Scepticism about influenza vaccine efficacy in Japan.
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Biomedical subjects
Publications and source records attributed to M Kaji.
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Differentiation of herpes simplex virus (HSV) types 1 and 2 in cerebrospinal fluid of 17 patients with serologically diagnosed HSV encephalitis and meningitis or acute limbic encephalitis was determined by stringent hybridization of polymerase chain reaction--amplified DNAs. Ten of 17 patients were positive; six with HSV 1 isolates and four with HSV 2 isolates. We detected HSV type 1 in two cases of meningitis, although meningitis is generally thought to be caused by type 2. Additionally, HSV type 2 was found in one case of acute adult encephalitis, which is generally due to HSV type 1. HSV DNAs could be detected for over 1 month after onset, although our patients included several prolonged and recurrent cases. HSV DNA genomes were not detected in three cases of acute limbic encephalitis. Our study indicates that this method can be used for type differentiation in HSV CNS infections.
Eight pancreas carcinoma cell lines of duct cell origin (PCI-6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI-24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of anti-PCI LAK induction were investigated, with the focus on a search for lymphokine-activated killer (LAK) activity that differentiates neoplastic (PCI) from non-neoplastic (HUVEC) cells. Interferon-gamma (IFN-gamma), IFN-alpha, IL-4, IL-6, and IL-7, but not tumor necrosis factor-alpha (TNF-alpha) or IL-1 beta, induced a weak LAK activity against PCI-24, whereas IL-2-induced (1000 U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL-2 (100 U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL-2 (1000 U/mL). Both IL-2-induced and SpA-induced LAK had a potent, dose-dependent cytotoxicity against HUVEC. HUVEC inhibited both IL-2- and SpA-induced LAK cytotoxicity against PCI-24 to almost the same extent as seen with PCI-24. Thus, two potent LAK-inducers did not generate LAK activity that differentiates neoplastic from non-neoplastic cells. Thus, in vitro cytotoxicity of LAK against non-neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.
In Western countries, prevention of influenza has been a major public health concern, promoting the vaccination program to high-risk individuals including the elderly. On the other hand, in Japan, there has been no systematic approach to such a selective vaccination on the social basis. This is due to the deep-rooted skepticism on vaccine efficacy. A number of epidemiologic studies have so far reported conflicting results in this country. We investigated the principles and methods of influenza epidemiology focusing on the field evaluation of vaccine efficacy. General and methodologic problems in vaccine field trials with naturally occurring influenza include; unpredictability of the time of its occurrence; antigenic differences between the vaccine strains and epidemic viruses; preexistence of already-immune individuals; indirect effect of hard immunity by vaccination on nonvaccinees; possible difference in the virus exposure between compared groups, particularly when epidemic scale is small; possible misdiagnosis of cases, if not laboratory-confirmed. To cope with these, the following measures are essential in conducting epidemiologic study on influenza. 1) Influenza epidemics show differential occurrence by time and place. Therefore, much attention should be pain when analyzing the pooled data obtained from various study samples at different locations. 2) It should be the first step of a research to consider whether the outbreak of acute respiratory illnesses observed among subjects is caused by influenza virus exposures. 3) In general, failings to detect vaccine efficacy are attributable to the dilution of outcome with noninfluenzal illnesses; cases defined by clinical symptoms include substantial number of acute respiratory illnesses other than influenza. To minimize this nondifferential misclassification, three methods are thought to be important; confining observation period during the peak epidemic; applying a strict criteria to measure the outcome, preferably with laboratory examination; and conducting the study in the season with large-scale epidemic. 4) It is also important to take into account the preexistence of already-immune individuals. "Antibody efficacy" is a keen index to assess vaccine effectiveness in this instance. Besides, further research is required to clarify the individual characteristics related to influenza attack, which affect the validity of analytic epidemiologic study on vaccine efficacy by yielding bias or confounding effect.
Cellular adhesion between sialyl Lewis a (SLea)-positive pancreas carcinoma and endothelial cells is augmented by exogenous cytokines such as interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha through an upregulated E-selectin expression on endothelial cells. Preincubation of pancreas carcinoma cells with endothelial cells for 4-6 hours at the ratio of 1:10 induced E-selectin expression on endothelial cell surface, and dramatically increased subsequent attachment of SLea-positive pancreas carcinoma with endothelial cells. Paraformaldehyde-fixed PCI cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells. Culture supernatants from all six pancreas carcinoma cell lines contained soluble, E-selectin-inducible factors. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased pancreas carcinoma-to-endothelial attachment. These findings suggested that SLea-positive pancreas carcinoma cells produced E-selectin-inducing cytokines, both in the soluble and the membrane bound forms, resulted in augmented attachment to endothelial cells in vitro. The soluble factor lost its activity to induce E-selectin at 70 degrees C, and was different from IL-1-beta or TNF-alpha, because the supernatants contained no measurable IL-1 beta and TNF-alpha. Moreover, pretreatment of the supernatants with specific antibodies to IL-1 beta and TNF-alpha could not neutralize the E-selectin-inducing activity. Instead, all six pancreas carcinoma cell lines produced proteins of IL-1 alpha, and preincubation of the supernatant with specific antibody to IL-1 alpha almost completely removed the E-selectin-inducing activity from the supernatants. The collecting evidence suggests that substances such as IL-1 alpha produced by pancreas carcinoma cells may contribute to hematogenous metastasis of cancers in non-inflamed distant locations.
We reported four cases of acute encephalitis, in which MRI abnormalities localized in the limbic system. In the four cases, fever and consciousness disturbance were commonly found and convulsive seizures appeared in three. Within 10 days, their consciousness level became clear, but severe amnestic syndrome remained as sequela. Cerebrospinal fluid (CSF) at the acute stage revealed mild lymphocytic pleocytosis and elevated protein. MRI revealed abnormal signal intensities in both hippocampi and amygdaloid bodies, although CT scans were normal. Herpes simplex encephalitis selectively affects one or both temporal lobes and the limbic system, But our cases spared the temporal lobes. Additionally, serum and CSF antibody titers by CF and ELISA for herpes simplex virus (HSV) were within normal range from the acute to convalescent stages. Neither HSV type 1 and 2 DNA genomes by sensitive PCR-hybridization method were detected in CSF taken from the acute stage of all four cases. On the other hand, paraneoplastic limbic encephalitis is known as a subacute encephalitis predominantly involving the limbic system. MRI shows high signal intensities on T2-weighted in both medial temporal lobes. In our cases, this type of limbic encephalitis was excluded because of the acute onset and lack of malignancy. Accordingly, our four cases are regarded as non-herpetic acute limbic encephalitis. Several Japanese similar cases have been reported. Further etiological studies should be performed.
Between April 1982 and March 1994, we did 384 pulmonary resections for lung cancer. Until March 1991, we did 249 pulmonary resections in which none of the bronchial stumps were reinforced; nine patients developed bronchopleural fistula (incidence, 4%). After April 1991, bronchial stumps of 135 patients were reinforced by an intercostal muscle pedicle flap for prophylaxis against bronchopleural fistula. Only one patient developed it (incidence, 1%). In these two periods, the proportion of patients in stage IIIa or more advanced stages increased from 24% to 41%, resulting in more extensive operations and more patients being given chemo-radiation therapy in the perioperative period. These are risk factors for bronchopleural fistula, but the incidence of the fistula decreased. These results suggest that reinforcement of the bronchial stump with an intercostal pedicle flap is useful for prophylaxis against developing bronchopleural fistula.
A 36-year-old man developed massive ascites, of which cytology proved Class V, and upper gastrointestinal endoscopy disclosed Borrmann type 4 gastric cancer. We performed dual arterial infusion chemotherapy (DAIC) through the celiac axis and superior mesenteric artery, followed by the operation including continuous hyperthermic peritoneal perfusion, total gastrectomy, subtotal colectomy, massive intestinal resection, splenectomy, cholecystectomy, appendectomy, and total parietal peritonectomy (TPP). Ascites disappeared and the CA125 level was normalized by DAIC. This operation was well tolerated. Though the histopathological study revealed multiple peritoneal disseminations on the visceral peritoneum of stomach, small intestine, colon, and parietal peritoneum such as Douglas' pouch, there were denatured cancer cells in the visceral peritoneum to which blood supply under DAIC was distributed. These results suggested the effect of neoadjuvant DAIC and the significance of TPP.
Serum zinc and copper were measured in 47 patients undergoing pulmonary operation. They were divided into two groups according to the extent of the operation. Group A consisted of 32 patients with lung cancer, in whom lobectomy with lymphadenectomy was performed through the postero-lateral thoracotomy. Group B consisted of 15 patients with benign pulmonary lesion or metastatic pulmonary tumor, in whom wedge resection was performed through the axillary thoracotomy. In Group A, the serum zinc concentration most decreased 6 hours after surgery. It returned to normal level in 5-7 days and to the preoperative level within 14 days. In Group B, the maximal fall in serum zinc was at 3 hours after operation. Restoration to normal level was at 2nd postoperative day and to the preoperative level was at 5th postoperative day. The differences in serum zinc between two groups were significant (p < 0.05) from just after operation to 4th postoperative day. The degree of maximal decrease in serum zinc in Group A was more than that in Group B. Blood loss, operation time and pulmonary function did not influenced the change of serum zinc concentration in our series. These results show that degree and duration of reduction in serum zinc depends on the surgical trauma. On the other hand, no significant difference in serum copper levels was observed between two groups. The influence of pre- and post-operative pneumonia on serum zinc concentrations were followed in 3 patients. Fall and rise in serum zinc levels coincided with manifestation of and recovery from pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleura into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions, in malignant mesothelioma.
The frequency of infection by methicillin-resistant Staphylococcus aureus (MRSA) is high in Japan and control of such strains is urgently needed. Arbekacin (ABK), a semisynthetic aminoglycoside, has potent activity against S. aureus, including resistant strains, and against Gram-negative bacteria as well. For this reason, in surgical infections (which are often caused by more than one bacterium), this drug might be particularly effective. We calculated the MIC and the decrease in the MIC when cultures of 59 resistant strains of S. aureus isolated in our wards at Osaka City University Hospital, contained arbekacin in the medium. We also used the drug to treat 12 infections caused by resistant strains of S. aureus. The MICs of vancomycin had a single peak at 0.5 microgram/ml, and those for ABK had double peaks at 0.5 and 4.0 micrograms/ml. The effect of arbekacin in lowering the MIC of minocycline (MINO) was slight because of the low MIC of MINO. Effects on fosfomycin (FOM), ampicillin, clavulanic acid/ticarcillin, cefotiam, cefuzonam, flomoxef, and imipenem/cilastatin were strong; the peaks were lowered by 1/2(7)-1/2(11). When 1.0 micrograms/ml ABK was present in the medium, the efficacy of FOM was increased enough that, by prediction from the pharmacokinetics of FOM (blood level when given at the usual dose), all but one (2%) of the 47 resistant strains would be eradicated clinically. If 2.0 micrograms/ml ABK were in the medium, all strain would be eradicated, by our calculations. We treated 11 infections and one colonization by resistant strains of S. aureus with ABK and evaluated the response in these cases of infection. Four infections were treated with FOM as well. The clinical efficacy was good in four infections (three patients), fair in four, and poor in three, for an efficacy rate of 36%. All presumed causative bacteria were eradicated in two (18%) of the 11 infections and S. aureus strains were eradicated in three (27%) of the 11 infections. No symptoms of side effects were reported, but blood urea nitrogen and creatinine rose in a 72-year-old woman with duodenal perforation and peritonitis. The MIC levels of ABK were satisfactory, but clinical efficacy for staphylococcal infections caused by resistant strains was unsatisfactory.
A 39-year-old male was admitted to our ICU following traffic accident. The major symptoms were short breathness and unconsciousness due to cerebral hemorrhage. He was treated by mechanical ventilation which delayed the diagnosis of traumatic diaphragmatic hernia. On the 6 day after traffic accident we performed thoracotomy and repaired ruptured diaphragm. It was difficult to diagnose the patient as diaphragmatic hernia who was treated by mechanical ventilation.
Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.
BACKGROUND: Proliferative activities of tumors are thought to be prognostic features of malignant tumors, but their value as measured by proliferating cell nuclear antigen (PCNA) labeling remains unclear in gastric cancer. METHODS: PCNA labeling rates (LR) were quantified in 121 paraffin-embedded biopsy specimens from primary tumors by immunocytochemistry. RESULTS: Immunohistochemical analyses have demonstrated that PCNA presents an intense staining in the nuclei of tumor cells and mucous neck cells of gastric glands. The PCNA LR ranged from 12% to 79% (mean +/- standard deviation), and a significant correlation was found between bromodeoxyuridine labeling indices and PCNA LR: PCNA LR were closely associated with tumor size, serosal invasion, and nodal involvement. The patients with tumors with high PCNA LR (greater than 40%) were dead significantly earlier than were those with tumors with low PCNA LR: When the PCNA LR and all the clinicopathologic parameters were entered into a Cox regression model, PCNA LR emerged as an independent prognostic factor. CONCLUSION: These results indicate that PCNA LR may be a potentially useful prognostic factor for gastric cancer.
Two patients are reported with growth hormone deficiency due to head trauma in childhood. Although their injuries were outwardly only slight and there was no loss of consciousness and no subsequent neurological deficits, they exhibited gradual growth retardation from the time of the trauma. Provocative endocrinological tests showed growth hormone deficiency and MRI showed transection of the pituitary stalk. These findings suggest that ordinary head trauma, as well as perinatal insult and congenital abnormalities, could be a cause of growth hormone deficiency.
A 77-year-old man was admitted to our hospital, because of cough for one month. Chest X-ray examination revealed a tumor in the right upper lobe. A right pneumonectomy was done. Histopathologically, the tumor was diagnosed as true pulmonary carcinosarcoma, because it consisted partly of squamous cell carcinoma surrounded by spindle cell stroma and partly of chondrosarcoma. Lymph nodes were free of tumor. The patient was very well until nine months after surgery, when speech and gait disturbance appeared. And, metastatic involvement of the right cerebellar hemisphere was confirmed on the brain CT-scan. He died of acute bronchopneumonia. The component of the metastatic brain tumor was verified pathologically only carcinomatous. Pulmonary carcinosarcoma is a rare malignant tumor, and can be divided into two types: true carcinosarcoma and so-called carcinosarcoma. Only eight cases of pulmonary carcinosarcoma presenting brain metastasis including ours are known.
Serum sCD23 and sCD25 levels in asthmatic patients and healthy subjects were assayed. Serum sCD23 levels in asthmatic patients were significantly higher than those in healthy subjects (p < 0.05). Serum sCD25 levels in asthmatic patients were also significantly higher than those in healthy subjects (p < 0.02). There was a significant correlation between serum sCD23 and sCD25 levels in asthmatic patients (r = 0.52, p < 0.001). It is well known that sCD23 and sCD25 levels are regulated by different cytokines, and this study suggests that T cells play important roles in the pathogenesis of asthma.
Myokymia is one of the involuntary movements, which is characterized by undulatory muscle spasm, similar to the worm's crawl. Sometimes muscle pain, itchy sensation, dysautonomia and other symptoms are associated with it. Cases showing normal neurological findings are rare. Myokymia is caused by various diseases, such as, multiple sclerosis, hypothyroidism, Guillan-Barre syndrome and so on. Generally myokymia is classified into two types, i.e. limb myokymia and facial myokymia according to the site. On the other hand, myokymia with hyperhidrosis is known as Issacs syndrome. There are many opinions about the pathogenesis and mechanism in the myoneural junction, peripheral nerve or spinal cord, however these are not established. Further investigation of myokymia is expected.