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Biomedical subjects

T Tashiro

Publications and source records attributed to T Tashiro.

At least 487 records · Page 27Linked to original sources

Organization and slow axonal transport of cytoskeletal proteins under normal and regenerating conditions.

The organization of the axonal cytoskeleton was investigated by analyzing the solubility and transport profile of the major cytoskeletal proteins in motor axons of the rat sciatic nerve under normal and regenerating conditions. When extracted with the Triton-containing buffer at low temperature, 50% of tubulin and 30% of actin were recovered in the insoluble form resistant to further depolymerizing treatments. Most of this cold-insoluble form was transported in slow component a (SCa), the slower of the two subcomponents of slow axonal transport, whereas the cold-soluble form showed a biphasic distribution between SCa and SCb (slow component b). Changes in slow transport during regeneration were studied by injuring the nerve either prior to (experiment I) or after (experiment II) radioactive labeling. In experiment I where the transport of proteins synthesized in response to injury was examined, selective acceleration of SCb was detected together with an increase in the relative proportion of this component. In experiment II where the response of the preexisting cytoskeleton was examined, a shift from SCa to SCb of the cold-soluble form was observed. The differential distribution and response of the two forms of tubulin and actin suggest that the cold-soluble form may be more directly involved in axonal transport.

Actins↗

Immunocytochemical identification of axons containing coexistent serotonin and substance P in the cat lumbar spinal cord.

Axons containing both serotonin-like (5-HT)-LI and substance P-like (SP)-LI immunoreactivity were identified in all laminae of the cat spinal cord at the level of the lumbar enlargement. Using an immunologically-specific, double immunofluorescence method, coexistent 5-HT-LI and SP-LI immunoreactivity could be visualized in the same tissue section with appropriate FITC and rhodamine fluorescent filter sets. The fewest number of coexistent axons were observed in the superficial laminae of the dorsal horn, while their number increased in the more ventral dorsal horn laminae. Numerous coexistent axons were observed in the area adjacent to the central canal. The greatest number of coexistent axons was found in the ventral horn, especially in the motoneuronal cell groups. This study demonstrates that axons containing coexistent 5-HT-LI and SP-LI immunoreactivity are found in all laminae of the cat lumbar spinal cord and are thus involved in both sensory and motor functions. Their more frequent occurrence in the ventral horn suggests a greater role for coexistent 5-HT and SP in motor function. Since axons containing coexistent 5-HT and SP, and those containing only 5-HT, likely originate from different populations of neurons, our observations provide evidence for a diverse origin of descending 5-HT afferents to the different spinal laminae.

Animals↗

Effect of severity of stress on whole-body protein kinetics in surgical patients receiving parenteral nutrition.

A study was conducted to clarify the quantitative relationship between the alteration of protein metabolism and the severity of surgical stress to further understand the mechanisms of body nitrogen losses in surgical trauma. Twenty-one patients undergoing esophagectomy for esophageal cancer (group E), and 22 undergoing gastrectomy or colorectal operations for gastric or colorectal cancer (Group GC) were studied. All patients were fed exclusively by parenteral nutrition (PN) providing 1.5 g protein.kg-1.d-1 and 35 kcal.kg-1.d-1 before and after the operation. The measurements of whole-body protein turnover, synthesis, and breakdown were performed preoperatively and on postoperative days (PODs) .3 and 10. Urinary excretion of total nitrogen and total catecholamines was also measured. Urinary excretion of the total catecholamines of group E was twice as high as that of group GC on the POD 3 and well reflected the severity of surgical stress. Negative correlation of nitrogen retention to urinary excretion of the total catecholamines was also observed (r = 0.64; P < 0.01). The correlations between the urinary excretion of the total catecholamines and the whole-body protein flux, synthesis, and breakdown were statistically significant (r = 0.57, 0.27, and 0.57, respectively; P < 0.01 in all). Rate of elevation in breakdown according to the stress level was greater than that of synthesis. Consequently the progressive aggravation of nitrogen balance according to the severity of surgical stress was observed.

Catecholamines↗

Effects of total parenteral nutrition on endotoxin translocation and extent of the stress response in burned rats.

Postburn endotoxin translocation has been well documented. However, the relationship between the secretion of catabolic hormones, degree of endotoxin translocation, and intestinal atrophy has not been previously demonstrated. In this experiment, modulation of the secretion of catabolic hormones according to the route of nutrient administration was examined in burned animals. A total of 55 rats, with and without a burn injury, were orally or parenterally fed. Urinary excretion of epinephrine and norepinephrine (U-EN) of each rat was measured for 48 h after burn injury as an indicator of the stress response. Evaluations of intestinal atrophy and endotoxin contents in the liver and spleen were also done 48 h after burn injury. U-EN after burn injury in rats administered total parenteral nutrition (TPN) was higher than in those fed orally. Endotoxin translocation and intestinal atrophy after thermal injury were also augmented by TPN. A significant positive correlation between U-EN and endotoxin content of the liver, and a negative correlation between U-EN and weight of the intestine, were observed. TPN enhances the stress response after burn injury. An increase in endotoxin translocation and intestinal atrophy by TPN are closely related to enhancement of the stress response.

Animals↗

Chemistry of thermal degradation of abasic sites in DNA. Mechanistic investigation on thermal DNA strand cleavage of alkylated DNA.

The chemistry of thermal degradation of aldehydic abasic sites in DNA was investigated. Sequencing gel analysis of duocarmycin A-treated 5'-32P-end-labeled DNA fragment indicated that upon heating at neutral pH alkylated DNA was cleaved to provide fragments possessing a modified sugar moiety which is readily decomposed to 3'-phosphate terminus by piperidine treatment. To identify the structure of modified sugar product and to investigate the mechanism of thermal cleavage, thermal degradation of various oligonucleotides containing abasic sites was investigated in detail. It was found that heating the DNA containing an abasic site induces beta-elimination to provide 3'-termini possessing a trans-alpha,beta-unsaturated aldose residue together with 5'-phosphate termini. Upon prolonged heating at pH 7.0, the trans-alpha,beta-unsaturated aldose terminus is isomerized to a cis isomer or is further degraded to its hydrated products and a 3'-phosphate terminus via delta-elimination. This type of thermal degradation also occurs in the abasic site-containing calf thymus DNA. Investigation of the stereochemical course of the thermal beta-elimination reaction using a 2-pro-R-D-containing abasic site has demonstrated that the reaction proceeds via a syn-elimination process as observed for the enzymatic reaction of UV endonuclease V and endonuclease III.

Alkylating Agents↗

Changes in cerebral blood flow in bulimia nervosa.

Bulimia nervosa is an eating disorder of which characterized psychopathological symptoms are a recurrent episode of binge eating. The changes in cerebral blood flow (CBF) in a patient with bulimia nervosa between his or her different eating phases are presented. CBF was measured quantitatively by means of single photon emission computed tomography using I-123 N-isopropyl-p-iodoamphetamine. CBF of the global brain during a binge-eating phase was higher than that during an anorexic state phase. In the anorexic state, the CBF in the temporal, parietal, and occipital lobes on the right side was lower than that on the left side. In the binge-eating state, a lack of laterality between the right and left cerebral hemispheres was found. This finding suggests that cerebral activity differs between the two phases, and that asymmetry is dependent of the eating state.

Adult↗

Anatomical reconstruction of the patellar tendon: a new technique with hamstring tendons and iliotibial tract.

A new technique of patellar tendon reconstruction was performed in a patient who lost tendon and tibial tuberosity during wide excision surgery for a malignancy. In this procedure, the tendon was anatomically replaced by a graft composed of ipsilateral hamstring tendons and iliotibial tract, with the biomechanical conditions considered. Both ends of the graft were secured in the size-matched bone tunnels in the patella and tibia by screw post fixation, which is a technique established in ligament reconstruction surgery in the knee joint. At the twenty-month follow-up, the result was deemed successful.

Bone Neoplasms↗

Superficial siderosis of the central nervous system. A case report on examination by ECoG and DPOAE.

This is a case of superficial siderosis of the central nervous system (SSCN). The diagnosis of SSCN was based on the result of T2-weighted magnetic resonance imaging and on suggestive clinical manifestations. The pure-tone audiogram showed bilateral progressive sensorineural hearing loss with a poor speech discrimination score and Jerger type IV. The remarkable elevation of the detective threshold of cochlear microphonics on electrocochleography was found and distortion product otoacoustic emission (DPOAE) showed no response: These electrophysiologic examinations, including electrocochleography and DPOAE, revealed that the progressive sensorineural hearing loss in this case was caused by both retrocochlear and cochlear damages.

Central Nervous System Diseases↗

In vitro-in vivo correlation in anticancer drug sensitivity test using AUC-based concentrations and collagen gel droplet-embedded culture.

To improve the ability of an in vitro drug sensitivity test to predict in vivo effects, we applied a drug concentration that was pharmacokinetically equivalent to plasma levels and collagen gel droplet-embedded culture with a high cloning efficiency. We reported that the cell-killing effect of cell cycle phase-nonspecific drugs such as mitomycin C, cisplatin and Adriamycin depends on the area under the drug concentration-time curve (AUC). The plasma AUC values of these drugs were estimated after an injection into nude mice at the maximal tolerated doses (MTD). Tumor cells isolated from human tumor xenografts implanted into nude mice and cultured in collagen gel droplets were exposed to drugs under conditions that can reproduce the plasma AUC in vitro. The in vitro sensitivity to a drug was compared with the in vivo response of the same tumor treated with the MTD of the drug. When the criterion of sensitivity was taken as 50% or less of the growth inhibition (growth rate of treated group/that of control group, T/C), the correlation between the in vitro and in vivo growth inhibition of all 3 drugs tested was relatively high (86% of the true-positive rate, 82% of the true-negative rate and 83% of the correlation rate).

Animals↗

Combination therapy with fluconazole and flucytosine for pulmonary cryptococcosis.

We investigated, in vitro, the combined effects of fluconazole (FLCZ) and flucytosine (5-FC) against different strains of Cryptococcus neoformans, and retrospectively analyzed the clinical efficacy of combination therapy of FLCZ and 5-FC in patients with pulmonary cryptococcosis. The minimum inhibitory concentrations (MICs) of antifungal agents and drug interaction were determined by the broth microdilution method and checkerboard titration. FLCZ and 5-FC showed synergistic activity against 8 (32%) of 25 strains of C. neoformans. The clinical efficacy of the 2 drugs when combined together was good in 9 (90%) patients and fair in 1 (10%) patient with pulmonary cryptococcosis. Renal dysfunction occurred in 1 patient. Our results suggest that a combination therapy using FLCZ and 5-FC is clinically useful in patients with pulmonary cryptococcosis who otherwise show a limited response to monotherapy.

Adult↗

Whole body protein turnover, synthesis, and breakdown in patients receiving total parenteral nutrition before and after recovery from surgical stress.

This study was conducted to understand further the mechanisms underlying the loss of body nitrogen after trauma. Six patients who underwent abdominal surgery and six for control were studied. The measurement of whole body protein turnover was made on the 3rd and 10th postoperative day during total parenteral nutrition with constant infusion of [15N]glycine according to Picou and Taylor-Roberts. The measurement was also made on six control patients during total parenteral nutrition in the nonstressed state. The rates of whole body protein turnover, synthesis, and breakdown were calculated from the plateau 15N enrichment of urinary total N, which was analyzed with a mass spectrometer. The values were compared with control by Student's t-test, and the changes in the individual patients were examined by a paired t-test. Immediately after the operation, whole body protein turnover and breakdown were significantly elevated (p less than 0.05 and less than 0.02, respectively), and decreased with the improvement of N balance after recovery from stress by 0.95 +/- 0.21 and 0.61 +/- 0.13 g . protein/kg . day, respectively. The changes in whole body protein turnover and breakdown were statistically significant (p less than 0.005 and less than 0.005, respectively). However, no tendency of alteration in whole body protein synthesis was found throughout the study. It is concluded that protein turnover rate increases in surgical stress, and that the increased protein catabolism rather than the alteration in synthesis could account for the postoperative nitrogen losses.

Abdomen↗

Alteration of lipoprotein profile during total parenteral nutrition with intralipid 10%.

Eight patients were studied for lipoprotein profiles over a period of 3-7 weeks. Four patients received total parenteral nutrition (TPN), including 1000 ml/day of Intralipid 10%. Three patients received fat-free TPN, and one patient was tube fed 1000 ml/day of Intralipid 10% enterally. Fat-free TPN lowered plasma lipid, especially low density lipoprotein (LDL) and high density lipoproteins (HDL). On the other hand, intravenous administration of Intralipid 10% caused a marked increase of LDL, together with increases of phospholipid and cholesterol, especially free cholesterol. Triglyceride, VLDL, and HDL remained within the normal range in this group. Enteral administration of the same amount of Intralipid 10% did not cause a rise of LDL. Lipid composition of the increased LDL approximated that of lipoprotein X with the intravenous Intralipid 10%. From these findings, we suggest that phospholipids in Intralipid 10% formed abnormal LDL as the result of mobilization of cholesterol from extravascular tissues, when administered intravenously.

Aged↗

Effects of severity of surgical trauma on whole body protein turnover in patients receiving total parenteral nutrition.

This study was conducted to resolve discrepancies in the literature with regard to changes in protein metabolism following surgical stress. Twelve patients who had undergone abdominal surgery and six who were controls were studied. Whole body protein turnover was measured on the third and 10th postoperative day, during isonitrogenous and isocaloric total parenteral nutrition (TPN), by the method of constant infusion of [15N]glycine. Six patients who underwent abdominal surgery without any complications showed positive nitrogen balance on the 10th postoperative day (group I). However, nitrogen balance was still negative on the 10th postoperative day in another six patients who showed some critical complications after abdominal surgery (group II). A significant increase in whole body protein breakdown was seen in groups I and II on the third postoperative day (p less than 0.02, p less than 0.01, respectively), compared with control. Breakdown was greater in group II (p less than 0.05) than in group I. Protein synthesis tended to increase in group II, whereas in group I, it was at the same level as control. It was concluded that protein synthesis was unchanged in moderate stress, concomitant with increment of breakdown, but it tended to increase with a greater increase of breakdown in severe stress.

Adult↗

Evaluation of the endotoxin retention capabilities of inline intravenous filters.

The capabilities of inline filters to retain bacteria and endotoxin were examined during simulated extended infusions for up to 168 hr. The tested inline filters were the ELD96 (Pall Biomedical Corp) and the IVEX 2 (Millipore Corp). Approximately 1 x 10(8) total cells of Escherichia coli B. were challenged to the upstream site of the filter. The test solution of 5% dextrose in water, 0.9% saline, Paremental A (A basic solution for total parenteral nutrition (TPN), a TPN solution in use in our clinic were infused continuously up to 168 hr and flow rate was maintained at 83 ml/hr. The effluents were analyzed using the Limulus Amebocyte Lysate (LAL) test to detect endotoxin and also passage of the challenged bacteria was tested at 24-hr intervals over 168 hr. The results were as follows: (1) The viability control culture showed the presence of viable bacteria throughout the 168-hr period of the experiment. (2) During the experiments, all filters produced sterile effluents. (3) LAL assay indicated that only the effluents from the ELD96 contained no detectable endotoxin for 168 hr.

Catheterization, Central Venous↗

Alteration of whole-body protein kinetics according to severity of surgical trauma in patients receiving total parenteral nutrition.

This study was conducted to clarify the mechanisms of body nitrogen losses according to the severity of surgical trauma. Thirteen male patients who underwent operation for esophageal cancer (group E), and 11 men (who underwent gastric or colorectal surgeries (group GC) were studied. The measurement of whole-body protein turnover, synthesis, and breakdown were made preoperatively on the 3rd and 10th postoperative day with constant infusion of [15N]glycine during isocaloric and isonitrogenous total parenteral nutrition. Significant increases in the rates of whole-body protein turnover (flux) and breakdown were seen in group E on the 3rd postoperative day (p less than 0.01, p less than 0.01, respectively), whereas the increases were not significant in group GC. The rates of whole-body protein flux and breakdown were significantly greater in group E than group GC (p less than 0.01, p less than 0.01, respectively). The rate of protein synthesis significantly increased in group E (p less than 0.05), but did not alter or slightly decreased in group GC. The rates of whole-body protein flux and breakdown in group E were still significantly greater on the 10th postoperative day than preoperatively. It was concluded that unchanged or slightly decreased rates of whole-body protein synthesis with slightly increased breakdown were seen in the group of patients who underwent gastric or colorectal surgery, whereas synthesis increased significantly with a greater increase of breakdown in patients receiving severe surgical procedures, esophagectomy for esophageal cancer.

Adult↗