Spatial fragment distribution from a therapeutic pencil-like carbon beam in water

The latest heavy ion therapy tends to require information about the spatial distribution of the quality of radiation in a patient's body in order to make the best use of any potential advantage of swift heavy ions for the therapeutic treatment of a tumour. The deflection of incident particles is described well by Molière's multiple-scattering theory of primary particles; however, the deflection of projectile fragments is not yet thoroughly understood. This paper reports on our investigation of the spatial distribution of fragments produced from a therapeutic carbon beam through nuclear reactions in thick water. A DeltaE-E counter telescope system, composed of a plastic scintillator, a gas-flow proportional counter and a BGO scintillator, was rotated around a water target in order to measure the spatial distribution of the radiation quality. The results revealed that the observed deflection of fragment particles exceeded the multiple scattering effect estimated by Molière's theory. However, the difference can be sufficiently accounted for by considering one term involved in the multiple-scattering formula; this term corresponds to a lateral 'kick' at the point of production of the fragment. This kick is successfully explained as a transfer of the intra-nucleus Fermi momentum of a projectile to the fragment; the extent of the kick obeys the expectation derived from the Goldhaber model.     

Growth hormone releasing hormone receptor (GHRH-r) gene mutation in Indian children with familial isolated growth hormone deficiency: a study from western India

BACKGROUND: Various mutations of the growth hormone releasing hormone receptor (GHRH-R) gene have been recently described to cause familial isolated growth hormone (GH) deficiency (FIGHD), with the GHRH-R nonsense mutation E72X reported in patients with FIGHD from South Asia. The molecular genetic basis of FIGHD in Indian children is not known. Objective: To look for the GHRH-R E72X non-sense mutation in our patients with FIGHD and describe its clinical phenotype. PATIENTS AND METHOD: A total of 31 patients from 22 families diagnosed 4-20 years previously, 20 patients with familial IGHD-IB from 11 families and 11 patients with non-familial isolated GH deficiency (NFIGHD) (phenotypes IGHD-IB in eight patients and -IA in three) were included. Twenty-eight of 31 patients with IGHD-IB came from two states of Western India, 27 of them Hindus from 18 families (three consanguineous) and one from an inbred Moslem kindred. RESULTS: Twenty-two of the patients (71%) (18 FIGHD and four NFIGHD) had a homozygous G-->T transversion in exon 3, with this GHRH-R gene mutation E72X in 90% (18/20) of patients with FIGHD, 36% (4/11) of NFIGHD, altogether 78% (22/28) with phenotype IB. One parent pair with IGHD had homozygous E72X mutation, the rest were heterozygous carriers. Two siblings with IGHD due to homozygous E72X mutation were also heterozygous carriers for GH-1 gene 6.7 kb deletion, inherited from their mother, heterozygous for both GH-1 and GHRH-R mutations. Initial chronological age was 10.89 +/- 3.69 years, bone age 6.4 +/- 3.4 years, and mean height SDS was -5.83 +/- 1.41. The clinical phenotype, with sharp features, lean habitus, lack of frontal bossing or hypoglycemia, was characteristic. The mean peak GH was 1.25 +/- 0.75 ng/ml, IGF-I and IGFBP-3 below -2 SDS with no response to GHRH in those tested. MRI (n = 10) showed pituitary hypoplasia, mean vertical height 2.61 +/- 0.76 mm. Among the other 7/11 NFIGHD patients, four with phenotype IB were negative for genotypes tested in this study; of three patients with phenotype IA, two had the GH-1 gene 6.7 kb deletion, and one was a compound heterozygote with 6.7 and 7.6 kb deletions. CONCLUSIONS: The majority of patients with FIGHD from different communities belonged to non-consanguineous Hindu families from Western India. The GHRH-R gene E72X mutation was found in 71% of this series, in 90% of FIGHD, 36% of NFIGHD, and in 78% with phenotype IB. The characteristic phenotype helped in suspecting this mutation. GHRH-R gene mutations may be the most reasonable candidate for IGHD-IB with the E72X mutation predominating in the Indian subcontinent. More extensive studies need to be undertaken.     

Expression of tumor necrosis factor-alpha stimulated gene-6 mRNA in cultured human uterine cervical fibroblasts

BACKGROUND: Uterine cervical ripening process is an active biochemical process similar in part to inflammatory reaction. In this process, hyaluronan plays important roles including facilitation of tissue hydration, release of matrix metalloproteinases and migration of inflammatory cells. The activities of hyaluronan are mediated by the hyaluronan binding proteins, hyaladherins. In the present study, we investigated the mRNA expression of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a member of the hyaladherin family, in cultured human uterine fibroblasts and uterine cervical tissues. METHODS: We developed one-step RT-PCR method for the quantification of TSG-6 mRNA and quantified the expression of TSG-6 mRNA in cultured human uterine fibroblasts, treated with or not proinflammatory cytokines, and TSG-6 mRNA in uterine cervical tissues. RESULTS: We clarified that [1] TSG-6 mRNA was expressed constitutively in cultured human uterine cervical fibroblasts, [2] expression of TSG-6 mRNA was upregulated in a dose dependent manner by proinflammatory cytokines, such as IL-1beta and TNF-alpha, which were key mediators in the cervical ripening process, [3] expression of TSG-6 mRNA in uterine cervices during parturition was significantly (P < 0.05) higher than that in a non-pregnant state. CONCLUSIONS: Our results suggest that TSG-6 might participate in the cervical ripening process.     

Relationship between ABO histo-blood group type and an outbreak of norovirus gastroenteritis among primary and junior high school students: results of questionnaire-based study

Noroviruses are common causative agents of epidemic gastroenteritis in humans. Recent studies showed that human susceptibility to noroviruses was associated with ABO histo-blood group type. It was also observed that various degrees of susceptibility were exhibited by different norovirus strains. In January 2003, an outbreak of acute gastroenteritis including 661 affected primary and junior high school students occurred through lunch bread contaminated with norovirus in Hokkaido, Japan. To clarify the relationship between ABO histo-blood group type and the norovirus infection, we performed a written questionnaire to schoolchildren about the consumption of the bread, onset of symptoms and person-to-person transmission in their household. Questionnaires were returned from 722 schoolchildren (response rate, 65.8%), of whom 55.3% suffered gastroenteritis. As a result of this survey, it was found that schoolchildren with blood group type A (71.1%, 133/187) were more susceptible to the norovirus infection, whereas, schoolchildren with blood group type AB (55.3%, 26/47) were less affected (P (Z0) < 0.025). In addition, the presumptive prevalence rate of person-to-person transmission in each household indicated that schoolchildren with blood group type AB (19.2%, 5/26) had a lower risk of infection than those with blood group type A or O [A : 41.4%, 55/133 O : 39.5%, 49/124 (unknown for one case) ] [P (Z0) < 0.025]. Our findings suggested that persons with blood group type AB were less affected by the norovirus infection in this outbreak.     

GPR40 gene Arg211His polymorphism may contribute to the variation of insulin secretory capacity in Japanese men

GPR40 is a member of the G-protein-coupled receptors. Recent studies suggest that GPR40 is highly expressed in pancreatic beta cells and insulin-secreting cell lines, and that fatty acids increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion by activating GPR40. Despite identification of the Arg211His polymorphism in the GPR40 gene, there have been no clinical studies concerning this polymorphism. The present study was performed to investigate the effects of the GPR40 gene Arg211His polymorphism on clinical and metabolic parameters, including serum insulin level, in 327 healthy Japanese men, using the TaqMan polymerase chain reaction method. Serum insulin level, homeostasis model of insulin resistance (HOMA-IR), and beta-cell function (HOMA-beta were significantly different (P = .0075, .0152, and .0039, respectively) and were lowest in Arg/Arg homozygotes and highest in His/His homozygotes, although plasma glucose and serum lipids were not significantly different. Multiple regression analyses showed that serum insulin level, HOMA-IR, and HOMA- beta were significantly correlated with this polymorphism after adjusting for age and body mass index. After Bonferroni's correction for multiple comparisons was made, only HOMA- beta was significantly different among the 3 genotypes. These results suggest that the Arg211His polymorphism in the GPR40 gene may contribute to the variation of insulin secretory capacity in Japanese men.     

Information processing flow and neural activations in the dorsolateral prefrontal cortex in the Stroop task in schizophrenic patients. A spatially filtered MEG analysis with high temporal and spatial resolution

Using a spatially filtered magnetoencephalography analysis (synthetic aperture magnetometry), we estimated neural activations in the Stroop task in nearly real time for schizophrenic patients with/without auditory hallucinations and for normal control subjects. In addition, auditory hallucinations were examined through the information processing flow of the brain neural network, including the frontal regions. One hundred unaveraged magnetoencephalography signals during the incongruent stimulus responses were analyzed with a time window of 200 ms in steps of 50 ms. In the 25-60-Hz band, cortical regions that showed significant current source density changes were examined for each time window. The three groups showed significantly decreased current source density, corresponding to neural activation, with temporal overlap along the fundamental cognitive information processing flow: sensory input system, executive control system, motor output system. Transient neural activations in the dorsolateral prefrontal cortex were bilateral with left-side dominancy for normal controls, left-lateralized for nonhallucinators and right-lateralized for hallucinators. Our results suggest that the dysfunction in the left dorsolateral prefrontal cortex was related to auditory hallucinations, while the information processing flow was unaffected in the schizophrenic subjects in the Stroop task.     

Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous brain amine and its content in parkinsonian brain is decreased compared with that in control brain. There is some evidence that 1MeTIQ protects dopaminergic neurons against dysfunction such as that seen in Parkinson's disease. In this study, we examined the neuroprotective effect of 1MeTIQ against four dopaminergic neurotoxins, 1-methyl-4-phenylpyridinuim ion, 6-hydroxydopamine, rotenone, and l-benzyl-1,2,3,4-tetrahydroisoquinoline, in cultured rat mesencephalic neurons. 1MeTIQ exerted neuroprotective action against all these toxins. Furthermore, (R)-1MeTIQ was neuroprotective, while (S)-1MeTIQ had little effect, indicating that the effect is stereoselective. The protective action of 1MeTIQ was most effective in mesencephalic neurons, especially in tyrosine hydroxylase-positive neurons. 1MeTIQ showed no affinity for dopamine receptors and did not influence the inhibition of mitochondrial respiratory complex I by rotenone, 1-methyl-4-phenylpyridinuim ion, or 1-benzyl-1,2,3,4-tetrahydroisoquinoline. These results raise the possibility that 1MeTIQ indirectly acts as an anti-oxidant such as the induction of anti-oxidative enzymes, because all these four neurotoxins can burden oxidative stress in common. This is the first report to confirm a protective effect of 1MeTIQ at the cultured neuron level, and it may have potential as a lead compound for the development of new agents to treat Parkinson's disease.