Cannabinoid hyperemesis syndrome co-occurring with superior mesenteric artery syndrome in adolescents.

OBJECTIVES: Both superior mesenteric artery syndrome (SMAS) and cannabinoid hyperemesis syndrome (CHS) may present with abdominal pain, nausea, and emesis - making them difficult to differentiate or determine when they co-occur in adolescents who regularly use cannabis. Here, we present nine cases of CHS co-occurring with SMAS and characterize their clinical courses. METHODS: Patients admitted at Children's Hospital of Colorado between January 1, 2015, and March 23, 2023, who had both cannabis use (F12.1-F12.99) and chronic vascular disorders of the intestine (K55.1) on their problem lists were identified from the electronic medical record using ICD 10 codes. Nine met criteria for SMAS and chronic cannabis use. RESULTS: Six of nine patients were female. The most common presenting symptoms were nausea (9), vomiting (9), and weight loss (9). Four patients received cannabis cessation support. Patients lost a mean of 6.0 kg, had an average body mass index (BMI) of 15.61 percentile (17.7 kg/m2) and BMI Z-scores of -1.5. Symptoms were present for a mean of 19.6 weeks before diagnosis. CONCLUSIONS: Adolescents who experience nausea, vomiting, abdominal pain, and weight loss in association with chronic cannabis use and/or SMAS can present with confusing and overlapping symptoms. Our cohort was described as having CHS with co-occurring SMAS on imaging. Although the etiology of weight loss cannot be definitively ascertained, we postulate that the recurring emetic attacks from CHS led to weight loss resulting in SMAS. Improvement in diagnostic criteria for this population as well as cannabis cessation programming may aid in deceasing morbidity from these co-occurring conditions.

Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions.

Background: Delirium following cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. Preoperative protein signatures may identify patients at increased risk for worse postoperative outcomes, including delirium. In this study, we aimed to identify plasma protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery, while also uncovering possible pathophysiological mechanisms. Methods: SOMAscan analysis of 1,305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (PREOP) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the ELLA multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology. Results: A total of 115 and 85 proteins from SOMAscan analyses were found altered in delirious patients at PREOP and POD2, respectively (p<0.05). Using four criteria including associations with surgery, delirium, and biological plausibility, 12 biomarker candidates (Tukey's fold change (|tFC|)>1.4, Benjamini-Hochberg (BH)-p<0.01) were selected for ELLA multiplex validation. Eight proteins were significantly altered at PREOP, and seven proteins at POD2 (p<0.05), in patients who developed postoperative delirium compared to non-delirious patients. Statistical analyses of model fit resulted in the selection of a combination of age, sex, and three proteins (angiopoietin-2 (ANGPT2); C-C motif chemokine 5 (CCL5); and metalloproteinase inhibitor 1 (TIMP1); AUC=0.829) as the best performing predictive model for delirium at PREOP. The delirium-associated proteins identified as biomarker candidates are involved with inflammation, glial dysfunction, vascularization, and hemostasis, highlighting the multifactorial pathophysiology of delirium. Conclusion: Our study proposes a model of postoperative delirium that includes a combination of older age, female sex, and altered levels of three proteins. Our results support the identification of patients at higher risk of developing postoperative delirium after cardiac surgery and provide insights on the underlying pathophysiology. ClinicalTrials.gov ( NCT02546765 ).

Perceived stress, resilience, well-being, and COVID 19 response in Isha yoga practitioners compared to matched controls: A research protocol.

OBJECTIVES: The COVID-19 pandemic has been a significant stressor worldwide and reports of psychological distress, depression, sedentary lifestyles, and overall decreased wellbeing are increasing. Yoga practices have been found to improve mental and physical health. The purpose of this randomized controlled trial is to compare Isha yoga practitioners to controls on perceived stress, resilience, wellbeing, and protection and recovery from COVID-19. Trial Design. In this prospective randomized control trial, the effects of yoga practices are being compared between seasoned yoga practitioners with two controls who are age (±3 years), gender matched, and living in the same neighborhood. METHODS: Participants will be asked to complete a series of web-based surveys at baseline, six weeks, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess stress, mood states, resilience, and overall wellbeing. Questionnaires, weekly activity diaries, and medical history, will be collected using REDCap. RESULTS: We hypothesize that routine yoga practice during the COVID-19 pandemic will reduce stress, enhance well-being, and provide protective effects against COVID-19. CONCLUSION: With the growing concern about the physical and mental impacts of COVID-19 and increased interest in alternative practices such as yogic practices, this study will contribute to the growing body of evidence about the safety and efficacy of yoga for emotional, mental, and physical health conditions.

Role of Gordonia sp JAAS1 in biodegradation of chlorpyrifos and its hydrolysing metabolite 3,5,6-trichloro-2-pyridinol.

UNLABELLED: Paddy field soil with prior exposure to chlorpyrifos was chosen for the biodegradation of the pesticide by employing bacteria with special emphasis given to actinomycetes. Actinomycetes are organisms predominantly known for their bioactive compounds, but there is dearth of work pertaining to their role in bioremediation. So this work was carried out to screen for actinomycetes and assess their potential in degradation of the pesticide. Actinobacterial strains were isolated from paddy field soil, with capabilities to degrade chlorpyrifos and its major metabolite 3,5,6-trichloro-2-pyridinol (TCP). Two strains were successfully isolated among which one strain was efficient and was able to tolerate high concentrations of chlorpyrifos. This strain was selected for further investigation; it was identified as Gordonia sp based on 16S rRNA analysis and designated as Gordonia sp JAAS1. The actinobacterial strain was able to degrade 110 mg l(-1) of chlorpyrifos within 24 h incubation, and TCP was found to accumulate in the culture medium. However, after 72 h of incubation, TCP was degraded, and finally, diethylthiophosphoric acid (DETP) was obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: Biodegradation of chlorpyrifos results in the formation of an antimicrobial compound 3,5,6-trichloro-2-pyridinol (TCP). It is more mobile compared with the parent molecule due to its higher water solubility thus, causing widespread contamination and has antimicrobial property. Therefore, biodegradation of TCP, the major metabolite of chlorpyrifos, is crucial as if left to accumulate, it will kill all the beneficial microbes in the soil. In this study, Streptomyces belonging to genus Gordonia sp JAAS1 strain capable of degrading not only chlorpyrifos but also TCP was observed. This is a first report pertaining to biodegradation of chlorpyrifos and its metabolite TCP from Gordonia genus. The ability to degrade chlorpyrifos and its metabolite TCP makes this strain a useful candidate for the remediation of contaminated sites.

Identification of opportunistic pathogenic bacteria in drinking water samples of different rural health centers and their clinical impacts on humans.

International drinking water quality monitoring programs have been established in order to prevent or to reduce the risk of contracting water-related infections. A survey was performed on groundwater-derived drinking water from 13 different hospitals in the Mahabubnagar District. A total of 55 bacterial strains were isolated which belonged to both gram-positive and gram-negative bacteria. All the taxa were identified based on the 16S rRNA gene sequence analysis based on which they are phylogenetically close to 27 different taxa. Many of the strains are closely related to their phylogenetic neighbors and exhibit from 98.4 to 100% sequence similarity at the 16S rRNA gene sequence level. The most common group was similar to Acinetobacter junii (21.8%) and Acinetobacter calcoaceticus (10.9%) which were shared by 7 and 5 water samples, respectively. Out of 55 isolates, only 3 isolates belonged to coliform group which are Citrobacter freundii and Pantoea anthophila. More than half (52.7%, 29 strains) of the phylogenetic neighbors which belonged to 12 groups were reported to be pathogenic and isolated from clinical specimens. Out of 27 representative taxa are affiliated have eight representative genera in drinking water except for those affiliated with the genera Exiguobacterium, Delftia, Kocuria, and Lysinibacillus.

Association between erectile dysfunction and coronary artery disease and its severity.

BACKGROUND/AIMS: To investigate the prevalence of erectile dysfunction (ED) in patients with coronary artery disease (CAD), its relationship between the severity of ED and the extent of coronary vessel involvement and to register the mean time interval between them. METHODS: 240 patients with CAD divided into three age-matched groups: Group 1 (n = 60), ACS with one-vessel disease (1VD); group 2 (n = 60), ACS with 2,3VD; group 3 (n = 60), CSA. Control group (C, n = 60) was composed of patients with suspected CAD who were found to have entirely normal coronary arteries by angiography. ED as any value <26 according to the Gensini's scores and according to the International Index of Erectile Function (IIEF). RESULTS: ED prevalence was 76%. ED prevalence was lower in G1 vs. G3 (22 vs.65%). G2 ED rate [55%, P < 0.0001] IIEF = 24 (17-29) & Gensini's scores-21 (12.5-32) were significantly different from G1 and similar to G3, ED in ACS differs according to the extent of CAD. G3 patients who had ED symptoms prior to CAD symptoms and time interval between ED and CAD symptom onset in CCS according to number of vessels. Onset of sexual dysfunction occurred before CAD onset with a mean time interval of 24 m [12-36]. CONCLUSION: Early diagnosis of ED, cardiovascular assessment and aggressive treatment of cardiovascular risk factors might have contributed to prevent the acute events of this patient. Patients should be systematically screened for ED as a part of periodic examination programs. This would lead to early detection of modifiable vascular risk factors, or already existing vascular disease and to prevent ED and vascular disease progression through pharmacological and life style modifications.

Inflammatory Markers-Serum Level of C-Reactive Protein, Tumor Necrotic Factor-α, and Interleukin-6 as Predictors of Outcome for Peripartum Cardiomyopathy.

AIM/OBJECTIVE: Peripartum cardiomyopathy (PPCM) is a disorder of unknown etiology in which symptoms of heart failure occur between the last month of pregnancy and 5 months post-partum. These findings prompted us to carry out a more detailed study aimed at correlating plasma levels of C-reactive protein TNF-α and IL-6 as prognostic value for major clinical in-hospital events and 6-month follow-up in patients with PPCM. MATERIALS AND METHODS: After ethical clearance, in the present prospective case-control study, a total of 86 subjects were enrolled [patients (n = 46) and controls (n = 40)]. After checking for the inclusion and exclusion criteria, informed consent was obtained and patients were enrolled. The details of history of pre-eclampsia and mode of delivery were obtained from the patients. The history of onset of symptoms and signs was recorded at the first presentation and at 6 months. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. All patients received treatment with diuretics and the ACE inhibitor (ramipril), Carvedilol if not contraindicated, and inotropic support inj-Dobutamine. Inflammatory markers (C-reactive protein, TNF-α, and IL-6) were measured at baseline and at 6 months. Data were analyzed using the SAS version 9.1 statistical program. RESULTS: The characteristics of the study population at first presentation to the cardiac clinic are similar (compared with controls): 0.91 % of the study patients were diagnosed as PPCM patients for the first time and 49 % patients presented within one month after delivery. C-reactive protein (22 vs 08 mg/dl, p < 0.05), TNF-α (9.6 vs 3.2 pg/dl, p < 001), and IL-6 (73.19 ± 34.4 vs 31.52 ± 8.83 pg/dl, p < 0.005) were significantly abnormal, and these patients showed significantly higher LV dimensions, LV EDD (61.6 ± 7.1 vs 46 ± 9 mm p < 0.004) LV ESD (53.1 ± 7 vs 32 ± 8, p < 0.005), and significantly lower echocardiographic left ventricular ejection fraction (LVEF) (25.9 ± 8.2 vs 55 ± 12 p < 0.001) and correlate well with NYHA FC and death. LVEF improved from 25.9 ± 8.2 to 42.9 + 13.6 % at 6 months (p < 0.0001). Patients who completed 6 months of standard care showed a significant reduction of heart rate, LV dimensions, and NYHA FC (p < 0.001). However, normalization of LVEF (>50 %) was only observed in 11 (35 %) patients. Seven patients died within 6 months of diagnoses and eight patients were lost to follow-up. CONCLUSIONS: Plasma markers of inflammation were significantly elevated in PPCM patients and correlated with increased LV dimensions and lower EF at presentation. Baseline CRP, IL-6, TNF-α, and higher NYHA FC were the only predictors of mortality. These results contribute to inflammation which may contribute to the pathogenesis of PPCM and its complications and predictors of mortality.

Edgelist phase unwrapping algorithm for time series InSAR analysis.

We present here a new integer programming formulation for phase unwrapping of multidimensional data. Phase unwrapping is a key problem in many coherent imaging systems, including time series synthetic aperture radar interferometry (InSAR), with two spatial and one temporal data dimensions. The minimum cost flow (MCF) [IEEE Trans. Geosci. Remote Sens. 36, 813 (1998)] phase unwrapping algorithm describes a global cost minimization problem involving flow between phase residues computed over closed loops. Here we replace closed loops by reliable edges as the basic construct, thus leading to the name "edgelist." Our algorithm has several advantages over current methods-it simplifies the representation of multidimensional phase unwrapping, it incorporates data from external sources, such as GPS, where available to better constrain the unwrapped solution, and it treats regularly sampled or sparsely sampled data alike. It thus is particularly applicable to time series InSAR, where data are often irregularly spaced in time and individual interferograms can be corrupted with large decorrelated regions. We show that, similar to the MCF network problem, the edgelist formulation also exhibits total unimodularity, which enables us to solve the integer program problem by using efficient linear programming tools. We apply our method to a persistent scatterer-InSAR data set from the creeping section of the Central San Andreas Fault and find that the average creep rate of 22 mm/Yr is constant within 3 mm/Yr over 1992-2004 but varies systematically with ground location, with a slightly higher rate in 1992-1998 than in 1999-2003.

Fate of imidacloprid and acetamiprid residues during black tea manufacture and transfer into tea infusion.

The objective of this paper is to investigate the loss/stability of neonicotinoids (imidacloprid and acetamiprid) residues during the manufacture of black tea and to study the transfer of these pesticides from made tea to its infusion. For orthodox black tea, the manufacturing process involves leaf harvesting (plucking two leaves and a bud), withering, rolling, fermentation (oxidation), and drying. Initial withering and final drying resulted in the loss of pesticide residues, but no significant reduction in residue levels resulted from the rolling and fermentation steps. The drying process resulted in a residue transfer of 64-70% and 69-74% of the initial level, whereas the brewing process resulted in a residue transfer of 37-39% and 45-49% of imidacloprid and acetamiprid, respectively, from dried tea into the infusion. The decrease in acetamiprid levels during drying was also significant (8-13%), whereas the total loss during the manufacturing process ranged from 26 to 31%. Further, brewing for longer periods (an extended brewing time) resulted in higher transfer (up to 44% for imidacloprid and 53% for acetamiprid) of pesticides to tea infusion. Further, the extent of pesticide leaching depends on its water solubility, partition coefficient, and the brewing time.

Fenvalerate residue level and dissipation in tea and in its infusion.

Fenvalerate is a non-systemic insecticide/acaricide used in controlling a wide range of pests, including those resistant to organochlorine, organophosphorus and carbamate insecticides. The study investigated the dissipation behaviour (residue level) of fenvalerate in tea and its transfer during infusion. Fenvalerate was applied on tea crop at two dosages, 100 and 200 g a.i. ha(-1) (recommended and double the recommended) in the dry and wet seasons under field conditions. Samples (green tea shoots, made tea, its infusion and spent leaves) were analysed for fenvalerate by high-performance liquid chromatography using diode array detection. The residue dissipated faster in the wet season than in the dry season. Seven days after the treatment (normal round of plucking) the residues observed in the green shoots at the two dosages were 0.5 +/- 0.01, 1.1 +/- 0.01 and 0.4 +/- 0.02, 0.9 +/- 0.01 mg kg(-1) in the dry and wet seasons, respectively. During processing of green tea shoots to made tea a 30-40% loss of residue was observed. The transfer of residue from made tea to infusion was in the range 10-30% for both seasons, whereas 50-70% of the residues remained in the spent leaves. However, the degradation rate in both seasons followed first-order kinetics. The half-lives were in the range of 2-3 days for green shoots and made tea in both seasons.

Immunopotentiation in mice bearing a spontaneous transplantable T-cell lymphoma: role of thymic extract.

Progressive ascitic growth of a spontaneous transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), in a murine host has been shown to be associated with an involution of thymus accompanied by a massive depletion of the cortical region and an alteration in the distribution of thymocytes by a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ phenotypes caused by an enhanced induction of apoptosis in thymocytes. Moreover, an inhibition of humoral and cell mediated immune responses involving non-specific as well as antigen-specific T cell proliferative and cytolytic abilities with a decrease in the production of interferon gamma (IFNg) by the T cells of DL bearing mice has been observed. Results of the present study show that the administration of total thymic extract (TE) in DL bearing mice results in an increased survival of the DL bearing mice alongwith a significant increase in the weight of thymus and the total number of thymocytes with a lesser number of percent apoptotic thymocytes as compared to that in untreated DL-bearing mice. It is also shown that TE administration has a positive immunomodulatory effect on T cell functions as T cells obtained from TE administered DL bearing mice show an increased IFNg, production and an improved antigen specific proliferative ability. Moreover, the study indicates that TE acts directly on T cells as in an in vitro assay TE antagonised DL growth-associated induction of thymocyte apoptosis. Taken together, the results support the immunomodulatory function of the adult thymus and utilization of thymus derived factors as a potential immunotherapeutic agent for reversing tumor growth-associated immunosuppression.

Leaching of pesticides in tea brew.

A cup of tea that cheers can also be an important route of human exposure to pesticide residues. It is important to evaluate the percent transfer of pesticide residue from dried (made) tea to tea infusion, as tea is subjected to an infusion process prior to human consumption. To investigate the pesticide translocation, 13 pesticides commonly used on tea were studied by subjection of fortified teas to infusion. Analytes of interest were quantified by gas-liquid chromatography with nitrogen-phosphorus and electron capture detectors. Interestingly, water solubility of pesticides did not necessarily indicate a shift of residues toward their preferential accumulation in infusion. The pesticides with larger partition coefficient (K(ow)) values remained nonextractable in infusing water. Further, boiling for longer periods (extended brewing time) resulted in higher transfer of pesticides to tea brew.

A modified extraction and clean-up procedure for the detection and determination of parathion-methyl and chlorpyrifos residues in tea.

Recent advances in methodology and instrumentation have made possible the detection and determination of pesticides at microgram kg-1 (ppb) levels. The sensitivity of a method of analysis depends greatly on the efficient extraction of the pesticide and the subsequent clean-up of the extract. The extract from green tea leaves is a mixture of aroma components, polyphenols and caffeine. The preparation of made tea from green tea leaves adds to this complexity by concentrating these coextractives. Conventional clean-up techniques provide poor recoveries for parathion-methyl and chlorpyrifos from both green tea leaves and made tea. This arises from interference by caffeine during gas chromatography, as it has a similar retention time to the two pesticides and peaks overlap. A modification to the protocol based on a solvent partitioning process using dichloromethane and subsequent washing of the extracts with warm water removed the caffeine, and pigments were removed by column chromatography. Recoveries ranging from 80 to 90% were then obtained for both pesticides.

Characterization of factors inducing apoptosis in thymocytes of mice bearing a transplantable T-cell lymphoma of spontaneous origin.

It has been observed that the progressive ascitic growth of a transplantable T-cell lymphoma of spontaneous origin in murine host, designated as Dalton's lymphoma (DL), induces inhibition of various immune responses and is associated with an involution of thymus accompanied by a massive depletion of the cortical region and alteration in the distribution of thymocytes caused by induction of apoptosis with a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ thymocytes. Here, we report that serum of DL-bearing mice contains soluble factors capable of inducing thymocyte apoptosis, the effectiveness of which increases with the progression of tumor growth. A decline of essential cytokines and hormones in the body due to their depletion by DL cells, which being a T-cell phenotype may have similar growth factor requirements, is ruled out by our results, suggesting additional apoptosis-inducing factors to be present in the tumor serum. Partial characterization of the serum to identify the biochemical nature of the putative serum-borne apoptosis inducing factor(s) showed that the same was proteinaceous. Further analysis of the sera of normal and DL-bearing mice by gel filtration using fast protein liquid chromatography (FPLC) and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that protein profile in the two sera differed quantitatively as well as qualitatively. FPLC analysis could resolve six peaks in both the sera, out of which the peak containing protein(s) in the range of MW 35 kD showed a higher magnitude and apoptotic activity followed by peaks containing proteins of MW in the range of 67 and 116 kD respectively as compared to that of the corresponding peaks in the normal serum. These observations were also confirmed by SDS-PAGE, with the resolution of additional proteins in the range of 25-26 kD which were found to be absent in normal serum. Further, the paper discusses different possible factors that could be associated with the progression of DL growth.

Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic involution. 2. Induction of apoptosis in thymocytes.

It has been observed that the progressive ascitic growth of a transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), induces inhibition of various immune responses and is associated with an involution of the thymus accompanied by a massive depletion of the cortical region and alteration in the distribution of thymocytes, with a decrease in CD4+CD8+, CD4+CD8- and CD4-CD8+ thymocytes. Morphological evaluation of thymocytes from DL-bearing mice revealed that with the progression of DL, a majority of thymocytes exhibited morphological features characteristic of apoptotic cell death, which included contracted cell bodies, condensed, uniformly circumscribed and densely stained chromatin, and membrane-bound apoptotic bodies containing one or more nuclear fragments. Quantitative and qualitative analysis of the DNA extracted from the thymocytes of DL-bearing mice revealed DNA fragmentation that increased concomitantly with the progression of DL and showed an oligonucleosomal DNA ladder pattern upon agarose gel electrophoresis, a hallmark of apoptotic cell death. Attempts to identify apoptotic factor(s) showed that the serum of DL-bearing mice contained certain soluble factor(s) that augmented the induction of apoptotis in thymocytes in a time- and dose-dependent manner. Although DL cells or their products, such as DL-cell-conditioned medium or DL-cell-free ascitic fluid, could also induce apoptosis of thymocytes in vitro, the magnitude of the same was consistently lower than that induced by the serum of DL-bearing mice. Further, elucidation of the mechanism of apoptosis induction in thymocytes with respect to the involvement of apoptosis-related genes revealed that the death pathway followed an interleukin-1 beta-converting-enzyme-dependent, Fas-mediated apoptotic cascade, with a concomitant increase in the protein products of the bax, bad, p53, fas and fasL genes and cleavage of the 23-kD N-terminal fragment of Bcl-2 that exhibited Bax-like death effector properties.

Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic involution. 1. Alterations in the CD4/CD8 distribution in thymocytes.

We have previously shown that the progressive ascitic growth of a transplantable T cell lymphoma of spontaneous origin in a murine host, designated as Dalton's lymphoma (DL), induces the inhibition of various immune responses. In a quest to understand the mechanism(s) of tumor-growth-dependent immunosuppression, we were interested to investigate if the thymus, the center for the differentiation of immunocompetent T cells, undergoes any alteration concomitant with the growth of DL. Thus, DL was grown as an ascitic tumor in BALB/c mice for a period of 4 or 17 days, designated as the early and late tumor stages, respectively, and the thymuses were examined immediately after sacrifice of the animals on the 4th or 17th day of tumor transplantation. Progressive growth of DL was observed to be associated with thymic atrophy, as well as an involution of thymic organization and a depletion of cell mass. Histological sections of thymus from DL-bearing mice revealed a complete disintegration of the thymic architecture with a massive depletion of the cortical region and disappearance of the corticomedullary junctions. Flow cytometric analysis of alterations in the distribution of thymocytes revealed a decrease in CD4+CD8-, CD4-CD8+ and CD4+CD8+ cell populations, whereas the CD4-CD8- population showed an increase, suggesting an impairment in thymocyte differentiation at an early T cell maturation stage. Furthermore, tumor growth was shown to suppress the proliferation ability of thymocytes. Moreover, an increase in thymocytes of smaller size was also found with the progression of DL, which is an indication that a large fraction of thymocytes of a small, abnormal size could be apoptotic cells. Furthermore, the paper discusses the immunological implications of thymic atrophy in a host bearing a T cell lymphoma.

Mechanism of thymocyte apoptosis induced by serum of tumor-bearing host: the molecular events involved and their inhibition by thymosin alpha-1.

The observations presented in this paper indicate that serum of Dalton's lymphoma (DL) bearing mice contained certain soluble factor(s) that augmented the induction of apoptosis in thymocytes in a time- and dose-dependent manner. DL-ascitic fluid and DL-conditioned medium could also induce apoptosis of thymocytes in vitro, though the magnitude of the same was consistently lower than that induced by serum of DL-bearing mice. It was observed that the interaction of FasL and TNFalpha with their respective receptors could trigger apoptosis in thymocytes. Elucidation of the signal transduction mechanism revealed involvement of protein tyrosine kinase, protein kinase C and ser/thr phosphatases with concomitant increase in the level of protein products of apoptosis associated genes p53, bax, bad, fas and fas ligand and cleavage of N-terminal 23 kDa fragment of Bcl-2 that exhibited Bax-like death effector properties. Further, we report, for the first time, the ability of thymosin alpha-1, an immunopotentiating thymic hormone, to antagonize apoptosis in thymocytes induced by factors present in serum of DL-bearing mice. The underlying mechanism of tumor serum induced apoptosis inhibition by thymosin alpha-1 was also analyzed. The signal transduction cascade evoked by thymosin alpha-1 involves activation of protein kinase C with a decrease in the level of protein products of proapoptotic genes like bax and bad and increase in the protein products of bcl-2 gene.

Impairment of T-cell functions with the progressive ascitic growth of a transplantable T-cell lymphoma of spontaneous origin.

It has been observed that the progressive ascitic growth of a transplantable T-cell lymphoma of spontaneous origin, designated Dalton's lymphoma (DL), in a murine host induces inhibition of various immune responses and is associated with an involution of thymus accompanied by a massive depletion of the cortical region and alteration in the distribution of thymocytes caused by tumour serum-dependent induction of apoptosis with a decrease of CD4(+)CD8(+), CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. Here, we report that thymocytes of DL-bearing mice are defective in their proliferative ability and in their response to non-specific mitogenic stimulus in vitro. Also, antigen-specific T-cell proliferative ability representing the fundamental T(H) function declines under DL-bearing conditions and upon treatment with serum of DL-bearing mice. Moreover, a significant inhibition of T-cell cytolytic activity with a decreased ability to produce interferon gamma is shown by the T cells of DL-bearing mice and by the T cells treated with DL-ascitic fluid, DL-conditioned medium or serum of DL-bearing mice. Further, addition of interleukin-2 and anti-interleukin-10 to the cultures of thymocytes treated with serum of DL-bearing mice is found to inhibit the induction of apoptosis in thymocytes, a phenomenon associated with the progression of DL growth. Analysis of the results indicates an immune deviation with the predominance of a T(H2)-type response with the progression of tumour. We further discuss the possible mechanisms that may explain the observed tumour-induced diminution of T-cell immunity.