Evaluation of diseased coronary arterial branches by polar representations of thallium-201 rotational myocardial imaging

The perfusion territories in polar representations of stress Tl-201 rotational myocardial imaging in patients with angina pectoris who had one diseased coronary segment were analyzed. The lesions proximal or distal to the first major septal perforator in left anterior descending arteries were detected by the presence or absence of defects at the base of the anterior septum. Right coronary artery lesions were detected by the presence of defects at the basal posterior septum, in contrast to the preservation of myocardial uptake at this portion in lesions of the left circumflex artery. The specific defect patterns were detected in cases with lesions at the first diagonal, obtuse marginal, and posterolateral branches. Recognition of these defects in the polar maps allows detailed detection of diseased coronary arterial branches.     

Phenytoin desensitization monitored by antigen specific T cell response using carboxyfluorescein succinimidyl ester dilution assay

We evaluated drug-specific T cell responses in a patient with refractory partial seizures and paroxysmal kinesigenic choreoathetosis successfully treated with clinical desensitization to phenytoin. Drug-induced lymphocyte transformation test before desensitization was negative with a stimulation index of 130%. The frequencies and cytokine-producing phenotypes of phenytoin-specific T cells were examined simultaneously by using a carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Before desensitization, the proportion of CFSElow CD4+ cells in whole CD4+ was 3.09%; 13.6% of CFSElow CD4+ cells were stained with anti-interferon gamma antibody. After desensitization, phenytoin-specific CFSElow CD4+ cells decreased to background level. These results indicate that CFSE dilution assay will be useful for the diagnosis and monitoring of drug hypersensitivity.     

Differing Patterns of P-Selectin Expression in Lung Injury

Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of ¹²⁵I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression was sustained for the next 7 hours, in striking contrast to the pattern of P-selectin expression in the cobra venom factor model, in which upregulation was very transient (within the 1st hour). In the immune complex model, injury and neutrophil accumulation were P-selectin dependent. Upregulation of P-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor α. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl sulfoxide sensitive but neutrophil independent. Different mechanisms that may explain why upregulation of lung vascular P-selectin is either transient or sustained are discussed.     

Effects of body and head positions on bilateral difference in tympanic temperatures

Summary We have examined the nonparallel changes in tampanic membrane temperatures (T _ty) from the two ears in response to various changes in body and head positions. Upon assuming a lateral recumbent position, the T _ty on the lower side increased while that on the upper side decreased. Pressure application over a wide area of the lateral chest only caused inconsistent and obscure asymmetric changes in T _ty. A lateral flexion of the head with the subject sitting upright and a rotation of the head to the side in a supine position induced an increase in the T _ty on the lower side compared to that on the upper side. The temperature and blood flow of the forehead often decreased on the lower side and increased on the upper side, although such responses were not always concomitant with the asymmetric changes in T _ty. A dorsal flexion of the head with the subject in a reclining position caused a slight increase in the T _ty, whereas raising the head upright induced a slight decrease in them. Two additional experiments were carried out with single photon emission computed tomography using ^99mTc-hexamethylpropyleneamine oxime as tracer, and a slight, relative decrease in counts was noted in the right hemisphere during rotation of the head to the right. These results would strongly suggest that unilateral increases and decreases in T _ty could have been caused by one-sided decreases and increases, respectively, in blood flow to the brain and/or the tympanic membrane, induced by a vasomotor reflex involving vestibular stimulation.     

Vasculitis and Pyrexia Associated with Superficial Spreading Gastric Carcinoma

A case of low grade fever developing about a month before the discovery of gastric carcinoma is reported. No findings of infection or collagen disease were revealed. The fever continued for about 3 months, but promptly disappeared after surgical removal of the tumor. A superficial spreading mucosal carcinoma with minimal invasion to the sub-mucosa was seen in the antrum, showing the features of poorly differentiated adenocarcinoma. In addition, unique venous inflammation was recognized beneath and around the neoplasm. Arteries and lymph vessels did not exhibit any inflammatory changes. It was presumed that the gastric carcinoma had induced phlebitis, which subsequently brought about the fever. As to the pathogenetic mechanism, it was suggested that a substance produced by the carcinoma cells flowed into nearby veins to induce the phlebitis. Acta Pathol Jpn 42 : 293-297, 1992.     

Desynchronization of carbachol-induced theta-like activities by alpha-adrenergic agents in guinea pig hippocampal slices

The effect of alpha-adrenergic agents on theta-like activity (TLA) in guinea-pig hippocampal slices was studied. TLA was induced by a cholinergic agent, carbachol. TLA had a frequency of 4.66+/-0.08 Hz (mean+/-S.E.M.) and an amplitude of 96.3+/-8.3 microV in the dentate gyrus (DG). The alpha-adrenergic agents epinephrine and clonidine increased the frequency and decreased the amplitude of TLA in a concentration-dependent manner. The agents also increased antidromic and orthodromic population spike (PS) amplitudes of the granule cells, but did not have any effect on population EPSP. Another alpha-adrenergic agent, guanabentz, had the same effect as clonidine. The adenylate cyclase inhibitor SQ22536 suppressed the increase in PS amplitude by clonidine. The results suggest that these alpha2-adrenergic agents facilitate the activity of granule cells through the activation of the alpha2-adrenoreceptor and cAMP pathway, and the facilitation causes the desynchronization of TLA.     

Hippocampal theta-related cellular activity in the superior colliculus of the urethane-anesthetized rat

In the present study, 93 cells in the superior colliculus (SC) were recorded extracellularly during the simultaneous occurrence of spontaneous theta field activity, sensory-induced (tail pinch) theta field activity, and large amplitude irregular (LIA) field activity, recorded from an electrode located in the stratum moleculare of the hippocampal formation (HPC). The effect of the intravenous administration of atropine sulfate (ATSO4) was also tested on SC cellular activity. The field activities of theta and LIA were recorded from all layers of the SC and were found to be temporally coherent with the same activities recorded simultaneously from the HPC, during all conditions tested. By using the criteria of Colom and Bland (1987) for the classification of theta-related cells, 75 of 93 cells (81%) were found to be related to the generation of theta field activity in the HPC and 18 of 93 (19%) were nonrelated. All cells recorded discharged in a tonic, nonrhythmic pattern during the theta HPC field states. Of the 75 theta-related cells, 61 (81%) were classified as tonic theta-ON cells and 14 (19%) as tonic theta-OFF cells. Although these cell types were found in all three layers of the SC, the majority of tonic theta-ON cells were recorded in the intermediate layer, and the tonic theta-OFF cells were dispersed evenly between the intermediate layer and the deep layer of the SC. The intravenous administration of ATSO4 abolished theta field activity in the HPC and SC, and the theta-related increase in the discharge rate of all tonic theta-ON cells tested. However, the same treatment did not have any effect on the discharge properties of tonic theta-OFF cells. The same stimuli that resulted in the inhibition of the discharge rates of these cells (tail pinch and electrical stimulation of the PH) in the predrug condition did so after the administration of ATSO4.     

Membrane structures of human oligodendroglioma

Summary Two cases of McArdle's syndrome are reported. One is a classical exaple; the other is unusual because of the in vitro presence of muscle phosphorylase activity. In the latter case. the electronmicroscopic investigation confirmed the diagnosis.The fine structural changes characteristic of this disease are summarized and it is concluded that histochemical studies alone are insufficient to exclude the diagnosis of McArdle's myopathy.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.