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Biomedical subjects

Y Tokunaga

Publications and source records attributed to Y Tokunaga.

At least 91 records · Page 5Linked to original sources
PubMed1998

Semiquantitative evaluation for diagnosis of Helicobacter pylori infection in relation to histological changes.

OBJECTIVES: Several methods are used to detect Helicobacter pylori (HP) infection. However, few reports have evaluated the accuracy of each method and compared the grade of HP infection with the severity of histological changes. HP infection was evaluated semiquantitatively in relation to the severity of gastritis, and the sensitivity, specificity, and accuracy of several methods to detect HP infection were compared. METHODS: Biopsy specimens, obtained from a total of 64 patients who underwent endoscopy for evaluation of gastroduodenal diseases, were studied using a rapid urease test, culture, and histological assessment. An immunohistochemical method was used as the gold standard and graded according to the number of individual bacteria seen, as follows: 0 = 0; 1+ = <10; 2+ = 10-29; 3+ = 30-99; 4+ = >100. The severity of gastritis was evaluated histologically in each specimen and compared with the grade of HP infection. RESULTS: The rapid urease test had a sensitivity of 53%, specificity of 100%, and accuracy of 73%. The culture method had a sensitivity of 75%, specificity of 100%, and accuracy of 86%. Sensitivities of the rapid urease test and the culture method decreased in a positive correlation with the decrease in total number of HP bacteria counted. Using the rapid urease test, sensitivity was <30% when the grade of HP infection was < or =2+, whereas 100% sensitivity was obtained when the grade of HP infection was 4+. On the other hand, sensitivity of the culture method remained between 80% and 90% when HP infection was > or =2+. The severity of gastritis determined with Rauws scores increased in a positive correlation with the grade of HP infection as evaluated by immunohistochemical stain. CONCLUSIONS: The rapid urease test and culture of HP may result in false-negative tests for a mild infection, although they had high sensitivity and specificity for moderate to severe infection. Immunohistochemical stain provides a reliable semiquantitative diagnosis of HP infection and a positive correlation with histological changes. Clinicians should be aware of the characteristics of each method to detect HP infection and select the appropriate one(s) for their purposes.

Bacteriological Techniques↗
PubMed1998

Effects of closed-system drain in surgery: focus on methicillin-resistant Staphylococcus aureus.

OBJECTIVE: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has made a strong impact on the strategy of peri-operative antibiotic prophylaxis, since MRSA has become one of the most common causative organisms of nosocomial infection in recent years. In this study, we conducted a bacteriological evaluation of surgical drains before and after introducing strategies to decrease MRSA infection rates. DESIGN AND PATIENTS: Between January 1987 and December 1994, we performed a total of 2, 755 surgical operations on inpatients, including 1,635 major and 1, 120 minor operations. Almost all surgical drains were examined bacteriologically when they were removed. The number of drains examined was 460 +/- 47 (mean +/- SEM) per year. Since the increased incidence of MRSA infection, we started exclusively using a closed drainage system and first-generation cephalosporins in 1991. The strategy was evaluated by comparing the positive rates of drain cultures, changes in bacteriological features, and incidence of MRSA infection for the 4-year periods before and after 1991. RESULTS: The positive rate of bacteria in the drains decreased significantly (p < 0.01) from 25 +/- 2 to 16 +/- 1%. Bacteriologically, the positive rate of Staphylococcus spp. decreased significantly (p < 0.05) from 7 +/- 2 to 3 +/- 0.3%. Positive rates of MRSA decreased significantly (p < 0.05) from 2.1 +/- 0.3 to 1.3 +/- 0.3%. Streptococcus declined dramatically from 3.0 +/- 0.3 to 0.3 +/- 0.1%. Of gram-negative strains, Pseudomonas and Escherichia coli were most often isolated. They showed no significant difference in positive rates between the terms. CONCLUSION: A closed drainage system and thorough use of the first-generation cephalosporins for prophylaxis were effective in decreasing positive bacterial culture of drains and reducing the incidence of MRSA on drains after surgery.

Adult↗
PubMed1998

Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. I.v. effects of osteotropic estradiol on bone mineral density and uterine weight in ovariectomized rats.

An osteotropic drug delivery system (ODDS) based on the bisphosphonic prodrug was designed for 17beta-estradiol (E2) in order to improve patient compliance in estrogen replacement therapy of postmenopausal osteoporosis. The bisphosphonic prodrug of E2, disodium [17beta-(3 '-hydroxy- 1',3',5'-estratrienyloxy) carbonylpropyl carboxamidomethylene] bisphosphonate (E2-BP) was synthesized and its effects on bone mineral density and uterine weight were investigated in ovariectomized (OVX) rats. E2-BP was injected intravenously once a week (4 injections/experiment), and E2 was administrated orally 5 times a week (20 administrations/experiment). Once a week treatment with 0.1 mg/kg E2-BP significantly restored bone mineral reduction by 61.8% without significantly increasing uterine weight. Similarly, once in 4 weeks treatment with 1.0 mg/kg E2-BP (1 injection/experiment) showed almost the same therapeutic effects. On the other hand, 5 times a week oral treatment with 1.0 mg/kg E2 significantly improved bone mineral density by 90.5%, but increased uterine weight up to 98.2% of that of the sham group. In vitro bone resorption analysis revealed that E2-BP exhibits antiresorptive activity not as a bisphosphonate but as a prodrug of E2. These results demonstrated that E2-BP has the potential to improve patient compliance in estrogen therapy by its minimal adverse effects and less frequent medication.

Animals↗
PubMed1998

[Nitric oxide as a regulatory factor in sleep-wakefulness mechanisms].

Although several roles of neuronal nitric oxide (NO) have been suggested, the capacity of NO on sleep-wakefulness mechanisms is open to discussion. We examined the effects of nitric oxide synthase (NOS) inhibitors on rat sleep using a microdialysis technique. When NOS inhibitor L-NAME was administrated at the central region of diencephalon, paradoxical sleep (PS) significantly increased coinciding with decrease of wakefulness in the dose-dependent manner. The effect of L-NAME on PS was completely reversed by L-arginine. Additionally, administration of NO donor NOC 18 at the action site of L-NAME completely inhibited sleep. Our results suggest that NO could play a role in the continuation of vigilance around the midline thalamic nuclei.

Animals↗
PubMed1998

[Utilization of a direct sandwich ELISA kit for rapid diagnosis of adenovirus hemorrhagic cystitis in a patient with adult T-cell leukemia].

We report on a case of adenovirus hemorrhagi cystitis that developed in a 49-year-old woman during intensive chemotherapy for adult T-cell leukemia. Although rapid etiologic diagnosis is essential for the effective management of viral hemorrhagic cystitis, the isolation of adenovirus from urine is often too time-cousuming. We detected the adenovirus antigen in the patient's urine using an Adenoclone direct sandwich ELISA kit (Cambridge Bio Science), which is commonly employed for the diagnosis of adenovirus conjunctivitis. Treatment consisted of intravenous vidarabine and bladder irrigation, which resulted in prompt clinical improvement. The Adenoclone kit was useful for the rapid etiologic diagnosis of adenovirus hemmorrhagic cystitis.

Adenoviridae Infections↗
PubMed1998

[Semi-quantitative detection of Helicobacter pylori using immunohistochemical staining].

Several methods have been used for the detection of Helicobacter pylori (HP) infection. However, few reports have evaluated the accuracy of each method and compared the level of HP infection. HP infection was evaluated semi-quantitatively using immunohistochemical staining and accuracy of several methods to detect HP infection were compared. Biopsy specimens, obtained from a total 64 patients who underwent endoscopy for evaluation of gastroduodenal diseases, were studied using a rapid urease test, culture method, and immunohistochemical method. The infection was graded according to the number of the individual bacteria seen in a highly magnified visual field, and defined as follows: (0) = 0; (1+) < 10; (2+) = 10-29; (3+) = 30-99, (4+) > 100. The rapid urease test had a sensitivity of 53%, specificity of 100%, and accuracy of 73%. The culture method had a sensitivity of 75%, specificity of 100%, and accuracy of 86%. Sensitivity of rapid urease test and the culture method decreased in a positive correlation to the decrease in total number of HP bacteria counted. Using the rapid urease test, sensitivity was < 30% when the grade of HP infection was (2+) or less, while 100% sensitivity was obtained only when the grade of HP infection was (4+). On the other hand, sensitivity of culture method, remained between 80 and 90% when HP infection was (2+) or more. The rapid urease test and culture of HP may result in false negative tests for mild infection although those have high sensitivity and specificity for moderate to severe infection. Immunohistochemical stain provides a reliable semi-quantitative diagnosis of HP infection. Clinicians should be aware of the characteristics of each method to detect HP infection, and select the appropriate ones for their purpose.

Adult↗
PubMed1997

Electron-microscopic study of MAOB-containing structures in the nucleus accumbens shell: using MAOA-deficient transgenic mice.

MAOB-containing structures in the nucleus accumbens were ultrastructurally studied for the first time, using MAOA-deficient transgenic mice and MAO enzyme histochemistry. Among the striatal structures, the nucleus accumbens, and in particular its dorsal shell, showed the strongest MAOB activity. MAOB-active cell bodies were embedded in a dense MAOB-active fiber plexus. MAOB-positive terminals formed axo-dendritic synapses which were exclusively of the asymmetric type. It is suggested that dopamine in the nucleus accumbens shell is transported into MAOB-positive fibers where it is degraded by MAOB.

Animals↗
PubMed1997

An ultrastructural study of calcitonin gene-related peptide-immunoreactive nerve fibers innervating the rat posterior longitudinal ligament. A morphologic basis for their possible efferent actions.

STUDY DESIGN: The present study investigated ultrastructural characteristics of calcitonin gene-related peptide-immunoreactive nerve fibers in the posterior longitudinal ligament of the rat lumbar spine. OBJECTIVES: To provide a morphologic basis for assessment of the afferent and, in particular, efferent functions of calcitonin gene-related peptide immunoreactive nerves in the posterior longitudinal ligament and their eventual role in degenerative spondylarthropathies and low back pain. SUMMARY OF BACKGROUND DATA: Previous studies using light-microscopic localization of sensory neuronal markers such as calcitonin gene-related peptide have reported the presence of sensory fibers in the supporting structures of the vertebral column. Meanwhile, accumulating research data have suggested efferent properties for calcitonin gene-related peptide, i.e., a trophic action that alters the intrinsic properties of target cells not through transient action of synaptic transmission, but through long-lasting signal transmission by the secreted neuropeptides. To verify such trophic, paracrine actions of the calcitonin gene-related peptide-containing fibers in the posterior longitudinal ligament, however, ultrastructural details of the terminals and their spatial relationship to their eventual target structures have to be elucidated. METHODS: Rat posterior longitudinal ligaments were stained immunohistochemically for calcitonin gene-related peptide. Light-microscopic analysis of the semithin sections facilitated subsequent electron microscopy of specific sites of the posterior longitudinal ligament to determine ultrastructural details and nerve fiber-target relationships. RESULTS: The rat lumbar posterior longitudinal ligament was found to be innervated by two distinctive calcitonin gene-related peptide immunoreactive nerve networks. In immunoelectronmicroscopy, the fibers of the deep network had numerous free nerve endings, whereas those of the superficial network showed spatial associations with other non-calcitonin gene-related peptide immunoreactive components of the network. In both systems, naked axons not covered by the Schwann cells made close spatial contact with smooth muscle cells: of blood vessels and resident posterior longitudinal ligament fibroblasts. CONCLUSIONS: The ultrastructural characteristics of the innervation of the rat posterior longitudinal ligament would be compatible not only with a nociceptive function, but also with neuromodulatory, vasoregulatory, and trophic functions, as has already been established in some visceral organs.

Animals↗
PubMed1997

Two types of microsomal prostaglandin E synthase: glutathione-dependent and -independent prostaglandin E synthases.

Prostaglandin (PG) E synthase was found to be widely distributed in the microsomal fractions of rat organs. Among them, an extremely high activity was seen in the deferent duct (112 nmol/min x mg) and other genital accessory organs (10-20 nmol/min x mg). In non-genital organs, the kidney had the highest activity (8 nmol/min x mg). Most of the PGE synthase activity in these organs required glutathione (GSH). In contrast, the enzyme activity in the heart, spleen, and uterine microsomes did not require GSH for its catalytic activity. In view of these data and those of other enzymatic parameters (Km values for PGH2 or pH optima), we suggest that two different types of PGE synthases, GSH-dependent and GSH-independent enzymes, are present in microsomal fractions of rat tissues.

Animals↗
PubMed1997

Tyrosine hydroxylase-immunoreactive nerve fibres in rat posterior longitudinal ligament.

The nerve supply to the posterior longitudinal ligament (PLL) of the lumbar vertebrae has been the focus of considerable interest to gain insight into the pathogenesis of low back pain. The present study aimed to characterize the sympathetic fibres in the PLL by immuno-electronmicroscopy for tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. The posterior central branches of the segmental lumbar arteries received numerous communicating fibres from the sinuvertebral nerve (SVN), but only shortly after their entrance to the spinal canal. The non-vessel-associated branches of the SVN formed transverse bundles, which met fibres from the opposite side in a plexus-like mid-sagittal network. As these fibres approached the midline, they gradually lost their Schwann cell cover. The free and naked fibres contained numerous terminal-like varicosities. The TH-ir and 6-hydroxydopamine (6-OH-DA) sensitive fibres were intermingled with non-TH-ir fibres. The TH-ir sympathetic fibres had no obvious target structures except for the numerous, intermingled, closely related and communicating terminal-like axons in the mid-sagittal network in contact with non-TH-ir fibres. This may represent a neuroanatomical equivalent reflecting modulatory functions, which could participate in the pathogenesis of low back pain.

Animals↗
PubMed1997

Postsurgical sequential methotrexate, fluorouracil, and leucovorin for advanced colorectal carcinoma: a preliminary study.

BACKGROUND AND OBJECTIVES: The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of tegafur (UFT) and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma. METHODS: Between January 1990 and December 1995, a total of 46 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were stratified into two groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) ever other week after surgery for 2 months and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: The overall survival rates after surgery was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC Group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. CONCLUSIONS: The present results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular for those patients with a high risk of recurrence following potential curative resection.

Aged↗
PubMed1997

Calcitonin gene-related peptide, substance P, and tyrosine hydroxylase-immunoreactive innervation of rat bone marrows: an immunohistochemical and ultrastructural investigation on possible efferent and afferent mechanisms.

The presence of nerve fibers in bone marrow has been noted by various investigators, and recent developments in immunohistochemistry have enabled differential localization of the intramedullary nerve fibers. Much interest has been devoted to the efferent activities of the afferent fibers, which probably act on the target tissues by secreting a variety of neurotransmitters. The present study aimed to further characterize intramedullary substance P, calcitonin gene-related peptide, and tyrosine hydroxylase-immunoreactive nerve fibers of the rat lower limb by comparing those of the knee, ankle, and tarsal joints. The ultrastructural details of intramedullary calcitonin gene-related peptide-immunoreactive axons were also investigated to provide a morphological basis for their possible efferent actions. Intramedullary calcitonin gene-related peptide and substance P-immunoreactive fibers in the proximal tibia and the knee joint were found to be as reported earlier, but the marrow of the distal metaphysis was also noted to be richly innervated, and the tarsal joints displayed dense innervation at the subchondral regions that underlie the joint cartilage. The articular and intramedullary innervations that function for joint protection might participate in characteristic clinical features of joint damage secondary to the neuropathies. Ultrastructurally, the intramedullary calcitonin gene-related peptide-immunoreactive axons were minimally engulfed by the Schwann cell, and naked intramedullary calcitonin gene-related peptide-immunoreactive axons were noted along an extraordinarily long extension, suggesting much efferent activity.

Animals↗
PubMed1997

Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel endothelial cell monolayers.

The administration of chemotherapy to patients with tumors of the central nervous system is often blocked by the blood-brain barrier. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that promotes vascular permeability in addition to its pro-inflammatory effects. However, no direct evidence exists as to whether TNF-alpha may increase permeability of the BBB. We evaluated the effect of TNF-alpha on the transport of cisplatin (CDDP) or high molecular weight dextran labeled with fluorescein isothiocyanate (FITC-dextran) across bovine brain microvessel endothelial cell (BMEC) monolayers that was conducted on side-by-side diffusion chambers in vitro. The permeability coefficient for the transport of CDDP across the untreated monolayer was 3.80 x 10(-5) cm sec-1 at 30 minutes. After treating the BMEC monolayer with TNF-alpha (50 U ml-1 and 500 U ml-1) for 36 hours, the PC of CDDP increased significantly to 8.94 x 10(-5), and 14.43 x 10(-5) cm sec-1 respectively (p < 0.01). TNF-alpha had no effect on the transport of FITC-dextran across the BMEC monolayers. Electron microscopy showed that the tight junctions between the BMECs persisted even after treatment with TNF-alpha, whereas they had been partially disrupted following exposure to mannitol, 1600 mOsm kg-1. TNF-alpha selectively promoted the in vitro permeability of the blood-brain barrier to CDDP without disrupting tight junctions. This system could be used as a model for experimental studies of chemotherapy. Findings suggested that the combined administration of TNF-alpha and CDDP may be clinically useful.

Animals↗
PubMed1997

In-vivo microdialysis study of the distribution of cisplatin into brain tumour tissue after intracarotid infusion in rats with 9L malignant glioma.

Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats. Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg-1) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUC, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.

Animals↗
PubMed1997

Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. V. Biological disposition and targeting characteristics of osteotropic estradiol.

An osteotropic drug delivery system (ODDS) based on a bisphosphonic prodrug has been developed for 17 beta-estradiol (E2) to improve patient compliance in estrogen replacement therapy of postmenopausal osteoporosis. The biological disposition and the targeting efficiency of a bisphosphonic prodrug of E2, disodium [17 beta-(3'-hydroxy-1',3',5'-estratrienyloxy)carbonylpropyl carboxamidomethylene]bisphosphonate (E2-BP), was investigated in ovariectomized rats. After intravenous injection, E2-BP was rapidly taken up into the bone and subsequently cleared from the bone at a half-life of 13.5 d. The bone concentration of regenerated E2 was maintained throughout 28 d. In contrast, E2 injected intravenously showed extremely low bone distribution and rapid clearance from the bone, and E2 administered orally showed even lower bone distribution. Therapeutic availability (TA) and drug targeting index (DTI), which were calculated on the basis of the AUCs for E2 in the bone and plasma after injection of E2-BP and E2, were 64.6 and 451, respectively. These results suggest that ODDS has a potential to improve not only the apparent potency but also the therapeutic index of E2. As compared with the conventional estrogenic products, E2-BP should improve patient compliance with lower adverse effects and less frequent medication in long-term estrogen replacement therapy.

Animals↗
PubMed1997

A study of granulated metrial gland cells in the pregnant, alymphoplasia (aly/aly) mice.

During pregnancy, a population of uterine NK cells, commonly called granulated metrial gland (GMG) cells, differentiates in the uterus of both immune competent and various immunodeficient mice. Regulatory mechanisms controlling the differentiation of GMG cells are not fully known. It has been proven that GMG cells are derived from bone marrow, appear under the influences of progesterone and estrogen, do not require the presence of an embryo, and are associated in rodents with decidualization of the uterine stroma. Mice of genotype aly/aly are genetically deficient in lymph nodes and Peyer's patches due to a lymphoid-associated mesenchymal disorder. They are considered to be a useful model for the study of interactions between lymphocytes and stromal components. This immunodeficient animal is completely different from nu/nu and scid/scid mice who differentiate GMG cells during pregnancy. To determine whether the differentiation of GMG cells depends on mesenchymal interactions in the uterus, aly/aly mice were studied histologically between days 10 and 14 of pregnancy for differentiation of GMG cells and development of the metrial gland. Metrial gland tissue was present and appeared normal in aly/aly mice. There were no significant differences in the distribution of GMG cells in comparison to control pregnant aly/+ mice. Fewer GMG cells were present in aly/aly mice than aly/+ mice on days 12 and 14 of pregnancy. The features of individual GMG cells were different on days 10 and 12 of pregnancy. GMG cells in aly/aly mice were small in size and the granules were poorly developed. By day 14, however, GMG cells acquired a mature size and the granules appeared mature. It is likely that GMG cell differentiation was delayed in pregnant aly/aly mice, due to a mesenchymal disorder affecting metrial gland development in this animal.

Animals↗
PubMed1997

Fine structure of crest synapses in the locus coeruleus of the Japanese macaque (Macaca fuscata), with special reference to noradrenergic neurons.

The crest synapse and its related structures in the locus coeruleus (LC) of the Japanese monkey, Macaca fuscata, were electronmicroscopically studied using noradrenaline (NA) immunohistochemistry and tannic acid fixation. About 20% to 25% of the noradrenergic input to the LC terminated at noradrenergic neurons. About 1/3 of these NA-NA connections formed crest synapses, although conversely, NA-immunoreactive (IR) terminals were found in 10% of all terminals forming crest synapses. The crests showing parent dendrites were clearly NA-IR, and definite nonNA-IR dendritic crests were not found. Thus, crest synapses were present almost exclusively on noradrenergic neurons in the monkey LC. The crests were composed of parallel postsynaptic membranes 120 to 130 nm in width and 550 to 610 nm in length, accompanied by a thick-dense material of cytoplasm, and regular single rows of electron dense subjunctional bodies which were arranged in approximately 8 transverse rows. A maximum of 12 electron-dense subjunctional bodies per row were counted in the middle section, and decreased bilaterally in number. The crests further contacted with the dendritic spiny processes of neighboring NA-IR neurons. These results suggest that the crest synapse is an evolved and powerful synaptic structure which makes it possible for noradrenergic neurons in the LC to fire simultaneously at a slow and constant frequency depending on the behavioral state.

Animals↗