Evaluation of a pre-harvest bacteriophage therapy for control of Salmonella within bovine peripheral lymph nodes

2021 ◽  
Author(s):  
L. R. Wottlin ◽  
Tom Edrington ◽  
T. R. Brown ◽  
C. A. Zook ◽  
A. Sulakvelidze ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Post Mortem ◽  
Proof Of Concept ◽  
Bacteriophage Therapy ◽  
Transmission Electron ◽  
Peripheral Lymph ◽  
Final Study ◽  
Phage Cocktail ◽  
The Right ◽  
Phage Treatment

A series of proof of concept studies were developed to determine if a commercial bacteriophage (phage) cocktail could be utilized for the mitigation of Salmonella in bovine peripheral lymph nodes (LN). The first objective sought to determine if exogenous phage could be isolated from the LN following administration. If successful, the second objective sought to determine if once in the LN, could the phage effectively reduce Salmonella . Salmonella Montevideo was inoculated intradermally in multiple sites and administrations, later followed by delivery of the phage cocktail subcutaneously in two injections around each of the right and left prescapular and subiliac LN. At the conclusion of each study, animals were euthanized and the popliteal and above LN examined. The first study was successful, in that transmission electron microscopy revealed the presence of phage in the LN of the treated cattle, that were identical to the strains in the cocktail. Concentrations of phage were increased ( P < 0.01) in the pre-scapular and subiliac LN in the phage-treated versus control cattle. Subsequent studies modified the protocols to increase Salmonella and phage concentrations within the LN. Overall concentrations of Salmonella were increased in the LN compared to the first study and phage treatment decreased ( P < 0.01) Salmonella in the some of the LN. Phage concentrations were numerically ( P = 0.12), but not statistically, increased in the treated cattle. The final study was modified, hypothesizing that a 48h post-mortem period prior to LN removal would facilitate phage/ Salmonella interaction, however, there were no differences ( P > 0.10) in Salmonella concentrations among treatments. Results demonstrated that Salmonella- specific phages administered to live cattle can translocate to the LN, however once in the LN they had limited to no effect on Salmonella within these nodes.

scholarly journals Evaluation of two commercially-available Salmonella vaccines on Salmonella in the peripheral lymph nodes of experimentally-infected cattle

2020 ◽  
Vol 8 ◽  
pp. 251513552095776
Author(s):  
Thomas S. Edrington ◽  
Terrance M. Arthur ◽  
Guy H. Loneragan ◽  
Kenneth J. Genovese ◽  
Devin L. Hanson ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Research Effort ◽  
Booster Vaccination ◽  
Post Inoculation ◽  
Mesenteric Lymph Nodes ◽  
Experimental Conditions ◽  
Salmonella Newport ◽  
Peripheral Lymph ◽  
Duration Of Infection ◽  
The Right

Background: Salmonella is a common inhabitant of the ruminant gastrointestinal tract, where it often resides asymptomatically and may be shed into the feces. More recently it was discovered that Salmonella may be contained within the peripheral, non-mesenteric lymph nodes, where it is impervious to in-plant pathogen control interventions and may serve as a source of Salmonella-contamination of ground beef. Over the past 10 years considerable research effort has been expended at understanding how this pathogen gets to these lymph nodes, the duration of infection, and, most importantly, screening and developing potential intervention strategies that may be employed on farm prior to the animal being presented for slaughter. Methods: Utilizing an experimental model of Salmonella inoculation of bovine peripheral lymph nodes (PLNs), two pilot vaccine experiments were conducted to evaluate two Salmonella vaccines: Salmonella Newport Bacterial Extract (Experiment I) and Endovac-Bovi® (Experiment II) on preventing Salmonella acquisition by these nodes. In Experiment I, 4 months following the booster vaccination, 30 steers were inoculated with three Salmonella serotypes intradermally: Newport, Montevideo, and Anatum administered to the right legs, left legs, and to the caudal thorax and abdomen, respectively. Cattle were inoculated every other day over the course of five days (three total inoculation events) and 6 and 12 days following the final Salmonella inoculation, 16 and 14 head in each treatment were euthanized, respectively. In Experiment II, 12 head of Holstein steers were utilized. Seven days following the booster and weekly thereafter for 3 weeks (four total inoculation events), cattle were inoculated as above and euthanized 7 days following final inoculation. Right and left sub-iliac, popliteal and pre-scapular lymph nodes were collected in each experiment, weighed and cultured for Salmonella. Results: In Experiment I, no treatment differences were observed in Salmonella prevalence 6 days post-inoculation (necropsy 1). However, in vaccinated cattle at the second necropsy, a reduction ( p = 0.05) in Salmonella prevalence was observed in the sub-iliac and pre-scapular lymph nodes as well as when all nodes were evaluated collectively ( p = 0.04). In Experiment II, the vaccine reduced ( p = 0.03) Salmonella prevalence in the right popliteal and tended ( p = 0.09) to decrease prevalence in both popliteal lymph nodes. Conclusion: Under these experimental conditions, the data generated provide evidence of a partial vaccine effect on Salmonella within PLNs and indicate that further research may be warranted.

Influence of Route of Mycobacterium lepraemurium Injection on Susceptibility to Mouse Leprosy and on Lymphoblastic Transformation

1980 ◽  
Vol 28 (3) ◽  
pp. 660-668
Author(s):  
Raymond Turcotte
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
B Cell ◽  
Hind Footpad ◽  
Peripheral Lymph ◽  
Lymphoblastic Transformation ◽  
The Mean ◽  
Mycobacterium Lepraemurium ◽  
The Right ◽  
Observation Period

Groups of female C57BL/6 and C3H/St mice were inoculated intraperitoneally (i.p.) with 10 9 , 10 7 , and 10 5 bacilli and into the right hind footpad with 10 7 and 10 5 bacilli of Mycobacterium lepraemurium . The incidence of death from leprosy and the mean survival time of leprous mice were recorded. In addition, the blastogenic responses to the T-cell mitogens phytohemagglutinin and concanavalin A and to the B-cell mitogens lipopolysaccharide and dextran sulfate were evaluated at various times during the course of infection in the spleen and peripheral lymph nodes of mice infected with 10 7 bacilli. When M. lepraemurium was administered i.p., the two strains of mice succumbed to the disease at about the same time, except for the C57BL/6 mice infected with 10 9 bacilli, which died earlier than the C3H/St mice. Moreover, in both strains of mice, a progressive depression of blastogenesis, first to the T-cell mitogens and then to the B-cell mitogens in the spleen, and to the T-cell mitogens in the peripheral lymph nodes, occurred during the course of the infection, whereas the response to the B-cell mitogens in the nodes increased slowly during the advanced stage of the disease. When 10 7 and 10 5 bacilli were injected into the footpad, the C3H/St mice succumbed to the disease at 298 and 344 days, respectively, and the modifications of blastogenesis were similar to those observed in i.p.-infected C3H/St mice. In contrast, the C57BL/6 mice appeared resistant to footpad inoculation of M. lepraemurium , since they lived until the end of the observation period (466 days postinfection) and the depression of blastogenesis was not detectable until 1 year after the infection. Thus, it is concluded that for the C57BL/6 mice (but not for the C3H/St mice), the route of administration of M. lepraemurium can markedly influence the susceptibility or resistance to leprosy.

Ultrastructural investigation of an adenoma of the pituitary post mortem

1987 ◽  
Vol 45 ◽  
pp. 622-623
Author(s):  
Shirley Siew ◽  
W. C. deMendonca
Keyword(s):  
Deleterious Effect ◽  
Anterior Lobe ◽  
Definitive Diagnosis ◽  
Pars Intermedia ◽  
Post Mortem ◽  
Close Apposition ◽  
Autopsy Material ◽  
Progressive Loss ◽  
Transmission Electron ◽  
Means Of Transmission

The deleterious effect of post mortem degeneration results in a progressive loss of ultrastructural detail. This had led to reluctance (if not refusal) to examine autopsy material by means of transmission electron microscopy. Nevertheless, Johannesen has drawn attention to the fact that a sufficient amount of significant features may be preserved in order to enable the establishment of a definitive diagnosis, even on “graveyard” tissue.Routine histopathology of the autopsy organs of a woman of 78 showed the presence of a well circumscribed adenoma in the anterior lobe of the pituitary. The lesion came into close apposition to the pars intermedia. Its architecture was more compact and less vascular than that of the anterior lobe. However, there was some grouping of the cells in relation to blood vessels. The cells tended to be smaller, with a higher nucleocytoplasmic ratio. The cytoplasm showed a paucity of granules. In some of the cells, it was eosinophilic.

Distribution and Characteristics of Intrathoracic Lymphadenopathy in TB/HIV Co-Infection

2019 ◽  
Vol 19 (4) ◽  
pp. 414-420
Author(s):  
Payam Mehrian ◽  
Abtin Doroudinia ◽  
Moghadaseh Shams ◽  
Niloufar Alizadeh
Keyword(s):  
Lymph Nodes ◽  
Cross Sectional Study ◽  
Short Axis ◽  
Mediastinal Lymph Nodes ◽  
Sectional Study ◽  
Cross Sectional ◽  
Immunodeficiency Virus ◽  
Hilar Adenopathy ◽  
The Right ◽  
Pulmonary Abnormalities

Background: Intrathoracic Lymphadenopathy (ITLN) in Human Immunodeficiency Virus (HIV) infected patients may have various etiologies and prognoses. Etiologies of ITLN can be distinguished based on the distribution of enlarged lymph nodes. Sometimes tuberculosis (TB) is the first sign of underlying HIV infection. Objective: We sought to determine ITLN distribution and associated pulmonary findings in TB/HIV co-infection using Computed Tomography (CT) scan. Methods: In this retrospective, observational, cross-sectional study, chest CT scans of 52 patients with TB/HIV co-infection were assessed for enlarged intrathoracic lymph nodes (>10 mm in short axis diameter), lymphadenopathy (LAP) distribution, calcification, conglomeration, the presence of hypodense center and associated pulmonary abnormalities. LAP distribution was compared in TB/HIV co-infection with isolated TB infection. Results: Mediastinal and/or hilar LAP were seen in 53.8% of TB/HIV co-infection patients. In all cases, LAP was multinational. The most frequent stations were right lower paratracheal and subcarinal stations. Lymph node conglomeration, hypodense center and calcification were noted in 25%, 21.4% and 3.5% of patients, respectively. LAP distribution was the same as that in patients with isolated TB infection except for the right hilar, right upper paratracheal and prevascular stations. All patients with mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Conclusion: All patients with TB/HIV co-infection and mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Superior mediastinal lymph nodes were less commonly affected in TB/HIV co-infection than isolated TB.

Salmonella Persistence within the Peripheral Lymph Nodes of Cattle following Experimental Inoculation

2016 ◽  
Vol 79 (6) ◽  
pp. 1032-1035 ◽  
Author(s):  
T. S. EDRINGTON ◽  
G. H. LONERAGAN ◽  
K. J. GENOVESE ◽  
D. L. HANSON ◽  
D. J. NISBET
Keyword(s):  
Body Weight ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Enrichment Culture ◽  
Lower Leg ◽  
Challenge Strain ◽  
Peripheral Lymph ◽  
Experimental Inoculation ◽  
Duration Of Infection

ABSTRACT Utilizing a transdermal method of inoculation developed in our laboratory, the duration of infection of Salmonella in the peripheral lymph nodes of steers was examined. Thirty-six Holstein steers (mean body weight of 137 kg) were inoculated with Salmonella Montevideo (day 0) on each lower leg and both sides of the back and abdomen. Calves were euthanized beginning at 6 h and subsequently on each of days 1, 2, 4, 7, 9, 11, 14, and 21 postinoculation (four animals each time). The subiliac, popliteal, and superficial cervical (prescapular) lymph nodes were collected and cultured (quantitatively and qualitatively) for the challenge strain of Salmonella. The challenge strain was detected via direct culture within the lymph nodes at 6 h postinoculation and on each subsequent necropsy date. Salmonella levels in lymph node were 0.8 to 1.8 log CFU/g. Lymph nodes were generally positive after enrichment culture throughout the experiment. Salmonella elimination appeared to begin approximately 14 days postinoculation. However, elimination was not completed by day 21; therefore, a second experiment was conducted identical to the first except that the time from inoculation to necropsy was extended. Salmonella was recovered via direct culture on each of the necropsy days, and results in general were similar to those of experiment I, except that on days 20, 24, and 28 isolates from serogroups C2 and E1 were identified in addition to the inoculation strain C1 in multiple animals. The data from both experiments indicate that after a single inoculation event, Salmonella would be completely cleared by approximately 28 days. Further research with expanded times between inoculation and necropsy is required for verification.

scholarly journals EP22 A manifestation of severe sarcoid arthropathy in the distal interphalangeal joint

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rajiv Ark
Keyword(s):  
Case Report ◽  
Lymph Nodes ◽  
Cardiac Sarcoidosis ◽  
Treatment Options ◽  
Nasal Discharge ◽  
Pulmonary Manifestations ◽  
Distal Interphalangeal ◽  
The Right ◽  
Little Finger

Abstract Case report - Introduction In 2011 a gentleman in his 50s presented with nasal blockage and bloody discharge. He was diagnosed with sarcoidosis and after 9 years of failed strategies to control his disease, he developed dactylitis. X-ray of the hands showed severe arthropathy in the distal interphalangeal joints. This case demonstrates an uncommon extrapulmonary manifestation of sarcoidosis. Although most of his follow up was with a respiratory clinic, his main symptoms were not due to interstitial lung disease, highlighting the importance of a multidisciplinary approach. To reduce the need for steroids, several DMARDs were tried illustrating that there are limited treatment options. Case report - Case description This gentleman presented in June 2011 with left epiphora, bloody nasal discharge and fatigue. He had no family history of sarcoidosis and was of Caucasian ethnicity. He was referred by his GP to Ophthalmology and ENT. Septoplasty showed a 95% blockage at the lacrimal sac. A biopsy was performed, and histology showed a nasal sarcoid granuloma. He was referred to the respiratory team who requested a high-resolution CT scan showing sizeable lymph nodes. One inguinal node was biopsied confirming sarcoid granulomas before starting treatment. Calcium was briefly raised, and serum ACE was initially 123. He was started on 40mg of prednisolone for 6 weeks, which was tapered to 20/25mg on alternating days. There was a recurrence of his nasal discharge; steroids were increased again but he developed symptoms of muscle weakness from long term steroid use. He was referred to an interstitial lung disease clinic at a tertiary centre where he was investigated for cardiac sarcoidosis with MRI due to ventricular ectopics. Hydroxychloroquine was started to reduce the steroid use however he developed symptoms of tinnitus, so it was stopped. Methotrexate, Azathioprine and Leflunomide were all trialled to however they did not have any impact on controlling his disease. His Prednisolone was slowly reduced by 1mg a month. When he had recurrence of his symptoms, he was given IV methylprednisolone. Nine years after his first presentation he presented with stiffness of the right thumb base. This progressed to dactylitis and slight fixed flexion deformity of right index finger and left little finger. An x-ray of his hands showed disease in the distal interphalangeal joints bilaterally with severe changes in the left little finger. The effects of long-term steroids led him to request a letter to support early retirement. Case report - Discussion The main rationale for changing treatment options was to reduce the prednisolone dose. Steroids were the only treatment option that showed evidence of controlling his disease when the dose was between 25mg and 40mg a day. Each of the DMARDs that were trialled had a different side effect profile and did not show any evidence of suppressing disease as symptoms recurred. Dose changes later in treatment fluctuated, reflecting a balancing act between disease recurrence and side effects of long-term steroids. There are many extra pulmonary manifestations of sarcoidosis that were investigated in this case. The first being the nasal granuloma, which can occur in sarcoid patients with symptoms of epistaxis, crusting, congestion, and pain. There were granulomatous changes seen in the hila as well as other lymph nodes such as the inguinal region; inguinal lymphadenopathy can lead to pain in the groin area. In addition to this it was important to exclude uveitis with ophthalmology review as he had symptoms of epiphora. Uveitis can be diagnosed in ophthalmological assessment of sarcoid patients in the absence of ocular complaints. Cardiac sarcoidosis was excluded with an MRI at a specialist heart and lung centre due to ventricular ectopics. Cardiac sarcoidosis can lead to heart block, arrhythmias, and congestive cardiac failure. Finally, he developed sarcoid arthropathy, review of his radiological images over time showed extensive damage to the joints of the hand. This gentleman had poor outcomes due to limited treatment options for his disease. Being restricted to long term steroid as the mainstay of treatment led to early retirement due to fatigue and muscle weakness. Conversely, under dosing steroids led to recurrence in symptoms. His disease is still not controlled as shown by an evolving sarcoid arthropathy. Case report - Key learning points An illustration of sarcoid arthropathy is also shown in this case. Sarcoid arthropathy is an uncommon manifestation of the disease primarily affecting joints in the hands and feet. In this case the distal interphalangeal joints and proximal interphalangeal joints were affected. The first symptom of arthropathy was stiffness of the base of the right thumb in 2017, this could fit with an osteoarthritic picture and could be mistaken for it in undiagnosed sarcoidosis. The most severe disease was in the DIP of the left little finger, which is not commonly affected. An oligoarthritic pattern with involvement of the ankle is seen more often. This is also an unusual case of sarcoidosis as there was no family history of the disease and his ethnicity did not predispose him to the condition. He also had a few uncommon extra pulmonary manifestations of sarcoidosis. The importance of a multidisciplinary approach in managing sarcoidosis was demonstrated in this case. Most of his follow up was with a respiratory clinic. However, respiratory symptoms were not the main issue during the patient journey; early ENT and rheumatology input was significant in managing his disease. Although pulmonary lymph nodes were enlarged, they did not affect his lung function.

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