Progress in the study of brain evolution: from speculative theories to testable hypotheses

Darwin's theory of evolution raised the question of how the human brain differs from that of other animals and how it is the same. Early students of brain evolution had constructed rather grand but speculative theories which stated that brains evolved in a linear manner, from fish to man and from simple to complex. These speculations were soundly refuted, however, as contemporary comparative neurobiologists used powerful new techniques and methodologies to discover that complex brains have evolved several times independently among vertebrates (e.g., within teleost fishes and birds) and that brain complexity has actually decreased in the lineages leading to modern salamanders and lungfishes. Moreover, the old idea that brains evolved by the sequential addition of new components has now been replaced by the working hypothesis that brains generally evolve by the divergent modification of preexisting parts. Speculative theories have thus been replaced by testable hypotheses, and current efforts in the field are aimed at making phylogenetic hypotheses even more testable. Particularly promising new directions for comparative neurobiology include (1) the integration of comparative neuroanatomy with comparative embryology and developmental genetics in order to test phylogenetic hypotheses at a mechanistic level, (2) research into how evolutionary changes in the structure of neural circuits are related to evolutionary changes in circuit function and animal behavior, and (3) the analysis of independently evolved similarities to discover general rules about how brains may or may not change during the course of evolution.     

Expression and function of endothelial cell alpha v integrin receptors in wound-induced human angiogenesis in human skin/SCID mice chimeras

Accumulating evidence indicates that endothelial cell integrins that bind to the matrix proteins associated with inflammation and wound healing are involved in the process of angiogenesis. The integrins containing the alpha v subunit appear to be particularly important. To study the involvement of these receptors in human angiogenesis, a model of wound-associated human angiogenesis was established in human skin transplanted onto severe combined immunodeficient (SCID) mice. Using this model, we studied the expression of several alpha v integrins and tested the hypothesis that blockage of the alpha v beta 3 integrin would inhibit human angiogenesis during human wound healing. These studies revealed that the alpha v beta 3, alpha v beta 5, and alpha v beta 6 integrins are up-regulated briefly during wound angiogenesis with different patterns of expression and that inhibition of the alpha v beta 3 integrin blocked new vessel formation during human wound healing.     

Family and individual therapy in anorexia nervosa. A 5-year follow-up

The high prevalence of premature attrition from psychotherapy is a phenomenon which has been well recognized in the psychological literature. The pressing concern that a number of clients may not be benefiting from treatment because they are dropping out has led to a plethora of research in the area of individual psychotherapy. No studies, however, have attempted to investigate the characteristics of dropout in group cognitive behaviour therapy for depression. To address this gap in research, the present study examined the factors associated with dropout in a group cognitive behaviour therapy for depression, using 131 Ss who went through the group therapy for 12 weeks. The results showed that sociodemographic measures (e.g. age) and measures of depressive symptoms (e.g. depression scores) did not discriminate dropouts from completers. An investigation of patterns of mood changes in the course of the therapy also failed to find significant differences between the dropouts and completers. However, weekly therapist rating of client participation revealed that dropouts participated significantly less than completers during the therapy sessions. The results are discussed in light of the findings of current literature and future research in premature attrition.     

Apparatus and methods for studying artificial feedback-control of the plantarflexors in paraplegics without interference from the brain

Apparatus has been built to explore the practical feasibility of using automatic control with electrical stimulation of paralysed legs to restore function. The experiments are performed with paraplegics with the aim of achieving a realistic postural task: to see whether the body may be maintained upright by stimulation of the plantarflexors when the other joints are braced. Significantly, the intact upper body, under natural control of the brain, cannot interfere with the automatic control. The "Wobbler" apparatus allows measurement of the ankle muscle properties in isometric conditions or in sinusoidal motion. Using the biomechanical properties of the body, which are also measured, controllers for stabilising the body can be designed. Controllers can be dynamically tested, imitating anterior-posterior sway, while the body is held upright, before "actual standing" is attempted.     

Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy

Aberrant glycosylation is a hallmark of cancer cells. The blood group precursors T (Thomsen-Friedenreich) and Tn epitopes are shielded in healthy and benign-diseased tissues but uncovered in approx. 90% of carcinomas. T and Tn glycoproteins are specific, autoimmunogenic pancarcinoma antigens. These antigens may also be found in neoplastic blood cells (and on LTV-II infected T lymphocytes). Fundamental chemical and physical aspects of these glycoproteins of primary carcinomas are discussed first. Tn and T epitopes are cell and tissue adhesion molecules, essential in invasion by and metastasis of carcinoma which includes adherent and proliferative phases. These properties are then delineated next, followed by consideration of pathophysiological and clinical aspects of these antigens. Immunohistochemical studies of the extent of Tn antigen expression in primary breast carcinoma demonstrate it highly significant correlation with clinicopathological tumor stages, and hence its value as a reliable prognosticator. On the other hand, there is no significant, prognostically useful association between T antigen expression and clinical disease course. Everyone has "preexisting" anticarcinoma anti-Tn and anti-T antibodies, induced predominantly by the intestinal flora, while cellular immune responses to T and Tn epitopes are evoked only by carcinomas and some lymphomas. Carcinoma dedifferentiation leading to predominance of Tn over T epitopes is described, as is the role of Tn and T epitopes in very early, including preclinical, carcinoma detection. The highest sensitivities in carcinoma detection are for preclinical and the earliest clinical stages. Obviously, preclinical carcinoma detection is of practical importance. T/anti-T tests detected preclinical carcinoma in 77% of 48 patients long (mean 6 years) before their biopsy/X-ray results became positive. There were no false predictions of carcinoma in 38 control persons with benign diseases (observation average 4.8 years). These findings open a novel window for both curative approaches and pathophysiological studies. The autoimmunogenicity of carcinoma T/Tn antigen led us more than two decades ago to begin intradermal vaccination of patients with advanced breast carcinoma of stages IV-IIb, predominately after modified radical mastectomy and sometimes lumpectomy plus axillary dissection always followed by adjuvant radio/chemotherapy. The vaccine consists of human group O red blood cell membrane derived, HLA-free T/Tn antigen containing as adjuvant Ca3(PO4)2 plus a trace of phosphoglycolipid A hyperantigen, i.e., S typhi vaccine (USP), which itself has T and Tn specificities. Our efforts have now for up to 20 years remained successful in a large majority of the 32 patients. All 32 patients survived at least 5 years; 10-year survival was statistically highly significantly improved (5-year survival: P < 1 x 10(-7); 10-year survival: P < 1 x 10(-5)) compared to statistics of the United States National Cancer Institute. Because these vaccinations are successful, their extension to large populations with major types of carcinomas should be considered, and even immunological carcinoma prevention may be contemplated.     

Anxiety and depression in adult untreated celiac subjects and in patients affected by inflammatory bowel disease: a personality "trait" or a reactive illness?

BACKGROUND/AIMS: Psychiatric illness and psychological behavioral pathologies may be present in celiac disease and in IBD patients. In these subjects anxiety and depression could be a main cause in the reduction of the compliance to the treatment. Aim of our study was to carry out a psychometric evaluation using appropriate means to determine the level of anxiety and depression and to distinguish between "state" and "trait" forms. The correction of such disturbances would improve the quality of life and the patients' compliance to treatment. MATERIAL AND METHODS: Sixteen adult celiac patients, 16 subjects affected by IBD and 16 healthy control subjects matched for sex, residence and marital status were studied by psychological assessment. All the subjects were given the State and Trait Anxiety Inventory and the Ipat Depression Scale Questionnaire. RESULTS: State anxiety was present in a higher percentage of celiac subjects and in the patients affected by IBD with respect to the healthy controls. Anxiety as a trait was present in a similar percentage in all the subjects evaluated. Depressive syndrome was present in a percentage of celiac patients statistically superior versus the healthy control group (p < 0.01). CONCLUSION: Our results shown that anxiety is present as a "reactive" form and personality trait anxiety has no effect in celiac and IBD patients. As regard depression, our data confirm a possible linkage between brain functions and malabsorption.     

The classification of and identification methods for bifidobacteria and lactobacilli

Overall thirty-eight patients with exertional angina who had episodes of asymptomatic change of position of T-segment were examined. The above patients were divided into two groups: group I was placed on anaprilin treatment (80-120 mg daily), group II received corinfar (60 mg daily). Episodes of asymptomatic ischemia of the myocardium (AIM) showed two peaks in their 24 h-span occurrence, with the greatest number of these being recordable in early morning hours (from six a.m. to noon), somewhat less--within the time span 12 o'clock-0.6 p.m. Anaprilin monotherapy is more effective than corinfar monotherapy in respect to reduction of AIM episodes occurrences. However, corinfar, unlike anaprilin, prevented the appearance of the evening peak of episodes of "silent" ischemia.