A random-primed complementary DNA library was constructed from plasma containing the uncharacterized non-A, non-B hepatitis (NANBH) agent and screened with serum from a patient diagnosed with NANBH. A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections. This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive-stranded with respect to the encoded NANBH antigen. These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae. This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents.

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Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome

A specific assay has been developed for a blood-borne non-A, non-B hepatitis (NANBH) virus in which a polypeptide synthesized in recombinant yeast clones of the hepatitis C virus (HCV) is used to capture circulating viral antibodies. HCV antibodies were detected in six of seven human sera that were shown previously to transmit NANBH to chimpanzees. Assays of ten blood transfusions in the United States that resulted in chronic NANBH revealed that there was at least one positive blood donor in nine of these cases and that all ten recipients seroconverted during their illnesses. About 80 percent of chronic, post-transfusion NANBH (PT-NANBH) patients from Italy and Japan had circulating HCV antibody; a much lower frequency (15 percent) was observed in acute, resolving infections. In addition, 58 percent of NANBH patients from the United States with no identifiable source of parenteral exposure to the virus were also positive for HCV antibody. These data indicate that HCV is a major cause of NANBH throughout the world.

https://science.sciencemag.org/content/sci/244/4902/362.full.pdf

An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis

To estimate the global illness and deaths caused by rotavirus disease, we reviewed studies published from 1986 to 2000 on deaths caused by diarrhea and on rotavirus infections in children. We assessed rotavirus-associated illness in three clinical settings (mild cases requiring home care alone, moderate cases requiring a clinic visit, and severe cases requiring hospitalization) and death rates in countries in different World Bank income groups. Each year, rotavirus causes approximately 111 million episodes of gastroenteritis requiring only home care, 25 million clinic visits, 2 million hospitalizations, and 352,000–592,000 deaths (median, 440,000 deaths) in children <5 years of age. By age 5, nearly every child will have an episode of rotavirus gastroenteritis, 1 in 5 will visit a clinic, 1 in 60 will be hospitalized, and approximately 1 in 293 will die. Children in the poorest countries account for 82% of rotavirus deaths. The tremendous incidence of rotavirus disease underscores the urgent need for interventions, such as vaccines, to prevent childhood deaths in developing nations.

/pdf/global-illness-and-deaths-caused-by-rotavirus-disease-in-4r3lieayv1.pdf

Global Illness and Deaths Caused by Rotavirus Disease in Children

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.5.9908022

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease.

Hepatitis C virus antibodies among risk groups in Spain.

Exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. To study the effects of rhinovirus infection on respiratory epithelium, a primary target for respirat...

Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1β

Between December 1984 and December 1986, a microplate technique was adopted for isolation of viruses from infants and children with acute respiratory infections. By using two kinds of tissue culture microplates, i.e., the HHVM plate, containing human embryonic fibroblast (HEF), HEp-2, Vero and MDCK cells, and the MK plate which contains secondary monkey kidney cells, 1,080 field viruses were isolated from 1,061 (24.9%) out of 4,254 throat swabs. Of these 1,080 isolates, 1,003 (92.9%) were recovered in the HHVM plates and the remaining 77 (7.1%) in the MK plates. With the HHVM plate, influenza A and B viruses were cultivated in MDCK, RS virus in HEp-2, parainfluenza and mumps viruses in Vero, adenoviruses in both HEF and HEp-2, polioviruses in HEF, HEp-2 and Vero, coxsackie B viruses in both HEp-2 and Vero, rhino and echo viruses in HEF, herpes simplex virus in both HEF and HEp-2, and cytomegalovirus in HEF, although MK were more sensitive than Vero to parainfluenza and coxsackie B viruses. There was no difference in the rate of isolation of viruses between the microplate and ordinary tube methods. Cross contamination in the microplates was negligible for routine work.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1348-0421.1987.tb01340.x

A Microplate Method for Isolation of Viruses from Infants and Children with Acute Respiratory Infections

Interspecies transmission of influenza C virus between humans and pigs

A viral etiology of acute hemorrhagic cystitis was sought in 11 children seven to 15 years of age. Type 11 adenovirus was recovered from the urine of nine of these, and a significant rise in neutralizing antibody titer against Type 11 adenovirus was demonstrated in all. No virus was isolated from the urine of normal children or children with other diseases. Type 11 adenovirus is proposed as an etiologic agent of acute hemorrhagic cystitis.

Acute hemorrhagic cystitis in children. Isolation of adenovirus type II.

To establish the viral origin of acute hemorrhagic cystitis in children as well as adults, 28 patients (23 children and five adults) were examined virologically or serologically during the period 1967–1972. Adenovirus Type 11 was isolated from the urine in 11 of 25 cases. With use of fresh urine without storage, the virus was isolated from 11 of 12 subjects. Seroconversion to adenovirus Type 11 occurred in 19 of the 28 patients, including all who were virus positive, except for one in whom paired serum samples were not available. A total of 17 children and three adults out of 28 (71.4 per cent) were diagnosed as having adenovirus Type 11 infection. These results support the finding in a previous report that adenovirus Type 11 may be specifically associated with acute hemorrhagic cystitis. (N Engl J Med 289:344–347, 1973)

https://www.nejm.org/doi/pdf/10.1056/NEJM197308162890704?listPDF=true

Yoshio Numazaki

Papers

Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1β

A Microplate Method for Isolation of Viruses from Infants and Children with Acute Respiratory Infections

Interspecies transmission of influenza C virus between humans and pigs

Acute hemorrhagic cystitis in children. Isolation of adenovirus type II.

Further Study on Acute Hemorrhagic Cystitis Due to Adenovirus Type 11