scholarly journals A GENETIC STUDY OF SUSCEPTIBILITY TO EXPERIMENTAL TUBERCULOSIS IN MICE INFECTED WITH MAMMALIAN TUBERCLE BACILLI

1965 ◽  
Vol 121 (6) ◽  
pp. 1051-1070 ◽  
Author(s):  
Clara J. Lynch ◽  
Cynthia H. Pierce-Chase ◽  
Rene Dubos

A study has been made of the genetic aspects of the difference between two inbred strains of mice (C57B1/6 and Swiss) in response to experimental infection with mammalian tubercle bacilli. Males and females, 4 to 6 weeks of age were inoculated intravenously with 0.2 ml of a 1/50 culture dilution of Mycobacterium tuberculosis var. bovis (Vallée strain) grown in tween albumin medium. Mean survival time for C57B1 animals was 28.1 ± 0.6 days and for Swiss, 55.3 ± 0.6 days postinfection. The characteristic survival time of the two strains was reversed in mice receiving a smaller infective dose. The age of mice at the time of inoculation also affected the results of infection: both C57B1 and Swiss, inoculated at 12 months of age, died at the same rate, but when inoculated at older ages, C57B1 survived slightly longer. Bacteriologic studies demonstrated that there was no significant difference between the two mouse strains with regard to the numbers of viable units of tubercle bacilli recovered from various organs during the 2 week period following infection with a 10–3 culture dilution of Vallée. Moreover, the standard infective inoculum (1/50 culture dilution) did not activate corynebacterial pseudotuberculosis in C57B1 mice, a strain known to be latently infected with Corynebacterium kutscheri, rapid multiplication of tubercle bacilli occurred, but no corynebacteria were recovered. When C57B1 and Swiss strains were crossed, survival tests after infection with the standard inoculum demonstrated that mice of the F1 generation were more resistant than either parent. Whether the overdominance was due to a new combination of parental genes for resistance or to heterosis was not determined. The increased litter size of the F1 mice, an evidence of increased vigor, supports the view that heterosis was involved. In backcrosses to the resistant strain (Swiss), survival time gradually became stabilized at approximately the parental level. In the 1st backcross to the susceptible strain (C57B1), survival times fell into two classes indicating segregation of genes, with perhaps dominance of genes from the Swiss. After repeated backcrosses to C57B1, mice of the 4th backcross generation had a survival time essentially the same as that of the original parental strain. On the basis of having obtained progeny characterized by the original parental susceptibilities after genetic tendencies had been intermingled by crossbreeding, it was concluded that hereditary factors influenced the response of mice to experimental infection with M. tuberculosis. The number of genes was not determined.

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.


Genetics ◽  
1981 ◽  
Vol 99 (2) ◽  
pp. 285-307
Author(s):  
R D McCall ◽  
D Frierson

ABSTRACT Most mammals tested, when exposed to increasing pressure in helium/oxygen atmospheres, exhibit progressive motor disturbances culminating in two, usually successive, well-differentiated convulsive seizures. The seizures are highly reproducible components of the constellation of events that collectively constitute the High Pressure Neurologic Syndrome (HPNS). In the present study, we present evidence that the mean difference in seizure threshold pressures of the first seizure to occur (HPNS Type I) between inbred mouse strains DBA/2J and C57BL/6J is predominantly determined (> 60%) by the expression of a major locus—possibly linked to the H-2 locus on chromosome 17—and a minor locus, probably unlinked. This outcome is derived from applications of the maximum likelihood modeling procedure of Elston and Stewart (1973) and Stewart and Elston (1973) to eleven models of genetic determinacy and tests (including breeding tests) of "preferred" models so derived using BXD recombinant inbred strains that show the following: The major locus exhibits conditional dominance characteristics depending upon compression rate and minor locus genotype. At a constant mean compression rate of 100 atm hr-1, the major locus manifests strong, though incomplete, dominance apparently independent of minor locus genotype. Its expression is, however, highly sensitive to compression rate, losing its dominance altogether at a linear rate of 1,000 atm hr-1. The major locus interacts with the weakly dominant and relatively compression-rate-insensitive minor locus to retain dominance at fast compression only when the dominant alleles of both loci are present. A principal finding of this study is that employing two compression rates permits fuller genetic characterization of murine high-pressure seizure susceptibility differences than could be achieved by use of a single compression rate.


1983 ◽  
Vol 59 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Junkoh Yamashita ◽  
Hajime Handa ◽  
Yasuhiko Tokuriki ◽  
Young Soo Ha ◽  
Shin-Ichi Otsuka ◽  
...  

✓ The authors examined the growth rate of mouse 203 glioma cells in vitro and found it to be markedly inhibited after exposure to ACNU for 5 minutes at a drug concentration of 100 µg/ml. Rats that had undergone intracranial implantation of T1 neurogenic tumor were treated by 5 mg/kg of ACNU administered either intravenously or intra-arterially. The median survival times for the control animals and the animals undergoing intravenous or intracarotid administration of ACNU were 23, 29, and 46 days, respectively. The difference in survival time between the intravenous and intracarotid administration groups was statistically significant (p < 0.01) when examined by the Cox-Mantel test. In a clinical trial, 17 patients with glioblastoma were treated by ACNU, eight intravenously and nine by the intra-arterial route. The drug was given in doses of 2 to 3 mg/kg at least twice before and twice after a course of postoperative radiotherapy. Intra-arterial administration was performed over a period of 5 minutes under local anesthesia. The median postoperative survival time for the patients in the intra-arterial group was 12.5 months, compared with 9.0 months for those in the intravenous group. The survival rate for the intra-arterial group was slightly higher, although statistically not significant, probably because the number of cases was small. The degree of thrombocytopenia due to ACNU tended to be less marked in the intra-arterially treated patients. The theoretical advantages of the intra-arterial administration of ACNU are discussed.


1999 ◽  
Vol 277 (2) ◽  
pp. L372-L380 ◽  
Author(s):  
Daniel R. Prows ◽  
Mark J. Daly ◽  
Howard G. Shertzer ◽  
George D. Leikauf

Acute lung injury (or acute respiratory distress syndrome) is a devastating and often lethal condition. This complex disease (trait) may be associated with numerous candidate genes. To discern the major gene(s) controlling mortality from acute lung injury, two inbred mouse strains displaying contrasting survival times to 10 parts/million ozone were identified. A/J (A) mice were sensitive [6.6 ± 1 (SE) h] and C57BL/6J (B) were resistant (20.6 ± 1 h). The designation for these phenotypes was 13 h, a point that clearly separated their survival time distributions. Our prior segregation studies suggested that survival time to ozone-induced acute lung injury was a quantitative trait, and genetic analysis identified three linked loci [acute lung injury-1, -2, and -3 ( Ali1–3, respectively)]. In this report, acute lung injury in A or B mice was characterized histologically and by measuring lung wet-to-dry weight ratios at death. Ozone produced comparable effects in both strains. To further delineate genetic loci associated with reduced survival, a genomewide scan was performed with F2 mice generated from the A and B strains. The results strengthen and extend our initial findings and firmly establish that Ali1 on mouse chromosome 11 has significant linkage to this phenotype. Ali3 was suggestive of linkage, supporting previous recombinant inbred analysis, whereas Ali2 showed no linkage. Together, our findings support the fact that several genes, including Ali1 and Ali3, control susceptibility to death after acute lung injury. Identification of these loci should allow a more focused effort to determine the key events leading to mortality after oxidant-induced acute lung injury.


1964 ◽  
Vol 120 (2) ◽  
pp. 267-281 ◽  
Author(s):  
Cynthia H. Pierce-Chase ◽  
Robert M. Fauve ◽  
Rene Dubos

The susceptibility of mice to experimental infection with Corynebacterium kutscheri was studied by comparing the host response to this organism of mice obtained from 31 different colonies, representing 15 different genetic types. A standardized infective dose, administered intravenously, made it possible to separate the animals into two sharply differentiated groups. All the animals of the following colonies died: Swiss Lynch, Swiss R/J, A/Jax, Princeton, RFVL, and CF1 (SPF). All the animals of the following colonies survived: CFW, ICR, Balb/C, BSVS, BRVR, RIII, YBR/He, DBA/2 (from 3 different colonies), and C57B1/6 (from 12 different colonies). The two highly inbred strains, Swiss Lynch and C57Bl/6, were selected as prototypes of susceptible and resistant animals respectively, for more detailed studies. Following injection of an infective dose of 0.2 x 10–4 ml of culture of C. kutscheri, all Swiss Lynch animals died within 3 to 11 days (the majority within 4 to 7 days); whereas all C57Bl/6 animals survived. The outcome of the infection in each strain was independent of age and sex of the animals. In Swiss Lynch animals, the corynebacteria multiplied rapidly in lungs, liver, kidneys, and to some extent in the spleen. In C57Bl/6 mice, there was no increase of the corynebacterial population in the lungs, liver, or spleen, but multiplication occurred in the kidneys during the early phase of the infectious process with resultant abscess formation. However, the renal infection soon subsided leaving no residual pathology. C. kutscheri could not be recovered from any organs of C57Bl/6 mice sacrificed 16 days after infection. Homogenates of organs from Swiss Lynch mice obtained while the infection was progressing contained only typical C. kutscheri. In contrast, the lungs and livers of similarly infected C57Bl/6 animals occasionally yielded large numbers of small translucent colonies distinctly different from those of typical corynebacteria. The use of mouse strains differing markedly in response to experimental infection with C. kutscheri is presented as a biologic model lending itself to further studies concerning factors which condition resistance to corynebacterial pseudotuberculosis, a disease of practical importance for investigators conducting experiments with murine species.


1989 ◽  
Vol 53 (3) ◽  
pp. 193-199 ◽  
Author(s):  
Janet Jones ◽  
Josephine Peters ◽  
Carol Rasberry ◽  
Bruce M. Cattanach

SummaryThe behaviour of the X- and Y-borne Sts locus has been studied in male and female mice. There was considerable heterogeneity in STS activity between inbred mouse strains, with a four fold difference in activity between the highest (101/H) and lowest (Ju/Ct) activity strains, which can be interpreted in terms of allelic differences. In all inbred strains male STS levels were higher than those of female STS levels and in the majority of strains tested male STS levels were nearly twice as high as female levels. Reciprocal crosses between C3H/HeH and the STS-deficient substrain, C3H/An, demonstrated that activities of the X- and Y-borne genes in males are essentially the same and this suggested that the lower STS level in females derives from X-inactivation of the locus. The possibility that hormonal differences could instead be responsible for the lower activity in females was ruled out by the findings that (a) castration of males did not reduce their STS levels and (b) sex-reversed males, X / X Sxr, had STS levels typical of females. Final proof that the mouse Sts locus can be subject to the X-inactivation process was provided by the observation that XX females had STS levels that were only slightly (20%) higher than those of XO females. The difference may indicate incomplete inactivation of the locus. Linkage data verifying the location of Sts on the distal end of the X chromosome are provided.In total, the results of this study show that the murine Sts locus can be subject to the X-inactivation process and this, together with the existence of functional loci of near-equal activities on the X and Y chromosomes, results in an imbalance of STS levels between the sexes. X-inactivation does not therefore serve as a dosage compensation mechanism for the Sts locus in the mouse. All of these findings were made in C3H/HeH mice or in animals carrying C3H/HeH functional Sts alleles, and it is pointed out that the diverse results previously obtained by other investigators may be attributable to their use of different strains and crosses between strains but could also be complicated by technical factors.


2017 ◽  
Author(s):  
Jiaxing Wang ◽  
Ying Li ◽  
Rebecca King ◽  
Felix L. Struebing ◽  
Eldon E. Geisert

AbstractThe present study is designed to identify the influences of genetic background to optic nerve regeneration using the two parental strains C57BL/6J and DBA/2J and 7 BXD recombinant inbred strains. To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using AAV, and a mild inflammatory response was induced by an intravitreal injection of zymosan with CPT-cAMP, and the axons were damaged by optic nerve crush (ONC). Regenerating axons were labeled by Cholera Toxin B and quantified 14 days after ONC. The number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we measured the distance that 5 axons had grown down the nerve and the longest distance a single axon reached. Results showed a considerable amount of differential axonal growth across all 9 BXD strains. There was a significant difference (P=0.014 Mann-Whitney U test) in the regenerative capacity in the number of axons reaching 0.5 mm from a low of 1487.6 ± 264.9 axons in BXD102 to a high of 4175.8 ± 648.6 axons in BXD29. There were also significant differences (P=0.014 Mann-Whitney U test) in the distance axons traveled, looking at a minimum of 5 axons with the shortest distance was 787.2 ± 46.5µm in BXD102 to a maximum distance of 2025.5 ± 223.3µm in BXD29. These results reveal that genetic background can modulate axonal regeneration and that the BXD strains are a particularly well-suited model system.


2018 ◽  
Vol 23 (3) ◽  
pp. 149-154
Author(s):  
Krisha Desai ◽  
Alexandra M. Vinograd ◽  
Mary Kate F. Abbadessa ◽  
Aaron E. Chen

Abstract Background: Ultrasound-guided peripheral intravenous lines are frequently used in patients with difficult access. We have previously reported on the longevity and complication rates of ultrasound-guided peripheral intravenous lines, but there are limited data comparing outcomes of ultrasound-guided peripheral intravenous lines to traditionally placed peripheral intravenous lines in children. The aim of this study was to compare the longevity and complication rates of ultrasound-guided peripheral intravenous lines to traditionally placed intravenous lines in a pediatric population. Methods: This study analyzed 300 ultrasound-guided peripheral intravenous lines and 552 traditionally placed intravenous lines using patient records to determine the reason and timing for intravenous line removal. A t-test was used to compare overall mean survival times, and a log-rank test was used to compare Kaplan-Meier survival curves. Complication rates were compared using a chi-squared test. Results: The survival times of ultrasound-guided peripheral intravenous lines (mean = 73 hours, SD = 68 hours) were significantly longer than those of traditionally placed intravenous lines (mean = 38 hours, SD = 29.4 hours), t(559) = 8.51, P &lt; .0001. Kaplan-Meier survival analysis yielded a median ultrasound-guided peripheral intravenous line survival time of 143 hours (IQR = 68–246) and a median traditionally placed intravenous line survival time of 100 hours (IQR = 65–106) with a significant difference between the 2 survival curves by the log-rank test. There was also no significant difference in complication rates between ultrasound-guided peripheral intravenous lines (34.8%) compared to traditionally placed intravenous lines (31.8%), x2(1, N = 517) = 0.465, P = .50. Conclusions: Our data suggests that ultrasound-guided peripheral intravenous lines are a viable option for children, including those with a history of difficult access. Survival times were longer for ultrasound-guided peripheral intravenous lines versus traditionally placed intravenous lines, and complication rates of the ultrasound-guided peripheral intravenous lines and traditionally placed intravenous lines were similar.


2020 ◽  
Author(s):  
Qi Feng ◽  
Donglai Wang ◽  
Zibo Zang ◽  
Jiangang Feng

Abstract Objective: To investigate the efficacy and safety of cement augmented fenestrated screws in the posterior approach for spinal metastases.Methods: A total of 52 patients with spinal metastases who underwent surgery with posterior approach separation and internal fixation with pedicle screw in the Department of Orthopaedics of the Fourth Hospital of Hebei Medical University from January 2015 to January 2017 were analyzed retrospectively. There were 28 cases in the cement augmented pedicle screw group and 24 cases in the conventional pedicle screw group. The clinical data, preoperative and postoperative pain, and neurological function between the two groups were compared. After follow-up, every 3 months, the local progression-free survival time of patients in the two groups was recorded to explore the safety of cement augmented pedicle screws in posterior separation of spinal metastases, and to analyze the difference in efficacy between the two groups.Results: There were no significant differences in sex, age, segments of the affected vertebra, Tomita score, Tokuhashi score, spinal instability neoplastic score (SINS), intraoperative blood loss and average postoperative hospital stays between the two groups. The average operation time was 161 ± 21 minutes in the cement augmented pedicle screw group and 135 ± 19 minutes in the conventional pedicle screw group, with a statistically significant difference. A total of 218 screws were implanted in the 28 patients of the cement augmented pedicle screw group, with an average of 1.3 ± 0.4 ml of cement injected into each screw. There was 1 case of cerebrospinal fluid leakage in each of the two groups, and no incision hematoma formation or infection occurred. There was no symptomatic pulmonary cement embolism in the cement augmented pedicle screw group. The preoperative VAS scores were not statistically different between the two groups. However, the VAS scores in the two groups decreased 3 months after surgery, which were 2.93 ± 1.33 and 4.17 ± 1.34, respectively, with statistical significance. The recovery of Frankel grading was found in 84.6% of all patients (44 cases in 52 patients), but there was no significant difference in Frankel grades between the two groups before and 3 months after surgery. During the follow-up period of 6-24 months, there were 10 cases of adjacent segmental metastasis (2 cases in cement augmented pedicle screw group and 8 cases in conventional pedicle screw group) and 8 cases of internal fixation failure (1 case cement augmented pedicle screw group and 7 cases in conventional pedicle screw group). The difference was statistically significant. Compared with the conventional pedicle screw group, the conventional pedicle screw group had a longer survival time of progression-free in the local and adjacent segments, and the difference was statistically significant. Conclusion: The application of cement augmented pedicle screw in surgery of spinal metastases with the posterior approach is safe, and the pain score decreases more obviously 3 months after surgery. It can effectively reduce the adjacent segmental metastasis and failure rate of internal fixation and prolong the local progression-free survival time.


2017 ◽  
Vol 5 (1) ◽  
pp. 7 ◽  
Author(s):  
Seyed Hossein Moslemzadeh ◽  
Aydin Sohrabi ◽  
Ali Rafighi ◽  
Morteza Ghojazadeh ◽  
Somaieh Rahmanian

Background: Maintaining the results of orthodontic treatment and keeping the teeth in the corrected position is a great challenge in orthodontics. This study aimed to compare the survival time of three types of retainers including Hawley, 1-mm Vacuum-Formed (VF), and 1.5-mm VF within 6-month period. Methods: In this randomized clinical study, 152 patients were allocated into three groups to receive one type of the retainers. They were visited 1, 3, and 6 months after retainer delivery and checked for breakage, loss, local perforation, and discoloration from the patient's and clinician's point of view as indicators of failure. Chi-square and Fisher's exact tests were used as appropriated. Result: The results revealed that breakage was among the main reasons of failure of retainers within 6 months, which was statistically significantly different between Hawley and VF retainers, as well as between 1-mm and 1.5-mm VF retainers in the three intervals (p<0.05). Concerning the loss of retainer and discoloration from the clinician's point of view, there was no significant difference between the retainers in any interval (p>0.05). Assessing the discoloration from the patient's point of view revealed statistically significant differences between Hawley and VF retainers within the first month; however, the difference was not significant at the third and sixth months (p<0.05). The difference between the two thicknesses of VF retainer was not significant in any interval (p>0.05). By the end of the sixth month, some of the VF retainers had perforation; while, perforation was not observed in Hawley retainers.Conclusion: Considering the higher breakage rate of 1-mm VF, 1.5-mm VF seems the retainer if choice.Key words: survival time; retainer; Hawley retainer; Vacuum-formed retainer;


Sign in / Sign up

Export Citation Format

Share Document