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Biomedical subjects

N Sugaya

Publications and source records attributed to N Sugaya.

At least 19 recordsLinked to original sources

The influence of selection on the evolutionary distance estimated from the base changes observed between homologous nucleotide sequences.

In most studies of molecular evolution, the nucleotide base at a site is assumed to change with the apparent rate under functional constraint, and the comparison of base changes between homologous genes is thought to yield the evolutionary distance corresponding to the site-average change rate multiplied by the divergence time. However, this view is not sufficiently successful in estimating the divergence time of species, but mostly results in the construction of tree topology without a time-scale. In the present paper, this problem is investigated theoretically by considering that observed base changes are the results of comparing the survivals through selection of mutated bases. In the case of weak selection, the time course of base changes due to mutation and selection can be obtained analytically, leading to a theoretical equation showing how the selection has influence on the evolutionary distance estimated from the enumeration of base changes. This result provides a new method for estimating the divergence time more accurately from the observed base changes by evaluating both the strength of selection and the mutation rate. The validity of this method is verified by analysing the base changes observed at the third codon positions of amino acid residues with four-fold codon degeneracy in the protein genes of mammalian mitochondria; i.e. the ratios of estimated divergence times are fairly well consistent with a series of fossil records of mammals. Throughout this analysis, it is also suggested that the mutation rates in mitochondrial genomes are almost the same in different lineages of mammals and that the lineage-specific base-change rates indicated previously are due to the selection probably arising from the preference of transfer RNAs to codons.

Animals↗

The Japanese experience with vaccinating schoolchildren against influenza.

BACKGROUND: Influenza epidemics lead to increased mortality, principally among elderly persons and others at high risk, and in most developed countries, influenza-control efforts focus on the vaccination of this group. Japan, however, once based its policy for the control of influenza on the vaccination of schoolchildren. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. For more than a decade, vaccination was mandatory, but the laws were relaxed in 1987 and repealed in 1994; subsequently, vaccination rates dropped to low levels. When most schoolchildren were vaccinated, it is possible that herd immunity against influenza was achieved in Japan. If this was the case, both the incidence of influenza and mortality attributed to influenza should have been reduced among older persons. METHODS: We analyzed the monthly rates of death from all causes and death attributed to pneumonia and influenza, as well as census data and statistics on the rates of vaccination for both Japan and the United States from 1949 through 1998. For each winter, we estimated the number of deaths per month in excess of a base-line level, defined as the average death rate in November. RESULTS: The excess mortality from pneumonia and influenza and that from all causes were highly correlated in each country. In the United States, these rates were nearly constant over time. With the initiation of the vaccination program for schoolchildren in Japan, excess mortality rates dropped from values three to four times those in the United States to values similar to those in the United States. The vaccination of Japanese children prevented about 37,000 to 49,000 deaths per year, or about 1 death for every 420 children vaccinated. As the vaccination of schoolchildren was discontinued, the excess mortality rates in Japan increased. CONCLUSIONS: The effect of influenza on mortality is much greater in Japan than in the United States and can be measured about equally well in terms of deaths from all causes and deaths attributed to pneumonia or influenza. Vaccinating schoolchildren against influenza provides protection and reduces mortality from influenza among older persons.

Aged↗

[Clinical evaluation of an immunochromatography test for rapid diagnosis of influenza].

We evaluated a rapid diagnostic kit that detects influenza type A and B viral antigens by immunochromatography, Quick Vue Influenza Test (Quidel Corp., San Diego, CA, USA), with 425 specimens collected from patients with influenza-like symptoms at three hospitals between January and March 2001. The specimens included 184 nasal aspirates, 140 nasal swabs, and 101 throat swabs. The test correctly identified 179 of the 204 culture positive specimens and 203 of the 221 culture negative specimens; the sensitivity and specificity compared with the culture were 87.7% and 91.9%, respectively. The sensitivity of the test was 92.6% (112/121) for nasal aspirates, 83.7% (41/49) for nasal swabs, and 76.5% (26/34) for throat swabs, which is similar to the results for conventional rapid enzyme immunoassay kits for influenza virus infection. The sensitivity and specificity of the QuickVue Influenza Test were equivalent to those of Flu OIA (BioStar, Inc., Boulder, CO, USA), with the agreement of 84.2%. Although the QuickVue Influenza Test does not differentiate between influenza A and B viruses, the easy-to-use kit detects both types in the physician's office, allowing physicians to make a decision on prescription of neuraminidase inhibitor therapy during the initial visit.

Evaluation Studies as Topic↗

[Evaluation of immunochromatography method for rapid detection of influenza A and B viruses].

We have evaluated a new rapid detection kit for influenza A and B viruses, known as the QuickVue Influenza test (Quidel Coporation, USA); which is based on immunochromatography using virus isolates and clinical specimens. Twelve strains of influenza A and B were tested for evaluate the reactivity and detection limits of this test. The QuickVue Influenza test showed a positive result for all twelve strains of influenza virus and a negative result for fourteen different kinds of other respiratory viruses. The detection limits for six strains were 5 to 30 pfu/ml for a cell culture, 1.0 x 10(3) to 6.0 x 10(4) pfu/ml for 1st PCR, 1 to 50 pfu/ml for nested PCR, 3.0 x 10(5) to 6.0 x 10(5) pfu/ml for the QuickVue Influenza test, 1.5 x 10(5) to 1.0 x 10(6) pfu/ml for the Directigen Flu A, and 7.5 x 10(5) to 5.0 x 10(6) pfu/ml for the FLU OIA. Furthermore, the QuickVue Influenza test were clinically evaluated using 92 throat swab specimens collected from patients with influenza-like illnesses. By cell culture, influenza viruses were detected in 49 of the 92 specimens (AH1N1: 20, AH3N2: 7, B: 22); the titers of the influenza viruses were between 2.5 pfu/ml and 7.0 x 10(5) pfu/ml. Compared to cell culture, the QuickVue Influenza test showed a sensitivity of 75.5%, a specificity of 93.0%, a positive predictive value of 92.5%, a negative predictive value of 76.9%, and an efficiency value of 83.7%. On the other hand, influenza viruses were detected in 54 of the 92 specimens (AH1N1: 19, AH 3N2: 10, B: 25) by RT-PCR. Compared to RT-PCR, the QuickVue Influenza test showed a sensitivity of 72.2%, a specificity of 97.4%, a positive predictive value of 97.5%, a negative predictive value of 71.2%, and an efficiency value of 82.6%. Overall, only one throat swab specimen produced a false positive result using the QuickVue Influenza test; thus, this test appears to have a high specificity. We conclude that the QuickVue Influenza test is a simple one-step test with a sensitivity and specificity equivalent to those of other conventional diagnostic kits. The test is useful and suitable for the diagnosis of influenza and for identifying influenza patients requiring antiviral therapy.

Influenza A virus↗

[Patient assessment for zanamivir therapy--a survey of patients with influenza who were prescribed zanamivir during the 2000/2001 season in Japan].

Patients clinically diagnosed as influenza who were prescribed zanamivir were surveyed from December 2000 to March 2001 in Japan. A total of 723 survey questionnaires were returned. Following the first zanamivir treatment, symptom relief was reported by 34.9% of the patients within 12 hours, 63.1% within 24 hours and 85.7% within 48 hours. 46.1% of the patients resumed normal activities within 48 hours and 78.0% within 72 hours. 98.8% of the patients reported that the Diskhaler could be used as instructed by the doctor or pharmacist and 92.5% found the device easy or very easy to use. 70.8% of the patients were satisfied or very satisfied with zanamivir, and 89.0% of the patients would recommend zanamivir to a friend. These results showed that 1) the effect of zanamivir started very fast, especially for the vaccinated patients where the effect was more rapid, 2) most of the patients managed to use the diskher properly and felt "very easy to use" or "easy to use", 3) there is no difference of efficacy in spite of with/without underlying disease, and the diskhaer was well accepted by pediatric and elderly patients.

Administration, Inhalation↗

Leiomyomatous hamartoma of the incisive papilla.

A case of unusual hamartoma in a six-year-old otherwise healthy Brazilian girl is reported, with emphasis on histological and immunohistochemical features. A mass observed in the incisive papilla was detected whose appearance was similar to congenital epulis or fibroma. Histological findings showed interlacing fascicles of large spindle cells resembling smooth muscle cells. Immunohistochemical staining for desmin and for smooth-muscle actin was positive. The histological diagnosis was leiomyomatous hamartoma, based on clinical and microscopic observations.

Actins↗

Influenza vaccine, anti-influenza drugs, and rapid diagnosis in Japan.

The percentage of individuals receiving influenza vaccine is markedly lower in Japan than in many other economically advanced countries. To increase the rate of coverage, the current practice of giving people two inoculations instead of one needs to be changed. In addition, free vaccination services for the elderly and high-risk patients need to be offered. Amantadine is available for the treatment of influenza type A infection in Japan. Moreover, zanamivir, a neuraminidase inhibitor effective against both influenza type A and B viruses, has been approved in Japan. A rapid diagnosis kit for influenza type A virus is available in Japan. With the current threat of new pandemic influenza viruses emerging, it is necessary to actively confront influenza in Japan by increasing the vaccine coverage rate, by employing amantadine and neuraminidase inhibitors for influenza virus infection, and by providing rapid diagnosis of influenza.

Amantadine↗

Influenza-associated encephalopathy in Japan: pathogenesis and treatment.

It is estimated that more than 100 children die of influenza-associated encephalopathy (influenza encephalopathy) every year in Japan. Influenza encephalopathy is distinct from Reye's syndrome. Specifically, 20% of influenza encephalopathy patients exhibit bilateral thalamic necrosis on neuroimaging, a lesion referred to as acute necrotizing encephalopathy (ANE). Influenza encephalopathy may develop by the same pathogenetic mechanisms as ANE, possibly via vasoactive substances or a process leading to vasoconstriction in the central nervous system (CNS). A novel substitution at the receptor-binding site (Tyr 137 to Phe) was reported to be found exclusively in influenza type A (H3N2) viruses isolated from patients with influenza encephalopathy, suggesting that encephalopathy may be caused by a variant influenza type A (H3N2) virus. Recently, it has been reported that cytokines may mediate the disease and that a high plasma concentration of interleukin-6 could be an indicator of progression to encephalopathy. Although it is unknown whether influenza virus invades the CNS, amantadine therapy for influenza encephalopathy has been tried in Japan, in patients in whom influenza type A infection has been demonstrated by rapid antigen detection tests.

Amantadine↗

Influenza A-associated encephalopathy with bilateral thalamic necrosis in Japan.

Two cases of acute encephalopathy in young children clearly showed evidence of influenza A virus infection and bilateral thalamic lesions. Influenza-associated encephalopathy with bilateral thalamic lesions has mostly been reported in Japan; it differs from Reye's syndrome in several respects. Other factors in addition to influenza virus infection may have contributed to the etiology of encephalopathy in our case patients.

Brain Diseases↗

[Clinical evaluation of rapid diagnostic kit detecting separately influenza A and B viruses].

The Directigen Flu A + B kit, a rapid diagnostic device for influenza virus A and B was evaluated. The nasopharyngeal aspirates were obtained from 239 patients who visited our hospital, between January and March, 2000, presenting flu-like symptoms. Influenza virus AH1: 77 and AH3: 51 were isolated from 128 specimens and none from 111 specimens. Directigen Flu A + B showed 115 specimens positive and 106 specimens negative. The sensitivity and specificity of this kit were 89.8% (115/128) and 95.5% (106/111) compared with viral isolation. Agreement on positive and negative interpretations between Direction Flu A and this kit was 97.9% (234/239). In the evaluation of this kit for influenza B virus, 60 frozen nasopharyngeal aspirates collected from February to April, 1999 were used. The sensitivity and specificity of this kit were 88.9% (16/18) and 88.1% (37/42) compared with viral isolation. Agreement on positive and negative interpretations between FLU OIA and this kit was 91.7% (55/60). The Directigen A + B demonstrated sensitivity and specificity equivalent to the conventional kits in nasopharingeal aspirates. This kit can also differentiate influenza A and B viruses, a feature which is useful for treatment using anti-viral agents such as amantadine and neuraminidase inhibitor. To date, the kit is the most effective tool for the rapid diagnosis of influenza.

Evaluation Studies as Topic↗

[Sensitivity and specificity of rapid diagnosis kit detecting separately influenza A and B viruses].

Sensitivity and specificity of the Directigen Flu A + B kit, a rapid test for influenza virus A and B, were evaluated. This test detects influenza A and B viruses separately by EIA. Reactivity of the kit was tested using a total of 23 isolates: 13 isolates of human influenza virus A (H1N1, H3N2) and 10 isolates of human influenza virus B. All of the isolates were tested positive and no difference in reactivity was found in antigenic variables and subtypes. The kit was only reactive to influenza virus A and B, not reactive to other viruses. Typical influenza A and B strains were tested for detection limit. 7.8 x 10(3) pfu/ml was a detection limit for influenza virus A (H1N1: Beijing/262/95), 4.7 x 10(4) pfu/ml for influenza virus A (H3N2: Kitakyusyu/159/93), and 3.1 x 10(4) pfu/ml for influenza virus B (Guangdong/05/94). The Directigen Flu A + B kit was a easy-to-use, rapid detection device and the kit has sensitivity and specificity equivalent to other diagnostic devices, suggesting the kit are useful in medical institutions.

Evaluation Studies as Topic↗

[Evaluation of the rapid detection test for influenza A and B viruses using neuraminidase activity].

The ZstatFlu test (ZymeTx, USA) is a rapid detection kit for influenza A and B viruses. This test is based upon the reaction between viral neuraminidase from influenza viruses and a chromogenic substrate. The clinical performance of the ZstatFlu test was determined by comparison with viral isolation in cell culture. A total of 176 respiratory specimens from 172 pediatric patients with influenza like illnesses during the 1998/99 season were tested. Influenza viruses were recovered from 97 specimens (type A: 6, type B: 91) in cell culture. ZstatFlu demonstrated 67.4% sensitivity (29/43) and 62.7% specificity (37/59) for throat swabs. Of the 22 ZstatFlu-positive, culture-negative throat swabs tested by RT-PCR, 18 were positive by RT-PCR. ZstatFlu showed 48.1% sensitivity (26/54) and 90.0% specificity (18/20) for nasopharyngeal aspirates. Of the two ZstatFlu-positive, culture-negative nasopharyngeal aspirates tested by HI titer of paired sera, one showed a 4-fold increase of HI titer. Nasopharyngeal aspirates therefore showed lower sensitivity than throat swabs at this test, different from EIA test kits such as Directigen FluA or FLU OIA. Overall, only 5 specimens were false positive by the ZstatFlu test. Therefore, this test demonstrated high specificity and positive predictive value. In conclusion, the ZstatFlu test is useful for the rapid detection of influenza A and B viruses to identify patients who need antiviral treatment.

Adolescent↗

[Serum concentration of amantadine in the treatment of children with influenza type A infection].

Fifteen children with influenza type A (H3N2) virus infection (mean age, 38 months) were treated with amantadine. Amantadine was prescribed as 5 mg/kg/day and the serum concentration was measured in 5-7 days. As a result, the mean serum concentration of amantadine was 164.6 +/- 92.5 ng/ml (range, 67.4-446.9 ng/ml). Adverse reactions were not associated to them. Amantadine therapy against influenza type A infection is probably safe in children because of the low serum concentration shown in this study.

Amantadine↗

The impact of winter epidemics of influenza and respiratory syncytial virus on paediatric admissions to an urban general hospital.

To demonstrate the impact of influenza epidemics on pediatric hospital admissions, admissions that were attributable to influenza and respiratory syncytial virus (RSV) infection to the pediatric ward of an urban general hospital in Japan were followed-up during a 4-month period from December to March 1991 through 1998. During the 1997-1998 influenza type A (H3N2) epidemic, a diagnosis of influenza type A (H3N2) was made in 26.3% of all patients admitted aged 15 years or lower. During the peak of the epidemic, as many as 50-70% of the admissions were attributable to influenza type A (H3N2). In the seven winters from 1991 to 1988, 14.0% of all admissions were associated with infection with influenza virus (mean age 4.4 years), and 17.5% were due to RSV. More patients were admitted to hospital for influenza than RSV infection in three of the seven seasons. Among the patients with influenza, 74.5% of the cases were previously healthy children. Influenza and RSV infection are leading causes of pediatric hospital admissions during the winter. Effective methods of prophylaxis are needed not only for high-risk patients, but for healthy young children.

Adolescent↗

[Use of a rapid detection assay for influenza virus, on nasal aspirate specimens].

We investigated the usefulness of a rapid antigen detection kit using optical immunoassay for influenza virus (FLU OIA, BioStar, USA). Nasal aspirates were taken from 92 influenza suspected outpatients between March to April of 1999. Compared with virus isolation and PCR, the sensitivity of FLU OIA was 88.5% and 81.6%, and the specificity was 65.2% and 72.2%. All isolated viruses were influenza type B virus. It was difficult to differentiate the weak-positive and negative cases, leading to the rather low specificity, although the assay procedure was easy and quick. FLU OIA may be a useful rapid diagnosis kit for influenza in pediatric outpatient clinics and wards, because it can detect both influenza type A and type B viruses.

Antigens, Viral↗

[Optical immunoassay test for rapid detection of influenza A and B viruses: an evaluation].

The optical immunoassay test (FLU OIA, BioStar, USA) for rapid detection of influenza A and B viral antigens was compared with viral isolation in cell culture. A total of 103 respiratory specimens were tested on 75 pediatric patients with acute respiratory illnesses. Influenza viruses were recovered in 40 specimens (type A: 5, Type B: 35). FLU OIA demonstrated 80.0% sensitivity and 68.8% specificity for nasopharyngeal aspirates and 36.7% sensitivity and 83.9% specificity for throat swabs. We also tested FLU OIA, retrospectively, using 78 supernatant samples from pediatric patients with influenza A virus infection frozen after cell culture. FLU OIA demonstrated 91.4% sensitivity and 92.3% specificity for nasopharyngeal aspirates and 50.0% sensitivity and 91.7% specificity for throat swabs diluted in viral transport media. Nasopharyngeal aspirates showed higher sensitivity than throat swabs for detection of influenza virus by FLU OIA. We believe this rapid test kit is useful for the detection of influenza A and B viruses.

Adolescent↗

[A case of influenza A virus associated encephalopathy with bilateral thalamic hemorrhage].

A three-year old girl was hospitalized in a semi-conscious state following a febrile convulsion. She did not recover despite treatment and died 16 days after admission. Influenza A virus (H3N2) was detected from a throat swab from the patient, and serum hemagglutinin-inhibiting antibodies to the virus elevated from less than 8 to 256. Brain CT revealed bilateral thalamic hemorrhage and peripheral low density. Subarachnoid hemorrhage was also observed thereafter. Based on clinical manifestations and neuroimaging, this patient was diagnosed as an atypical case of acute necrotizing encephalopathy associated with influenza A virus infection. Such rapid progressive encephalopathies may occur due to intracranial vascular injury including vasculitis or spasms. Although it is clear that influenza A virus triggered this case, we cannot confirm that it was a pathogen. Also, it might be advisable to consider other possible contributing factors such as drugs administered before hospitalization.

Brain Diseases↗