Allelic loss of chromosome 6q in gastric carcinoma.

Loss of the long arm of chromosome 6 (6q) has frequently been reported in gastric carcinoma, and most gastric cancer patients have evidence of intestinal metaplasia in the stomach. However, the relationship between loss of chromosome 6q and intestinal metaplasia has not been studied. In the first part of the study, we define the critical deletion region of chromosome 6q using loss of heterozygosity technique (LOH). Seventeen microsatellite markers were used to detect loss of heterozygosity (LOH) in 37 microdissected gastric tumors. We also examined intestinal metaplasia (IM) foci of the stomach in the same cancer patient (17 cases). Losses on chromosome 6q were detected in high frequency (51%) by LOH. Two distinct regions of common allelic loss were identified: one centered on the marker D6S300 (at 6q16.1) and the second on D6S446 (at 6q27), with LOH frequency of 36% and 31.3%, respectively. The deletions fall into 2 discrete regions, suggesting the existence of at least 2 tumor suppressor genes in 6q. The losses at 6q27 were confirmed by fluorescence in situ hybridization study (FISH). In the cases with LOH in the tumor, no LOH were detected in the autologous IM areas, but losses were detected by FISH. In some cases, these genetic changes may be acquired in the transition from normal gastric mucosa to intestinal metaplasia.     

Fluoxetine and 8-OH-DPAT in the lateral septum enhances and impairs retention of an inhibitory avoidance response in rats.

The present study investigated the role of lateral septal serotonin (5HT) in memory consolidation and the subtype of 5HT receptors involved in this process. Rats with cannulae implanted bilaterally into the lateral septum were trained in an inhibitory avoidance task. Immediately after training, the septal serotonergic function was manipulated by pharmacological agents selectively blocking 5HT reuptake (fluoxetine and zimelidine), antagonizing 5HT2 receptors (ketanserin and ritanserin), or activating 5HT1A receptors, respectively. Results indicated that direct fluoxetine infusions into the lateral septum at a dose of 6 micrograms/0.5 microliter and zimelidine at a dose of 5 micrograms/0.5 microliter both markedly enhanced memory. Intralateral septal injections of ketanserin (0.3 microgram/0.5 microliter and 0.5 microgram/0.5 microliter) and ritanserin (0.3 microgram/0.5 microliter and 0.6 microgram/0.5 microliter) did not have a significant effect by themselves on memory, and neither did they attenuate the memory-facilitating effect of fluoxetine in the same area. Intralateral septal infusions of 8-hydroxy-2-(di-n-propylamino)tetralin at 5 micrograms/0.5 microliter significantly impaired memory retention. These findings altogether support the notion that the lateral septal nuclei of rats are involved in the memory processes of inhibitory avoidance learning. Furthermore, postsynaptic 5HT receptor activation (not the 5HT2 receptor subtype) probably exerts a facilitatory effect while presynaptic 5HT1A receptor activation exerts an impairing effect on the memory consolidation process, probably due to autoreceptor inhibition of 5HT release.     

Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome?

A number of systemic abnormalities associated with cholestasis have been reported in the literature. This paper describes two unrelated patients with cholestasis and an unusual constellation of abnormalities including cleft palate/lip, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum.     

Comparative analysis of the NS 1 gene sequences of dengue-1 viruses prototype Hawaii strain and Thai isolate TH-Sman,and determination of the intratypic variation of NS 1 protein among dengue-1 viruses

Summary In view of a previous report on significant antigenic and biophysical differences between the purified soluble complement-fixing antigens of dengue-1 virus strains Hawaii and TH-Sman, the NS 1 genes of both virus isolates were cloned, sequenced, and compared in an attempt to define the genetic basis for the observed differences. Sequence comparison revealed ten encoded amino acid differences between the NS 1 genes of both viruses. Three of these amino acid differences, which are associated with a change in charge distribution, are clustered within the major antigenic region previously defined by studies of recombinant dengue-1 NS 1 protein expressed inE. coli. In parallel, the NS 1 sequences of both Hawaii and TH-Sman isolates were also aligned and compared with two other published dengue-1 NS 1 protein sequences to determine the intratypic variation of dengue-1 NS 1 antigen. Pairwise comparisons between the encoded amino acid sequences revealed a variability of 1.1% to 3.1% difference in the NS 1 protein among dengue-1 strains, which is comparable to that reported for dengue-1 envelope protein (0.2% to 3.6% difference) but less than that of dengue-2 NS 1 protein (0.6% to 7.4% difference).     

Microradiography with an x-ray image magnifier: application to dental hard tissue

The superior spatial resolution obtained with parallel-beam microradiography over conventional contact microradiography has allowed us to image microstructural features of dental hard tissue not previously reported. Our efforts to extend these techniques to provide a real-time capability for viewing in situ demineralization and remineralization effects, at and below the 1-micron level, have resulted in an instrument with several novel and unique features. Using a synchrotron radiation source of x rays and diffraction image magnification, we are now able to change magnification at will (x-ray zoom lens). In addition, the energy range over which the instrument operates gives one considerable flexibility in optimizing image contrast. The techniques of parallel-beam microradiography, and diffraction image magnification are applicable to problems in many other areas of science. Using examples within dental research, the uniqueness and versatility of these new techniques are discussed.     

Rapid and complete donor chimerism after unrelated mismatched cord blood transplantation in 5 children with beta-thalassemia major.

Hematopoietic stem cell transplantation is currently the only curative therapy for beta-thalassemia major. However, <30% of patients have unaffected HLA-identical siblings to serve as donors. We investigated the feasibility of using umbilical cord blood transplants from unrelated HLA mismatched donors and a myeloablative preparative regimen that did not involve total body irradiation. Between October 2003 and November 2004, 5 children with beta-thalassemia major received busulfan, cyclophosphamide, and antithymocyte globulin before cord blood transplantation (median dose, 8.8 x 10(7) cells per kilogram of body weight) from unrelated donors (1 or 2 of 6 HLA antigens were mismatched) and were then evaluated for engraftment, adverse effects, and treatment outcome. The median times to neutrophil engraftment, red blood cell transfusion independence, and platelet engraftment were 12, 34, and 46 days after transplantation, respectively. All patients showed grade II or III acute graft-versus-host disease; none developed extensive chronic graft-versus-host disease until the date of last contact. All patients were alive at a median follow-up of 303 days after transplantation, with complete donor chimerism and transfusion independence. These results are encouraging and clearly show the feasibility of unrelated mismatched umbilical cord blood transplantation in the treatment of children with beta-thalassemia major.     

Intravenous regional analgesia with a forearm tourniquet

Lidocaine 0.5 per cent in a dose of 2 mg X kg-1 was used for intravenous regional analgesia with the tourniquet cuff placed over the forearm. The level of tourniquet cuff pressure employed was the arterial "occlusion pressure" plus 50 mmHg. In 48 normotensive patients successful analgesia was achieved; in seven hypertensive patients, four were pain-free, but the other three required more lidocaine to achieve adequate analgesia. No toxic symptoms and signs were observed. Measurement of serum lidocaine concentrations in 12 patients confirmed the safety of the technique, although small leakage of lidocaine past the inflated forearm tourniquet was detected in some patients.     

Application of Moment Analysis to Nonlinear Drug Disposition Described by the Michaelis–Menten Equation

An equation for the mean residence time (MRT) of drug in the body is derived for the system where drug is injected intravenously into a one-compartment model and eliminated by a single, capacity-limited process. This MRT is a complex function of dose, volume, V _m, and K _m but degenerates into the classical volume/clearance expression under limiting low-dose conditions (K _m C ₀). The equation was validated by comparison of the MRT obtained by direct calculation versus numerical area estimation for simulated data. The equation may be useful analytically in the estimation of the fundamental Michaelis–Menten parameters, V _m and K _m, from experimental data.     

Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.     

Time-Restricted Eating for 12 Weeks Does Not Adversely Alter Bone Turnover in Overweight Adults

Weight loss is a major focus of research and public health efforts. Time-restricted eating (TRE) is shown to be effective for weight loss, but the impact on bone is unclear. Short-term TRE studies show no effect on bone mineral density (BMD), but no study has measured bone turnover markers. This secondary analysis examined the effect of 12 weeks of TRE vs. unrestricted eating on bone turnover and BMD. Overweight and obese adults aged 18–65 y (n = 20) were randomized to TRE (ad libitum 8-h eating window) or non-TRE. Serum N-terminal propeptide of type I collagen (P1NP), cross-linked N-telopeptide of type I collagen (NTX), and parathyroid hormone (PTH) levels were measured and dual-energy X-ray absorptiometry (DXA) scans were taken pre- and post-intervention. In both groups, P1NP decreased significantly (p = 0.04) but trended to a greater decrease in the non-TRE group (p = 0.07). The treatment time interaction for bone mineral content (BMC) was significant (p = 0.02), such that BMC increased in the TRE group and decreased in the non-TRE group. Change in P1NP was inversely correlated with change in weight (p = 0.04) overall, but not within each group. These findings suggest that TRE does not adversely affect bone over a moderate timeframe. Further research should examine the long-term effects of TRE on bone.