Poliomyelitis in Intraspinally Inoculated Poliovirus Receptor Transgenic Mice

AbstractMice transgenic with the human poliovirus receptor gene develop clinical signs and neuropathology similar to those of human poliomyelitis when neurovirulent polioviruses are inoculated into the central nervous system (CNS). Factors contributing to disease severity and the frequencies of paralysis and mortality include the poliovirus strain, dose, and gender of the mouse inoculated. The more neurovirulent the virus, as defined by monkey challenge results, the higher the rate of paralysis, mortality, and severity of disease. Also, the time to disease onset is shorter for more neurovirulent viruses. Male mice are more susceptible to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy number and produce 3-fold more receptor RNA and protein levels in the CNS than TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative neurovirulence show that these mouse lines are similar in disease frequency and severity, demonstrating that differences in receptor gene dosage and concomitant receptor abundance do not affect susceptibility to infection. However, there is a difference in the rate of accumulation of clinical signs. The time to onset of disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage affects the rate of appearance of poliomyelitis in these mice

HU Journal, Volume 7 Issue 21

https://dh.howard.edu/huj_v7/1020/thumbnail.jp

Comparative growth studies of the lactose and non-lactose fermenting strains of Shigella sonnei.

Thesis (M.A.)--Boston UniversityDuval and Schorer (Bact. and Clin. studies from the Rockefeller Inst. for Med. Res., 1904) first isolated the organism now known as Shigella sonnei from cases of infantile diarrhea. Other investigators reported the isolation of organisms closely resembling Duval's bacillus in outbreaks of dysentery. However, it was Sonne (Cent. Bakt. labt. org., 75: 408, 1915) who identified the organism as specific and distinct from the pseudodysentery organisms previously described by Kruse. Thjotta emphasized the variable fermentation of lactose by this organism. Sears and Schoolnik (J. Bact., 31: 309, 1936), Reynolds, etal. (J. Infect. Dis., 55: 207, 1934) and later Cook, Knox and Tomlinson (Brit. J. Exper. Path., 32: 203, 1951) isolated lactose-fermenting (Lac+) mutants from cultures of normal organisms. Kacoyanis (Diserations, Boston University Graduate School, 1955, 1957) found as few as from one to ten Lac+ mutants grew in the presence of large numbers of normal organisms and produced prompt fermentation of lactose and concluded that delayed fermentation of lactose was due to the absence of lactose rather than to the inhibitory action of the normal cells. He stated further that aeration in the presence of lactose favored the appearance of Lac+ mutants. Although Lac+ mutants and normal Sh. sonnei are known to exist, only normal organisms are found in nature. The purpose of the present investigation is to determine the factors that result in the more successful competition or the normal organism in mixed cultures. The comparative growths or the Lac+ mutant and the normal organism were studied by growing them in various liquid media in both pure and mixed culture under aerated and non-aerated (still) conditions. [TRUNCATED

Some factors influencing lactose fermentation by Shigella Sonnei

Thesis (Ph.D.)--Boston UniversityThe fermentation of lactose by Shigella sonnei has been associated with the presence of mutants. We observed that lactose-fermenting (lactose) mutants of Sh. sonnei could be isolated from all lactose broth cultures which had become acid within about ten days of incubation. However, lactose mutants could not be isolated from cultures which had become acid after this time. It was thought that the absence of lactose-fermenting organisms in these cultures might be due to the death of the mutants because of increased acidity produced by lactose fermentation. The pH of all acid cultures was measured but no apparent difference was found between those from which lactose mutants were isolated and those in which lactose mutants could not be detected. The possibility existed that acid production might have been caused by lactose mutants present in numbers too few to be detected by loopful sampling. By the method described by Kacoyanis and Baker (Proc. Bact., 1935, p.103) entire bacterial cultures were screened for lactose mutants. However, lactose mutants could not be detected. The fact that Sh. sonnei did not produce acid in the same medium containing no lactose established that acid production was due to utilization of lactose. In the hope of explaining the apparent production of acid by normal Sh. sonnei, the effect of various cultural conditions on both the production of lactose mutants and the apparent production of acid by normal organisms was examined. Increased concentrations of lactose, meat extract or peptone in the medium; neutralized filtrates of acid cultures of lactose cells; and aging of ctutures in nutrient broth to which lactose was added did not increase the rate of lactose mutant production. Aeration of normal organisms in lactose broth favored the production of lactose mutants. Nearly all cultures became acidified within five days and then became alkaline again. Lactose mutants could be isolated for several days afterward. Eventually, the lactose mutants disappeared in the aerated cultures and only normal cells could be isolated. Lactose mutants could not be isolated from cultures of normal organisms when aerated in lactose-free nutrient broth. The stimulatory effect of aeration on the production of lactose mutants is apparent only when lactose is present. When lactose broth cultures of Sh. sonnei were grown under anaerobic conditions, all cultures became acid on the sixth day of incubation, but lactose mutants were not detected. The possibility that this phenomenon might be due to reduction of the indicator or to accumulation of carbon dioxide was examined and ruled out experimentally. Acid did not occur in cultures grown anaerobically in nutrient broth without lactose indicating that the presence of lactose was required for the production of acid in these cultures. When lactose cells were inoculated into lactose: broth and grown anaerobically, acid appeared within forty-eight hours. Under these conditions the lactose mutants produced considerably more acid than did normal organisms. Furthermore, lactose mutants could be isolated from these cultures. It is apparent that anaerobic conditions inhibit the production of lactose mutants. Furthermore, it seems probable that the production of acid by normal Sh. sonnei growth under anaerobic conditions occurs by some unknown mechanism different from that used by lactose-fermenting mutants. Relative growth rates of lactose mutants and normal organisms were studied. Lactose mutants grew at a better rate in lactose synthetic broth than normal organisms when subcultured from cultures grown in nutrient broth. However, the lactose mutants did not grow as well in lactose as in glucose synthetic broth, a lag occurring in the rate of growth. Lactose mutants subcultured from lactose broth medium into fresh lactose synthetic broth did not grow significantly better than lactose organisms which were subcultured from nutrient broth. Therefore, it appeared that enzymatic adaptation did not occur in this mutant. It seems that this lactose mutant may differ from mutants described by other investigators. Ultraviolet irradiation of normal Sh. sonnei neither increased nor decreased the rate of production of lactose mutants. In addition, chemical mutagenic agents (manganous chloride, formaldehyde, phenol and sodium desoxycholate) were used in an effort to induce an increase in the rate of production of lactose mutants. Under these experimental conditions, the physical and chemical agents used had a lethal but not a mutagenic action on Sh. sonnei. Preliminary work suggested that aeration of lactose mutants in nutrient broth induced the rise of lactose mutants. This was confirmed in detailed studies which also indicated that these lactose mutants are favored by aeration in the absence of lactose. The results seem to point to the selective action of lactose in the rise of lactose mutants. However, the possibility of a stimulatory effect of lactose cannot be eliminated

Haemophilia: Recent history of clinical management, vol. 4

Scientists, haematologists, carers and haemophiliacs themselves discussed the changes in the treatment and clinical management of haemophilia over the past 50 years and highlighted important events, such as the extraordinary situation in which triplet siblings frequently received life-saving transfusions from their mother; the preparation and isolation of factor VIII by Ethel Bidwell; and how, even today, the spectre of contamination of blood products haunts haemophiliacs. Participants included: Professor Christine Lee (Chair), Dr Ethel Bidwell, Dr David Evans, Professor Ilsley Ingram, Dr Peter Jones, Dr Charles Rizza, Mr Clifford Welch. Introduction by E M Tansey. Tansey E M, Christie D A. (eds) (1999) Haemophilia: Recent history of clinical management. Wellcome Witnesses to Twentieth Century Medicine, vol. 4. London: The Wellcome Trust, ix+90pp, 8 illustrations, 1 chart, 1 diagram, glossary, subject and name index.Size: 298mm x 210mm x 6mm. [Published September 1999]

Subacute myoclonic measles encephalitis – An opportunistic HIV-associated infection

IntroductionAn unusual cluster of myoclonic epilepsy was observed in a Romanian pediatric HIV cohort concurrent with measles outbreaks. We describe this particular form of subacute measles encephalitis (SME) in a group of HIV-infected children and adolescents with severe immunosuppression.MethodsThis is a single-center study, starting in 1997 and covering 4 measles outbreaks in Romania. The presumptive diagnosis of subacute myoclonic measles encephalitis (SMME) was based on: (1) epidemiological data, previous measles episode or presumed contact with measles virus (MV), (2) clinical presentation with initial localized myoclonic jerks with rapid extension and subsequent motor deficit with preserved mental status, and (3) neuroimaging studies revealing cortical gray matter lesions. Definitive diagnosis was based on a neuropathological exam and immunohistochemistry of brain tissues, and measles RNA detection in the cerebrospinal fluid (CSF).ResultsThirty-six patients were diagnosed with a particular form of SME during consecutive measles outbreaks in Romania: 1996–1998 (22); 2005–2008 (12); 2010–2011 (1) and 2016-2018 (1). Most children were born in the late 80s and had parenterally acquired HIV infection in early childhood. Before the episode of SMME, 11 patients had confirmed measles, while the rest, without typical rash, had a respiratory tract infection and/or presumed previous measles contact. In all patients, the clinical onset was sudden, with unilateral myoclonus. MRI findings revealed mainly focal cortical gray matter lesions. Neurologic symptoms progressed rapidly to coma and death in most patients. Three patients survived SMME, they had higher CD4 count at onset, slower progression of neurological symptoms, and benefit of immune recovery with cART. Immunocytochemistry studies revealed MV in the brain with a pattern suggesting an ascending viral neural infection. MV was isolated from CSF in 7 out of 8 patients. Sequence analysis of MV RNA from both nasopharyngeal swabs and CSF was available for one patient with similar N-450 strain characteristics.ConclusionDuring an outbreak of measles, neurological manifestations, especially myoclonus in immunosuppressed patients, can be related to measles even in the absence of an acute episode. This particular form of subacute myoclonic measles encephalitis is an opportunistic fatal disease. Immune recovery due to effective antiretroviral treatment might increase survival