Psychological Intervention Can Partly Alter P300-Amplitude Abnormalities in Schizophrenics

Abstract: In the present study, we investigated whether psychological interventions can alter P300-abnormalities, specifically enhancing reduced P300-amplitudes, in schizophrenics. A three-tone discrimination task was employed for recording P300s, in which psychological intervention to facilitate target detection was performed through delivering a buzzer sound one second after each designated target tone that informed its occurrence. This procedure was done exclusively during the third and fourth sessions among the six sessions in total. When the data for all the patients were analyzed as a whole, no significant change was observed. However, when the patients were broken down into two groups based on the P300-amplitudes in the first and second sessions, significant effects of the intervention emerged. The group with smaller P300-amplitudes showed a significant increase in P300-amplitudes as well as improved performance levels during and after the intervention sessions. On the contrary, the group with larger P300-amplitudes displayed a significant decrease in P300-amplitudes in these sessions. Interestingly, the above results were consistent with the subjective difficulty changes experienced by the patients through the sessions. Overall, the above results indicate that psychological interventions can partly enhance reduced P300-amplitudes in schizophrenics.     

Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas

BACKGROUND. Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE. A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS. He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION. When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.     

Urinary concentrations of cytokines in patients with pyelonephritis and cystitis

We measured concentrations of interleukin-1β,-6 and-8, and tumor necrosis factor-α in the urine and blood of patients with urinary tract infections. We also examined the relationships between the severity of pyuria and concentrations of interleukin-6 or interleukin-8 in urine. Concentrations of interleukin-6 and-8 were significantly higher in the urine of patients with urinary tract infections than that of healthy subjects or patients with fever unrelated to the urinary tract infection. A close relationship was observed between the severity of pyuria and the concentration of interleukin-8. Concentrations of interleukin-6 and-8 in the blood were higher in patients with pyelonephritis than in patients with cystitis. These results suggest that the interleukin-6 and-8 were generated in the urinary tract during pyelonephritis and cystitis, and that the interleukin-8 induced leukocyte influx into the urine.     

Differential expression of proteinase inhibitor-9 and granzyme B mRNAs in activated immunocompetent cells

The role of proteinase inhibitor (PI)-9 in hematopoietic cells remains unclear. To clarify the role of PI-9 in these cells, we compared the expressions of PI-9 mRNA and antigen with those of granzyme B (GrB). While the strongest expression of PI-9 mRNA was observed in a NK cell line YT-N10, it was also expressed in a B-acute lymphoblastic leukemia cell line U-Tree02, an Epstein-Barr Virus (EBV)-transformed B cell clone, a CD8+ T lymphocyte clone and a megakaryocytic cell line CMK, but not in a T cell line Jurkat. Phorbol 12-myristate 13 acetate (PMA) enhanced PI-9 mRNA expression in the CD8+ T lymphocyte clone and YT-N10 cells prior to GrB mRNA expression. IL-2 and IL-12 also had similar effects. PMA increased PI-9 mRNA expression in the EBV-transformed B cell clone and CMK cells, but IL-6 showed no effect. No changes were noted in PI-9 and GrB antigens after the addition of these agonists. Patients with graft-versus-host disease (GVHD) may have activated CTLs and NK cells. We therefore examined the expression of PI-9 and GrB mRNAs in eight patients after allogeneic hematopoietic stem cell transplantation with GVHD (n = 4) or without chronic GVHD (n = 4). Expression of GrB mRNA was significantly increased in three patients with GVHD and one patient without GVHD. Surprisingly, PI-9 mRNA expression was decreased in the eight patients. These results indicate that earlier synthesis of PI-9 may be essential for the prevention of autolysis of immunocompetent cells, and that the expression of PI-9 and GrB mRNAs may be controlled through different pathways.     

Dehydrothermal treatment of collagen influences on bone regeneration by octacalcium phosphate (OCP) collagen composites

We have engineered a scaffold constructed of synthetic octacalcium phosphate (OCP) and collagen composites (OCP-collagen) and report that OCP-collagen significantly enhanced bone regeneration more than the implantation of OCP. We hypothesized that the dehydrothermal treatment (DHT) during the fabrication of OCP-collagen might influence bone regeneration by OCP-collagen. To examine this hypothesis, bone regeneration by the implantation of OCP-collagen with DHT [OCP/Col(+)] was compared with that by OCP-collagen without DHT [OCP/Col(-)]. It was confirmed that both OCP/Col(+) and OCP/Col(-) contained the characteristics of OCP structure in X-ray diffraction. Before implantation, calcium deposition derived from OCP was observed within the collagen of both OCP/Col(+) and OCP/Col(-) by undecalcified histological sections. OCP/Col(+) or OCP/Col(-) was implanted into the critical-sized defects in rat crania. Radiographic and histological examination was performed and the percentage of newly formed bone (n-Bone%) in the defect was determined by a histomorphometrical analysis. N-Bone% treated with OCP/Col(+) was significantly higher than that with OCP/Col(-) at 4 and 12 weeks after implantation, because fast degradation of the implanted collagen of OCP/Col(-) elicited disappearance of the scaffold for bone regeneration. The stiffness of the calcified collagen in OCP-collagen would be more important than the existence of calcified collagen to enhance the bone regeneration by OCP-collagen composites. The present study suggests that the dehydrothermal treatment would influence effective bone regeneration by OCP-collagen.     

Tumor targeting of gene expression through metal-coordinated conjugation with dextran.

Tumor targeting of plasmid DNA was achieved through the conjugation of dextran derivatives with chelate residues based on metal coordination. Diethylenetriamine pentaacetic acid (DTPA), spermidine (Sd), and spermine (Sm) were chemically introduced to the hydroxyl groups of dextran to obtain dextran-DTPA, dextran-Sd and dextran-Sm derivatives. Conjugation of the dextran derivative by Zn(2+) coordination decreased the apparent size of the plasmid DNA, depending on the derivative type. The negative zeta potential of plasmid DNA became almost 0 mV after Zn(2+)-coordinated conjugation with dextran-Sm. When the dextran derivative-plasmid DNA conjugates with Zn(2+) coordination were intravenously injected subcutaneously into mice bearing Meth-AR-1 fibrosarcoma, the dextran-Sm-plasmid DNA conjugate significantly enhanced the level of gene expression in the tumor, in contrast to the conjugate of other dextran derivatives and free plasmid DNA. The enhanced gene expression produced by the Zn(2+)-coordinated dextran-Sm-plasmid DNA conjugate was specific to the tumor, whereas a simple mixture of dextran-Sm and plasmid DNA was not effective. The level of gene expression depended on the percentage of chelate residues introduced, the mixing weight ratio of the plasmid DNA/Sm residue used for conjugate preparation, and the plasmid DNA dose. A fluorescent microscopic study revealed that localization of plasmid DNA in the tumor tissue was observed only after injection of the dextran-Sm-plasmid DNA conjugate with Zn(2+) coordination. In addition, the gene expression induced by the conjugate lasted for more than 10 days after the injection. We conclude that Zn(2+)-coordinated dextran-Sm conjugation is a promising way to enable plasmid DNA to target the tumor in gene expression as well as to prolong the duration of gene expression.     

Contractions to histamine in pulmonary and mesenteric arteries from endotoxemic rabbits: modulation by vascular expressions of inducible nitric-oxide synthase and histamine H1-receptors

The inducible isoform of nitric-oxide synthase (iNOS) is highly expressed after induction of endotoxemia and contributes to vascular hypocontractility in endotoxemia. Circulating levels of histamine are elevated in animal models of sepsis and in patients with septic shock. This study assessed whether the vascular effects of histamine play a significant role in the pathophysiology of endotoxemic shock despite the hyporesponsiveness to vasoconstrictors associated with iNOS up-regulation. Rabbits were rendered endotoxemic by lipopolysaccharide (LPS; 100 microg/kg, i.v.). In mesenteric arteries taken from animals at 6 h of LPS administration, the contractile response to histamine was significantly impaired but histamine-evoked contractions in pulmonary arteries were unchanged. Western blot revealed a drastic increase in iNOS expression in mesenteric vessels after LPS, but endotoxin-induced iNOS increase was not so marked in pulmonary vessels. On the other hand, expression of endothelial nitric-oxide synthase was suppressed under LPS challenge in both types of vessels. In the presence of NG-nitro-l-arginine or (S)-ethylisothiourea used for iNOS inhibition, histamine-evoked contractions of endotoxemic pulmonary and mesenteric vessels were significantly enhanced. This was possibly associated with a dramatic increase in H1-receptor expression at the gene and protein levels, as determined by Northern blot and immunoblot analyses. Furthermore, we found that LPS-induced endotoxemia caused prominent increases in production of histamine through induction of histidine decarboxylase in tissues, including blood vessels. From these results, we propose that histamine may contribute to the development of endotoxin-induced pulmonary hypertension.     

Clinical and molecular features of treatment‐related neuroendocrine prostate cancer

Treatment‐related neuroendocrine prostate cancer is a lethal form of prostate cancer that emerges in the later stages of castration‐resistant prostate cancer treatment. Treatment‐related neuroendocrine prostate cancer transdifferentiates from adenocarcinoma as an adaptive response to androgen receptor pathway inhibition. The incidence of treatment‐related neuroendocrine prostate cancer has been rising due to the increasing use of potent androgen receptor pathway inhibitors. Typically, treatment‐related neuroendocrine prostate cancer is characterized by either low or absent androgen receptor expression, small cell carcinoma morphology and expression of neuroendocrine markers. Clinically, it manifests with predominantly visceral or lytic bone metastases, bulky tumor masses, low prostate‐specific antigen levels or a short response duration to androgen deprivation therapy. Furthermore, although the tumor initially responds to platinum‐based chemotherapy, the duration of the response is short. Based on the poor prognosis, it is imperative to identify novel molecular targets for treatment‐related neuroendocrine prostate cancer. Recent advances in genomic and molecular research, supported by novel in vivo models, have identified some of the key molecular characteristics of treatment‐related neuroendocrine prostate cancer. The gain of MYCN and AURKA oncogenes, along with the loss of tumor suppressor genes TP53 and RB1 are key genomic alterations associated with treatment‐related neuroendocrine prostate cancer. Androgen receptor repressed genes, such as BRN2 and PEG10, are also necessary for treatment‐related neuroendocrine prostate cancer. These genetic changes converge on pathways upregulating genes, such as SOX2 and EZH2, that facilitate lineage plasticity and neuroendocrine differentiation. As a result, on potent androgen receptor pathway inhibition, castration‐resistant prostate cancer transdifferentiates to treatment‐related neuroendocrine prostate cancer in a clonally divergent manner. Further understanding of the disease biology is required to develop novel drugs and biomarkers that would help treat this aggressive prostate cancer variant.     

Extrinsic Factors as Component Positions to Bone and Intrinsic Factors Affecting Postoperative Rotational Limb Alignment in Total Knee Arthroplasty

Background

This study aimed to identify the factors affecting postoperative rotational limb alignment of the tibia relative to the femur. We hypothesized that not only component positions but also several intrinsic factors were associated with postoperative rotational limb alignment.