MIB-1 proliferation index predicts survival among patients with grade II astrocytoma.

The purpose of this study was to determine whether a relationship existed between MIB-1 labeling index (LI) percentages and survival in patients with grade II astrocytomas. From archival paraffin-embedded surgical specimens of 50 patients of the University of Michigan Medical Center with World Health Organization grade II astrocytomas, 22 patients had a Ki-67 LI of less than or equal to 2.0; and 28 patients had a MIB-1 LI of more than 2.0. Over a median follow-up interval of 10 years, ranging up to 16 years, 23% (n = 5) died of tumor in the first group while 82% (n = 23) died in the second group, a distinct difference in survival between these groups. Univariate analysis showed that a high MIB-1 predicted shorter survival (p < 0.0001), and that increased age was associated with shorter survival (p = 0.007). Gender, tumor location and radiotherapy had no significant association with survival. When adjusting for these (excluding tumor location) in the Cox proportional hazards model simultaneously, MIB-1 and age were independently prognostic. The hazard ratios were 1.301 per 1% MIB-1 LI (p = 0.0001), and 1.045 per year of age (p = 0.0028). From other studies, we know that histopathologic grade and age predict survival for glioma patients. However, even within grade II astrocytomas there is still a wide heterogeneity in how long a patient survives. We conclude that among grade II astrocytomas older patients and, independently, patients with higher MIB-1 labeling index have shorter survival.

Leptin stimulates fetal and adult erythroid and myeloid development.

The ob gene product, leptin, has been shown in several studies to be involved in weight control and recombinant leptin recently has entered clinical trials to treat obesity. The leptin receptor (OB-R/B219) is expressed in a variety of protein isoforms not only in the central nervous system, but also in reproductive, and hematopoietic tissues. We reported recently that the OB-R/B219 was associated with a variety of hematopoietic lineages as well as the small fraction of cells containing the long-term reconstituting hematopoietic stem cells. Herein we report that leptin significantly stimulates the proliferation and differentiation of yolk sac cells and fetal liver cells and stimulates directly hematopoietic precursors. Leptin alone can increase the number of macrophage and granulocyte colonies, and leptin plus erythropoietin act synergistically to increase erythroid development. These data show that leptin has a significant, direct effect on early hematopoietic development and can stimulate the differentiation of lineage-restricted precursors of the erythrocytic and myelopoietic lineages. These observations along with a recent report strongly support our previous hypothesis that leptin has an unanticipated important role in hematopoietic and immune system development.

Growth factors and hematopoietic stem cells.

The hematopoietic system is mediated in part by cell-to-cell interactions and soluble mediators or growth factors (cytokines). A large number of cytokines directly and potently control hematopoietic stem and precursor cell proliferation and differentiation. This review focuses on the recent studies devoted to the role of cytokines in the ex vivo expansion and differentiation of hematopoietic stem and precursor cells.

Retention and acquisition of classical trace conditioned responses by rabbits with hippocampal lesions.

The effects of dorsal hippocampal lesions on retention of classical trace conditioned responses were examined using the rabbit nictitating membrane preparation. Animals were trained to criteria and then lesioned either in the cortex or in the hippocampus and the cortex. Hippocampal damage had no effect on the retention of responses but produced significantly longer onset latencies. A control group of hippocampal animals acquired conditioned responses (CRs) at least as quickly as the prelesion subjects, and they also exhibited longer response onset latency. A second experiment evaluated the performance of hippocampal lesioned animals in classical trace conditioning with either a low-intensity periorbital shock or corneal air puff as the unconditioned stimulus (UCS). Hippocampal animals successfully acquired CRs under both conditions but exhibited an alteration of response onset which was dependent on the form of the UCS. Hippocampal animals displayed shorter response onset in the air-puff condition and longer response onset in the shock condition. Cortical animals timed responses consistently regardless of the UCS. These findings strongly suggest that the hippocampus modulates temporal characteristics of learned behavior.

Failure of hippocampectomy to facilitate classical conditioning at an optimal interstimulus interval is not due to a "ceiling effect".

The effects of amphetamine injection, hippocampal lesions, and cortical lesions were examined during classical conditioning of the rabbit nictitating membrane response. An optimal interstimulus interval was employed. Whereas neocortical and hippocampal damage had no significant effect on the rate of acquisition, amphetamine treatment produced a marked facilitation. A control group of amphetamine-treated animals, which received explicitly unpaired presentations of the conditioned stimulus and unconditioned stimulus, failed to exceed spontaneous response rates throughout training. The failure of hippocampectomy to accelerate conditioning under an optimal interstimulus interval (ISI) does not appear to be due to a "ceiling effect." Rather, it was suggested that the response system is predisposed to conditioned responses of a given latency. Optimal ISIs may fall within this range. Thus, in short or long intervals, temporal aspects of the motor response must be adjusted to conform to the stimulus configuration. It appears that the hippocampus is a likely source of response modulation. Thus, loss of hippocampal input accelerates conditioning under nonoptimal intervals at the expense of proper timing. Conditioning under an optimal interval would occur at normal rates because no modulation is required.

Differential effects of hippocampectomy on classically conditioned rabbit nictitating membrane response related to interstimulus interval.

The effects of hippocampal ablation on acquisition rates and temporal characteristics of classically conditioned nictitating membrane responses were examined in groups of rabbits trained with a 150-, 300-, or 600-ms interstimulus interval. Acquisition rates were accelerated in the 150- and 600-ms groups. No effect was present in the 300-ms group. Response onset latencies were also affected in the 150-ms group. These findings were interpreted to support the notion that the hippocampus modulates learned motor behavior by a neural model of the response to be executed.

Ulcer reduction by non-nutritive bulk in pylorus ligated rats.

The effects of solid non-nutritive diet on pylorus-ligation ulcers were tested. An experimental group of 16 rats received a bulky mixture of silica and methylcellulose during 48 hr prior to ligation. Control rats were food deprived for the same period of time. A multivariate analysis of variance was applied to nine measures of the study. It was found that rumenal ulceration and total acidity were lower in experimental animals than in controls. This finding confirms a previous observation indicating that the physical property of diet has antiulcerogenic effects.

Synthesis of substituted benzoquinones and naphthoquinones with potential antituberculous activity.

Compounds were prepared through the reaction of benzoquinone, naphthoquinone and 2-methyl-1.4-naphthoquinone with several sulphonamides in common use. It is hoped that incorporation of these bacteriostatic agents with the high lipid solubility of the quinone used may afford a better bacteriostatic activity. Determination of the partition coefficient of some representative samples proved these compounds to have high lipid solubility.