Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy

Background: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty‐three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single‐blind, parallel‐group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre‐ and postoperative interleukin (IL)–6, C‐reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL‐6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre‐ and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). Conclusions: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.     

Adult bone marrow-derived stem cells use R-cadherin to target sites of neovascularization in the developing retina.

Adult bone marrow contains a population of hematopoietic stem cells (HSCs) that can give rise to cells capable of targeting sites of neovascularization in the peripheral or retinal vasculature. However, relatively little is known about the mechanism of targeting of these cells to sites of neovascularization. We have analyzed subpopulations of HSCs for the expression of a variety of cell surface adhesion molecules and found that R-cadherin, a calcium-dependent cell-cell adhesion molecule important for normal retinal endothelial cell guidance, was preferentially expressed by functionally targeting HSCs. Preincubation of HSCs with function-blocking anti-R-cadherin antibodies or novel R-cadherin-specific peptide antagonists effectively prevented targeting of bone marrow-derived cells to the developing retinal vasculature in vivo. Whereas control-injected HSCs targeted to all 3 normal developing retinal vascular layers, blocking R-cadherin-mediated adhesion resulted in mistargeting of the HSCs to the normally avascular outer retina. Our results suggest that vascular targeting of bone marrow-derived HSCs is dependent on mechanisms similar to those used by endogenous retinal vascular endothelial cells. Thus, R-cadherin antagonists may be useful in the treatment of neovascular diseases in which circulating HSCs contribute to abnormal angiogenesis.     

Differential involvement of neurons in the dorsal and ventral premotor cortex during processing of visual signals for action planning

We examined neuronal activity in the dorsal and ventral premotor cortex (PMd and PMv, respectively) to explore the role of each motor area in processing visual signals for action planning. We recorded neuronal activity while monkeys performed a behavioral task during which two visual instruction cues were given successively with an intervening delay. One cue instructed the location of the target to be reached, and the other indicated which arm was to be used. We found that the properties of neuronal activity in the PMd and PMv differed in many respects. After the first cue was given, PMv neuron response mostly reflected the spatial position of the visual cue. In contrast, PMd neuron response also reflected what the visual cue instructed, such as which arm to be used or which target to be reached. After the second cue was given, PMv neurons initially responded to the cue's visuospatial features and later reflected what the two visual cues instructed, progressively increasing information about the target location. In contrast, the activity of the majority of PMd neurons responded to the second cue with activity reflecting a combination of information supplied by the first and second cues. Such activity, already reflecting a forthcoming action, appeared with short latencies (<400 ms) and persisted throughout the delay period. In addition, both the PMv and PMd showed bilateral representation on visuospatial information and motor-target or effector information. These results further elucidate the functional specialization of the PMd and PMv during the processing of visual information for action planning.     

Expression of heat shock proteins in developing and degenerating rat testes

In the testis, several types of heat shock proteins (HSPs) have been identified and characterized, although the cellular basis of the HSPs remains elusive. In the present study, alterations in the cellular localization of HSPs, including HSP 25, 60, 70, and 90, were studied during the developing and degenerating periods in the rat testis using immunohistochemistry and Western blotting. HSP25 was expressed in neither germ cells nor somatic cells on all days examined. In contrast, HSP 60 was expressed in Leydig cells during neonatal and prepuberty periods, and only in spermatogonia and primary spermatocytes after puberty. HSPs 70 and 90 were expressed in germ cells, Sertoli cells, and Leydig cells during neonatal and early developing testes, and in spermatocytes and round spermatids after puberty. Besides, there was faint expression of HSP 90 protein in spermatogonia in this period. In the degenerative condition, all HSP proteins were markedly expressed in germ cells after surgery. It would appear that HSPs play roles in unique homeostasis in testes.     

Simultaneous acquisition of iodine-123 emission and technetium-99m transmission data for quantitative brain single-photon emission tomographic imaging

The aim of this study was to obtain quantitative iodine-123 brain single-photon emission tomographic (SPET) images with scatter and attenuation correction. We used a triple-headed SPET gamma camera system equipped with fan-beam collimators with a technetium-99m line transmission source placed at one of the focal lines of the fan-beam collimators. Four energy windows were employed for data acquisition: (a) 126–132 keV, (b) 132–143 keV, (c) 143–175 keV and (d) 175–186 keV. A simultaneous transmission-emission computed tomography scan (TCT-ECT) was carried out for a brain phantom containing ¹²³I solution. The triple energy window scatter correction was applied to the ¹²³I ECT data measured by means of the windows (b), (c) and (d) acquired by two detectors. Attenuation maps were reconstructed from ^99mTc TCT data measured by means of the windows (a), (b) and (c) acquired by one detector. Chang’s iterative attenuation correction method using the attenuation maps was applied to the ¹²³I ECT images. In the phantom study cross-calibrated SPET values obtained with the simultaneous mode were almost equal to those obtained with the sequential mode, and they were close to the true value, within an error range of 5.5%. In the human study corrected images showed a higher grey-to-white matter count ratio and relatively higher uptake in the cerebellum, basal ganglia and thalamus than uncorrected images. We conclude that this correction method provides improved quantification and quality of SPET images and that the method is clinically practical because it requires only a single scan with a ^99mTc external source. Received 6 June and in revised form 27 July 1998     

Investigation of mtDNA control region sequences in an Egyptian population sample

The sequences of mitochondrial DNA (mtDNA) control region were investigated in 101 unrelated individuals living in the northern region of Nile delta (Gharbia, N = 55 and Kafrelsheikh, N = 46). DNA was extracted from blood stained filter papers or buccal swabs. HV1, HV2 and HV3 were PCR amplified and sequenced; the resulted sequences were aligned and compared with revised Cambridge sequence (rCRS). The results revealed presence of total 93 different haplotypes, 86 of them are unique and 7 are shared haplotypes, the most common haplotype, was observed with a frequency, 2.97% of population sample. High mtDNA diversity was observed with genetic diversity and power of discrimination, 0.9982 and 0.9883, respectively. In this dataset the west Eurasian haplogroups predominated over the African haplogroups. The results would be useful for forensic examinations and human genetic studies.     

Alendronate inhibits urinary calcium microlith formation in a three-dimensional culture model

Osteoporosis is associated with the pathogenesis of urinary stone formation. Urinary stones are similar to bone diseases such as osteoporosis and bone metabolism in terms of pathogenesis. Bisphosphonates are potent inhibitors of bone resorption, and are used in the management of bone disease. Furthermore, bisphosphonates have a strong affinity for calcium, and a reported inhibitory effect on calcium oxalate crystallization in vitro. Thus, bisphosphonates might also inhibit urinary stone formation. Madin-Darby canine kidney (MDCK) cells form calcium phosphate microliths at the basolateral side in vitro. We investigated the inhibitory effects of new generation bisphosphonates (alendronate and incadronate) on calcium phosphate microlith formation and on the expression of osteopontin, which is an important urinary stone matrix. MDCK cells formed two types of colonies in three-dimensional soft agar culture; dark colonies containing calcium phosphate microliths and clear colonies free from microliths. We applied purified alendronate and incadronate at concentrations of 10^–11, 10^–9, 10^–7 and 10^–5 M to MDCK cells cultured in three-dimensional soft agar and investigated the efficiency of colony formation and the dark colony ratio (number of dark colonies relative to the total number of colonies). The administration of 10^–9 and 10^–7 M alendronate decreased the dark colony ratio compared with controls, whereas incadronate did not significantly alter this colony ratio compared with controls. The expression of osteopontin in cultured cells was inhibited by the 10^–7 M alendronate administration. The present findings show that alendronate inhibits calcium stone formation, suggesting that it is effective in the prevention of urolithiasis.     

The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia

Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients.