Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

OBJECTIVE: Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. APPROACH AND RESULTS: This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0-79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. CONCLUSIONS: Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention.

Pharyngeal Haemorrhage Immediately After Intake of Fried Foods: Angina Bullosa Haemorrhagica.

Angina bullosa haemorrhagica (ABH) is a disease of unknown cause that occurs most frequently in middle-aged and older adults and is characterized by the destruction of blood vessels in the submucosal layer of the middle pharynx and larynx centred on the soft palate, resulting in the formation of haemorrhagic blisters. It usually resolves within a day and heals without scarring within about a week. No treatment is necessary. However, cases of airway obstruction due to haematemesis have been reported, and this potential risk should be considered when tracheal intubation or upper gastrointestinal endoscopy is being performed. In this report, we describe the case of a 50-year-old man who developed a haematoma in the pharynx following upper endoscopy, which spontaneously ruptured and healed, leading to the diagnosis of ABH. The main purpose of this case report is to remind the reader that ABH improves without treatment, thus eliminating the need for unnecessary examination, and that there is a risk of airway obstruction depending on the site of the lesion. LEARNING POINTS: The key to the diagnosis of angina bullosa haemorrhagica (ABH) is a history of acute haemorrhagic vesicles caused by an external stimulus such as food or intubation, which resolve without scarring within a week or so.ABH can occur at any oropharyngeal site, but its occurrence in the pharyngeal region raises the risk of airway obstruction due to haematemesis.

Hybrid PBL and Pure PBL: Which one is more effective in developing clinical reasoning skills for general medicine clerkship?-A mixed-method study.

This study aims to compare the effectiveness of Hybrid and Pure problem-based learning (PBL) in teaching clinical reasoning skills to medical students. The study sample consisted of 99 medical students participating in a clerkship rotation at the Department of General Medicine, Chiba University Hospital. They were randomly assigned to Hybrid PBL (intervention group, n = 52) or Pure PBL group (control group, n = 47). The quantitative outcomes were measured with the students' perceived competence in PBL, satisfaction with sessions, and self-evaluation of competency in clinical reasoning. The qualitative component consisted of a content analysis on the benefits of learning clinical reasoning using Hybrid PBL. There was no significant difference between intervention and control groups in the five students' perceived competence and satisfaction with sessions. In two-way repeated measure analysis of variance, self-evaluation of competency in clinical reasoning was significantly improved in the intervention group in "recalling appropriate differential diagnosis from patient's chief complaint" (F(1,97) = 5.295, p = 0.024) and "practicing the appropriate clinical reasoning process" (F(1,97) = 4.016, p = 0.038). According to multiple comparisons, the scores of "recalling appropriate history, physical examination, and tests on clinical hypothesis generation" (F(1,97) = 6.796, p = 0.011), "verbalizing and reflecting appropriately on own mistakes," (F(1,97) = 4.352, p = 0.040) "selecting keywords from the whole aspect of the patient," (F(1,97) = 5.607, p = 0.020) and "examining the patient while visualizing his/her daily life" (F(1,97) = 7.120, p = 0.009) were significantly higher in the control group. In the content analysis, 13 advantage categories of Hybrid PBL were extracted. In the subcategories, "acquisition of knowledge" was the most frequent subcategory, followed by "leading the discussion," "smooth discussion," "getting feedback," "timely feedback," and "supporting the clinical reasoning process." Hybrid PBL can help acquire practical knowledge and deepen understanding of clinical reasoning, whereas Pure PBL can improve several important skills such as verbalizing and reflecting on one's own errors and selecting appropriate keywords from the whole aspect of the patient.

Group B Streptococcus Bacteremia Mimicking Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome.

Group B Streptococcus (GBS) causes septic arthritis in healthy adults, and a significant number of GBS septic arthritis cases involve multiple joints. Nevertheless, septic arthritis is commonly monoarticular. Here, we report a case of a 45-year-old man who complained of subacute fever and right shoulder and right buttock pain for three weeks despite undergoing garenoxacin treatment for one week. Although synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome could be a possible differential diagnosis for this patient, the fever and subacute clinical course could not be explained. Blood cultures revealed the presence of GBS; therefore, he was diagnosed with septic arthritis. After antibiotic treatment for six weeks, his symptoms resolved.

Does scoring patient complexity using COMPRI predict the length of hospital stay? A multicentre case-control study in Japan.

OBJECTIVE: To clarify the factors associated with prolonged hospital stays, focusing on the COMplexity PRediction Instrument (COMPRI) score's accuracy in predicting the length of stay of newly hospitalised patients in general internal medicine wards. DESIGN: A case-control study. SETTING: Three general internal medicine wards in Chiba Prefecture, Japan. PARTICIPANTS: Thirty-four newly hospitalised patients were recruited between November 2017 and December 2019, with a final analytic sample of 33 patients. We included hospitals in different cities with general medicine outpatient and ward facilities, who agreed to participate. We excluded any patients who were re-hospitalised within 2 weeks of a prior discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients' COMPRI scores and their consequent lengths of hospital stay. RESULTS: The 17 patients (52%) allocated to the long-term hospitalisation group (those hospitalised ≥14 days) had a significantly higher average age, COMPRI score and percentage of participants with comorbid chronic illnesses than the short-term hospitalisation group (<14 days). A logistic regression model (model A, comprising only the COMPRI score as the explanatory variable) and a multiple logistic regression model (model B, comprising variables other than the COMPRI score as explanatory variables) were created as prediction models for the long-term hospitalisation group. When age ≥75 years, a COMPRI score ≥6 and a physician with 10 years' experience were set as explanatory variables, model A showed better predictive accuracy compared with model B (fivefold cross-validation, area under curve of 0.87 vs 0.78). The OR of a patient with a COMPRI score of ≥6 joining the long-term hospitalisation group was 4.25 (95% CI=1.43 to 12.63). CONCLUSIONS: Clinicians can use the COMPRI score when screening for complexity assessment to identify hospitalised patients at high risk of prolonged hospitalisation. Providing such patients with multifaceted and intensive care may shorten hospital stays.

Giant frontal lobe meningioma.

A 90-year-old woman presented with gradual onset of generalized weakness, imbalance, urinary incontinence, progressive impairment of memory, and deviant sexual behavior. The Reversed Hasegawa's Dementia Scale, a brief cognitive scale, was 13 (dementia cutoff point of 21/20).

Primary sensory neurons with dichotomizing axons projecting to the facet joint and the low back muscle in rats.

BACKGROUND: Clinically, the origin of low back pain is unknown. The pain may originate from the lumbar muscles directly, or it may be referred pain from the spine. Dorsal root ganglion (DRG) neurons with dichotomizing axons have been reported in several species and are thought to be related to referred pain. However, these neurons, which have dichotomizing axons to the lumbar facet joints and to the lumbar muscle, have not been fully investigated. METHODS: Two neurotracers - 1,1'-dioctadecyl-3,3,3',3'- tetramethyl-indocarbocyanine perchlorate (DiI) and fluorogold (FG) - were used in the present double-labeling study. DiI crystals were placed in the right L5/6 facet joint, and FG was applied to right multifidus muscles at the L5 level in 10 rats. Two weeks later, bilateral DRGs from L1 through L6 were harvested, sectioned, and observed under a fluorescence microscope. RESULTS: DiI-labeled DRG neurons innervating the L5/6 facet joint (5.17% of the total DRG neurons) were distributed from L1 to L6. FG-labeled DRG neurons innervating the lower back muscle (15.9% of the total) were also distributed from L1 to L6. Double-labeled DRG neurons were found from L1 to L6. The ratio of total double-labeled/total DiI-labeled DRG neurons was 17% and that of total double-labeled/total FG-labeled DRG neurons was 7%. Approximately 17% of all DRG neurons innervating the facet joints had other axons that extended to the lower back muscle. CONCLUSIONS: This finding provides a possible neuroanatomical explanation for referred low back muscle pain from the lower facet joints.

Concurrent chemoradiotherapy with intravenous cisplatin and docetaxel for advanced oral cancer.

Concurrent chemoradiotherapy (CCRT) is a common treatment for advanced oral cancer, and its efficacy has been reported in many reviews. We have performed concurrent CCRT with intravenous cisplatin and docetaxel in patients with advanced oral cancer. The purpose of this report was to evaluate this treatment and to compare the outcome of this treatment with that of standard CCRT treatments for advanced head and neck cancer using intravenous administration. The patients were treated for primary advanced oral squamous cell carcinoma in our department between February 2003 and November 2015. In all, 17 patients (14 men, 3 women) with stage III (2 patients) stage IVA (10 patients), and stage IVB (5 patients) oral cancer were treated. The patient ages ranged from 44 to 87 years (average age: 65.4 years). The follow-up duration ranged from 5 to 117 months (average follow-up duration: 41 months, median follow-up duration: 39 months). The primary cancer sites were the maxillary gingiva (7 cases), mandible gingiva (3 cases), buccal mucosa (3 cases), tongue (3 cases), and floor of the mouth (1 case). The 3-year and 5-year survival rates were 52.9% and 33.0%, respectively, and both the 3-year and 5-year locoregional control rates were 50.9% as determined by the Kaplan-Meier method. The response rate was 94% (CR: 8 cases: 47% and PR: 8 cases: 47%). The incidences of toxicity greater than grade 3 included dermatitis and stomatitis in 9 cases each (52.9%), anemia in 3 cases (18.7%) and liver dysfunction in 1 case (6.2%). We found that the results of this therapy were equivalent to those of standard CCRT treatments for advanced head and neck cancer using intravenous administration, and the incidences of toxicity were lower than those of standard treatments. These findings suggested that this treatment is safe and useful for advanced oral cancer.

Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called "gray zone," is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. METHODS/DESIGN: This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. DISCUSSION: This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with "gray zone" FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526 . Registered on 1 March 2018.

Fatal necrotizing myositis from fulminant Streptococcus dysgalactiae subspecies equisimilis (SDSE) infection: A case report of autopsy images.

Over the past few decades, Streptococcus dysgalactiae subspecies equisimilis (SDSE) have been considered as weak pathogenicity compared with S. pyogenes (GAS). Some recent reports argue that SDSE may bring severe soft tissue infection as same as GAS. No reports have been tried to reveal the clinical characteristics and autopsy images of fulminant SDSE infection. In this case report, we aimed to present a case of fatal necrotizing myositis from fulminant SDSE infection at iliopsoas, including autopsy appearance.

Glutamatergic modulation of noradrenaline release in the rat median preoptic area.

The present study was carried out to investigate whether glutamatergic receptor mechanisms modulate the release of noradrenaline (NA) in the region of the median preoptic nucleus (MnPO) using intracerebral microdialysis techniques in freely moving rats. Perfusion of N-methyl-d-asparatate (NMDA, 10 and 50µM) through the microdialysis probe significantly enhanced dialysate NA concentration in the region of the MnPO. Local perfusion of the NMDA antagonist dizocilpine (MK801, 10 and 50µM) did not change the basal release of NA in the MnPO area. MK801 (10µM) administered together with NMDA antagonized the stimulant effect of NMDA (50µM). Perfusion of the non-NMDA agonist quisqualic acid (QA, 10 and 50µM) or kainic acid (KA, 10 and 50µM) significantly increased the NA release in the MnPO area. Perfusion of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 and 50µM) had no effect on the NA release. CNQX (10µM) administered together with either QA (50µM) or KA (50µM) in the MnPO area prevented the stimulant effect of the agonists on the NA release. Nonhypotensive hypovolemia following subcutaneous injections of polyethylene glycol (PEG, 30%, 5ml) significantly elevated the NA level in the MnPO area. The PEG-induced elevation in the NA release was attenuated by perfusion of either MK801 (10µM) or CNQX (10µM). The present results suggest that glutamatergic synaptic inputs may act to enhance the release of NA in the MnPO area through both NMDA and non-NMDA receptors, and imply that these glutamatergic receptor mechanisms may be involved in the noradrenergic reguratory system for the body fluid balance.

Synthesis of single-phase L10-FeNi magnet powder by nitrogen insertion and topotactic extraction.

Tetrataenite (L10-FeNi) is a promising candidate for use as a permanent magnet free of rare-earth elements because of its favorable properties. In this study, single-phase L10-FeNi powder with a high degree of order was synthesized through a new method, nitrogen insertion and topotactic extraction (NITE). In the method, FeNiN, which has the same ordered arrangement as L10-FeNi, is formed by nitriding A1-FeNi powder with ammonia gas. Subsequently, FeNiN is denitrided by topotactic reaction to derive single-phase L10-FeNi with an order parameter of 0.71. The transformation of disordered-phase FeNi into the L10 phase increased the coercive force from 14.5 kA/m to 142 kA/m. The proposed method not only significantly accelerates the development of magnets using L10-FeNi but also offers a new synthesis route to obtain ordered alloys in non-equilibrium states.

Involvement of NMDA receptor mechanisms in the modulation of serotonin release in the lateral parabrachial nucleus in the rat.

Microdialysis was employed to investigate whether N-methyl-d-asparatate (NMDA) glutamate receptor mechanisms are involved in the modulation of serotonin (5-hydoxytryptamine, 5-HT) release in the region of the lateral parabrachial nucleus (LPBN) in freely moving rats. Perfusion of NMDA (10 and 50 microM) through the microdialysis probe significantly enhanced extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the LPBN area. Local perfusion of the NMDA antagonist dizocilpine (MK801, 10 and 50 microM) did not change the basal 5-HT and 5-HIAA levels in the LPBN area. MK801 (10 microM) administered together with NMDA antagonized the stimulant effect of NMDA (10 microM). The intake of 0.3M NaCl and water induced by subcutaneous injections of the diuretic furosemide (FURO, 10 mg/kg) and the angiotensin converting enzyme inhibitor captopril (CAP, 5 mg/kg) produced significant increases in the 5-HT and 5-HIAA concentrations in the LPBN area. The increased levels of 5-HT and 5-HIAA caused by the combined treatment with FURO and CAP were attenuated by perfusion of MK801 (10 microM). These results indicate the participation of NMDA receptors in the control of 5-HT release in the LPBN area.

Suicide gene therapy using adenovirus vector for human oral squamous carcinoma cell line in vitro.

Recently, suicide gene therapy using the herpes simplex virus thymidine kinase (HSVtk) gene followed by ganciclovir (GCV) administration was evaluated for the treatment of cancer. The purpose of this study was to investigate the effectiveness of suicide gene therapy using the replication-deficient recombinant adenovirus vector for human oral squamous carcinoma cell lines. To evaluate transduction efficiency, each cell line was transduced in vitro with an adenovirus vector containing the beta-galactosidase gene. By 24 hours after transduction, nearly 100% of the cells were transduced at a multiplicity of infection (MOI) of 10, and from 30 to 10% at an MOI of 1. Next, each cell line was transduced with an adenovirus vector containing the HSVtk gene, and a subsequent administration of GCV for the assessment of suicide gene therapy. A subsequent administration of GCV resulted in complete tumor cell death. In addition, we conducted a morphological analysis of that cell death using video-enhanced contrast differential interference contrast microscopy, and we observed that it included both apoptosis and necrosis after HSVtk gene and GCV treatment. These results suggest that adenovirus-mediated suicide gene therapy induced remarkable cytotoxicity with a bystander effect in human oral squamous cell carcinoma thus suggesting an effective treatment strategy for that tumor.

Decreased monoamine release in the median preoptic area following ventricular treatment with the angiotensin II antagonist saralasin in normotensive and spontaneously hypertensive rats.

Previous findings have shown that some of the neurons in the median preoptic nucleus (MnPO) receive both catecholaminergic inputs from the brainstem and angiotensinergic inputs from the subfornical organ (SFO), and that alterations in the function of the brain renin-ANG system are implicated in hypertension, especially in spontaneous hypertensive rats (SHR). In an attempt to clarify the action of these inputs on MnPO neurons and to find the difference in the action between normotensive Wistar-Kyoto (WKY) rats and SHR, we used microdialysis to investigate the effects of injections of saralasin (Sar), an angiotensin II (ANG II) antagonist, into the third ventricle (3V) on monoamine release in the MnPO area of awake WKY and SHR. The content of noradrenaline (NA) in the MnPO area was significantly higher in SHR. No significant differences were observed between WKY and SHR in the concentrations of dopamine (DA) and of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In both WKY and SHR, Sar (Sar, 5 microg in 1 microl, three injections at 2-h intervals) injected into the 3V significantly decreased the extracellular concentrations of NA, DOPAC and HVA in the MnPO area. The decreases were much greater in SHR than in WKY rats. Similar injections of saline vehicle had no significant effect on the extracellular levels of NA, DA and the metabolites. These results suggest that central angiotensinergic circuits may serve to increase NA and DA release in the MnPO area, and support that a disorder in the ANG system may contribute, in part, to the elevated blood pressure of SHR.

Drinking decreases the noradrenaline release in the median preoptic area caused by hypovolemia in the rat.

Previous observations have suggested that the noradrenergic system in the median preoptic nucleus (MnPO) is implicated in the regulation of body fluid balance and cardiovascular function. The present study was carried out to investigate whether water intake alters the release of noradrenaline (NA) in the MnPO area caused by hypovolemia in freely moving rats. Nonhypotensive hypovolemia was induced by subcutaneous polyethylene glycol (PEG), and extracellular levels of NA were measured using intracerebral microdialysis techniques. Subcutaneous injections of PEG (30%, 5 ml) significantly enhanced the NA release in the MnPO area. Water ingestion significantly attenuated the elevation in the NA release in the MnPO area induced by the PEG treatment. These results show the involvement of the noradrenergic system in the MnPO in the maintenance of body fluid volume, and suggest that the system may play an important role in the elicitation of hypovolemia-induced dipsogenic response.

Involvement of serotonergic systems in the lateral parabrachial nucleus in sodium and water intake: a microdialysis study in the rat.

The present study was carried out to investigate whether 0.3 M NaCl and water intake alters the release of serotonin (5-hydoxytryptamine, 5-HT) in the region of the lateral parabrachial nucleus (LPBN) in freely moving rats. The ingestion of 0.3 M NaCl and water was induced by subcutaneous injections of the diuretic furosemide (FURO, 10 mg/kg) and the angiotensin converting enzyme inhibitor captopril (CAP, 5 mg/kg), and extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured using intracerebral microdialysis techniques. The intake of 0.3 M NaCl and water significantly enhanced the 5-HT and 5-HIAA levels in the LPBN area. The combined treatment with FURO and CAP elicited significant decreases in the 5-HT and 5-HIAA concentrations in the LPBN area under the condition that 0.3 M NaCl and water are not available for drinking. These results suggest that the serotonergic system in the LPBN area may play an important role in the modulation of sodium appetite and thirst.

Polyamine levels in brain and plasma after acute restraint or water-immersion restraint stress in mice.

To investigate the relationship between polyamines and stress, we measured polyamine levels in the frontal cortex, hippocampus, hypothalamus, and plasma of mice after acute restraint or water-immersion restraint stress. In all parts of the brain, putrescine levels were elevated (139-157% of the control) 24 h after water-immersion restraint stress. In the case of restraint, however, elevation of the putrescine level (130% of the control) was detected only in the frontal cortex. Spermidine and spermine levels were unchanged or slightly reduced (80-85% of the control) in the brain 6 and 24 h after water-immersion restraint stress. There was no change in plasma polyamine levels at any time subsequent to the stress. Pretreatment with diazepam (5 mg/kg, i.p.) completely blocked the stress-induced putrescine increases. These results indicate that the magnitude of the putrescine increase is dependent upon the intensity of the stressor, and suggest that polyamine metabolism is linked to psychological stress.

Improvement of transduction efficiency of recombinant adenovirus vector conjugated with cationic liposome for human oral squamous cell carcinoma cell lines.

Adenovirus (Ad) vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by immune responses that reduce transgene expression and decrease the efficiency of repeated vector administration. In this study, the efficacy of gene transduction and the tumor-cell killing effect on four human oral (SAS, HSC-2, HSC-3, HSC-4) and one murine squamous cell carcinoma cell (SCC-7, a kind gift of Dr. M. Hiraoka, Kyoto University) lines in vitro with Ad vector conjugated with catioic liposome (Ad/SUV) was evaluated. Ad/SUV resulted in two to five-fold over higher transduction efficiency in four human and one murine cell lines in vitro than Ad vector alone. The optimal Ad-SUV ratio was determined as 10(6) pfu of Ad vector with 1 micromol SUV. Ad/SUV showed more tumor-cell killing effect than Ad vector alone. Furthermore, the shielding effects of Ad vector with Ad/SUV from neutralizing antibody were evaluated. We also found that Ad/SUV is less susceptible to inactivation by neutralizing antibodies in vitro. The efficacy of gene transduction with Ad vector was blocked more than 70% with neutralizing serum, while Ad/SUV retained approximately 50% of the control activity in vitro. On the basis of these results, the anti-tumor effect with suicide gene therapy using Ad/SUV in vivo was evaluated. Three injections of Ad/SUV showed the inhibition of tumor growth compared with control in vivo. Our results suggested that an enhanced anti-tumor effect on human oral squamous cell carcinoma would be obtained with repeated administrations of Ad/SUV.

Enhanced response of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to angiotensin II in spontaneously hypertensive rats.

Thirty subfornical organ (SFO) neurons in normotensive Wistar-Kyoto (WKY) rats and 32 SFO neurons in spontaneously hypertensive rats (SHR) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) under urethane anesthesia. The spontaneous firing rate was significantly higher in SHR than in WKY rats. No significant differences in the latency, conduction velocity, and threshold of antidromic response were observed between WKY and SHR. All the identified SFO units were tested for a response to intracarotid injection of angiotensin II (ANG II, 20-ng/kg b.w.t.). Injections of ANG II elicited an increase in the activity of 21 units in WKY and 20 units in SHR and a depression in the firing of one unit in WKY rats, but did not affect the remaining units. The magnitude of the excitatory response caused by the ANG II injection was much greater in SHR than in WKY rats. These results show that there are differences between WKY and SHR in the spontaneous discharge rate of SFO neurons projecting to the PVN and in their response to circulating ANG II.