Tissue banking,biovigilance and the notify library

This issue is dedicated to the contributions of Professor Glyn O. Phillips to the field of tissue banking and the advancement of science in general. The use of ionizing radiation to sterilize medical products drew the interest of the International Atomic Energy Agency (IAEA). A meeting in 1976 in Athens Greece to present work on the effects of sterilizing radiation doses upon the antigenic properties of proteins and biologic tissues was my first introduction of Professor Phillips and the role that he was to play in Tissue Banking (Friedlaender, in Phillips GO, Tallentine AN (eds) Radiation sterilization. Irradiated tissues and their potential clinical use. The North E. Wales Institute, Clwyd, p 128, 1978). The IAEA sponsored subsequent meetings in the Republic of Korea, Czechoslovakia and Rangoon, the later including a visit to the tissue bank by Professor Phillips. His advocacy resulted in multiple workshops and teaching opportunities in a variety of countries, one of which led to the establishment of the Asia Pacific Surgical Tissue Banking Association in 1989 (Phillips and Strong, in Phillips GO, Strong DM, von Versen R, Nather A (eds) Advances in tissue banking, vol 3. World Scientific, Singapore, pp 403–417, 1999).     

Propensity of white women in the United States to adopt children

Demographically, adoption is a relatively rare event. In 1982, only 2.3 per cent (or about 650,000) of ever-married white women aged 15 to 44 had adopted one or more children. Adoption is an important and very relevant means of family formation for many women, particularly those for whom biological childbearing is difficult or impossible. Although there is a modest literature on adoption behavior, we have very little information about women who have shown a propensity to adopt children. How should the phenomenon of adoption propensity be conceptualized? How many women are there in the United States with such a propensity? How different is this number from the number of women who eventually adopt children? What are the characteristics of women with a propensity to adopt? The objectives of this paper are (1) to estimate the numbers of U.S. women at three different points in time (1973, 1976, and 1982) who have a propensity to adopt, according to various socioeconomic and demographic characteristics; and (2) to compare via log-linear analysis the major characteristics of these women with women who have not shown such a propensity.     

Response to a Respiratory Survey

Respondents to a respiratory survey of Berlin, New Hampshire, residents in 1961 have been studied to assess the relationship between co-operation and respiratory disease prevalence. Two hundred and forty-three unco-operative subjects, interviewed at home, had significantly more morning phlegm and a lower vital capacity than carefully matched subjects who attended the central clinic. Fifty-one volunteers had the same prevalence of respiratory disease symptoms and physiological abnormalities as carefully matched subjects drawn from a probability sample of the city.It is concluded that respiratory disease prevalence will be underestimated if calculated from studies of co-operative subjects who attend a clinic. Case-finding by respiratory disease screening clinics will also miss many persons who suffer from chronic bronchitis.     

Human genome and philosophy: what ethical challenge will human genome studies bring to the medical practices in the 21st century?

A human being or person cannot be reduced to a set of human genes, or human genome. Genetic essentialism is wrong, because as a person the entity should have self-conscious and social interaction capacity which is grown in an interpersonal relationship. Genetic determinism is wrong too, the relationship between a gene and a trait is not a linear model of causation, but rather a non-linear one. Human genome is a complexity system and functions in a complexity system of human body and a complexity of systems of natural/social environment. Genetic determinism also caused the issue of how much responsibility an agent should take for her/his action, and how much degrees of freedom will a human being have. Human genome research caused several conceptual issues. Can we call a gene 'good' or 'bad', 'superior' of 'inferior'? Is a boy who is detected to have the gene of Huntington's chorea or Alzheimer disease a patient? What should the term 'eugenics' mean? What do the terms such as 'gene therapy', 'treatment' and 'enhancement' and 'human cloning' mean etc.? The research of human genome and its application caused and will cause ethical issues. Can human genome research and its application be used for eugenics, or only for the treatment and prevention of diseases? Must the principle of informed consent/choice be insisted in human genome research and its application? How to protecting gene privacy and combating the discrimination on the basis of genes? How to promote the quality between persons, harmony between ethnic groups and peace between countries? How to establish a fair, just, equal and equitable relationship between developing and developed countries in regarding to human genome research and its application?     

History of the clinical use of umbilical cord blood hematopoietic cells

The first cord blood (CB) transplant was performed in 1988 in a patient with Fanconi anemia. The donor was his HLA-identical sister who was known by pre-natal diagnosis to be HLA identical and not affected by the Fanconi mutation. The CB was collected and cryopreserved at birth. The transplant was successful without GvHD and the patient is currently alive and free of disease more than 15 years after transplant, with full hematologic and immunologic donor reconstitution. At the time of the first transplant, little was known about the biologic properties of CB cells and it was thanks to the pioneering work of H. E. Broxmeyer and E. A. Boyse, who studied the progenitor cell content of CB, and of A. D. Auerbach, who realized the pre-natal diagnosis of Fanconi anemia, that this transplant was possible. Since this first transplant, many questions have been answered but others are still open for further research. For example: would a single CB unit contain enough stem cells to permanently engraft children and adults? Would maternal cell contamination in fetal blood engraft and give severe GvHD? What are the immunologic properties of CB cells? How does it interfere with GvHD, GvL and immune reconstitution? Is the immune immaturity of CB lymphocytes able to overcome the HLA barrier and authorize HLA-mismatched transplants? Is it possible to establish CB banks for unrelated and related transplants? What would be the criteria for collection, quality control and cryopreservation?     

A novel splicing mutation in the ABCA1 gene,causing Tangier disease and familial HDL deficiency in a large family

Tangier disease is a rare disorder of lipoprotein metabolism that presents with extremely low levels of HDL cholesterol and apoprotein A-I. It is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. Clinical heterogeneity and mutational pattern of Tangier disease are poorly characterized. Moreover, also familial HDL deficiency may be caused by mutations in ABCA1 gene.ATP-binding cassette transporter A1 (ABCA1) gene mutations in a patient with Tangier disease, who presented an uncommon clinical history, and in his family were found and characterized. He was found to be compound heterozygous for two intronic mutations of ABCA1 gene, causing abnormal pre-mRNAs splicing. The novel c.1510-1G?>?A mutation was located in intron 12 and caused the activation of a cryptic splice site in exon 13, which determined the loss of 22 amino acids of exon 13 with the introduction of a premature stop codon. Five heterozygous carriers of this mutation were also found in proband's family, all presenting reduced HDL cholesterol and ApoAI (0.86?±?0.16?mmol/L and 92.2?±?10.9?mg/dL respectively), but not the typical features of Tangier disease, a phenotype compatible with the diagnosis of familial HDL deficiency. The other known mutation c.1195-27G?>?A was confirmed to cause aberrant retention of 25 nucleotides of intron 10 leading to the insertion of a stop codon after 20 amino acids of exon 11. Heterozygous carriers of this mutation also showed the clinical phenotype of familial HDL deficiency.Our study extends the catalog of pathogenic intronic mutations affecting ABCA1 pre-mRNA splicing. In a large family, a clear demonstration that the same mutations may cause Tangier disease (if in compound heterozygosis) or familial HDL deficiency (if in heterozygosis) is provided.     

Identification of quantitative trait loci linked to Ceratocystis wilt resistance in cacao

Ceratocystis wilt (CW) in cacao (Theobroma cacao L.), caused by Ceratocystis cacaofunesta, is a drastic disease that results in plant death. The pathogen was recently identified in the major cacao-producing region of Brazil?CBahia. The identification of genetic markers tightly linked to disease resistance loci is a valuable tool for the development of resistant cultivars using marker-assisted selection (MAS). Branches of 143 six-year-old individuals of an F2 Sca 6?×?ICS 1 population were wounded by making a 3-mm deep cut with a sterile scalpel, and inoculated with a 20-??l drop of a spore suspension of 3?×?10⁴?CFU/ml. The inoculation method used allowed the population to be quantitatively phenotyped. The length of the xylem discoloration followed a continuous distribution. These results imply that the resistance was quantitatively inherited. Quantitative trait loci (QTL) analysis revealed two genomic regions (in linkage groups 3 and 9) associated with CW resistance. The QTL explained individually from 6.9 to 8.6?% of the phenotypic variation. The QTL identified are crucial for identifying genes for resistance and can be applied in the genetic breeding of cacao using MAS.     

Early Response to Sibutramine in Patients Not Meeting Current Label Criteria: Preliminary Analysis of SCOUT Lead‐in Period

The Sibutramine Cardiovascular Outcomes (SCOUT) trial protocol defines a patient population predominantly outside current European Union label criteria. This article explores responses to sibutramine during the 6‐week, single‐blind, lead‐in period between patients who conformed to the label requirements (“conformers”) and those who did not (“nonconformers”). SCOUT is an ongoing, randomized, double‐blind, placebo‐controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. In total, 10,742 patients received sibutramine and weight management during the lead‐in period. Initial responses were assessed post hoc in label conformers and nonconformers. Of that 8.1% patients met label criteria; 91.9%, the majority with cardiovascular disease and/or blood pressure >145/90 mm Hg, were nonconformers. Conformers and nonconformers had similar reductions in body weight (median change ?2.2 kg) and waist circumference (women: ?2.0 cm for both groups; men: ?1.5 cm vs. ?2.0 cm for conformers and nonconformers, respectively) over the 6‐week period. Greater blood pressure falls were evident in nonconformers (median change ?3.5/?1.0 vs. ?1.0/0.0 mm Hg). Both groups had small pulse rate increases; median 1.5 bpm (nonconformers) vs. 3.0 bpm (conformers). There was a low incidence of serious adverse events (conformers: 1.0%; nonconformers: 2.8%) and ～93% of patients in both groups completed the 6‐week period. The SCOUT lead‐in period evaluating weight management with sibutramine confirms its good tolerability and efficacy in patients who meet current label criteria. Preliminary data from high‐risk patients for whom sibutramine is currently contraindicated suggest a low discontinuation rate and few serious adverse events but confirmation from the SCOUT outcome data is needed.     

Hypophysectomy for palliation of breast cancer with especial reference to surgical technique

In a series of 19 patients who had hypophysectomy for palliation of cancer of the breast, all had striking relief of pain. Objective evidence of remission of disease was observed in ten patients. The survival time after operation averaged 19.8 months for patients who had remission and 2.1 months for patients who did not. Results were better in patients who had had cancer for a long time before operation than in those who had had the disease a relatively short time. Also it was noted that results were better in patients who had had preoperative response to endocrine therapy than in those who had not. Hence these factors may be considered in selection of patients for hypophysectomy.     

Ought We to Sentence People to Psychiatric Treatment?

In principle, there seem to be three main ways in which society can react when people commit crimes under influence of mental illness.
(1) The standard model. We excuse them. If they are dangerous they are detained in the interest of safety of the rest of the citizens.
(2) The Swedish model. We hold them responsible for their criminal offence, we convict them, but we do not sentence them to jail. Instead, we sentence them to psychiatric treatment.
(3) My model. We sentence them to jail, but offer them (voluntary) psychiatric treatment.
The advantages of my model are obvious. We get a clear delineation of roles. We allow the psychiatrist to be just a doctor, not a warden. We liberate psychiatry of the objective of deciding whether people who were mentally ill when they committed criminal offences 'could have acted otherwise'— a hopeless task. We allow that psychiatrists live up to their professional ethical code (the Hawaii Declaration). We treat psychically ill persons as 'normal', we allow them to repent their crimes, which renders easier their recovery.
However, two objections to my model come to mind. First of all, is it not unfair to sentence people to jail who could not help doing what they did? And, secondly, the question of fairness set to one side, is it not inhumane to sentence mentally ill persons to jail? Is it not inhumane to the mentally ill persons themselves, and does it not mean that they will be a burden to other prisoners?
In my paper I show that, if our system of criminal punishment takes a civilised form, neither of these objections carries any weight.     

Genetic engineering of Lactococcus lactis to produce an amylase inhibitor for development of an anti-diabetes biodrug

Diabetes is known as a multifactorial disease. The treatment of diabetes is complicated due to its inherent pathophysiological factors related to the disease. One of the complications of diabetes is postprandial hyperglycemia. Glucosidase inhibitors, particularly ?-amylase inhibitors can help manage postprandial hyperglycemia. The low molecular weight inhibitor of ? -amylases called PAMI (peptide amylase inhibitor) inhibits the ? -amylase. In this study we cloned this amylase blocker PAMI in Lactococcus lactis. Using this Lactococcus lactis expressing the PAMI, we prepared yogurt and fed it to diabetic mice models. There was decrease in the blood glucose level after 20 days of oral administration of the yogurt. This product be used as a biodrug in maintaining the blood glucose level in diabetic patients.     

Effects of FUT1 gene mutation on resistance to infectious disease

Alpha-(1,2)-fucosyltransferase (FUT1) gene has been identified as a candidate gene for regulating the expression of Escherichia coli F18 receptor gene (ECF18R) which promotes adherence of Enterotoxigenic (ETEC) and Verotoxigenic (VTEC) Escherichia coli (E. coli) via F18 fimbriae. In order to illustrate the polymorphisms of FUT1 and their effects on resistance to natural infection by Porcine Respiratory and Reproductive Symdrome Virus (PRRSV) and Haemophilus parasuis, the distributions of different genotypes and the relative risks of disease incidence in pigs were investigated. A total of 1,041 pigs representing three European breeds (Duroc, Landrace and LargeWhite), five Chinese local breeds (Wild pig, Small MeiShan, QinPing, JinHua, and JianLi) and three commercial populations (LargeWhite?×?JianLi, Duroc?×?Landrace?×?LargeWhite and Duroc?×?wild pig) were selected to analyze the genotype of the FUT1 gene by PCR-RFLP. Only the GG genotype associated with susceptibility to ECF18 bacteria was detected in Chinese local pig breeds and a population of LargeWhite?×?JianLi, while the AA genotype which confers resistance to ECF18 was detected in two European breeds (Duroc and LargeWhite), two populations of Duroc?×?wild pig and Duroc?×?Landrace?×?LargeWhite. Regarding relative risk of incidence, Duroc?×?Landrace?×?LargeWhite with genotypes GG or AG showed greater relative risk (OR?=?2.040, P?=?0.025; OR?=?1.750, P?=?0.081, respectively) than those with genotype AA during natural infection by both PRRSV and Haemophilus parasuis. It can be concluded that the mutation of FUT1 gene might play a role in pig infection by multi-pathogens, and that AA may be a favourable genotype for increasing the resistance to disease.     

小麦抗赤霉病外源种质的创制和育种利用

小麦赤霉病是危害小麦安全生产的重要病害之一,种植抗病品种是防治赤霉病最经济有效的手段。目前在生产上应用的抗源很少,越来越多的研究者将目光转移到小麦的近缘属种,寻找新的抗源以及寻求新的育种突破。携带抗性基因的外源染色体可以通过染色体工程手段以附加系、代换系和易位系等形式导入小麦。综述了将大赖草等多个小麦近缘种的抗赤霉病基因导入普通小麦、创制抗病外源种质和育种利用的最新研究进展,以期为小麦抗赤霉病育种提供参考信息。     

Case contribution to the study of hemoglobin C disease]

Haemoglobin-C disease represents a haemoglobinopathy seldom occurring in our latitudes. In its homocygotic form it coincides with haemolytic anaemia and splenomegaly. The diagnosis of haemoglobin-C disease could be ensured in a 33 years old Yugoslav patient who had been treated because of being suspected of a venous thrombosis of the spleen. The knowledge of this disease taking prognostically a benign course seems to be important in order to prevent patients from unnescessary diagnostic and therapeutic measures.     

Low dietary intake of linoleic acid predisposes to myocardial infarction

Thirty-two men who had recently had a myocardial infarction were matched individually for age with controls who had no evidence of heart disease. The patients had a significantly lower proportion of linoleic acid and a higher proportion of palmitic acid in their plasma triglyceride fatty acids. Analysis of the composition of red-cell membrane phosphatidyl choline, which reflects long-term dietary fat intake, showed a significantly lower proportion of linoleic acid in the patients.These differences suggest that the type of dietary fat consumed might be an important factor in the genesis of ischaemic heart disease.     

Dorothy Hodgkin Lecture 2012* Non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management

Diabet. Med. 29, 1098-1107 (2012) ABSTRACT: Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type?2 diabetes. Non-alcoholic fatty liver disease increases risk of Type?2 diabetes and cardiovascular disease. In people with Type?2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (～80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type?2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance.     

Rebound of relapses after discontinuation of rituximab in a patient with MOG-IgG1 positive highly relapsing optic neuritis: a case report

Background

Myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG1)-associated disease is suggested as a separate disease entity distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. Nonetheless, the optimal treatment regimen for preventing relapses in MOG-IgG1-associated disease remains unclear.

Case presentation

We describe the case of a 45-year-old man with MOG-IgG1-positive highly relapsing optic neuritis who had experienced 5 attacks over 21?months and had monocular blindness despite prednisolone and azathioprine therapy. He began treatment with rituximab, which reduced the rate of relapse markedly. Following discontinuation of rituximab, however, the patient experienced two successive optic neuritis attacks 2 and 4?months after B-lymphocyte restoration.

Conclusions

Highly relapsing MOG-IgG1-associated disease can be prevented with rituximab even when the MOG-IgG1 titers are relatively stationary. Discontinuation of rituximab and restoration of B-lymphocytes may be associated with the rebound of disease activity.

     

Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.