Prolonged excretion of an identical cytomegalovirus strain by two siblings and the intermittent isolation of an adenovirus from the urine of one of them

Restriction endonucleases were used to show the excretion of an identical strain of cytomegalovirus (CMV) by two brothers over a 2 1/2-yr period. The same enzymes were used to show that the younger brother, case report, excreted an adenovirus over at least a 3-mo period. We are unable to determine the contribution of each virus to this child's clinical picture; however, this is the first report of a prolonged excretion of an adenovirus associated with CMV excretion in an immunocompetent host.     

Inverse associations of human leukocyte antigen and malaria parasite types in two West African populations

Differences in allelic associations between populations continue to cause difficulties in the mapping and identification of susceptibility genes for complex polygenic diseases. Although well recognized, the basis of such interpopulation differences is poorly understood. We present an example of an inverse allelic association of an immune response genotype to an infectious disease in two neighboring West African populations. In this case, both the key environmental contributor, i.e., the malaria parasite, and a major biological mechanism are well defined. We show that this surprising result fits well with the predictions of a mathematical model describing the population genetics and dynamics of this interaction.     

The new genetics of bone marrow transplantation

There is now little doubt that functional immune polymorphism exists and can exert a significant effect on the severity of immunologic disease. Studies in this area are driven by the belief that an understanding of the influence of immune polymorphism on immunologic disease will improve our ability to predict disease occurrence and severity. The usefulness of this information is necessarily limited, however, by the fact that an individual has a fixed genome. If an individual has an allele which predisposes to increased disease severity, there is little we can do, other than treat the disease in that individual in a more aggressive manner or attempt to find preventative therapies. There is, however, one unique immunologic disorder that is an exception to this rule. Graft-versus-host disease (GVHD), the major complication of bone marrow transplantation, is an immunologic reaction mediated, in large part, by donor T cells. It is unique in that it is the only immunologic disorder in which we can choose the genetics of the immune system causing the disorder. In this disease, more than any other, an understanding of the role of immune polymorphism is essential since we could hypothetically use this information to choose a donor whose T cells will not mediate GVHD of life-threatening severity. In this review, I argue that there is highly suggestive evidence that allelic polymorphism in non-MHC genes encoding mediators of the immune response exerts a very significant effect on the severity of GVHD and that typing for such allelic polymorphisms will in future be as important as MHC-typing in choosing an appropriate donor for bone marrow transplantation.     

Genomic analysis of Caenorhabditis elegans reveals ancient families of retroviral-like elements.

Retrotransposons are the most abundant and widespread class of eukaryotic transposable elements. The recent genome sequencing of Caenorhabditis elegans has provided an unprecedented opportunity to analyze the evolutionary relationships among the entire complement of retrotransposons within a multicellular eukaryotic organism. In this article we report the results of an analysis of retroviral-like long terminal repeat retrotransposons in C. elegans that indicate that this class of elements may be even more abundant and divergent than previously expected. The unexpected presence, in C. elegans, of an element displaying a number of characteristics previously thought to be unique to vertebrate retroviruses suggests an ancient lineage for this important class of infectious agents.     

Building artificial humans to understand humans

If we could build an android as a very humanlike robot, how would we humans distinguish a real human from an android? The answer to this question is not so easy. In human–android interaction, we cannot see the internal mechanism of the android, and thus we may simply believe that it is a human. This means that a human can be defined from two perspectives: one by organic mechanism and the other by appearance. Further, the current rapid progress in artificial organs makes this distinction confusing. The approach discussed in this article is to create artificial humans with humanlike appearances. The developed artificial humans, an android and a geminoid, can be used to improve understanding of humans through psychological and cognitive tests conducted using the artificial humans. We call this new approach to understanding humans android science.     

Generation of homozygosity at the c-Ha-ras-1 locus on chromosome 11p in an adrenal adenoma from an adult with Wiedemann-Beckwith syndrome

Generation of homozygosity for the human c-Ha-ras-1 locus on the short arm of chromosome #11 (11p) has been demonstrated for an adrenal adenoma from an adult with Wiedemann-Beckwith syndrome (WBS). This is the first demonstration of loss of somatic heterozygosity for a locus on 11p in an adrenal neoplasm and is the first instance where a tumor of any type, from a patient with WBS, shows loss of heterozygosity in this region of the genome. Generation of homozygosity in an adenoma, rather than a carcinoma, demonstrates that this mechanism is an early event in tumorigenesis rather than a late event associated with tumor progression.     

From molecules to behavior: An integrative theory of autism spectrum disorder

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders for which various theories have been proposed. Each theory brings valuable insights and has experimental evidence backing it, yet none provides an overarching explanation for each of the pathological aspects involved in ASD. Here we present an integrative theory of ASD, centered on a sequence of events spanning from the molecular to the behavioral level. We propose that an abnormality in the interplay between retinoic acid and sex hormones predisposes an individual to specific molecular malfunctions. In turn, this molecular syndrome generates an altered brain connectivity between the cerebellum, the midbrain dopaminergic areas, and the prefrontal cortex. Lastly, this disconnection would generate specific behavioral traits traditionally involved in ASD. Therefore, this paper represents a step forward in unifying different levels of pathological features into novel integrated testable hypotheses.     

Artificial intelligence and machine learning overview in pathology & laboratory medicine: A general review of data preprocessing and basic supervised concepts

Machine learning (ML) is becoming an integral aspect of several domains in medicine. Yet, most pathologists and laboratory professionals remain unfamiliar with such tools and are unprepared for their inevitable integration. To bridge this knowledge gap, we present an overview of key elements within this emerging data science discipline. First, we will cover general, well-established concepts within ML, such as data type concepts, data preprocessing methods, and ML study design. We will describe common supervised and unsupervised learning algorithms and their associated common machine learning terms (provided within a comprehensive glossary of terms that are discussed within this review). Overall, this review will offer a broad overview of the key concepts and algorithms in machine learning, with a focus on pathology and laboratory medicine. The objective is to provide an updated useful reference for those new to this field or those who require a refresher.     

Cartographie des risques a priori. Sécurisation de la transfusion d’un produit sanguin labile,dans un établissement de santé : de sa réception à son administration

Following an ABO accident after transfusion of red blood cells, an a priori risk analysis study is being performed in a hospital. The scope of this analysis covers from the reception of the blood product in the medical unit to its administration. The risk analysis enables to identify the potentially dangerous situations and the evaluation of the risks in order to propose corrective measures (precautionary or protective) and bring the system back to an acceptable risk level. The innovative concept of an a priori risk analysis in the medical field allows the extension of the analysis of this transfusion risk to other hospitals. In addition, it allows the extension of the use of this approach to other medical fields.     

Application of a shape memory alloy for internal artificial organs

Shape memory alloy (SMA) is an actuator with high efficiency, and for this reason, SMA is suitable for totally implantable artificial internal organs. We have thought about the various possible applications, and one is an artificial sphincter. Many patients with cancer have a stoma, with which control of excretion is, of course, difficult. It limits the quality of life (QOL) of patients with stomata. If there is a sphincter for the stoma, control becomes possible. Therefore, an artificial anal sphincter was developed. Energy will be supplied by the use of a transcutaneous energy transmission system (TETS). The energy is used to raise the temperature and this becomes the drive energy in the SMA. This system can achieve very high efficiency; therefore, this actuator may be suitable for artificial internal organs. This system is currently in the stage of animal experimentation. By opening and shutting an artificial anal sphincter, excretion becomes possible. Application of this totally implantable system to artificial myocardium is considered in this article. SMA thread was sewn together, and the artificial myocardium was applied to the outside of a heart. For improvement of the cooling time, Peltier elements were adopted in this artificial myocardium. By the use of Peltier elements, rapid cooling becomes possible. Using this artificial myocardium, cardiac contraction may be assisted. In this way, various applications of the SMA are being considered in Tohoku University.     

Imagination and the Psychotherapeutic Process

SUMMARY. Imagination is a neglected topic in psychoanalysis and in psychotherapy because we have an inadequate conception of the phenomenon. This inadequate conception renders imaginative activity intractable to investigation. I offer a framework for thinking about imagination that remedies this defect, and I show how we might use this framework to develop a procedure by which to investigate different kinds of imaginative activity. I illustrate this procedure by investigating the kinds of imaginative activity that support two mental abilities. One is our ability to respond to fictional objects (characters in novels). The other is our ability to respond to the mental states of others - an ability I refer to as psychological understanding. Phantasy characteristically operates to block an imaginative understanding of others. And I propose that a fundamental condition for a person to achieve normal object relationships is an ability to imagine the mental life of another person. I conclude by suggesting how this framework allows us to investigate a psychotherapeutic culture. And I outline an approach to investigate the psychotherapeutic culture of a residential therapeutic community.     

The psoas quartus muscle

We report an unusual finding in an adult male cadaver. During the routine dissection of the posterior abdominal wall as part of an anatomy course at our institution, an anomalous muscle was noted. This muscle originated from the transverse process of the left L3 vertebrae and the medial aspect of the quadratus lumborum. We believe this muscle to represent a variety of the psoas quartus that, to our knowledge, has only been described once before in the extant medical literature. The presence of a psoas quartus muscle may contribute to femoral nerve compression. The clinician may wish to consider this rare muscular anomaly in patients with symptoms of femoral nerve compression in which no other clear etiology is found. Furthermore, clinicians who image the posterior abdominal wall should be aware of this potential anomaly when interpreting the anatomy of this region.     

Evolution of complement as an effector system in innate and adaptive immunity

For a long time, the complement system in mammals has been regarded as a biological system that plays an essential role in innate immunity. More recently, it has been recognized that the complement system contributes heavily to the generation and development of an acquired immune response. In fact, this ancient mechanism of defense has evolved from a primitive mechanism of innate immune recognition in invertebrate species to that of an effector system that bridges the innate with the adaptive immune response in vertebrate species. When and how did complement evolve into a shared effector system between innate and adaptive immunity? To answer this question, our group is interested in understanding the role of complement in innate and adaptive immune responses in an evolutionary relevant species: the teleost fish. The attractiveness of this species as an animal model is based on two important facts. First, teleost fish are one of the oldest animal species to have developed an adaptive immune response. Second, the complement system of teleost fish offers a unique feature, which is the structural and functional diversity of its main effector protein, C3, the third component of the complement system.     

Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case

We have studied an infant with cloverleaf skull, proptosis, radioulnar synostosis and broad thumbs and great toes diagnosed as Pfeiffer syndrome type 2. However, there were many overlapping findings with Antley-Bixler syndrome. The patient was found to have a G to T mutation in codon 290 exon 7 of the FGFR2 gene leading to a substitution of a cys for the normal trp at this locus. This is the third mutation characterized at this codon; therefore, this locus appears to be a mutational hotspot in the gene. However, the other known mutations lead to a milder, Crouzon-like phenotype. The introduction of an additional cys into a region characterized by immunoglobulin-type loops maintained by cys S-S crosslinking may provide an explanation for the severity of the clinical findings of this child. Am. J. Med. Genet. 75:252–255, 1998. © 1998 Wiley-Liss, Inc.     

A method of calculating the output factors of arbitrarily shaped electron fields

It has been well demonstrated in the past that the dose output of an electron beam is highly dependent upon the design of the collimation system, the beam energy, and the field dimensions. Various approaches have been taken to calculate the output factor of an arbitrary rectangular beam. These methods, however, cannot be readily extended to accurately calculate the output factor of an irregular field. In this work, the output factor of an arbitrarily shaped electron field is calculated as the product of three terms: a weighting factor which is explicitly derived from a discrete electron pencil beam model, the known output factor of the regular electron field defined by an applicator or a set of trimmers from which the irregular field is formed, and a machine-dependent term which models the scatter contribution from the shielding. For the machine and fields of clinical interest discussed here, it was found that this latter term could be neglected; this may not be true in general. Results from this calculation are compared to measured data.     

Development of instruction in hospital electrical safety for medical education

Although hospital electrical safety is receiving increased attention in the literature of engineers, it is not, at present, reflected in the curricula of medical schools. A possible reason for this omission is that biomedical and/or clinical engineers knowledgeable in electrical safety are not usually trained to teach. One remedy for this problem is to combine the knowledge of engineers with that of instructional developers to design a systematic curriculum for a course in hospital electrical safety. This paper describes such an effort at the University of Texas Health Science Center at San Antonio (UTHSCSA). A biomedical engineer and an instructional developer designed an instructional module in hospital electrical safety; the engineer taught the module, and both evaluated the results. The process and outcome of their collaboration are described. This model was effectively applied in the classroom as a four-hour segment in hospital electrical safety for first-year medical students at UTHSCSA. It is hoped that an additional benefit of this system will be that it offers an opportunity for continuing improvement in this kind of instruction at other medical schools and hospitals.     

The meniscal flounce: a valuable arthroscopic sign

PURPOSE: The purpose of this study was to characterise the incidence and significance of the meniscal flounce. TYPE OF STUDY: Prospective Cohort Study. METHOD: A prospective study of 1088 consecutive knee arthroscopies. RESULTS: Intact menisci tended to have a flounce of characteristic size and position. The presence of this 'normal' flounce was closely correlated with an intact meniscus (p<0.0001). For the medial meniscus with a small flounce in zone 3 the sensitivity, specificity, and positive predictive value (PPV) for an intact medial meniscus were 68.5%; 92.9%; and 92.1% respectively. Conversely the presence of meniscal pathology correlated closely with either an absent or abnormal flounce (p<0.0001). The absence of a medial flounce had sensitivity, specificity, and PPV for a meniscal tear of 82.8%; 84.9%; and 81.9% respectively. CONCLUSIONS: The findings of this study are useful for arthroscopists especially when there is difficulty visualising all of the posterior half of the meniscus. In this situation the presence of a normal flounce is likely to signify an intact meniscus. However the presence of an abnormal or absent flounce may be the sign of an occult meniscal tear requiring better exposure.     

Non-alcoholic duct-destructive chronic pancreatitis: recognition before definitive treatment

Non-alcoholic duct-destructive chronic pancreatitis is a new entity that differs morphologically and pathogenetically from alcoholic chronic pancreatitis. Some clinical and imaging features of this entity resemble those of pancreatic cancer, and hence most of the reported cases underwent pancreatic resections including an invasive pancreaticoduodenectomy. Recognition of this new entity before a definitive treatment is therefore important to avoid an unnecessary pancreatic resection. Recently, we experienced a case of non-alcoholic duct-destructive chronic pancreatitis in an 80-year-old man presenting with obstructive jaundice and whose radiologic features were characteristic as originally described. Recognition of this new entity before definitive treatment enabled us to manage this patient optimally. In addition, the relation between non-alcoholic duct-destructive chronic pancreatitis and chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct is discussed.     

Rare case of the inferior mesenteric artery arising from the superior mesenteric artery

The authors observed a variation of the inferior mesenteric artery, which arose from the superior mesenteric artery, in a 69-year-old Japanese male cadaver during dissection in 1984. In this case, no rudiment of the ordinary inferior mesenteric artery could be found on the abdominal aorta. There are few reports of this variation, and an extensive search of the available literature revealed only four cases, including two in Japan. Such a variation had been somewhat inadequately described as an "absence of the inferior mesenteric artery" in the previous reports, but we avoided this terminology, because all of the cases possessed an artery, which, though arising from the superior mesenteric artery instead of the abdominal aorta, had the same branches as a normal inferior mesenteric artery. Consistent with findings observed in the previous cases, the unusual inferior mesenteric artery arose as the first branch of the superior mesenteric artery, with the common trunk of both mesenteric arteries originating from the abdominal aorta at a level at which an ordinary superior mesenteric artery would arise. It is for this reason that we did not adopt another acceptable name, that is, "the common mesenteric artery," for this variation. The variation can be explained as the result of an unusual development of the embryonic artery system, which comprises a number of ventral splanchnic arteries interconnected by longitudinal anastomotic channels to supply the primitive digestive tube.     

An altered peptide ligand corresponding to a novel epitope from heat-shock protein 60 induces regulatory T cells and suppresses pathogenic response in an animal model of adjuvant-induced arthritis

Induction of immune tolerance as therapeutic approach for autoimmune diseases constitutes a current research focal point. In this sense, we aimed to evaluate an altered peptide ligand (APL) for induction of peripheral tolerance in patients with rheumatoid arthritis (RA). A novel T-cell epitope from human heat-shock protein 60 (Hsp60), an autoantigen involved in the pathogenesis of RA, was identified by bioinformatics tools and an APL was design starting from this epitope. We investigated the ability of this APL for inducing regulatory T cells (Treg cells) in mice and evaluated the therapeutic effect of this peptide in an adjuvant-induced arthritis (AA) rat model. Clinical score, TNFα levels and histopathology were monitored, as well as the capacity of this APL for inducing Treg cells. Finally, the potentialities of the APL for inducing Treg cells were evaluated in ex vivo assays using mononuclear cells isolated from peripheral blood (PBMC). The APL induced an increase of the proportions of Treg cells in the draining lymph nodes of the injected site in mice. The APL efficiently inhibited the course of AA, with significant reduction of the clinical and histopathology score. This effect was associated with an increase of the proportions of Treg cells and a decrease of TNFα levels in spleen. Finally, stimulation of PBMCs from RA patients by the APL increases the proportions of the CD4⁺CD25^highFoxP3⁺ Treg cells. These results indicate a therapeutic potentiality of APL and support further investigation of this candidate drug for treatment of RA.