Squamous Cell Carcinoma Larynx with Malignant Ascites: a Rare Entity.

Usual sites of the spread of the squamous cell carcinoma (SCC) larynx is regional-cervical lymphadenopathy. The lung is the most frequent site of distant metastasis, accounting for 66% of distant metastasis. Other metastatic sites include bone (22%), liver (10%), skin, mediastinum, and bone marrow. Occurrence of distant metastasis adversely affects the survival and alters the treatment planning completely, more towards palliative intent. Here, we present a case with very rare presentation of malignant ascites in a case of SCC larynx.

Human endogenous retroviruses and their implication for immunotherapeutics of cancer.

Human endogenous retroviruses (HERVs) have recently caught increased attention as a potential internal trigger to sensitize tumor cells to immunotherapies. HERVs are remnants of retroviral germline infections that resulted in chromosomal integration into all the cells of the progeny. Today, HERVs constitute ∼8% of the human genome, but most elements are highly degenerated, under strict epigenetic regulation, and rarely expressed in healthy tissues. However, cancer cells are specifically prone to reactivate the expression of HERV elements due to epigenetic dysregulation that accumulate during malignant transformation and when using epigenetic therapies. HERV expression can induce an interferon response due to induction of the viral defense pathway, so-called 'viral mimicry'. By mimicking viral infections, HERVs could function as an 'intrinsic adjuvant', possibly sensitizing cancer cells to immunological recognition. Furthermore, translated HERV elements may in themselves form a valuable pool of tumor-associated antigens. Epitopes derived from HERVs have been recognized by cytotoxic CD8+ T cells, leading to cancer cell recognition. The combination of 'viral mimicry' and T-cell recognition could provide a powerful combination with existing immune stimulatory therapies, such as checkpoint inhibition. This combination is currently being evaluated in clinical trials in a large number of cancers.

Novel tools to assist neoepitope targeting in personalized cancer immunotherapy.

Current cancer immunotherapy approaches utilize the remarkable surveillance capacity of the human immune system, which is capable of recognizing and eliminating cancer cells based on identification of tumor-associated antigens arising as a consequence of the transformation process. Among these, mutational-derived neoepitopes have proved to be powerful targets for tumor elimination and mutational load has been shown to correlate with the clinical response to treatment with checkpoint inhibitors in many different tumor types. This suggests a crucial role for neoepitope recognition in T-cell-mediated tumor eradication. Consequently, strategies to further boost neoepitope recognition, through vaccination or adoptive cell transfer, has received substantial interest. Although such strategies have enormous potential, there are also considerable challenges associated with these approaches. In the present review, we will focus on how novel technological developments can facilitate and improve feasibility and efficacy in neoepitope targeting.

A randomized controlled trial of burping for the prevention of colic and regurgitation in healthy infants.

BACKGROUND: Efficacy of burping in lowering colic and regurgitation episodes in healthy term babies lacks evidence in literature. METHODS: We conducted a randomized controlled trial to compare efficacy of burping versus no-burping in 71 mother-baby dyads in community setting. Primary outcome was reduction in event rates of colic and regurgitation episodes over 3 months. RESULTS: Baseline characteristics were similar in two groups. Difference in incidence rates of colic between the control and burping group was 1.57 episodes/infant/100 weeks [95% confidence interval (CI): -0.63 to 3.76]. There was statistically no significant reduction in colic episodes between burping and non-burping study subjects during 3 months of follow-up (adjusted relative risk 0.64; 95% CI: 0.22-1.86, P-value 0.41). Incidence rate difference of regurgitation episodes/infant/week between burping and control group was 4.36 (95% CI: 4.04 to 4.69) and there was statistically significant increase in burping group (adjusted relative risk 2.05; 95% CI: 1.92-2.18, P-value < 0.0001). CONCLUSIONS: Although burping is a rite of passage, our study showed that burping did not significantly lower colic events and there was significant increase in regurgitation episodes in healthy term infants up to 3 months of follow-up.

Note: Multi channel Doppler tuned spectrometer to study highly charged ions.

We describe the design and implementation of a multi channel Doppler tuned spectrometer setup to study physics of highly charged ions at high resolution in a direct way. A unique Soller slit assembly coupled with a long one dimensional position sensitive proportional counter enables us to get distinct x-ray peaks at different angles, which allows us to cover large number of angle in one shot. By using this setup, 1s2s (3)S1 - 1s(2) (1)S0 M1 transition in He-like Fe has been resolved from its satellite line 1s2s2p 4P(5/2)° - 1s(2)2s (2)S(1/2) M2 transition in Li-like Fe and measured the lifetime of their respective upper levels with high precision.

Fast ion surface energy loss and straggling in the surface wake fields.

We have measured the stopping powers and straggling of fast, highly ionized atoms passing through thin bilayer targets made up of metals and insulators. We were surprised to find that the energy losses as well as the straggling depend on the ordering of the target and have small but significantly different values on bilayer reversal. We ascribe this newly found difference in energy loss to the surface energy loss field effect due to the differing surface wake fields as the beam exits the target in the two cases. This finding is validated with experiments using several different projectiles, velocities, and bilayer targets. Both partners of the diatomic molecular ions also display similar results. A comparison of the energy loss results with those of previous theoretical predictions for the surface wake potential for fast ions in solids supports the existence of a self-wake.

Effect of Emblica officinalis (Gaertn) on lens regeneration in the frog, Rana cyanophlyctis (Schneider).

Emblica officinalis (Amla) accelerated cell proliferation and dedifferentiation of pigmented epithelial cells of dorsal iris and consequently induced lens regeneration in R. cyanophlyctis. Further it enhanced the percentage of lens regeneration not only in young tadpoles but also is adult frogs. Lens regeneration ability declined with the age of animals in both control as well as treated groups.

Synthesis, opioid receptor binding, and biological activities of naltrexone-derived pyrido- and pyrimidomorphinans.

A series of pyrido- and pyrimidomorphinans (6a-h and 7a-g) were synthesized from naltrexone and evaluated for binding and biological activity at the opioid receptors. The unsubstituted pyridine 6a displayed high affinities at opioid delta, mu, and kappa receptors with K(i) values of 0.78, 1.5, and 8.8 nM, respectively. Compound 6a was devoid of agonist activity in the mouse vas deferens (MVD) and guinea pig ileum (GPI) preparations but was found to display moderate to weak antagonist activity in the MVD and GPI with K(e) values of 37 and 164 nM, respectively. The pyrimidomorphinans in general displayed lower binding potencies and delta receptor binding selectivities than their pyridine counterparts. Incorporation of aryl groups as putative delta address mimics on the pyrido- and pyrimidomorphinan framework gave ligands with significant differences in binding affinity and intrinsic activity. Attachment of a phenyl group at the 4'-position of 6a or the equivalent 6'-position of 7a led to dramatic reduction in binding potencies at all the three opioid receptors, indicating the existence of a somewhat similar steric constraint at the ligand binding sites of delta, mu, and kappa receptors. In contrast, the introduction of a phenyl group at the 5'-position of 6a did not cause any reduction in the binding affinity at the delta receptor. In comparison to the unsubstituted pyridine 6a, the 5'-phenylpyridine 6c showed improvements in mu/delta and kappa/delta binding selectivity ratios as well as in the delta antagonist potency in the MVD. Interestingly, introduction of a chlorine atom at the para position of the pendant 5'-phenyl group of 6c not only provided further improvements in delta antagonist potency in the MVD but also shifted the intrinsic activity profile of 6c from an antagonist to that of a mu agonist in the GPI. Compound 6d thus possesses the characteristics of a nonpeptide mu agonist/delta antagonist ligand with high affinity at the delta receptor (K(i) = 2.2 nM), high antagonist potency in the MVD (K(e) = 0.66 nM), and moderate agonist potency in the GPI (IC(50) = 163 nM). Antinociceptive evaluations in mice showed that intracerebroventricular (icv) injections of 6d produced a partial agonist effect in the 55 degrees C tail-flick assay and a full agonist effect in the acetic acid writhing assay (A(50) = 7.5 nmol). No signs of overt toxicity were observed with this compound in the dose ranges tested. Moreover, repeated icv injections of an A(90) dose did not induce any significant development of antinociceptive tolerance in the acetic acid writhing assay. The potent delta antagonist component of this mixed mu agonist/delta antagonist may be responsible for the diminished propensity to produce tolerance that this compound displays.

Anaerobic exercise testing in children with asthma.

Twenty-two males with asthma and 22 healthy males (7-18 years old) performed a Wingate Anaerobic Test. The subjects with asthma had a lower mid-maximal expiratory flow rate (78.3+/-25.3 vs. 100.1+/-24.5%, p < 0.01) than the controls. Aerobic and anaerobic exercise performance (peak power: PP; mean power: MP) were similar for the two groups whether expressed in absolute or relative terms to body weight. The subgroup with asthma with a lower percent body fat (<25%) had a higher PP and MP than the subjects with a higher percent body fat (>25%). Pulmonary function or maturation were not independent correlates of anaerobic power. Our results fail to show differences in anaerobic exercise performance in children with asthma compared to healthy controls. Nutrition appears to be an important factor for performance during this test.

Allergic bronchopulmonary mycosis to Fusarium vasinfectum in a child.

BACKGROUND: A 12-year-old boy with asthma and 6 years of recurrent pneumonias who had normal serum immunoglobulin concentrations was suspected of having allergic bronchopulmonary aspergillosis (ABPA). OBJECTIVE: To search for and secure a fungal etiology for a child who did not have ABPA but was suspected of having an allergic bronchopulmonary mycosis. METHODS: Immediate skin testing with fungal extracts, high resolution computerized tomography, and establishment of an ELISA procedure to detect serum IgE and IgG antibodies to Fusarium vasinfectum. RESULTS: Immediate skin reactivity was present for Fusarium, Cladosporium, Helminthosporium, and Aspergillus fumigatus. The ELISA demonstrated serum IgE and IgG antibodies to Fusarium vasinfectum 8.5 and 5.6 times nonatopic control sera. CONCLUSIONS: This 12-year-old with asthma has sufficient criteria for a diagnosis of allergic bronchopulmonary mycosis (ABPM) to Fusarium vasinfectum. Bronchiectasis was not present despite recurrent pneumonias and hemoptysis. This case appears to be the first pediatric example of ABPM to Fusarium species, a fungus more recognized for causing rotting of tomatoes and melons than human disease.

Liver involvement in familial granulomatous arthritis (Blau syndrome).

We describe hepatic granulomata in a patient with familial granulomatous synovitis (Blau syndrome). While visceral involvement is a previously unrecognized manifestation of Blau syndrome, its occurrence has been well documented in a similar disease, childhood sarcoidosis. Our findings suggest that the 2 conditions (Blau syndrome and childhood sarcoidosis) are more closely related than thought.

MnPcS4: a new MRI contrast enhancing agent for tumor localisation in mice.

Manganese-tetrasulfonated phthalocyanine (MnPcS4) has been evaluated as a potential contrast agent in Magnetic resonance imaging (MRI) for tumor localisation in mice. MnPcS4 showed favourable molar relaxivity, much better than Gd-DTPA and comparable to tetrasulfonated manganese complex of porphyrin (TPPS4). Tumors showed selective retention of the metal complex (dye) with the peak value reached at 24 hours following intravenous administration. Dye concentration in tumors remained consistently higher than either kidney or muscle tissue both at 1 and 24 hours and a 10-fold increase in tumor-to-muscle ratio over the control was seen at 24 hr. Normal liver tissue, however, showed higher concentration than tumor at all times during the study. A linear correlation was found between longitudinal relaxation rate (1/T1) and the corresponding concentration of MnPcS4 in various tissues. MR imaging done in animals using 1.5 T superconducting clinical imager showed a mean percent increase in signal intensity of 131.8% (SD +/- 32.86) in the tumor and a 70% increase in tumor-to-muscle ratio over the pretreatment value, at 24 hr. The results suggest that MnPcS4 is a potential tumor-selective contrast agent in MRI.

The role of saliva in aggregation and adherence of Pseudomonas aeruginosa in patients with cystic fibrosis.

The aggregation and adherence activity of P. aeruginosa, mediated by whole saliva from cystic fibrosis (CF) patients and non-CF subjects, was investigated. CF saliva-mediated aggregation of P. aeruginosa was stronger than the activity of non-CF saliva. Likewise, P. aeruginosa adherence to buccal epithelial cells (BEC) of CF patients was stronger than to BEC of non-CF subjects. Adherence of non-mucoid P. aeruginosa to BEC of CF patients was increased by saliva, whereas the mucoid variant was not. CF patients colonized with P. aeruginosa showed higher adherence of the non-mucoid variant than non-colonized CF patients. CF patients with high saliva-mediated adherence of non-mucoid P. aeruginosa also had high salivary aggregation activity. Increased CF saliva-mediated aggregation activity may be linked to the increased non-mucoid P. aeruginosa adherence to BEC of CF patients.

Age related modulation of circadian time structure of blood, plasma and tissue variables in male domestic fowls.

To study modulation of circadian time structure of 11 blood, plasma and tissue variables in male domestic fowls, as a function of age, three experiments were made in one-day-old fowls (72) standardized by 12L:12D. In the first experiment, at 6 week age, 24 birds were killed by decapitation, four each at six different circadian stages (2, 6, 10, 14, 18 and 22 hr after light onset, HALO). Equal number of birds were killed at similar circadian stages at the age of 12 and 18 week in the second and the third experiments, respectively. Age affected both, the circadian patterns and the mesors (24 hr mean values). The circadian pattern included amplitude (half of the total extent of variation) and acrophase (estimated time of peak) for each variable. The results clearly suggest that the pattern of circadian rhythm may vary as a function of age of the bird.

Circadian features of carbohydrate metabolism in domestic fowls exposed to weekly 120 degree-shifts of synchronizer schedule.

Effects of weekly 8 hr advance- or delay-shifts on the circadian rhythm of plasma glucose, liver glycogen and muscle glycogen in male domestic fowls, beginning at about 3 days of age, were examined. Circadian rhythm in the aforesaid indices of carbohydrate metabolism in control birds was also studied. Blood and tissue samples were collected from birds in all the three groups at 4 hr intervals over a single 24 hr time scale both at 6th and 12th week of age. Plasma glucose and glycogen content in the tissues were determined by employing standard techniques. Cosinor rhythmometry was used for analyzing time series data. In general, a statistically significant circadian rhythm was documented for all the three indices in control and advance-schedule birds, irrespective of age. In contrast, in delay-schedule birds, statistically significant circadian rhythm could not be detected, excluding in muscle glycogen at 12th week of age. The poor growth rate in the delay-schedule birds could be imputed to the disappearance of circadian rhythm in the indices of carbohydrate metabolism.

Desynchronization of oral temperature, pulse and performance circadian rhythms in shift working Indian nurses.

Circadian time structure in shift working Indian nurses was studied. In shift workers desynchronization between circadian rhythms in different physiological variables was observed. Circadian amplitudes of oral temperature, pulse and random add speed rhythms decreased significantly in shift workers as compared to control subjects. Circadian mesors of performance rhythms increased significantly in shift workers indicating that the time taken by them was more for performing the tasks. It can be concluded that the subjects studied herein are intolerant to shift work and amplitude decrement may be considered as a chronobiologic index to determine the tolerance of individual workers to shift work.

Effects of zeitgeber shifts on gonadal function in male domestic fowls.

Effects of shifting light dark (LD) schedule of 8 hr/week on comb height and gonadal development were investigated in male domestic fowls. Three-day-old birds were exposed to repeated delay (westward shift) or repeated advancement (eastward shift) of the LD schedule at weekly intervals till they attained the age of 20 weeks. Control birds were held in fixed LD 12:12 hr light/dark schedule. Comb height was monitored at weekly intervals beginning at the age of 7 weeks. At 12th, 16th and 20th week 5 birds from each schedule were sacrificed and gonadal volume was recorded. Results indicate that comb and gonadal growth were significantly higher in advance-schedule birds when compared with control and delay-schedule birds. Histologically, testes of advance-schedule birds were more active when compared with those of control and delay-schedule birds. It appears that the eastward shifts of the synchronizer schedule may exert stimulatory influence on gonads.

Influence of human urinary erythropoietin and L-thyroxine on blood morphology and energy reserves in two tropical species of fed and starved teleosts.

Erythropoietic responses of fed and starved species of teleosts, viz., Clarias batrachus and Heteropneustes fossilis, to human urinary erythropoietin and thyroxine have been examined. The effects of these hormones on energy reserves have also been evaluated. Twenty-four C. batrachus were divided into two groups: half were fed regularly; the remaining fish were starved 20 days. On the 21st day each group was further divided into three subgroups of four each and received either saline, thyroxine (8 micrograms), or erythropoietin (6 IU) over 4 consecutive days. The experimental protocol was identical for H. fossilis; however, for H. fossilis two identical studies were conducted approximately 1 year apart. A decline in the rate of erythropoiesis and a stimulatory response to human urinary erythropoietin followed starvation in both species of teleosts. In addition, erythropoietin had a pronounced effect on hepatic glycogenesis of fed H. fossilis and stimulated erythropoiesis in the fed teleosts of both species. Prolonged starvation drastically depleted hepatic glycogen in C. batrachus. In contrast, it had no effect on hepatic glycogen in H. fossilis and on muscle glycogen and protein in both species. In general, while both species could respond to erythropoietin and withstand prolonged starvation, H. fossilis alone exhibited remarkable tolerance to fasting.

Effects of repeated eastward and westward synchronizer phase-shifts on growth, blood morphology and biochemical variables in male domestic fowls.

The effects of repeated synchronizer phase-shifts on growth (increment in body weight), blood morphology and growth related biochemical variables in 3-day-old juvenile male chicks were evaluated till they become 20 weeks old. The control birds were kept under a fixed LD 12:12 light schedule throughout, while the LD 12:12 regimen of experimental birds was shifted weekly either by delaying (westward shift) or by advancing (eastward shift) the time of light onset by 8 hr. The rate of growth was more in fowls which were exposed to repeated advancement of synchronizer schedule than the controls and those exposed to westward shifts of the synchronizer schedule. Hematological indices, viz., hemoglobin concentration, number of circulating erythrocytes, hematocrit and biochemical variables, such as concentration of glucose and protein in plasma; glycogen, protein and lipid in liver; and muscle tissues were significantly more in chicks exposed to repeated eastward shifts, when compared with the control birds (LD 12:12). It is suggested that the eastward shift of the synchronizer may be beneficial for the poultry birds.