Pituitary metastasis of thyroid follicular adenocarcinoma--case report.

A rare case of pituitary metastasis of thyroid follicular adenocarcinoma occurred in a 62-year-old female manifesting as left retro-orbital pain and diplopia. Computed tomography and magnetic resonance imaging revealed a tumor in the pituitary fossa extending to the left cavernous sinus, sphenoid sinus, and prepontine cistern, destroying the upper portion of the clivus. An asymptomatic thyroid mass, probably malignant, was also found. She also had an incidental small meningioma in the posterior fossa. The pituitary tumor was partially removed, and the thyroid and posterior fossa tumors were totally removed in two operations. Both pituitary and thyroid tumors were verified to be follicular adenocarcinoma. Postoperatively, she developed panhypopituitarism for which cortisol and thyroxine replacement therapy was necessary. Three years after first therapy, she was alive but her symptoms did not improve.     

Roles of kallikrein-kinin system in acute inflammation: studies on high- and low-molecular weight kininogens-deficient rats (B/N-Katholiek strain)

Carrageenin-induced paw edema in HMW- and LMW-kininogens-deficient rats was significantly less than that in normal rats. There are three kininogens, HMW-, LMW- and T-kininogens, in normal rat plasma, but B/N-Katholiek rat plasma contains only T-kininogen. The pretreatment with captopril, a kiniase II inhibitor, enhanced paw swelling of normal rats, but not that of the deficient rats, indicating that bradykinin released from HMW-kininogen may have a role for the swelling but T-kinin may not be released in this inflammation.     

Tetronothiodin, a novel CCKB receptor ligand, antagonizes cholecystokinin-induced Ca2+ mobilization in a pituitary cell line.

We found a novel nonpeptide CCKB receptor antagonist, tetronothiodin (Ro 09-1468), in the culture broth of Streptomyces sp. NR0489. The structure of the compound (C31O8H38S), which has a 19-membered ring with an alpha-acyltetronic acid and tetrahydrothiophene moiety, is completely different from that of any known CCK receptor antagonist. Tetronothiodin inhibited [125I]CCK-8 binding to rat brain CCKB receptors with an IC50 of 3.6 nM, whereas it showed only weak affinity for rat CCKA receptors (IC50 = 70 microM). As demonstrated autoradiographically, tetronothiodin concentration dependently inhibited [125I]CCK-8 binding to CCKB receptors in rat forebrain slices. The effects of tetronothiodin on cytosolic Ca2+ concentrations in GH3 cells, a rat anterior pituitary tumor cell line, were investigated with the fura-2 method. Tetronothiodin inhibited CCK-8-induced Ca2+ mobilization without affecting basal cytosolic Ca2+ concentrations. In conclusion, tetronothiodin is a new, potent and highly selective CCKB receptor antagonist. It is a useful tool for investigating the pharmacological and physiological roles of CCKB receptors.     

Analysis of T Cell Receptor Variability in Fresh Tumor-infiltrating Lymphocytes from Human Head and Neck Cancer

In this study, we analyzed T cell receptor (TCR) gene rearrangements in tumor-infiltrating lymphocytes (TIL) freshly obtained from 15 patients with head and neck cancer using the reversely transcribed polymerase chain reaction (RT-PCR) method. These TILs showed preferential expression of Vα10, Vα8 and Vα1, detected in 13 (87%), 11 (73%), and 9 cases (60%), respectively. The TCRVβ gene revealed diversity without preferential usage. The head and neck region is exposed to bacteria and viruses, so it is possible that the tumor site can become infected and accumulate T cells involved in infection and inflammation. Therefore, we also investigated TCR gene usage in T cells infiltrating in chronic sinusitis mucosa to address the question of whether the Vα1, Vα8, and Vα10 subfamilies are characteristic in TIL from squamous cell carcinoma of head and neck. TCR Vα10 gene usage was also the most common in Vα segment in T cells infiltrating the sinus mucosa, but Vα and Vα8 were not detected in the T cells in sinusitis. These results indicate that the Vα10 subfamily, the preferred T cell population in both TIL and T cells in inflammatory disease, might he involved mainly in inflammation or infection. On the other hand, Vα1 and Vα8 appear to be relatively specific populations for antitumor immunity in head and neck cancer.     

Comparison of [I]metaiodobenzylguanidine kinetics with heart rate variability and plasma norepinephrine level

Background. [¹²³I]Metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. We evaluated the clinical significance of myocardial MIBG imaging as a measure of cardiac sympathetic nervous system function by comparing it to heart rate variability and plasma norepinephrine level.Methods and Results. In 211 subjects, we analyzed heart rate variability with 24-hour electrocardiography, performed scintigraphy with MIBG, and measured plasma norepinephrine levels. Time and frequency domain measures of heart rate variability were calculated with the Marquette heart rate variability program (Marquette Electronics, Milwaukee, Wis.). Early and late myocardial MIBG uptakes were measured at 15 and 150 minutes after injection, respectively. MIBG clearance rate from the heart and heart-to-lung and heart-to-mediastinum ratios of MIBG activities were calculated. On the whole, heart rate variability, including low-frequency power, correlated positively, but modestly so, with late MIBG uptake and negatively with MIBG clearance rate. The plasma norepinephrine level correlated negatively with late MIBG uptake and with heart rate variability, including low-frequency power, and positively with MIBG clearance rate. Similar correlations were also observed in patient subgroups with coronary artery disease, diabetes mellitus, and renal failure, but these correlations were weak (R² < 0.5).Conclusions. Increased cardiac sympathetic nervous system activity may be associated with increased myocardial MIBG clearance and decreased heart rate variability, including low-frequency power. Because these associations were not strong, however, the combination of heart rate variability with MIBG may allow an interactive assessment of the cardiac autonomic nervous system.     

Pyrroloquinolones and pyrazoloquinolones as potential antibacterial agents. Synthesis and antibacterial activity

Diethyl 1-cyclopropyl-5,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3,6-dicarboxylate 4 as a key-intermediate was synthesized via the Dieckmann reaction. The reaction of 4 with nucleophiles proceeded regioselectively at C-5. Facile cyclization between the C-5 and C-6 side chains of the resulting products gave novel pyrroloquinolones 10 and 12 and pyrazoloquinolones 15. They were converted into a series of cyclic amino-substituted pyrroloquinolones 17–21 and pyrazoloquinolones 22–24, and their in vitro antibacterial activities were tested. 1H-Pyrrolo[2,3-f]quinolone 17a and 2H-pyrrolo[3,4-f]quinolone 21a exhibited a potent in vitro antibacterial activity.     

A Comparison of Two Simple Measures to Evaluate the Health Status of Asthmatics: The Asthma Bother Profile and the Airways Questionnaire 20

Simple and concise measures for health status are desirable in clinical practice. The Asthma Bother Profile (ABP), which consists of 23 items, has been developed to assess how much asthma bothers patients. The Airways Questionnaire 20 (AQ20) is a simple instrument which consists of 20 items. The purpose of this study was to investigate how the ABP and AQ20 evaluate the health status of patients with asthma. A total of 166 patients with chronic asthma (age: 48 ± 16 yr, 77 males) completed pulmonary function testing, measurement of airway hyperresponsiveness, dyspnea rating, assessments of their anxiety and depression (HADS; Hospital Anxiety and Depression Scale), and assessments of their health status. The health status was assessed using the ABP, AQ20, the short-form 36 health survey questionnaire (SF-36), the Living With Asthma Questionnaire (LWAQ) and the Asthma Quality of Life Questionnaire (AQLQ). The Japanese version of the ABP included only 15 'bother' items out of the original 23 items due to cultural differences. The scores on the ABP were widely distributed, whereas the scores on the AQ20 were skewed towards the milder end of the scale. The ABP had a strong correlation with the Avoidance and Distress constructs on the LWAQ, and Anxiety and Depression on the HADS (Rs = 0.56 ∼ 0.79), and its strongest correlation with the General Health (Rs = - 0.64) scale among the 8 subscales on the SF-36. The AQ20 had a less significant correlation with the LWAQ, AQLQ, and SF-36 than the ABP. The ABP and AQ20 were short and simple to complete, and both measures could easily be used in clinical practice. The ABP can evaluate patients more specifically with respect to distress and bother than the AQ20.     

Comparative studies on clinical features and CSF proteins of motor neuron disease patients

Clinical features such as types of diseases, sex ratio, age of onset, sites of initial involvement, the appearance of bulbar signs, and duration of illness were studied in 52 patients with motor neuron disease (MND) with a special reference to immunoglobulin in cerebrospinal fluid (CSF) and serum. Although MND has been thought to be a degenerative disease of unknown cause, our data suggested there are some immunological abnormalities in this disease. The duration of illness and the abnormalities of CSF immunoglobulins appeared to be correlated with the type of disease and the site of initial involvement. However, whether or not these abnormalities in CSF immunoglobulins are directly related to the pathogenesis of MND remains unclear.     

CD14 is not involved in Rhodobacter sphaeroides diphosphoryl lipid A inhibition of tumor necrosis factor alpha and nitric oxide induction by taxol in murine macrophages.

Taxol, a microtubule stabilizer with anticancer activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages in vitro. Recently, it was shown that taxol-induced macrophage activation was inhibited by the LPS antagonist Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA). To investigate the mechanisms of taxol-induced macrophage activation, the present study focused on the interaction of LPS, RsDPLA, and taxol in the activation of and binding to macrophages. Taxol alone induced murine C3H/He macrophages to secrete tumor necrosis factor alpha (TNF) and to produce nitric oxide (NO) with kinetics similar to that of LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, in contrast, did not yield any detectable TNF and NO production in response to LPS or taxol. RsDPLA inhibited taxol-induced TNF and NO production from C3H/He macrophages in a dose-dependent manner. The inhibition by RsDPLA was specific for LPS and taxol in that RsDPLA did not inhibit heat-killed Listeria monocytogenes- or zymosan-induced TNF production. Polymyxin B blocked the inhibitory effect of RsDPLA on taxol-induced TNF production. The inhibitory activity of RsDPLA appeared to be reversible since macrophages still responded to taxol in inducing TNF production after the RsDPLA was washed out with phosphate-buffered saline prior to the addition of taxol. Taxol-induced TNF production was not inhibited by colchicine, vinblastine, or 10-deacetylbaccatine III. A mutant cell line, J7.DEF3, defective in expression of a CD14 antigen, responded equally well to taxol by producing TNF as did the parent J774.1 cells. This suggested that the activation of macrophages by taxol does not require CD14. Taxol-induced TNF production by the mutant cells was also inhibited by RsDPLA. 125I-labeled LPS and 3H-labeled taxol was reported to bind to J774.1 cells predominantly via CD14 and microtubules, respectively. The binding of 125I-labeled LPS to J7.DEF3 cells was about 30 to 40% of that to J774.1 cells. The binding of 125I-LPS to J774.1 cells was inhibited by unlabeled LPS and RsDPLA but not by taxol. On the other hand, 3H-labeled taxol bound to both J774.1 cells and J7.DEF3 cells in similar time- and dose-dependent manners. The binding of [3H]taxol to these cells was inhibited by taxol but not by LPS or RsDPLA. Although the binding studies failed to examine cross competition for binding to macrophages, a possible explanation of these results is that LPS, RsDPLA, and taxol share the same molecule(s) on murine macrophages for their functional receptor(s), which is neither CD14 nor tubulin.