Intra-articular administration of hyaluronate (HA) is an effective treatment for arthritis. HA injections can decrease not only joint pain but also synovial effusion, although little is known concerning the mechanism of HA action. The aim of this study was to investigate the role of HA on the expression and production of matrix metalloproteinase (MMP) in synovial cells activated by interleukin (IL)-1β in order to achieve a better understanding of exogenous HA function in the extracellular matrix degradation in arthritic joints. Human synovial cells were incubated with HA (0.1-1000 μg/ml) and/or IL-1β (1 ng/ml). The expression of MMP-1 and MMP-3 mRNAs was analyzed by quantitative real-time polymerase chain reaction. The protein levels of MMP-1 and MMP-3 in cultured media were measured by immunoblotting. Expression of MMP-1 and MMP-3 mRNAs was induced by IL-1β. The IL-1β-mediated induction of MMP-1 mRNA expression was attenuated by 10 μg/ml HA (p=0.026) and that of MMP-3 mRNA was strongly down-regulated in the presence of 10 or 1000 μg/ml HA (p<0.001). The increased protein levels of MMP-1 and MMP-3 were also reduced by 1000 μg/ml HA. These data suggest that HA inhibits the expression and production of MMP-1 and MMP-3 in IL-1β-stimulated human synovial cells. We therefore prepose that intra-articular HA may rescue inflamed joints from bone and cartilage destruction by reducing the production of MMP-1 and MMP-3.
Among the various types of biometric personal identification systems, DNA provides the most reliable personal identification. It is intrinsically digital and unchangeable while the person is alive, and even after his/her death. Increasing the number of DNA loci examined can enhance the power of discrimination. This report describes the development of DNA ink, which contains synthetic DNA mixed with printing inks. Single-stranded DNA fragments encoding a personalized set of short tandem repeats (STR) were synthesized. The sequence was defined as follows. First, a decimal DNA personal identification (DNA-ID) was established based on the number of STRs in the locus. Next, this DNA-ID was encrypted using a binary, 160-bit algorithm, using a hashing function to protect privacy. Since this function is irreversible, no one can recover the original information from the encrypted code. Finally, the bit series generated above is transformed into base sequences, and double-stranded DNA fragments are amplified by the polymerase chain reaction (PCR) to protect against physical attacks. Synthesized DNA was detected successfully after samples printed in DNA ink were subjected to several resistance tests used to assess the stability of printing inks. Endurance test results showed that this DNA ink would be suitable for practical use as a printing ink and was resistant to 40 hours of ultraviolet exposure, performance commensurate with that of photogravure ink.
Recently, many cancer patients have been cared for at home in Japan. Cancer pain control is one of the most important factors for terminal cancer patients to maintain functional lives at home. Morphine has long been the gold standard in the control of cancer pain. This paper examined the present status of the frequency of morphine use and its prescribing route for pain control in cancer patients at home monitored by doctors offering home care medicine in Japan. We reviewed the data based on the replies to questionnaires about morphine use in a textbook edited in 2001 by the doctors supportive of home care medicine nationwide in Japan. 301 (92.9%) among 324 doctors administered morphine for at-home cancer patients. 257 doctors’ replies were analyzed as to the prescribed pattern of morphine after excluding data without information on the administration route. The oral administration was most frequently used in 247 (96.1%) doctors and rectal administration was used in 217 (84.4%) doctors, while intravenous injection and epidural infusions were less common. The pattern of morphine administration was similar between doctors who worked at hospitals and clinics, except that doctors who worked at hospitals administered subcutaneously more frequently than doctors who worked at clinics (69.2% in the hospital vs. 39.4% in the clinic setting). This study has revealed that morphine is commonly prescribed to control pain in at-home cancer patients by doctors who support home care medicine in Japan. The restricted administration routes of morphine among the doctors and less prevalent use of the subcutaneous routes in doctors who work at clinics are also shown in the home cancer care setting. These findings might result from mutual relationship between the thought and experience of doctors and clinical characteristics of patients under home care medicine.
Stanniocalcin is a glycoprotein hormone that regulates the calcium level in fish. We found that mRNA of human stanniocalcin 1 (STC-1) is detectable in phytohemagglutinin-stimulated T cells and in most human leukemia cell lines, suggesting a role of STC-1 for cell proliferation. This finding prompts us to study the usefulness of STC-1 for monitoring acute leukemia. The levels of STC-1 transcripts increased in patients with acute leukemia at diagnosis and relapse, as judged by quantitative real-time RT-PCR. Levels of transcripts rapidly decreased to within the cut-off levels, when the blast numbers decreased with chemotherapy. Prolonged elevation of STC-1 levels after treatment was associated with a poor prognosis. All of 7 patients relapsed 1 to 4 months after they showed an elevated level of the transcripts in clinical remission. These results indicate that STC-1 is a novel marker for minimal residual disease of acute leukemia, and for an early diagnosis of relapse.
As a clinical association is thought to exist between diabetes and tuberculosis, this study was set up to examine whether GK/Jcl diabetic rats are more susceptible to Mycobacterium tuberculosis infection than non-diabetic rats. GK/Jcl diabetic rats were infected aerially with M. tuberculosis and their capacity to control mycobacterial growth, granuloma formation, cytokine secretion by alveolar macrophages and nitric oxide (NO) production was examined. The rats developed large granulomas but not necrotic lesions in their lungs, liver or spleen. This is consistent with a significant increase in number of colony-forming units of M. tuberculosis in the lungs (p<0.01). Expression levels of interferon-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-12 mRNA were lower in GK/Jcl diabetic rats than those in control Wistar rats. Alveolar macrophages from GK/Jcl rats secreted less TNF-α and IL-12, and produced less NO compared with those from Wistar rats. No significant difference was observed between phagocytosis of tubercle bacilli by alveolar macrophages from GK/Jcl or Wistar rats. These data show that there is a close association between experimental tuberculosis and diabetes in animals, and that alveolar macrophages from GK/Jcl diabetic rats are not fully activated by M. tuberculosis infection.
The aim of this prospective study was to investigate the diurnal change in serum nitric oxide (NO) levels in active and remission phases of patients with panic disorder. This study included 15 patients fulfilling the criteria for panic disorder of Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition and 15 healthy controls matched for age and sex. All patients were receiving a selective serotonin reuptake inhibitor at therapeutic doses. The serum nitrite and nitrate levels of subjects were determined at 10:00 a.m. after overnight fasting and at 3:00 p.m. 2 hours after lunch. NO levels of all patients measured in the morning were significantly higher than those of controls. The patients were also divided into active and remission groups according to clinical status and Panic Agoraphobia Scale’s cut-off point. There were no statistically significant differences in serum nitrite and nitrate levels of the active group between the 10:00 a.m. and 3:00 p.m. measurements. In contrast, statistically significant differences were found in the serum levels of nitrite (p<0.05) and nitrate (p<0.05) in the remission group. Notably, the afternoon nitrite and nitrate levels of the remission group were higher than those of the morning levels as seen in control subjects. Thus, diurnal variation of NO production is altered in patients with panic disorder but is resumed in the remission phase. The present study suggests that serum NO levels are a good marker for evaluation of panic disorder.
Hyperhomocysteinemia is an independent risk factor for atherothrombotic cerebral stroke. Vitamin B12 and folic acid are important determinants of homocysteine metabolism. We aimed to evaluate the relationship, if present, between vitamin B12 and folic acid levels and acute cerebral stroke in this study. Blood aliquots drawn within 24 hours after the stroke from hospitalized patients (n=66) with the diagnosis of acute ischemic cerebrovascular episode and also blood samples from 38 healthy controls without any vascular risk factor were analyzed. With a competitive, chemoluminescence assay, serum levels of vitamin B12 and folic acid were measured in blood samples taken within 24 hours after the stroke. The differences and correlations were tested using frequency test, student-t test and multivariate analysis. Mean serum vitamin B12 levels were significantly lower in the patients than in the control subjects, 245.40 (S.D.: 72.9) and 343.2 (S.D.: 113.0) pg/ml respectively (p=0.0001). This difference was independent from other risk factors. Likewise, mean serum folic acid levels were lower in the patients than in the control subjects, 4.62 (S.D.: 1.94) and 5.97 (S.D.: 1.19) ng/ml, respectively (p=0.003). Mean serum levels of vitamin B12 and folate at the convalescence phase were 253.05 (S.D.: 68.78) pg/ml and 4.48 (S.D.: 2.08) ng/ml, respectively; the values obtained at the acute phase were not significantly different from the values obtained at the convalescence phase. We conclude that low vitamin B12 and folic acid concentrations are associated with an increased risk of stroke, and the relationship for vitamin B12 is independent from the other known modifiable stroke risk factors. For understanding the effects of B12 and folate in stroke patients, more detailed follow-up studies with long period are needed.
Head and neck squamous cell carcinomas (HNSCC) manifest various clinical behaviors according to their origin, i.e., from various parts of the head and neck mucosa. However, genetic factors involved in the carcinogenesis of HNSCC in different tissues have not yet been studied and evaluated. Three hundred and two specimens of HNSCC were characterized for allelic loss of certain areas of the genome, i.e., 3p21, 9p21 and 17p13, and were examined for genetic factors that might correlate with the tissue specificity of HNSCC and influence their clinical features. Loss of heterozygosity (LOH) at 3p21, 9p21 and 17p13 was detected in 54.5%, 57.4% and 57.1% of the informative cases, respectively. The frequencies of LOH in hypopharyngeal and in laryngeal cancers were significantly higher than in oral cancers. There were significant correlations between LOH at 3p21 and lymph node involvement and between LOH at 17p13 and tumor size, resulting in positive correlations with clinical stage of HNSCC in the patients. These results indicate that not only the functions of tumor suppressor genes differ among HNSCC in various regions, but also that allelic loss plays a key role in the acquisition of a malignant phenotype of these tumors.