Does schizophrenia result from developmental or degenerative processes?

The debate as to whether schizophrenia is a neurodevelopmental or a neurodegenerative disorder has its roots in the latter part of the 19th century when authorities such as Clouston (1891) posited that at least some insanities were "developmental" in origin. These views were soon eclipsed by Kraepelin's (1896) concept of dementia praecox as a degenerative disease, and the latter view carried not only the day but also much of the 20th century. Then, in the 1980s several research groups again began to speculate that schizophrenia might have a significant developmental component (Feinberg, 1982-1983; Schulsinger et al., 1984; Murray et al., 1985; Murray and Lewis, 1987; Weinberger et al., 1987). What became known as the "neurodevelopmental hypothesis" received support from neuropathological studies implicating anomalies in early brain development such as aberrant migration of neurons. Unfortunately, these studies proved difficult, if not impossible, to replicate (Harrison, 1999). The pendulum, therefore, began to swing again, and in the latter part of the 1990s came renewed claims that the clinical progression of the illness was accompanied by continued cerebral ventricular enlargement and reduction in the volumes of certain brain structures. Nevertheless, since few doubt that there is a developmental component to schizophrenia, the question which we will address in this paper is whether schizophrenia is a) simply the final consequence of a cascade of increasing developmental deviance (Bramon et al., 2001), or b) whether there is an additional brain degeneration following onset of psychosis which is superimposed on the developmental impairment (Lieberman, 1999).     

Extranodal marginal zone B-cell lymphoma genotyping by Alu-polymerase chain reaction

DNA amplification by polymerase chain reaction (PCR) with primers designed on the widely distributed Alu sequences allows the production of specific inter-Alu DNA-fingerprints. Amplification of tumour and matched normal DNA can show differences due to genetic alterations within the tumour genome. We applied this approach to study low-grade extranodal marginal zone B-cell lymphoma (of MALT type). After digestion with restriction enzymes, DNA samples were separately amplified by PCR with three different Alu-primers. A comparison between the fingerprint pattern from lymphoma and normal samples was made. Inter-Alu bands differing between the two samples were excised from the gel, cloned and sequenced. Nine cases of low-grade MALT-lymphomas have been analysed, giving seventeen different bands between tumour and normal. DNA sequence analysis showed identities for three of them with sequences available at the GenBank. The methodology of Alu-PCR to detect DNA-based abnormalities, in addition or combination with RNA-based methods, is a powerful tool to identify candidate regions frequently altered in tumours. With the increased available genomic sequences through the Human Genome Project, there will be an increasing probability of picking up perfect homologies with these sequences using cloned differential Alu-PCR bands in BLAST searches through genome databases.     

Oxygen,carbon dioxide,and hydrogen ion concentration in arterial and uterine venous blood of pregnant goats

Using indwelling plastic catheters, blood samples were drawn from an artery and a uterine vein of unanesthetized pregnant goats at selected stages in gestation. Oxygen and carbon dioxide contents, pH, and oxygen capacity were determined on the samples. The coefficient of oxygen utilization by the uterus increased from 9 per cent early in gestation to 25 per cent in the last third of the gestation period of 145 to 147 days. The CO₂ tension of the arterial blood ranged between 25.1 and 31.9 mm. Hg (average, 28.6) and the pH was 7.32 to 7.49 (average, 7.41).     

The effect of two dietary and a synthetic phytoestrogen on transepithelial calcium transport in human intestinal-like Caco-2 cells

Summary Background Recently, dietary phytoestrogens (PEs) have been suggested as possible alternatives to estrogen therapy, as a means of preventing bone loss associated with ovarian hormone deficiency. PEs are non-steroidal, plant-derived compounds that exhibit some estrogen-like activity in some tissues, and which appear to prevent postmenopausal bone loss. While PEs act directly on bone cells, their protective effect on bone may be partly due to their ability to enhance Ca absorption. Aim of the study Therefore, the aim of this study was to investigate the effect of two dietary PEs (coumestrol and apigenin) as well as a synthetic PE, ipriflavone, on Ca absorption in human Caco-2 intestinal-like cells. Methods Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On d 21, the Caco-2 monolayers (n 10–16 per treatment), grown in estrogen-free or low-estrogen media, were then exposed to 10 nM-1,25 (OH)₂ D₃, or 50 µM ipriflavone, -coumestrol or -apigenin for 48 hours. After exposure, transepithelial and transcellular transport of ⁴⁵Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Results As expected, 1,25 (OH)₂ D₃ stimulated Ca absorption. Treatment with coumestrol or apigenin had no effect on Ca transport. On the other hand, ipriflavone increased total Ca transport (by about 1.5-fold, P < 0.05) under lowestrogen conditions, but not under estrogen-free conditions. This increase in total Ca transport by ipriflavone was via an increased transcellular Ca transport (by about 2-fold, P < 0.05) relative to control. Conclusion In conclusion, the protective effect of dietary PE on bone mass would appear to be due to their direct effect(s) on bone cells, as opposed to an indirect effect on bone by stimulation of intestinal Ca absorption.