Neuronal excitation in the ventral tegmental area modulates the micturition reflex mediated via the dopamine D1 and D2 receptors in rats

Involvement of the dopamine D(1) and D(2) receptors in the ventral tegmental area (VTA) in the micturition reflex was investigated using female Sprague Dawley rats under urethane anesthesia. Cystometrograms during continuous infusion of warmed saline into the bladder were recorded. When intervals of bladder contraction became constant, the excitatory amino acid DL-homocysteic acid (DLH) was microinjected into the VTA and changes in the cystometric parameters were observed. The selective D(1) antagonist SCH23390 (0.3 mg/kg) or D(2) antagonist eticlopride (0.1 mg/kg) was subcutaneously injected (s.c.) 15 min prior to the DLH treatment. A low dose of DLH (3 microg) facilitated the micturition reflex, whereas a high dose of DLH (30 microg) inhibited the micturition reflex. However, a middle dose of DLH (10 microg) did not show any effect. The facilitated micturition reflex induced by a low dose of DLH was inhibited by the selective dopamine D(2) antagonist eticlopride, but unaltered by SCH23390, a selective dopamine D(1) antagonist. In contrast, the inhibitory effect induced by a high dose of DLH on the micturition reflex was suppressed by SCH23390 but not eticlopride. These results suggested that the facilitated micturition reflex might be mediated via the dopamine D(2) receptors, while the inhibitory effects on the micturition reflex was mediated via the dopamine D(1) receptors.     

Coronary endarterectomy and on-lay patch anastomosis in a case with unstable angina due to diffusely diseased coronary artery

A 76-year-old woman with unstable angina due to diffusely diseased coronary artery successfully underwent coronary artery bypass grafting (CABG) using endarterectomy and on-lay patch anastomosis. She had triple vessel disease in the coronary artery and all of them were diffusely stenotic. It was impossible to undertake simple CABG. We were able to perform 3 coronary artery bypass grafting using endarterectomy and on-lay patch anastomosis. The postoperative course was uneventful and postoperative angiogram revealed well patent 3 grafts. Coronary endarterectomy and on-lay patch anastomosis were effective procedure in a patient with diffusely diseased coronary artery.     

Efficacy and pharmacokinetics of imatinib mesylate in a child with chronic myeloid leukemia

A 6-year-old girl with chronic myeloid leukemia (CML) was treated with imatinib 230 mg/m2/day and its pharmacokinetics were investigated. The patient had a complete hematologic response on day 21, but had a minor cytogenetic response and the CML progressed to a blast crisis on day 133. At present, she has maintained complete cytogenetic remission with allogenetic peripheral blood stem cell transplantation. The pharmacokinetics revealed that the maximum concentration (1.4 micrograms/ml); time to maximum concentration (5.1 h); half-life (11.0 h); trough concentration (0.4 microgram/ml); and, area under the concentration-time curve (28.1 micrograms.h/ml) were inferior to those for adult patients in the 400 mg/day group. This observation suggests that a suboptimal plasma concentration might be related to resistance to imatinib and/or blast crisis.     

Characterization of Two Novel Retinoic Acid-resistant Cell Lines Derived from HL-60 Cells Following Long-term Culture with all-trans-Retinoic Acid

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60–R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60–R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60–R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 μM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60–R9 cells, but not in HL-60–R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RARα gene in HL-60–R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60–R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RARα of HL-60–R9, but by other factor(s), which also affect the VD-response pathways, in HL-60–R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.     

Serous cystadenocarcinoma of the pancreas

A case of serous cystadenocarcinoma of the pancreas in an 85-year-old woman is reported. The tumor extensively involved the body and tail of the pancreas and contiguously invaded the spleen. The histopathology of the tumor was similar to that of serous cystadenoma, but mild nuclear hyperchromatism and atypism were noted, and the neoplastic invasion of nerve fibers in the stroma was observed. In the spleen neoplastic cells forming microcysts were diffusely insinuated in the red pulp without the fibrous stroma. The patient is in good health without recurrence and metastasis after the operation. The present case is the second example of this kind of neoplasm that showed direct splenic invasion. Because serous cystadenocarcinoma of the pancreas exhibits bland cytological features, diligent search for the invasion of the surrounding tissue or peripheral nerves is needed for the differentiation from its benign counterpart.     

The iliac wing sign: an indicator of the presence of bone and/or soft-tissue injury of the pelvis and hips

Purpose

To prospectively evaluate the feasibility of using the “iliac wing sign (IWS)” as an indicator of bone and/or soft-tissue injury of the pelvis and hips on magnetic resonance (MR) imaging. IWS means edema of the iliacus muscle attachment entering the iliac wing that is visualized as a linear high signal intensity on fat-suppressed T2-weighted MR images.

Methods

Consecutive 106 patients who complained of hip pain were enrolled in this study. We evaluated the correlation between IWS and bone and/or soft-tissue injury of the pelvis and hips using Fisher's exact test. Further, performance parameters of sensitivity, specificity, accuracy, the positive predictive value (PPV), and negative predictive value (NPV) of IWS were calculated.

Results

Thirty-eight of the 106 (36%) patients had bone and/or soft-tissue injury. Twenty-seven of these 38 (71%) patients with injury showed a positive IWS, while only 11 of 68 (16%) patients without injury showed a positive IWS (p < .0001). IWS, thus, yielded a sensitivity of 71%, specificity of 84%, accuracy of 79%, positive predictive value (PPV) of 71%, and negative predictive value (NPV) of 84%.

Conclusion

In cases with a positive IWS, the careful interpretation of MR images is needed because injury presence is highly likely, as suggested by the relatively high sensitivity and PPV. IWS absence may mean a low probability of injury because of the high specificity and NPV.     

Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation

Human luteal cells have been reported to express human leukocyteantigen-DR and lymphocyte functional antigen-3 on the cell surface,suggesting physiological interaction between luteal cells andT-lymphocytes through the menstrual cycle into early pregnancy.To elucidate the role of peripheral lymphocytes on corpus luteumdifferentiation, the effect of peripheral blood mononuclearcells (PBMC) on steroidogenesis by luteal cells was investigated.The production of Th-2 cytokines such as interleukin (IL)-4and IL-10 by the co-cultured cells was also examined, and theeffects of these cytokines on progesterone production by lutealcells were investigated. Corpora lutea were obtained from eightnon-pregnant women in the luteal phase and five women in earlypregnancy for luteal cell culture. PBMC were isolated from unrelatedwomen in the follicular phase, secretory phase, and early pregnancy.After co-culture with allogenic PBMC for 48 h, progesteroneproduction was significantly enhanced by PBMC from the secretoryphase and early pregnancy in the non-pregnant luteal cell culture.In the pregnant luteal cell culture, a significant increasein progesterone production was also observed by the co-culturewith PBMC from women in early pregnancy, showing that PBMC havea luteotrophic effect. The stimulatory effects of PBMC werealso observed in co-culture conditions which prevented directcell-to-cell interaction with luteal cells, showing the minorinfluence of mixed lymphocyte reaction. By co-culture with PBMC,the production of IL-10, but not IL-4, was significantly augmentedin luteal cell culture derived from non-pregnant women, whereasthe production of both IL-4 and IL-10 was significantly enhancedin the luteal cell culture derived from pregnant women. Moreover,IL-4 and IL-10 promoted progesterone production by culturedluteal cells, especially in the luteal cell culture derivedfrom corpora lutea of early pregnancy. These findings indicatethat PBMC stimulate progesterone production by luteal cellsand suggest the involvement of PBMC in corpus luteum functionand differentiation probably via the Th-2-type lymphocytes.     

Suppression of IFN-gamma production in atopic group at the acute phase of RSV infection

Several studies have suggested that respiratory syncytial virus (RSV) bronchiolitis induced the change of cytokine production profile in childhood. We sought to determine whether the RSV-induced cytokine production was affected by the patient's atopic background. We quantified interferon-gamma (IFN-gamma) and interleukin (IL)-4 in the supernatant of peripheral blood mononuclear cells (PBMCs) cultured for 24 h and in the presence of phytohemaglutinin (PHA), IL-12, or IL-18, from 14 infants who were divided into two groups, those who are non-atopic and an atopic group. In RSV-infected infants with atopic diseases, IFN-gamma production from IL-12- or especially IL-18-stimulated PBMCs was subtotally suppressed in the acute phase, whereas in RSV-infected infants without atopic diseases IFN-gamma production was not suppressed on acute phase. The IFN-gamma suppression observed in the atopic group is not caused by the immaturity of an infant's immune system since reduced IFN-gamma production to RSV is not observed in the infants of non-atopic group. IFN-gamma suppression in regard to RSV infection might be caused by some genetic factor involved in the development of atopic disease such as IL-18 signal cascade.     

Necrotic cervical nodes: Usefulness of diffusion-weighted MR imaging in the differentiation of suppurative lymphadenitis from malignancy

Purpose

The purpose of this study was to assess the efficacy of diffusion-weighted (DW) MR imaging for the differentiation between suppurative lymphadenitis and malignancy in necrotic cervical lymph nodes.

Materials and methods

Fifteen patients with suppurative lymphadenitis, 40 with squamous cell carcinoma (SCC), eight with lymphoma, and six with thyroid cancer were accompanied by necrotic cervical nodes. All 69 patients underwent 1.5-T MR imaging including DW and 58 underwent gadolinium-enhanced MR imaging. Necrotic area-to-spinal cord signal intensity ratios (SIR) on T1-, T2- and DW images and apparent diffusion coefficients (ADCs) [10⁻³ mm²/s] were correlated with the pathologies.

Results

Nineteen necrotic cervical nodes with suppurative lymphadenitis, 67 with SCC, 10 with lymphoma, and 12 with thyroid cancer were identified. SIR on DW images was higher in suppurative lymphadenitis (2.50 ± 1.21) than in malignancies (1.29 ± 0.67) (p < .01), and ADC value was lower in suppurative lymphadenitis (0.89 ± 0.21) than in malignancies (1.46 ± 0.46) (p < .01). SIR on T1-weighted images was higher in thyroid cancer (1.95 ± 0.53) than in suppurative lymphadenitis (0.87 ± 0.17), SCC (0.92 ± 0.13), and lymphoma (0.95 ± 0.09) (p < .01). No significant difference in SIR on T2-weighted images was found between suppurative lymphadenitis (1.46 ± 0.50) and malignancies (1.61 ± 0.56).

Conclusion

DW imaging with ADC measurements may play a supplementary role in the differentiation of necrotic cervical nodes between suppurative lymphadenitis and malignancy.