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Biomedical subjects

T Hisamitsu

Publications and source records attributed to T Hisamitsu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Suppressive effects of Tripterygium wilfordii Hook f., a traditional Chinese medicine, on collagen arthritis in mice.

The effect of chloroform extract of Tripterygium wilfordii Hook f. (TWH extract), a traditional immunosuppressive Chinese herb, on type II collagen (C II)-induced arthritis (CIA) in DBA/1J mice was studied. In the first set of experiments, we examined the effect of TWH extract on cellular immune responses to C II. As compared with mice treated with saline, TWH extract administered orally at doses of more than 400 microg kg(-1) once a day for 14 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-2 and interferon-gamma when the cells were obtained from mice 21 days after immunization and cultured in vitro with C II. Treatment with TWH extract also inhibited production of macrophage cytokines interleukin-1beta and tumor necrosis factor-alpha in response to in vitro stimulation of lymph node cells with C II. In the second part of the experiment, we evaluated the influence of TWH extract on the incidence and development of arthritis in murine CIA. Mice were immunized twice at a 3-week interval with bovine C II, with TWH extract being given orally once a day for 14 days with four different regimens. A 14-day course of TWH extract treatment at a daily dose of 400 microg kg(-1), which began on the day of the first C II immunization, suppressed the development of arthritis, as well as antibody production and delayed-type hypersensitivity to C II. Treatment with TWH extract, which started on the same day as the booster immunization, also resulted in inhibition of development of arthritis and of immune responses to C II. On the other hand, therapeutic administration with TWH extract did not affect the clinical course of the disease and the immune response to C II.

Animals↗
PubMed1998

Suppressive activity of the chloroform extract of Tripterygium wilfordii Hook f on effector T cell activation during Hymenolepis nana infection in mice.

The chloroform extract of Tripterygium wilfordii Hook f (TWH extract) administered into mice daily at doses of 80.0 to 200.0 micrograms/kg (but not 40.0 micrograms/kg) caused suppression of protective immunity to Hymenolepis nana when the extract was injected subcutaneously during the induction phase of protective immunity. Daily administration of 200.0 micrograms/kg TWH extract, during the course of larval development from challenge, also suppressed protective immunity. Inhibition of protective immunity was only observed in mice that received TWH extract for 6 days at a daily dose of 200.0 micrograms/kg and were challenged 24 h after the final injection. TWH extract did not inhibit formation of effector cells that mediate delayed type hypersensitivity (DTH) to H. nana egg antigen when the extract was administered subcutaneously at a dose of 200.0 micrograms/kg/day for 5 days before cell preparation. However, TWH extract did inhibit DTH effector cell activation when cells prepared from infected, PBS-injected mice were transferred into 200.0 micrograms/kg TWH extract-treated recipient mice. These results strongly indicate that TWH extract cannot inhibit the generation of effector cells but will suppress their function in vivo.

Animals↗
PubMed1997

The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain.

We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra. Using in situ hybridization histochemistry, we studied the expression of this receptor in postmortem human brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.

Aged↗
PubMed1997

Inhibition of murine chronic graft-versus-host disease by the chloroform extract of Tripterygium wilfordii Hook f.

The effects of chloroform extract of Tripterygium Wilfordii Hook f (TWH extract) on chronic graft-versus-host disease (GVHD) were examined in a murine experimental model. Chronic GVHD was induced by intravenous transfer of parental DBA/2 spleen cells into unirradiated (C57BL/6 x DBA/2)F1 recipient mice. The effects of TWH extract on GVHD were assessed by measuring both the degree of splenomegaly and the total serum IgE levels 3 weeks after the cell transfer. Subcutaneous administration of TWH extract once a day for 3 weeks suppressed chronic GVHD in a dose-dependent manner. Significant suppression of splenomegaly was first noted in mice treated with 7.5 micrograms/kg of the agent. The maximum inhibition was observed when mice were treated with more than 10.0 micrograms/kg (but not 5.0 micrograms/kg) caused complete suppression of serum IgE hyperproduction. The ability of donor T cells purified from recipient spleen cells to produce interleukin 4 in response to stimulation with anti-CD3 monoclonal antibody was significantly abrogated when recipient mice were treated with 10.0 micrograms/kg of the agent. These results strongly suggest that TWH extract will be an addition to the cohort of immunosuppressive therapies used in solid organ and bone marrow transplantation.

Animals↗
PubMed1997

Enhancement of splenic interferon-gamma, interleukin-2, and NK cytotoxicity by S36 acupoint acupuncture in F344 rats.

The effect of Tsusanli acupuncture point (S36 acupoint) stimulation on splenic natural killer (NK) cytotoxicity was examined in Fischer 344 (F344) rats. Electro-acupuncture stimulation (voltage intensity, 1 to 5 V; duration, 1 ms; frequency, 1 Hz) was applied to bilateral S36 acupoints once a day (1 h) for 3 d. NK cytotoxicity was measured by the standard 4-h 51Cr release assay. Successive acupuncture treatment for 3 d significantly enhanced splenic NK cytotoxicity (p < 0.001) on the first day after final treatment as compared to that of the control. However, similar stimulation to abdominal muscle did not influence splenic NK cytotoxicity. We also examined endogenous cytokine activities in aqueous spleen extracts prepared from acupunctured and control rats. The extracts from rats acupunctured at the S36 acupoint contained high levels of interleukin (IL)-2 and interferon (IFN)-gamma as compared to those of abdominal muscle acupunctured and non-acupunctured control rats (p < 0.01). Furthermore, a significant positive correlation (p < 0.01) was observed between the levels of each cytokine tested and splenic NK cytotoxicity. The same positive correlation was also observed between the levels of IL-2 and IFN-gamma (p < 0.01). These observations indicate that electro-acupuncture stimulation of the S36 acupoint enhances splenic NK cytotoxicity and that IL-2 and IFN-gamma may function, at least in part, in the regulation of NK cell activity in this system.

Abdominal Muscles↗
PubMed1997

Induction of apoptosis in human leukemic cells by magnetic fields.

When human myelogenous leukemic cell lines, HL-60 and ML-1, were exposed to 50 Hz electromagnetic fields (EMFs), nucleosome-sized DNA fragmentation (a biochemical marker of apoptosis) was induced as assessed by agarose gel electrophoresis. However, EMFs could not induce detectable DNA fragmentation in either human peripheral blood leukocytes or polymorphonuclear cells. The minimum exposure period required for the onset of DNA fragmentation in leukemic cells was 1.0 h. Although adverse effects of EMFs on human health have been reported, the apoptosis-inducing action of EMFs on leukemic cells may suggest a possible medical application.

Apoptosis↗
PubMed1996

Increased c-fos expression in spinal neurons induced by electrical stimulation of the ureter in the rat.

The spinal processing of afferent input from the ureter was examined using an immunocytochemical technique to detect the expression of c-fos, an immediate early gene. Proximal and distal sites in one ureter were electrically stimulated separately or together at intensities that elicited a pseudo-affective response (an increase in arterial pressure). Very few Fos+ cells (range: 0.6-6.6 cells/half section were present in the L(1)-L(2), L(5)-S(2) spinal segments in sham operated control animals; however, following stimulation of the ureter, a significant increase in the numbers of Fos+ cells was detected at spinal levels L(1)-L(2) (mean 24.5-33.1 cells/half section) and L(6)-S(1) (mean 17.4-33.0 cells/half section). In L(6)-S(1), the numbers of Fos+ cells were significantly greater ipsilateral (mean 25.2 cells/half section) vs. contralateral (12.3 cells/half section) to stimulation; whereas in L(1)-L(2), the numbers were similar on both sides of the spinal cord. In L(1)-L(2), a greater percentage of Fos+ cells was present in superficial medial (MDH, 49.7%) and lateral dorsal horn (LDH, 40.8%); whereas in L(6)-S(1), the cells were more numerous in sacral parasympathetic nucleus (SPN, 38.7%) and LDH (25.6%*) regions. This distribution of Fos+ cells varies in a number of respects from that noted in previous experiments after chemical irritation of the urinary bladder and urethra which activated neurons only in L(6)-S(1) and primarily in the DCM and MDH. The results indicate that nociceptive afferent inputs from different areas of the urinary tract are processed in different regions of the spinal cord.

Animals↗
PubMed1996

Functional coupling of the Na+/Ca2+ exchanger with Ca2+ release from intracellular stores in cultured smooth muscle cells of guinea pig ileum.

The mechanism of increase in intracellular Ca2+ concentration ([Ca2+]i) by removal of extracellular Na+, which phenomena were reported previously (Japan. J. Pharmacol. 63 83-91 1993), was investigated in cultured guinea pig ileum longitudinal muscle cells loaded with a fluorescent Ca2+ indicator, fura-2, by digital ratio imaging microscopy. Isotonic substitution of choline chloride for NaCl induced a transient increase in [Ca2+]i. The pretreatment of thapsigargin (0.5 microM), but not nicardipine (10 microM), suppressed the transient increase completely. In solutions containing micromolar concentrations of free Ca2+ (nominally Ca2+-free solution), the Na+-free induced transient increase was observed, but neither the second cell exposure to the Na+-free solution nor the following application of histamine increased [Ca2+]i, indicating that removal of extracellular Na+ releases Ca2+ from intracellular stores including inositol 1,4,5-trisphosphate (IP3)-releasable pools. The Na+-free induced transient increase required the presence of more than micromolar concentrations of extracellular free Ca2+ and releasable Ca2+ within the stores, but ryanodine did not affect the transient increase. These results suggest that undetectable influx of Ca2+ by the reverse-mode action of the Na+/Ca2+ exchanger can release Ca2+ from the thapsigargin-sensitive intracellular stores including IP3-releasable pools.

Animals↗
PubMed1996

Acupuncture stimulation enhances splenic natural killer cell cytotoxicity in rats.

Acupuncture stimulation of the anterior tibial muscle, which is equivalent to Tsu-sanli point (S36) stimulation and which induces acupuncture analgesia, enhanced YAC-1 cell lytic activity of the splenic natural killer cells (NK activity) from pentobarbital anaesthetized Wistar rats. On the other hand, abdominal muscle stimulation, which does not induce acupuncture analgesia, did not affect NK activity. The serum from rats treated with acupuncture stimulation (acupuncture-stimulated rats) also enhanced the NK activity of other intact rats. The reinforcement effect of serum remained after heat inactivation (56 degrees C, 30 min). The serum from acupuncture-stimulated rats also had more potent complement activity than that from control rats. These results indicate the following considerations: 1) the Tsu-sanli point may be one of the specific points modulating immune activity, 2) this immune modulation system may share a common nervous pathway with the acupuncture analgesia-producing system, 3) acupuncture stimulation may modify NK activity through unknown heat stable humoral factors as well as the nervous system, and 4) acupuncture stimulation may activate the complement system.

Animals↗
PubMed1996

[Denervation of the cervical sympathetic nerve inhibited the splenic natural killer cell activity in rats].

Repeated applications of stellate ganglion block (SGB) are known to improve symptoms of allergic rhinitis but the mechanism of the effects is not clear. Correlation between nervous system and immune system has been reported. To examine if the blockade of a part of the sympathetic nervous system like SGB could affect immune system activity of whole body, YAC 1 cell lytic activities of the splenic natural killer cell (NK activity) were compared between the sham operation group (n = 12) and the cervical sympathetic denervation group (n = 10) 4 weeks after the operation. NK activity of denervation group was significantly lower than that of sham group. The result suggests the possibility of modulation of the immune activity of individuals by partial blockade of the sympathetic nervous system.

Animals↗
PubMed1995

Non-NMDA glutamatergic excitatory transmission in the descending limb of the spinobulbospinal micturition reflex pathway of the rat.

I.v. administration of GYKI-52466, a non-competitive AMPA/kainate glutamatergic receptor antagonist, inhibited bladder contractions elicited by electrical stimulation in the pontine micturition center (PMC) in urethane-anesthetized rats. The mean threshold dose of GYKI-52466 was 2 mg/kg i.v. (range = 1-4 mg/kg). Maximum inhibition (mean = 57.7 +/- 8.2%, range = 24-83.3% of control) occurred at a dose of 8 mg/kg. CNQX, a competitive AMPA/kainate glutamatergic receptor antagonist, did not significantly alter the evoked contractions. These results indicate that AMPA/kainate receptors are involved in bulbospinal excitatory pathway from the PMC to the parasympathetic nucleus in the lumbosacral spinal cord in the rat.

Animals↗
PubMed1995

Role of glutamate and NMDA receptors in the descending limb of the spinobulbospinal micturition reflex pathway of the rat.

MK-801, an NMDA receptor antagonist administered intravenously or intrathecally to the L6-S1 spinal cord inhibited in a dose dependent manner the amplitude of isovolumetric bladder contractions evoked by electrical stimulation in the pontine micturition center (PMC) in urethane anesthetized rats. The mean threshold dose of MK-801 was 10 +/- 6 micrograms/kg i.v. and 10 +/- 1 micrograms i.t. Bladder contractions were completely inhibited at doses ranging from 300 to 3000 micrograms/kg i.v. and from 18 to 48 micrograms i.t. These data indicate that NMDA glutamatergic receptors play an important role in excitatory transmission in the descending pathway from the PMC to the spinal segmental circuitry involved in the control of the urinary bladder.

Animals↗
PubMed1994

Cutaneous hyperalgesia induced by peripheral injection of interleukin-1 beta in the rat.

The contribution of the activity of afferent fiber filaments to pain and hyperalgesia after administration of a plantar injection of interleukin-1 beta (IL-1 beta) to the hind-paw skin was investigated by recording action potentials of the rat dorsal root in response to mechanical and thermal stimuli. Touch stimuli were delivered by stroking with a cotton-tipped applicator and thermal stimulation was applied by cooling or heating of the skin. After the administration of IL-1 beta (100 pg-1 microgram), responses to touch, cold, and heat stimulation increased to 143%, 200%, and 392%, respectively, of control values on average. IL-1 beta induced transient spontaneous discharge in 50% of experiments. The effects of IL-1 beta were apparent within 1 min. To examine responses to pressure stimulation, an area of 1 mm2 of the hind-paw skin was pressed by a mechanical stimulator. IL-1 beta (0.1 pg-200 ng) decreased the threshold value to 58% of the control pressure required for firing. IL-1 beta also increased responses to various levels of pressure (range: 1-20 g/mm2). These data suggest that IL-1 beta may play an important role in cutaneous hyperalgesia by activating polymodal receptors to mechanical and thermal stimulation.

Afferent Pathways↗
PubMed1994

All-or-none like responses in increment of cytoplasmic free calcium concentrations to histamine in single smooth muscle cells of guinea pig trachea.

Single smooth muscle cells were isolated from guinea pig trachea and cultured for 48 hours. The cells were then loaded with a fluorescent-free calcium indicator, fluo-3. Concentrations of cytoplasmic-free calcium ([Ca2+]i) were determined by using a confocal laser scanning fluorescence imaging system. Cells exposed to histamine at concentrations less than 1.0 microM did not indicate any changes of the fluorescence intensities, but stayed at the basal level of [Ca2+]i. Cells exposed to histamine at a concentration in the range of 1.5 to 10 microM indicated marked increases in [Ca2+]i. A further increase in [Ca2+]i by application of higher concentrations of histamine was not observed. The threshold concentration of histamine to increase [Ca2+]i and peak [Ca2+]i varied from cell to cell. In addition, half-maximal response time was shortened with increasing concentrations of histamine from 1.5 to 100 microM. These results indicate that [Ca2+]i responses to histamine is an all-or-none type in each cell. The heterogeneity in the required threshold concentration of histamine to increase in [Ca2+]i and the concentration dependency in half-maximal response time of histamine-induced [Ca2+]i increase may be related to the graded responses of histamine-induced contractions in preparations of the tracheal tissue.

Aniline Compounds↗
PubMed1994

The risk factor for development of thyroid disease during interferon-alpha therapy for chronic hepatitis C.

OBJECTIVES: To determine the risk factors for the development of thyroid diseases during interferon-alpha therapy, we analyzed the patients with chronic hepatitis C who were treated with interferon-alpha. METHODS: One hundred nine patients with chronic hepatitis C (77 men and 32 women, ages 20-72 yr) were treated with interferon-alpha (alpha, 48; alpha 2a, 38; alpha 2b, 23) for 14-40 wk. Thyroid function tests and seven autoantibodies were assessed at the beginning and end of interferon-alpha therapy, and every other month. A logistic multiple regression model was used in the statistical analysis of risk factors for development of thyroid diseases. RESULTS: Among the 106 patients with normal pretreatment thyroid function tests, nine patients (three men and six women, ages 33-62 yr) developed thyroid diseases. However, among three patients with abnormal thyroid function tests, exacerbation of thyroid disease was not observed during interferon-alpha therapy. Logistic multiple regression model revealed that positivity for microsome antibody was a significant risk factor for the development of thyroid disease (p < 0.0001, chi 2 = 20.18). Actually, compared to patients without microsome antibody at the beginning of therapy, the incidence of thyroid diseases in the patients with pretreatment microsome antibody was very high: 3.3% (3/99) versus 60% (6/10), respectively. Six patients developed hyperthyroidism and three patients developed hypothyroidism. The patients with hyperthyroidism had atypical clinical features. CONCLUSION: Our study revealed that positivity for microsome antibody at the beginning of interferon-alpha therapy is a risk factor for thyroid dysfunction.

Adult↗
PubMed1993

Optical resolution by high-performance capillary electrophoresis. Micellar electrokinetic chromatography with sodium N-dodecanoyl-L-glutamate and digitonin.

Optical resolution by micellar electrokinetic chromatography with sodium N-dodecanoyl-L-glutamate (SDGlu) and with digitonin-sodium taurodeoxycholate (STDC) mixed micelles was investigated. Addition of sodium dodecyl sulphate, urea and methanol to SDGlu micellar solutions could give improved peak shapes and resolution. With SDGlu, phenylthiohydantoin (PTH) derivatives of five DL-amino acids (alpha-aminobutyric acid, methionine, norvaline, tryptophan and norleucine) were separated from each other and each pair of enantiomers was optically resolved. On the other hand, three PTH-DL-amino acids (norvaline, valine and alpha-aminobutyric acid) were also successfully resolved with a digitonin-STDC-urea solution (pH 2.5).

Amino Acids↗
PubMed1993

The acupuncture point and its connecting central pathway for producing acupuncture analgesia.

Characteristics of the acupuncture point in producing acupuncture analgesia (AA) were examined by the inhibition of noxious responses in the brain stem reticular formation, potentials, and neuronal activity in the dorsal periaqueductal central gray (D-PAG), and analgesia caused by low frequency stimulation of the acupuncture point. As a result, stimulation of the muscle beneath the acupuncture point was found to be effective in producing AA. AA measured by tail flick, vocalization, and writhing tests was abolished by hypophysectomy, and by antiserum of beta-endorphin administered into the 3rd ventricle. The pathway from the D-PAG to the anterior hypothalamus (AA-AH) in the AA afferent pathway from the acupuncture point to the pituitary gland was determined. The lateral hypothalamus, lateral septum, cingulate bundle, dorsal-hippocampus, and habenulo-interpeduncular tract were found, in addition to regions previously found, to belong to the AA afferent pathway. A network of divergence and convergence in their rostral and caudal relations was observed. The AA afferent pathway diverges from the D-PAG, converges to the HP, and then projects to the AA-AH.

Acupuncture Analgesia↗