Showing papers in "Nihon rinsho. Japanese journal of clinical medicine in 2007"

[Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways].

Abstract: Since interaction between bone and lipid metabolism has been suggested, this study investigated the regulation of bone metabolism by adiponectin, a representative adipokine, by analyzing deficient and overexpressing transgenic mice. We initially confirmed that adiponectin and its receptors were expressed in osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone not only through an endocrine pathway as a hormone secreted from fat tissue, but also through an autocrine/paracrine pathway. There was no abnormality in bone mass or turnover of adiponectin‐deficient (Ad−/−) mice, possibly due to an equivalent balance of the two pathways. In the culture of bone marrow cells from the Ad−/− mice, osteogenesis was decreased compared to the wild‐type (WT) cell culture, indicating a positive effect of endogenous adiponectin through the autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we analyzed transgenic mice overexpressing adiponectin in the liver, and found no abnormality in the bone. Addition of recombinant adiponectin in cultured osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action of circulating adiponectin was negative for bone formation. In the presence of insulin, however, this suppression was blunted, and adiponectin enhanced the insulin‐induced phosphorylations of the main downstream molecule insulin receptor substrate‐1 and Akt. These lines of results suggest three distinct adiponectin actions on bone formation: a positive action through the autocrine/paracrine pathway by locally produced adiponectin, a negative action through the direct pathway by circulating adiponectin, and a positive action through the indirect pathway by circulating adiponectin via enhancement of the insulin signaling. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.

Molecular imaging for drug development

Abstract: In vivo molecular imaging has become a key technology for pathophysiological science and drug development. We are mostly utilizing PET(positron emission tomography) as a first-choice modality, because of its ultra-high sensitivity for molecules, adequate temporal and spatial resolution, and especially broad spectrum of target molecules. In vivo molecular imaging could bring the high-quality information about: 1. Molecular diagnosis for living patients with symptoms 2. Closer approach for etiology and differential diagnosis 3. Direct follow-up of key molecules as disease markers 4. Pharmacokinetics/Pharmacodynamics in primates/human 5. Dose finding information for individuals, corresponding to SNPs 6. Direct evidence for accumulation in non-target organs related to adverse effects 7. Drug effects with surrogate markers 8. Early decision of dropout substances (drug candidates) Here, the examples are shown as beta-amyloid imaging for Alzheimer's and mild cognitive impairment, serotonin transporter imaging for chronic fatigue, and dopaminergic components imaging for evaluation of drug for autistic spectrum disorder. In 2005, RIKEN and National Institute of Radiological Science were selected as the key centers for development of All-Japan research network to further promote mutual international and multi -disciplinary collaboration on in vivo molecular imaging.

Poorly differentiated carcinoma of the thyroid

Abstract: Poorly differentiated carcinoma is adopted as an independent entity in World Health Organization (WHO) and in General Rules for the Description of Thyroid Cancer by The Japanese Society of Thyroid Surgery (JSTS), but their definitions are significantly different. In this study, we investigated the prevalence and clinical significance of poorly differentiated carcinoma by WHO classification (poorly differentiated carcinoma [WHO]) and that in JSTS (poorly differentiated carcinoma [Sakamoto]), and tall cell variant in papillary carcinoma. In our series of 1,707 patients, 186 (10.9%), 15 (0.9%) and 62 (3.6%) were diagnosed as poorly differentiated carcinoma (Sakamoto), poorly differentiated carcinoma (WHO) and tall cell variant, respectively. Poorly differentiated carcinoma (WHO) and tall cell variant independently affected cause-specific survival (CSS) of patients, but poor differentiation (Sakamoto) did not. Therefore, it is suggested that poorly differentiated carcinoma (Sakamoto) predicted the likeliness of carcinoma recurrence, it is inappropriate to separate it as an independent histology.

Identification of bacteria

Abstract: There are many different types of bacteria. They differ in the structure of their cells, their metabolism and chemistry, and the structure of their cell walls. The differences among bacteria are used to classify them and to identify a species. Bacteria come in a number of shapes. Most, however, are cocci (round), bacilli (rod-shaped), or spirilla (spirals). The way these individual cells are arranged is also variable among bacterial species. Although some species exist singularly, bacteria can be linked together in a long chain (strepto-), clumped like grapes (staphylo-), paired (diplo-), and can exist in other arrangements as well. The differences in the cell wall structure of bacteria can be used to identify them. Using the Gram stain bacteria can be identified as Gram positive or Gram negative. Bacteria that give a positive Gram reaction have thick cell walls composed of peptidoglycan (consists of polymers of modified sugars cross linked by short polypeptides that vary), retain the initial stain and appear a violet color uder a microscope. Bacteria with a negative Gram reaction have a thin peptidoglycan ceall wall and have an additional outer member of lipopolysaccharides (carbohydrates bonded to lipids). This structure causes the cell to be easily decolorized and the bacteria will appear reddish pink, the color of the counter stain.

Bisphosphonates for osteoporosis

Abstract: One in three women and at least one in 12 men in the UK have osteoporosis, a condition which can lead to fractures, deformity, pain and disability, at a cost to the NHS of around £1.5 billion each year.1,2 Bisphosphonates offer a therapeutic option for preventing and treating osteoporosis. Here, we assess and compare the three bisphosphonates (alendronate, etidronate and ▼risedronate*) licensed for such use in the UK. We do not consider the four bisphosphonates (clodronate, pamidronate, tiludronate and ▼zoledronate) that are licensed in the UK only for the treatment of Paget's disease of bone and/or hypercalcaemia of malignancy.

Loop-mediated isothermal amplification

Abstract: We have developed the loop-mediated isothermal amplification (LAMP) method, an innovative gene amplification technique, which has the potential to become important in genetic testing. This method allows highly efficient amplification by a single enzyme at a constant temperature. It also has features such as high specificity, rapidity, and simplicity of detection. Therefore, application to various life sciences, such as clinical medicine, is expected.

Familial lipoprotein lipase deficiency

Abstract: People with familial lipoprotein lipase deficiency typically develop signs and symptoms before age 10, with one-quarter showing symptoms by age 1. The first symptom of this condition is usually abdominal pain, which can vary from mild to severe. The abdominal pain is often due to inflammation of the pancreas (pancreatitis). These episodes of pancreatitis begin as sudden (acute) attacks. If left untreated, pancreatitis can develop into a chronic condition that can damage the pancreas and, in rare cases, be lifethreatening.

Sleep disturbance in chronic fatigue syndrome

Abstract: Attempts to elucidate the complex pathophysiology of chronic fatigue syndrome (CFS) must consider subjective and objective sleep. Several reports of CFS showed the high rate of sleep disturbance such as insomnia, hypersomnia, circadian rhythm sleep disorder, sleep apnea/hypopnea syndrome and so on. To analyze pulse wave continuously in sleep of CFS patients by laser blood flowmeter, we set base line component (0.01-0.08 Hz) and pulse wave component(0.70-1.50 Hz). Results of FFT analysis indicate that the CFS can have at least three subtypes of pulse dynamics in sleep. There probably are different types of illnesses now contained within the CFS construct, in which identifying subtypes of sleep disturbance can be one important key.

Depression and sleep

Abstract: More than 80% of depressive patients have complaints about sleepiness and insomnia. Physiological researches demonstrate changes in sleep architecture and circadian rhythm in depressive patients. These researches suggest the enhancement of arousal function in daytime and nighttime and circadian changes in cholinergic and catecholaminergic neural system. Pharmacological therapy might be selected in considering the mechanism of these neural changes. The research about sleep deprivation therapy may give us the new advances in the further treatment.

Epidemiology of depressive disorders in Japan and the world

Abstract: Recent epidemiologic studies of community residents revealed that the prevalence of major depression according to DSM-IV criteria was 1-2% for 12 month and 3-7% for lifetime in Japan. The prevalence was much lower than that in Western countries but very similar with that reported in China, suggesting that the prevalence of major depression is lower in Asian countries. While women had a more risk of the disorder as seen in other countries, age and social class distributions were different from other countries. Among those who experienced major depression in Japan, 27% sought any medical treatment; only 14% saw a psychiatrist. The rate is lower than that reported from many Western countries, and is almost half of that in the U.S.

Antinuclear antibodies in patients with chronic fatigue syndrome

Abstract: Significance of antinuclear antibodies (ANA) in the patients with chronic fatigue syndrome (CFS) was reviewed. When indirect immunofluorescence with the HEp-2 cells as the substrates was used, prevalence of the positive ANA was reportedly 15-25%. The ANA titers were low and the immunofluorescent staining patterns were heterogeneous. One group in the USA reported that 'nuclear envelope staining pattern' was found in more than 50% of the patients with CFS. This results, however, have not been confirmed by any other research groups. Clinical significance of the positive ANA in the CFS patients resides in differential diagnoses of systemic lupus erythematosus and other diffuse connective tissue diseases. Recently, several ANAs specific to CFS have been described. We reported anti-68/48kD protein antibodies utilizing SDS-PAGE/ immunoblot method. These autoantibodies were found in 13% of 114 CFS patients and 0% in healthy subjects (p < 0.05). Hypersomnia and difficulty in concentration were found more frequently in the CFS patients with this specific autoantibody.

[Living with HIV/AIDS].

Abstract:  Your immune system helps you fight infection and illness.  White blood cells are an important part of your immune system. HIV kills certain white blood cells called CD4+ cells. If too many cells are killed, your body can’t fight infection or other illnesses.  HIV infection may progress to AIDS. People who have AIDS have a low number of CD4+ cells. They can get infections that healthy people don’t get.  Having HIV does not mean you have AIDS. Many people with HIV/AIDS are able to live long and active lives.  We can give you more information to help you manage your HIV/AIDS.

[Toll-like receptor (TLR)].

Abstract: Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Toll-Like Receptors (TLRs) play a critical role in the early innate immune response to invading pathogens by sensing microorganism and are involved in sensing endogenous danger signals. TLRs are evolutionarily conserved receptors are homologues of the Drosophila Toll protein, discovered to be important for defense against microbial infection. TLRs recognize highly conserved structural motifs known as pathogen-associated microbial patterns (PAMPs), which are exclusively expressed by microbial pathogens.

Pathophysiology of depression

Abstract: Neurobiological findings of depression are reviewed in this paper. Modern neurobiological methods have revealed pathophysiological mechanism associated with depression. Monoamine hypothesis, which was advocated in the 1950's, emphasizes that the deficiency of monoamine neurotransmitters bring about depressive symptoms. This theory played an important role in promoting the development of new antidepressants, but some inconsistent findings were pointed out concerning this theory. Neuroendocrine studies have revealed the hypothalamic-pituitary-adrenal (HPA) axis dysfunctions in depressive patients, and increased activity of HPA axis are considered as state marker of depression. Morphological changes of hippocampus, polymorphism of serotonin transporter gene, and down regulation of neurotrophin are also discussed in this review.

Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria

Abstract: Chronic fatigue syndrome (CFS) is an operational concept proposed by Centers for Disease Control and Prevention to clarify the unknown etiology of the syndrome characterized by the sensation of abnormally prolonged fatigue. Lots of investigators reported various abnormalities such as virus infection, immune abnormalities, HPA axis abnormalities, metabolic abnormalities, etc., but there are a few abnormalities common to vast majority cases of CFS. Therefore, lots of people as well as medical doctors are still skeptical about the presence of CFS. However, recent studies reveal that CFS can be understood to be a special condition based on the abnormality of neuroendocrine-immunologic system caused by the psycho-social stress and some genetic components. Under these conditions, a reactivation of various kinds of herpes virus infections and/or chronic infections might occur as a result of immune dysfunction, causing the abnormal production of several cytokines. A distinctive feature of CFS is thought to be the secondary brain dysfunction caused by the abnormal production of several cytokines. In this paper, I show the overview of CFS focusing around prevalence, economic impact and diagnostic criteria in Japan.

[Gene and cell therapy for relapsed leukemia after allo-stem cell transplantation].

Abstract: To control severe GvHD while maintaining strong GvL effects in the context of allo-stem cell transplantation (allo-SCT), a phase I/II clinical trial of infusions of donor lymphocytes transduced with the herpes simplex virus thymidine kinase (TK-DLI) started at the Tsukuba University Hospital. To date, five (2 AML, 2 ALL, and 1 MDS) out of eight patients enrolled in the trial received approximately 7x10(7) transduced cells per kilogram of body weight and four patients showed some clinical responses such inhibition of the leukemic cell proliferation or mitigation of lymph node swelling. Especially, one MDS patient achieved complete remission and has remained in CR for 2 years after the treatment. GvHD developed in two patients (1 acute and 1 chronic) and the acute (grade III) was successfully controlled by administration of ganciclovir without any immunosuppressive drugs. Since HSV-TK as a strong antigen induced CTLs against transduced cells in patients, however, TK-DLI is expected to provide a more effective adoptive immune cell therapy by performance just after allo-SCT where the patient's immune function is severely damaged.