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Nonconventional yeasts: their genetics and biotechnological applications.

To date, more than 500 species of yeasts have been described. Most of the genetic and biochemical studies have, however, been carried out with Saccharomyces cerevisiae. Although a considerable amount of knowledge has been accumulated on fundamental processes and biotechnological applications of this industrially important yeast, the large variety of other yeast genera and species may offer various advantages for experimental study as well as for product formation in biotechnology. The genetic investigation of these so-called unconventional yeasts is poorly developed and information about corresponding data is dispersed. It is the aim of this review to summarize and discuss the main results of genetic studies and biotechnological applications of unconventional yeasts and to serve as a guide for scientists who wish to enter this field or are interested in only some aspects of these yeasts.

Biotechnology↗

Neuropsychological effect of lead in occupationally exposed workers: a critical review.

In their discussion of field testing of health effects of environmental and industrial toxins, Gullion and Eckerman make the following observations which can be applied to the current literature survey: "The general inattention to methodological consistency makes it difficult to integrate the research to date into a clear picture of what is known and not known about the effects of toxic substances on human behavior. In view of the variation in methods of subject selection, measurement, and statistical analysis, the completion of a series of studies of a particular toxic substance does not assure that there has been a concurrent accumulation of reliable knowledge about the effects of that substance. Apparent replications or failures to replicate a significant relationship must be evaluated carefully, since different studies may have measured different things in different populations." Therefore, the issue of psychological and neuropsychological effects of low-level lead exposure in adults remains to be resolved in the studies reviewed. The methodologies were so varied and the cultures in which the studies were conducted so diverse that it is impossible to generalize across findings. For example, studies were conducted in the U.S., Denmark, Sweden, Finland, and Australia. Although, in some instances, equivalent versions of neuropsychological and psychological tests were used, this was generally not the case. Nevertheless, a few general statements can be made. Studies that have been carried out in recent years are beginning to pay attention to more methodology and therefore do a much better job of controlling for possible confounding variables. Also, their statistical methods are more sophisticated and reporting techniques are superior to the earlier investigations in this area. The issue of whether current blood lead levels or cumulative levels are preferable is still unresolved with regard to the relationship of neuropsychological impairment. In the area of psychosocial functioning, there appears to be at least some evidence to support the observation that increased irritability and fatigue may lead to the interpersonal problems noted in various studies. However, this observation may be related to other factors which have not been controlled for, such as the workers' attitudes toward their job, level of motivation, and overall level of mental health. With regard to neuropsychological functions, there is some suggestive preliminary evidence for subtle changes in the ability to process information quickly.(ABSTRACT TRUNCATED AT 400 WORDS)

Behavior↗

Invited review: Bovine milk fat globule membrane as a potential nutraceutical.

For the last 15 yr, a great deal of knowledge has been accumulated on health beneficial factors, protein and nonprotein, of bovine milk fat globule membrane (MFGM). Among the health-beneficial components of the MFGM are cholesterolemia-lowering factor, inhibitors of cancer cell growth, vitamin binders, inhibitor of Helicobacter pylori, inhibitor of beta-glucuronidase of the intestinal Escherichia coli, xanthine oxidase as a bactericidal agent, butyrophilin as a possible suppressor of multiple sclerosis, and phospholipids as agents against colon cancer, gastrointestinal pathogens, Alzheimer's disease, depression, and stress. All of the above compel us to consider bovine MFGM as a potential nutraceutical.

Animals↗

Toward more clarity in terminology: frameworks, theories and models.

Lack of precision in a person's choice of words, which perhaps indicates a lack of clarity and accuracy in ideas, may become a subtle form of negative teaching. It is suggested that such terms as "conceptual frame of reference" and "theoretical framework" should be used as broad terms for conceptions of reality, reserving "philosophy," "theory" and "conceptual model" as more restricted terms for conceptions of reality. Nurse authors do not agree that nursing theory exists, that nursing has its own body of knowledge, that nursing is a science or even a discipline. Yet nursing is fully equipped to justify its claim to such terms. Starting from a nursing perspective rather than from a borrowed one, nursing theory can be developed, nursing knowledge can be accumulated, and nursing science can be advanced, all in the interests of a worthwhile contribution to society's health.

Concept Formation↗

Electrophoresis in space.

Programs for free flow electrophoresis in microgravity over the past 25 years are reviewed. Several studies accomplished during 20 spaceflight missions have demonstrated that sample throughput is significantly higher in microgravity than on the ground. Some studies have shown that resolution is also increased. However, many cell separation trials have fallen victim to difficulties associated with experimenting in the microgravity environment such as microbial contamination, air bubbles in electrophoresis chambers, and inadequate facilities for maintaining cells before and after separation. Recent studies suggest that the charge density of cells at their surface may also be modified in microgravity. If this result is confirmed, a further cellular mechanism of "sensing" the low gravity environment will have been found. Several free fluid electrophoresis devices are now available. Most have been tried at least once in microgravity. Newer units not yet tested in spaceflight have been designed to accommodate problems associated with space processing. The USCEPS device and the Japanese FFEU device are specifically designed for sterile operations, whereas the Octopus device is designed to reduce electroosmotic and electrohydrodynamic effects, which become dominant and detrimental in microgravity. Some of these devices will also separate proteins by zone electrophoresis, isotachophoresis, or isoelectric focusing in a single unit. Separation experiments with standard test particles are useful and necessary for testing and optimizing new space hardware. A cohesive free fluid electrophoresis program in the future will obviously require (1) flight opportunities and funding, (2) identification of suitable cellular and macromolecular candidate samples, and (3) provision of a proper interface of electrophoresis processing equipment with biotechnological facilities--equipment like bioreactors and protein crystal growth chambers. The authors feel that such capabilities will lead to the production of commercially useful quantities of target products and to an accumulation of new knowledge relating to the complexities of electrostatic phenomena at the cell surface.

Animals↗

Kaposi's sarcoma-associated herpes virus and acquired immunodeficiency syndrome-related malignancy.

Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus-8 (HHV-8), is a recently described gamma-herpes virus that has been etiologically linked to two different acquired immunodeficiency syndrome (AIDS)-related malignancies by strong epidemiologic and pathologic evidence. Infection been shown to precede and predict the development of Kapasi's sarcoma (KS) in human immunodeficiency virus (HIV)-infected patients, and viral DNA has been found in KS lesions of all types and stages. Furthermore, KSHV is a lymphotropic virus and is present in nearly all cases of primary effusion lymphoma, a rare malignancy disproportionately affecting HIV-infected individuals. KSHV is also thought to dramatically affect the incidence, type, and course of multicentric Castleman's disease, another lymphoproliferative disorder over-represented in people with AIDS. KSHV encodes many potentially oncogenic products, including several apparently pirated from the human genome. These include various chemokines, cell cycle regulatory proteins, and survival and proliferation factors. Knowledge is rapidly accumulating concerning the viral pathogenic mechanisms and host cofactors necessary for KSHV-mediated disease.

Acquired Immunodeficiency Syndrome↗

Na+,K+-ATPase: 40 years of investigations.

Nobel Prize of 1997 in chemistry was awarded to three scientists fruitfully working in bioenergetics. J. Walker and P. Boyer were awarded the Prize for studies of structure and mechanism of functioning of the H+-transporting (mitochondrial) adenosine triphosphatase. The decision of the Nobel Committee was not unexpected, since these works were very impressive. Special attention was drawn to the fact that the investigations of Walker, the recognized specialist in protein structure, made possible the experimental confirmation of regularities in the mitochondrial ATPase functioning discovered by P. Boyer. The third member of this triumph of bioenergetics is Jens-Christian Skou who described the Na+,K+-activated ATPase in 1957 and then characterized the enzyme properties in detail. Forty years of his scientific biography were devoted to this enzyme. Along with accumulation of scientific knowledge, that constituted the fundamental contribution to bioenergetics (J.Skou is rightfully considered as one of founders of this branch in the present-day biology), the world-wide known school of scientists was established, and starting from 1974, members of this school organize regular conferences on this enzyme.

Biochemistry↗

[Guidelines for antiarrhythmic therapy].

Recentry, therapies for arrhythmias have been extremely advanced by accumulation of electrophysiological knowledge, improvement of diagnostic technique, and development of antiarrhythmic drugs and devices(pacemakers, catheter ablation and implantable cardioverter-defibrillators). After the report of the CAST(Cardiac Arrhythmia Suppression Trial), the Sicilian Gambit was presented as new strategies of drug therapy. Now in the United States, three AHA guidelines were published. Besides in Japan 'the guidelines for antiarrhythmic drugs' based on the Sicilian Gambit was published. 'The guidelines for management of Atrial fibrillation' and 'the guidelines for antiarrhythmic devices' were also reported. Here, these guidelines are reviewed.

Anti-Arrhythmia Agents↗

Networking between occupational health services, client enterprises and other experts: difficulties, supporting factors and benefits.

This study explores difficulties, supporting factors and benefits of networking to studied enterprises and other network partners (focus on OHS and client enterprises). The study also explores social capital as a resource produced in network relations, and trust as a core dimension of social capital, and trust as a binding element in networking. The study is a mixed methods research (both qualitative and quantitative research materials). The most important supporting factors were: committed and active focus person, teamwork skills, long relationships, familiarity, trust and two-way communication in co-operation, shared goals, norms and values, an equal cost and benefit ratio, and the high quality of services. The biggest problems were the lack of skills to operate in the network and difficulties in maintaining the network, weak communication, lack of confidence, inconvenient size or composition of the network, overlapping information, cliques, nodes and missing links. The benefits were versatile: knowledge and skills accumulate, the network multiplies resources, fluency of co-operation, innovations, commitment and trust increase, good practices expand, and moreover, the quality, many-sidedness and appropriateness of operations improve. Networking is beneficial but demanding. There are many limitations. Networks are not equal for every network partner (inequality in cost and benefit ratio). Networks produce social capital for participants. Successful networking requires trust relations between network partners.

Cooperative Behavior↗

Systemic inflammatory response to exhaustive exercise. Cytokine kinetics.

It has been documented that strenuous exercise not only induces pyrogenesis but also elicits mobilization and functional augmentation of neutrophils and monocytes whereas it suppresses cellular immunity leading to increased susceptibility to infections. As mediators of these phenomena, cytokines released into the circulation have been a recent focus of attention. Indeed, there are as many as one hundred original reports concerning exercise and cytokines, and half of them have been published in rapid succession from 2000, resulting in a tremendous accumulation of new knowledge within such a short term. The first aim of this review is to comprehensively summarize previous studies on systemic cytokine kinetics following exercise, with a special focus on reproducibility and quantitative comparison in human studies using specific immunoassays. Although tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta have traditionally been understood to be the main inducer cytokines of acute phase reactions, the majority of studies have shown that the circulating concentration of these cytokines is either unchanged following exercise, or exhibits relatively small, delayed increments. Plasma interferon (IFN)-alpha and IFN-gamma do not appear to change following exercise, whereas IL-2 decreases after endurance exercise. The small changes of these proinflammatory and immunomodulatory cytokines could well be mediated by anti-inflammatory cytokines such as IL-1 receptor antagonist (IL-1ra), IL-6 and IL-10 and cytokine inhibitors (cortisol, prostaglandin E2 and soluble receptors against TNF and IL-2), which are known to increase markedly in the circulation following endurance exercise. Moreover, it has been recently demonstrated that endurance exercise induces systemic release of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), IL-8 and monocyte chemotactic protein 1 (MCP-1). Although the majority of available data have been obtained following prolonged exercise, it remains to be elucidated whether short-duration intensive exercise also causes rapid systemic cytokine release. In addition, there have been few studies that have simultaneously compared the extent of each cytokine response to exercise from a wider perspective. The second aim of this study was to examine possible changes of not only plasma but also urine concentrations of a broad spectrum of cytokines (16 kinds) following maximal exercise, including the time course of recovery. Although plasma TNF-alpha could not be detected throughout, it was present in urine 2 h after exercise. Plasma IL-1 beta rose significantly 2 h after exercise, but plasma IL-1 ra increased more rapidly and markedly than IL-1 beta, thus IL-1 bioactivity should be blocked at least in the circulation. Although there was only a trend toward increased plasma IL-6 concentrations after exercise, urine IL-6 rose significantly 1 h after exercise, indicating that IL-6 was released systemically but eliminated rapidly into the urine. Furthermore, it is shown for the first time that plasma and urine IL-4 concentrations were significantly elevated 2 h after exercise. Therefore, it is possible that anti-inflammatory cytokines might be released into the circulation as a regulatory mode of the cytokine network for adaptation against systemic inflammatory stress. Additionally, we have demonstrated that plasma concentrations of G-CSF, granulocytemacrophage CSF (GM-CSF), M-CSF, IL-8 and MCP-1 increased immediately after short-duration exercise and that the urine concentrations of these cytokines were much more pronounced than the changes observed in plasma. In conclusion, cytokines that are considered to induce systemic bioactivity following exercise are not only anti-inflammatory cytokines but also colony-stimulating factors and chemokines, which were secreted in an earlier phase of exercise without the kinetic involvement of traditional proinflammatory cytokines. Although the wider physiological and pathological implications are still not clearly understood, these cytokine kinetics may partly explain suppressed cell-mediated immunity and increased allergic reactions derived from a lower type-1 to type-2 cytokine ratio, along with mobilization and functional augmentation of neutrophils and monocytes. The sources and stimuli of cytokine production are not fully elucidated at present, but several hypotheses based on recent experimental evidence are discussed in this review herein.

Anti-Inflammatory Agents↗

Pathophysiology and clinical relevance of Helicobacter pylori.

Considerable knowledge has recently accumulated on the mechanism by which Helicobacter pylori (H. pylori) induces chronic gastritis. Although H. pylori is not an invasive bacterium, soluble surface constituents can provoke pepsinogen release from gastric chief cells or trigger local inflammation in the underlying tissue. Urease appears to be one of the prime chemoattractants for recruitment and activation of inflammatory cells. Release of cytokines, such as tumor necrosis factor alpha, interleukin 1 and 6, and oxygen radicals, leads to a further tissue inflammation accompanied by a potent systemic IgA and IgG type of immune response. Chronic inflammation and antigens on glandular epithelial cells lead to a progressive destruction with loss of the epithelial barrier function. Within the gastric mucosa, patches of intestinal metaplasia develop, which may be a risk factor for subsequent development of gastric carcinoma. Hyperacidity in duodenal ulcer patients induces gastric metaplasia in the duodenal bulb, which represents a target for H. pylori colonization and ulcer formation. H. pylori can be detected in the majority of patients with peptic ulcers and, compared to age-matched healthy people, it is also found more often in patients with dyspepsia and gastric carcinoma. Although H. pylori can be detected in healthy people, the marked reduction of the ulcer recurrence rate by eradication of H. pylori (80 percent versus 20 percent relapse within one year) suggests that H. pylori is a major risk factor for duodenal ulcer formation. The potential role of H. pylori in non-ulcer dyspepsia and carcinogenesis is under investigation. Current regimens aimed at eradicating H. pylori use a combination of several drugs that are potentially toxic. Since the risk of complications may exceed the potential benefit in most patients, eradication treatment should be limited to clinical trials and to patients with aggressive ulcer disease. New drug regimens, e.g., the combination of proton pump inhibitors with one antibiotic, may provide less toxic alternatives. Beyond ulcer treatment, effective and well-tolerated eradication regimens may have a place in prophylaxis of gastric carcinoma.

Gastritis↗

Suicidal behavior of adolescent girls: profile and meaning.

In the last two decades the incidence of adolescent suicides has been very high (though it has been on the decrease in the U.S.A. over the last four years), giving rise to a multitude of empirical and theoretical studies. The extensive knowledge that has accumulated regarding adolescent suicidal behavior has led to a more differentiated attitude. Many studies try to clarify specific needs, motivations and the conceptualization of death and suicide in various adolescent subgroups (minorities, females, homosexuals), thereby enabling more specific and exact methods of evaluation, prevention and intervention. Adolescent girls' suicidal behavior is different in many aspects from boys' suicidal behavior: Girls mortality rate from suicide is a 3-5 times lower rate than boys, but their attempted suicide rate is four to hundreds time higher. Girls suicide mainly by drugs and their suicide is mainly in reaction to interpersonal difficulties. Their motivation is often a cry for help. The comorbidity of suicide and depression is much higher for adolescent girls than boys. These differences generate a different understanding and separate treatment strategies. Two theoretical approaches that may explain the profile which characterizes suicidal girls will be presented. One has a psychological developmental context, and the other a social cultural context. Implications for specific prevention measures include legal action on pack sizes of analgesics, compulsory registration of attempted suicide and more gender specific treatment and prevention programs.

Adolescent↗

[Neuropsychology of attention deficit hyperactivity disorder: relevant theories and empirical studies].

There is a rapidly accumulating body of knowledge related to the neurobiology of Attention Deficit Hyperactivity Disorder (ADHD) stemming from multidisciplinary neuropsychological and neuroimaging studies. This paper is a review of recent knowledge in the context of neuropsychological theory and research in this area. The final section of the article introduces animal models on the subject. It has been emphasized that the controversy regarding the results of neuropsychological studies is semantic rather than substantive. The semantic issue here is believed to be that the term "attention" has to be related to more than one anatomical network among several brain regions. ADHD, which has many cognitive and behavioral dimensions like attention deficit, hyperactivity and impulsivity, has a heterogeneous nature reflecting the neurobiological basis related to parallel information processing models. Based on clinical and neuropsychological data it has been stated that both the orbitofrontal cortex and dorsolateral prefrontal cortex are functionally disturbed in ADHD. However, whether these functional disturbances are related to the prefrontal cortex or other brain regions associated however primarily with this cortex is yet unclear. Dopamine and epinephrine as neurochemical factors and the frontal lobe and basal ganglia as anatomical factors have been found to be especially responsible. Valid endophenotypic features should be determined in order to specify genetic subtypes of neuropsychiatric syndromes. A review of the literature leads us to the conclusion that tests used to assess attentional components like the executive control network and behavioral inhibition could determine valid endophenotypes.

Animals↗

[Clinical experience of laparoscopic adrenalectomy: the National Defense Medical College experience].

Twenty-seven laparoscopic adrenalectomies (LapAdx) were performed at the National Defense Medical College between 1999 and 2004. We evaluated the results of LapAdx (group L) compared to the results of open adrenalectomy (group O). Twenty-six of the 27 LapAdx were successfully performed, but one patient with a large pheochromocytoma required open surgey because of arterial bleeding in the renal hilus. The mean operating time in group L (185 +/- 19 min) was not significantly different from that in group O (206 +/- 13 min). The mean estimated blood loss in group L (111 +/- 61 g) was significantly lower than that in group O (308 +/- 67 g). The starting time for oral feeding and for ambulation was significantly earlier in group L than in group O. There was a major complication (intraoperative bleeding) in which a group L patient required a blood transfusion. We also compared the surgical results of 26 patients in LapAdx divided chronologically into the first half and the last half to determine the surgical skill acquired. The operating time was significantly shorter and blood loss significantly less for patients in the last half. In addition, the operating time and blood loss for the first-time LapAdx operators were comparable with those of experienced surgeons. Our results support the efficacy and the minimal invasiveness of LapAdx. The accumulated experience and knowledge regarding laparoscopic surgery in our institute were important in improving surgical procedures and results.

Adrenal Gland Neoplasms↗

[Gastric cancer].

To prove the efficacy of adjuvant therapy for curatively resected advanced gastric cancer, large-scale randomized control trials are necessary based on the idea of EBM (Evidence Based Medicine). We had a long history of adjuvant therapy and many trials were conducted so far. However, many problems were also pointed out in past trials, even in the several trials with positive results. After accumulation of the knowledge of a good clinical trial, we started to organize study groups like JCOG (Japan Oncology Group) for high-quality clinical trials in Japan. The positive result of the National Surgical Adjuvant Study of Gastric Cancer (N. SAS-GC) is encouraging after the long period of negative results from adjuvant trials. This trial was well designed randomized clinical trial (RCT) with statistically significant difference of survivals,which suggest the efficacy of the adjuvant chemotherapy with UFT. However, because of the reduced sample size of this trial, we need one more trial with sufficient sample size to prove the efficacy of adjuvant chemotherapy for gastric cancer as the definitive evidence.

Antineoplastic Combined Chemotherapy Protocols↗

Computerized neuropsychological examination of impulsiveness: A selective review.

There is a rapidly accumulating body of knowledge related to the neurobiology of impulsiveness from multidisciplinary neuropsychological and neuroimaging studies. This paper reviews recent research on impulsiveness in the context of neuropsychological theory and research. It has been emphasized that the controversy regarding the results of neuropsychological studies is related to different aspects of impulsiveness. The term "impulsivity" is related to more than one anatomical network among several brain regions. Impaired inhibition control, which has cognitive and behavioral dimensions, has a heterogeneous nature. Analysis of performance suggests that impulsivity includes three cognitive mechanisms: "prepotent inhibition," "interruptive inhibition" and "interference control,' each having separate neurological bases. Based on neuropsychological data it has been stated that both the orbitofrontal cortex, dorsolateral prefrontal cortex and anterior cingulate cortex are functionally disturbed among impulsive individuals. Bringing together knowledge from clinical experience, neuroimaging examination and neuropsychological assessment will lead to better and wider understanding of behavioral symptoms in clinical psychiatric practice.

Anxiety Disorders↗

Chronic infections and autoimmunity.

The studies summarized in this chapter indicate that chronic bacterial, viral, and parasitic infections can serve as a trigger factor of autoimmune reactivity according to various mechanisms. The relationship between microbes and autoimmunity could be manifested by the presence of autoantibodies, autoimmune complexes, or T cells with autoactivity. The presence of autoimmune phenomena in chronic infections could be related to polyclonal B-cell activation, molecular mimicry between microbial and host antigens, altered self, abnormal expression of immunoregulatory molecules, and the anti-idiotypic network. In most cases, the appearance of self-reactivity in the sera of patients with chronic infections is not associated with clinical manifestations. These findings suggest that autoimmune disease is the result of a combination of factors including immunologic, genetic, hormonal, and environmental. Infectious agents have a role in the breakdown of tolerance and the appearance of autoreactivity. However, only patients with the proper immunogenetic and hormonal background may develop clinical manifestations of autoimmune disease. In spite of the extensive knowledge that has accumulated, the specific relationship between infections and autoimmunity is still obscure. Clearly, additional studies are required to clarify the relevance of microbes to the pathogenesis of autoimmune diseases.

Acquired Immunodeficiency Syndrome↗

[Cervical cancer].

Although the surgical treatment for the uterine cervical carcinoma has been accepted as until recently one of the most effective therapies in terms of radicality, various complications following the operation have tormented patients for a long time, resulting in the deterioration of the quality of their lives. The complications include a loss or an impairment of fecundability, morbidities due to the castration, problems of sexual life, urinary disturbances such as dysuria, incontinence and a loss of feeling of urgency, renal dysfunction, persistent constipation and lymphedema on legs. The serious psychological handicaps are included also. During many years, however, the accumulation of the knowledge which is related to a development of the cancer, recognition of the localisation and an extent of the lesion and prognostic factors, has encouraged the developments of improved methods to keep the essential physiological functions and avoiding a loss of radicality. Those are a laser therapy, retaining of ovaries and preservation of pelvic autonomic nerves including bladder branches. Here, indications, methods and the clinical results of those improved surgical methods are presented and the problems remaining to be resolved are discussed.

Female↗