

Synovitis-acne-pustulosis-hyperostosis-osteitis Syndrome with Bilateral Pleural Effusion

Pleural effusion is a rare manifestation in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, which is characterized by the presence of osteoarticular lesions and dermatological involvement. We herein report a 71-year-old man with pleural effusion resulting from SAPHO syndrome. He was successfully treated using corticosteroids and has experienced no recurrence for one year. We should consider SAPHO syndrome when encountering cases of anterior chest pain and pleural fluid.