Disseminated toxoplasmosis with atypical symptoms which developed with exacerbation of systemic lupus erythematosus.

Toxoplasma is a common parasite worldwide that mainly affects the brain, lungs and eyes. Although toxoplasmic encephalitis is a lethal disease without treatment, past case reports show most patients with systemic lupus erythematosus who developed toxoplasmic encephalitis were misdiagnosed and treated as neuropsychiatric systemic lupus erythematosus, which led to unfavorable outcomes. We herein describe a case of disseminated toxoplasmosis affecting all the above organs with atypical symptoms, which developed with exacerbation of systemic lupus erythematosus. She had initially manifested with retinochoroiditis without vitritis, mild cognitive impairment and an isolated lung mass. These are completely different from the classic symptoms of toxoplasmosis that have been reported in patients with HIV infection and/or those after hematopoietic transplantation. Our case, together with previously reported cases, suggests the manifestation of toxoplasmosis that develops in systemic lupus erythematosus patients can be different from that seen in conventional cases and varies between individual patients. Our case highlights both the difficulty in and the importance of diagnosing toxoplasmosis in patients with systemic lupus erythematosus and provides helpful information to identify this rare, devastating, yet treatable disease.

Development of mixed connective tissue disease and Sjögren's syndrome in a patient with trisomy X.

Increased risk of developing systemic lupus erythematosus (SLE) has been reported in patients with Klinefelter syndrome. Here, we describe a 16-year-old Japanese patient with trisomy X (47,XXX) who developed mixed connective tissue disease (MCTD) and Sjögren's syndrome. She had polyarthritis, edematous fingers with Raynaud's phenomenon, sicca syndrome, interstitial lung disease, possible myositis, and was positive for anti-nuclear antibody, anti-nRNP antibody and rheumatoid factor. This is the first report in the literature of a case of MCTD with female polysomy X, which further supports the link between the presence of extra X chromosome(s) and the development of autoimmune diseases.

The relationship between anagliptin concentration showing over 80% inhibition of plasma dipeptidyl peptidase-4 activity and its protective effect against glucagon-like peptide-1 degradation.

In dipeptidyl peptidase-4 (DPP-4) inhibitors, the inhibition of plasma DPP-4 activity by 80% is considered sufficient to have an effect on glycemic control improvement through the elevation of intact glucagon-like peptide-1 (GLP-1). To clarify whether or not the 80% inhibition is sufficient to protect against GLP-1 degradation, we investigated rats with a continuous infusion of exogenous GLP-1. When GLP-1 was infused into the femoral or portal vein, the steady state active GLP-1 levels in plasma significantly increased (P<0.05) at the 80% inhibitory concentration (IC80) of anagliptin (a highly selective DPP-4 inhibitor) against plasma DPP-4 activity, compared with control. In addition, the peptide levels increased in a concentration-dependent manner at drug concentrations from IC80 to 10-fold IC80, and the levels at the 10-fold IC80 were significantly higher (P<0.05) than those at IC80. The concentration dependency on GLP-1 increment was also confirmed based on the experiment in which the endogenous active GLP-1 levels were measured after an oral carbohydrate load. These findings suggest that an almost complete inhibition (80%) of plasma DPP-4 activity was insufficient to protect GLP-1 degradation, and much higher drug concentrations such as 10-fold IC80 are necessary to potently protect GLP-1 from degradation by DPP-4 commonly present in blood and tissues.

Subdiaphragmatic vagotomy promotes nociceptive sensitivity of deep tissue in rats.

To verify whether vagal dysfunction is associated with chronic pain, we evaluated the effects of subdiaphragmatic vagotomy (vgx) on the sensitivity toward noxious stimuli in rats. Vgx rats showed sustained hyperalgesia in the gastrocnemius muscle without tissue damage (no increase in vgx-induced plasma creatine phosphokinase or lactose dehydrogenase levels) accompanied by hypersensitivity to colonic distension. We found a dramatic increase in the levels of metabotropic glutamate receptor 5, protein kinase C (PKC) gamma and phosphorylated-PKCgamma within the spinal cord dorsal horn in vgx rats, which suggests that vgx may evoke sensory nerve plasticity. Morphine produced a dose-dependent increase in the withdrawal threshold in both vgx and sham-operated rats, but the effect of a lower dose in vgx rats was weaker than that in sham-operated rats. Muscle hyperalgesia in vgx rats was also attenuated by gabapentin and amitriptyline, but was not affected by diclofenac, dexamethasone or diazepam. These findings indicate that subdiaphragmatic vagal dysfunction caused chronic muscle hyperalgesia accompanied by visceral pain and both gabapentin and amitriptyline were effective for subdiaphragmatic vagotomy-induced pain, which are partially similar to fibromyalgia syndrome. Furthermore, this chronic muscle pain may result from nociceptive neuroplasticity of the spinal cord dorsal horn.

Brca1 heterozygous mice have shortened life span and are prone to ovarian tumorigenesis with haploinsufficiency upon ionizing irradiation.

BRCA1 mutation carriers have an 85% lifetime risk of breast cancer and 60% for ovarian cancer. BRCA1 facilitates DNA double-strand break repair, and dysfunction of BRCA1 leads to hypersensitivity to DNA damaging agents and consequently genomic instability of cells. In this communication, we have examined the tumor incidence and survival of Brca1 heterozygous female mice. Brca1 heterozygotes appear to have a shortened life span with 70% tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these mice. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence specific to ovarian tumors, but not lymphoma, when compared with the Brca1+/+ mice. All the tumors from heterozygous mice examined retain the wild-type allele and the cancer cells express Brca1 protein, precluding the chromosomal mechanism for loss of heterozygosity of Brca1 locus. Although the manifestation of BRCA1 haploinsufficiency may be different between human and mouse, this study suggests that women carrying Brca1 mutations may be more prone to ovarian tumor formation after IR exposure than nonmutation carriers.

Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells.

Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 transmits cell survival signals remains unclear. Here, we show that both a flavoprotein inhibitor, diphenylene iodonium (DPI), and small interfering RNAs designed to target Nox4 mRNA (siNox4RNAs) inhibited superoxide production in PANC-1 pancreatic cancer cells, and depletion of ROS by DPI or siNox4RNAs induced apoptosis. Parallely, DPI treatment and siNox4RNA transfection blocked activation of the cell survival kinase AKT by attenuating phosphorylation of AKT. Furthermore, AKT phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) on Ser-83 was reduced by DPI and siNox4RNAs. When ASK1Ser83Ala (an AKT phosphorylation-defective ASK1 mutant) was introduced into PANC-1 cells, this mutant alone induced apoptosis. But, addition of DPI or co-transfection of siNox4RNA had no additive effect, indicating that the mutant can substitute for these reagents in apoptosis induction. Taken together, these findings suggest that ROS generated by Nox4, at least in part, transmit cell survival signals through the AKT-ASK1 pathway in pancreatic cancer cells and their depletion leads to apoptosis.

Prediction of the origin of intracanalicular neoplasms with high-resolution MR imaging.

Correct diagnosis of intracanalicular neoplasms is important to avoid unnecessary operations or an unsuitable surgical approach. We investigated the capability of high-resolution three-dimensional MR imaging in predicting the origin of intracanalicular neoplasms. Twenty cases underwent three-dimensional Fourier-transformation (3DFT) constructive interference in steady state and contrast-enhanced 3DFT-fast low angled shot MR imaging and surgery. Seventeen cases underwent caloric test. MR diagnosis on the origin of intracanalicular neoplasms was compared with surgical results. For MR diagnosis, the origin of intracanalicular neoplasms was predicted according to the location of the tumor in the internal auditory canal (IAC) in two ways, i.e., determining (1) a single specific nerve of origin and (2) whether the tumor originated from the superior or inferior aspect of the IAC. Surgery could determine the nerve of origin in 16 cases (14 inferior and 2 superior vestibular schwannomas), but it was indeterminate in 4. Comparison between MR prediction and surgical results on a single nerve origin revealed exact agreement in five, but inconsistent in three. Regarding whether the tumor was derived from superior or inferior aspect of the IAC, agreement was found in 10 of the 16 cases (62.5%). Caloric test was abnormal in all patients examined but one with superior vestibular schwannoma. 3DFT-MR imaging was not particularly useful in predicting a precise nerve of origin of intracanalicular neoplasms. The prediction on whether the tumor originated in the superior or inferior aspect of the IAC was superior to caloric test, which might have clinical significance in treatment planning especially for hearing preservation surgery.

[Nifekalant hydrochloride as an effective treatment for postoperative ischemic heart disease].

We experienced 2 effective cases of nifekalant hydrochloride. One patient was 76-year-old female who underwent emergent coronary artery bypass grafting (CABG) because of unstable angina pectoris (AP) and ventricular fibrillation (Vf). Her cardiac function had been decreased preoperatively due to old myocardial infarction (OMI). One day after CABG, she revealed sustained ventricular tachycardia (VT) and Vf. Although administrations of neither lidocaine hydrochloride nor magnesium sulfate were effective, nifekalant hydrochloride finally stopped the life-threatening arrhythmia without hypotension. Another patient was 77-year-old male who underwent CABG and Dor operation. His cardiac function also had been decreased due to OMI. He revealed VT attack at midnight 3 days after operation. VT attack still appeared at next 2 midnight under lidocaine hydrochloride infusion, but finally it has disappeared after starting a drip infusion of nifekalant hydrochloride. Nifekalant hydrochloride is quite useful as a new therapeutic strategy for uncontrollable VT and Vf and for the patient who has a reduced left ventricular function because it has an inotropic effect.

The use of endoscopic ultrasound-guided fine-needle aspiration for investigation of submucosal and extrinsic masses of the colon and rectum.

BACKGROUND AND STUDY AIM: Ensdoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful technique for histological diagnosis of submucosal or extrinsic gastrointestinal and pancreatic lesions. The aim of this study was to evaluate the use of EUS-FNA for the diagnosis of lesions either within or adjacent to the wall of the colon and rectum. PATIENTS AND METHODS: A total of 22 patients with a lesion within the wall of, or adjacent to, the colon or rectum underwent EUS-FNA. They were divided into two groups: patients who had previously had a malignancy (the "previous +ve" group, n = 11), and patients who had not previously had a malignancy (the "previous -ve" group, n = 11). In the four patients who had lesions located proximal to the sigmoid colon, EUS-FNA was performed using a guide wire and overtube. The success rates for adequate tissue sampling and for detecting malignant and benign masses by EUS-FNA were evaluated and the success rate for detection was compared with the success rate of EUS and computed tomography. RESULTS: Sufficient tissue for evaluation was obtained from 21 of the 22 patients (95.5 %). The overall rate of detection of malignant and benign masses was 95.5 % (21/22) for EUS-FNA and 81.8 % (18/22) for pre-EUS-FNA imaging investigations. Of the 11 patients in the previous +ve group, ten were diagnosed with recurrences of primary malignancies; of the 11 patients in the previous -ve group, four were diagnosed with primary malignancies and seven were diagnosed with benign lesions. There were no complications related to the EUS-FNA procedure. CONCLUSIONS: EUS-FNA is a safe technique which is useful in the planning of treatment for patients who have a mass within the wall or adjacent to the wall of the entire length of the colon or rectum.

[Observation of the right atrial wall suture line after tricuspid valve supra-annular implantation].

Strength of the right atrial wall suture line after tricuspid valve supra-annular implantation (TVSI) is controversial. We observed the right atrial supra-annular position of a 63-year-old male during his third mitral operation who underwent mitral valve replacement (MVR) and TVSI 15 years ago. Eight years later, he received the second MVR and removal of the bioprosthetic valve from the tricuspid position due to primary tissue failures. The annular size of the tricuspid valve had decreased enough to be fixed by tricuspid annuloplasty (TAP) and re-TVSI was not needed at that time. In this operation, 7 years following bioprosthetic valve removal, the circularly bulging atrial wall still remained and seemed to have enough strength for holding the prosthetic valve. This finding may support the conclusion that the right atrial wall has enouth strength for holding a prosthetic valve in position.

Incoherent noise and quantum information processing.

Incoherence in the controlled Hamiltonian is an important limitation on the precision of coherent control in quantum information processing. Incoherence can typically be modeled as a distribution of unitary processes arising from slowly varying experimental parameters. We show how it introduces artifacts in quantum process tomography and we explain how the resulting estimate of the superoperator may not be completely positive. We then go on to attack the inverse problem of extracting an effective distribution of unitaries that characterizes the incoherence via a perturbation theory analysis of the superoperator eigenvalue spectra.

Differential effects of yohimbine, naloxone and 8-OH-DPAT on ejaculatory response in male dogs.

The aim of this study was to compare the effects of the alpha(2)-adrenergic-receptor antagonist yohimbine, the 5-HT(lA)-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the opioid-receptor antagonist naloxone (all of which have been shown to stimulate male sexual arousal/motivation in rats) on sexual responses in male dogs. Sexual responses (i.e., ejaculation, penile erection and pelvic thrusting behavior) were elicited by manual penile stimulation. Systemic administration of yohimbine (0.03-1.0 mg/kg) produced a biphasic dose response curve for the amount of ejaculated semen collected during genital stimulation (for 5 min), whereas 8-OH-DPAT (0.03-0.3 mg/kg) dose-dependently decreased the amount of ejaculated semen. Thus, yohimbine increased the amount of ejaculated semen at lower doses (0.03-0.3 mg/kg), but decreased it at the highest dose (1.0 mg/kg). The highest dose of yohimbine (1.0 mg/kg) and 8-OH-DPAT (0.3 mg/kg) also produced a significant delay of onset in both ejaculation and penile erection latency (time from starting the stimulation to the first ejaculation and full erection), and a decrease in the incidence of pelvic thrusting behavior. In contrast, administration of naloxone (0.03-1.0 mg/kg) did not affect the sexual responses elicited by genital stimulation. These results indicate that yohimbine and 8-OH-DPAT, but not naloxone, affect sexual responses, particularly ejaculation, and that the drugs which stimulate the mechanisms regulating sexual arousal/motivation in male rats do not show identical effects for sexual function in male dogs. The present findings also confirm our previous observations that the ejaculatory capacity in dogs can be stimulated by lower doses of yohimbine, as evidenced by an increase in the amount of ejaculated semen.

Involvement of adenosine A1 receptors in forced walking stress-induced analgesia in mice.

We investigated the involvement of adenosine receptors on forced walking stress-induced analgesia using a formalin-induced paw-licking test in male mice. Exposure to forced walking stress for 6 h showed stress-induced analgesia in the second phase (10-30 min), but not in the first phase (0-10 min). In the second phase, forced walking stress-induced analgesia was blocked by theophylline, a nonselective adenosine-receptor antagonist and DPCPX, an adenosine A1-receptor antagonist, but not ZM 241385, an adenosine A2A-receptor antagonist. These findings suggest that adenosine A1 receptors are involved in the analgesic mechanism activated by the forced walking stress.

Spinal anesthesia hypotension in elective cesarean section in parturients wearing extra-strong compression stockings.

We have routinely applied an extra-strong graduated compression stocking to cesarean section patients to reduce the incidence of spinal anesthesia hypotension. Because bupivacaine has recently become available in Japan, we compared the incidence of spinal hypotension using either 2.0 ml of hyperbaric 0.3% dibucaine or 0.5% bupivacaine. There were 98 full-term parturients wearing the stocking who received 2.0 ml injection of dibucaine or bupivacaine for elective cesarean section. When systolic blood pressure decreased to 90-100 mm Hg or to less than 70% of the pre-anesthesia value, ephedrine was injected intravenously. There was no significant difference in systolic blood pressure or heart rate during spinal anesthesia between the dibucaine and bupivacaine groups. Although the demographic data and various data related to anesthesia or surgery were similar in the groups, the fluid volume and the dose and incidence of ephedrine injection during anesthesia showed significant differences: the mean dose was 3.6 and 1.5 mg and the incidence was 41% and 19% in the dibucaine and bupivacaine groups, respectively. Spinal anesthesia using bupivacaine results in a lower incidence of spinal hypotension compared with dibucaine and, in combination with fitting the extra-strong stockings onto both legs, is clinically useful for cesarean sections.

Circulatory, respiratory and metabolic changes after thigh tourniquet release in combined epidural-propofol anaesthesia with preservation of spontaneous respiration.

Twelve elderly patients undergoing total knee arthroplasty received lumbar epidural anaesthesia and propofol infusion at 5 mg.kg(-1).h(-1) following a 1.5-2.0 mg.kg(-1) bolus dose with preservation of spontaneous respiration via a laryngeal mask airway. Circulatory, respiratory and metabolic variables were measured before and 1, 3, 5, 15 and 30 min after release of a pneumatic thigh tourniquet. The blood pressure was decreased at all time-points and the respiratory rate increased at 1 min. The P(a)CO(2) was increased only at 1 min. Arterial blood pH and base excess were decreased at 1 and 3 min and 1, 3 and 5 min, respectively. Arterial blood lactate levels were increased at all times. These characteristics were considered to be identical to those under regional anaesthesia with conscious spontaneous respiration, showing that spontaneous respiration under this anaesthetic regimen has a similar respiratory capacity to that of conscious spontaneous respiration.

Highly polymerized procyanidins in brown soybean seed coat with a high radical-scavenging activity.

1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity of the 70% aqueous acetone extract from the seed coat of the brown soybean variety, Akita-Zairai, was investigated. The activity of the seed coat of Akita-Zairai was much higher than that of three other reddish-brown varieties, but lower than that of two black varieties, and was closely dependent on the content of phenolic compounds. In the LH20 column chromatography of Akita-Zairai, high DPPH radical-scavenging activities were detected in the fractions eluted with MeOH and 70% aqueous acetone. Proanthocyanidins were also detected in fractions showing high radical-scavenging activities. Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis showed that the degree of polymerization (DP) of the procyanidins contained in the brown or black soybean seed coat was as high as DP30.

The Sos1-Rac1 signaling. Possible involvement of a vacuolar H(+)-ATPase E subunit.

We have purified and identified a 32-kDa protein interacting with the Dbl oncogene homology domain of mSos1(Sos-DH) from rat brains by glutathione S-transferase-Sos-DH affinity chromatography. Peptide sequencing revealed that the protein is identical to a positive regulatory E subunit (V-ATPase E) of a vacuolar H(+)-ATPase, which is responsible for acidification of endosome and alkalinization of intracellular pH. The interaction between V-ATPase E and Sos-DH was confirmed by yeast two-hybrid assay. A coimmunoprecipitation assay demonstrated that a V-ATPase E protein physiologically bound to mSos1, and the protein was colocalized with mSos1 in the cytoplasm, as determined by immunohistochemistry. mSos1 was found in the early endosome fraction together with V-ATPase E and Rac1, suggesting the functional involvement of mSos1/V-ATPase E complexes in the Rac1 activity at endosomes. Overexpression of V-ATPase E in COS cells enhanced the ability of mSos1 to promote the guanine nucleotide exchange activity for Rac1 and stimulated the kinase activity of Jun kinase, a downstream target of Rac1. Thus, the data indicate that V-ATPase E may participate in the regulation of the mSos1-dependent Rac1 signaling pathway involved in growth factor receptor-mediated cell growth control.

Alpha 2-adrenoceptor antagonists: effects on ejaculation, penile erection and pelvic thrusting behavior in dogs.

We previously reported that systemic administration of yohimbine, an alpha2-adrenoceptor antagonist, exerts a biphasic effect (stimulating and suppressing) on ejaculation in dogs, when this function is analyzed using the amount of ejaculated semen in response to genital stimulation. To clarify the effect of alpha2-adrenoceptor blockade on male sexual function, we investigated the effects of four selective alpha2-adrenoceptor antagonists, rauwolscine, idazoxan, RX821002 and mydaglizole, on sexual responses (ejaculation, penile erection and pelvic thrusting behavior) elicited by manual penile stimulation in dogs. Rauwolscine (intraperitoneal, 30 min before the testing) caused a biphasic effect on ejaculation; the amount of ejaculated semen produced by the stimulation was significantly increased by the lower doses (0.1 and 0.3 mg/kg), whereas it was decreased by the higher doses (1.0 and 2.0 mg/kg). The higher doses of rauwolscine also markedly inhibited both penile erection and pelvic thrusting behavior. Idazoxan and RX821002, at doses of 0.1 and 0.3 mg/kg, caused a significant increase in the amount of ejaculated semen without affecting other sexual functions. RX821002 (2.0 mg/kg), but not idazoxan (2.0 mg/kg), moderately inhibited both penile erection and pelvic thrusting behavior. Mydaglizole, a peripherally acting alpha2-adrenoceptor antagonist, did not affect the sexual responses at any doses (0.1-4.0 mg/kg). In the ejaculatory declining test, all alpha2-adrenoceptor antagonists (0.1 mg/kg), except for mydaglizole, completely prevented the decrease in ejaculatory capacity produced by antecedent ejaculation. These results indicate that, though the range of the effective dose is narrow, the alpha2-adrenoceptor antagonists that can block the central alpha2-adrenoceptors have the stimulatory effects on ejaculatory function. The difference of the sexual effects may be based on the action except for the alpha2-adrenoceptor blockade.

Pharmacodynamic analysis of steroid 5alpha-reductase inhibitory actions of Z-350 in rat prostate.

The pharmacodynamics of (S)-4-[3-[4-[1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy]benzoyl]indole-1-yl] butyric acid hydrochloride (Z-350), which has alpha(1)-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory effects, were investigated in rats. The disposition of Z-350 was a function of linear kinetics at doses from 1 to 30 mg/kg; the bioavailability was calculated to be 65.2%. The inhibition of 5alpha-reductase was dependent on the concentration of Z-350 in plasma and in the prostate. Analysis of the relationship between the concentration in the prostate and the inhibition seen after a single oral administration showed that the Hill constant was almost 1.0 and EC(50)(n(H)) was 47.4 ng/g of tissue; these parameters did not change after multiple administration. Z-350 inhibited 5alpha-reductase 1 h after oral administration at a dose of 3 mg/kg; maximum inhibition was observed after 2-4 h, and the inhibition (%) was maintained for 24 h after oral administration.

Extra-strong graduated compression stocking reduces usage of vasopressor agents during spinal anesthesia for cesarean section.

Because a standard type of graduated compression stocking is not effective for the prevention of spinal anesthesia hypothension during cesarean section, we have used an extra-strong type of graduated compression stocking. This study examined whether the extra-strong stocking reduces usage of vasopressor agents. Forty-eight and 47 full term parturients were fitted with the standard stocking and the extra-strong stocking, respectively. Spinal anesthesia was performed by injecting 2.0 ml 0.3% dibucaine hyperbaric solution. When systolic blood pressure decreased to 90-100 mmHg or to less than 70% of the pre-anesthesia value, ephedrine was injected. There was no significant difference in systolic blood pressure or heart rate during spinal anesthesia between the groups. The mean dose of ephedrine injected during anesthesia was 12.2 and 4.3 mg, and the incidence of ephedrine injected was 85 and 49%, in the standard and extra-strong stocking groups, respectively. The extra-strong stocking group showed significantly lower values. Fitting the extra-strong stocking on both legs for cesarean sections undergoing spinal anesthesia reduced usage of vasopressor agents, suggesting a promising use of this stocking for non-invasive prophylaxis.