Interaction and Modulation of Two Antagonistic Cell Wall Enzymes of Mycobacteria

Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA), an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein–protein interactions between enzymes with antagonistic functions

Growth, cell division and sporulation in mycobacteria

Bacteria have the ability to adapt to different growth conditions and to survive in various environments. They have also the capacity to enter into dormant states and some bacteria form spores when exposed to stresses such as starvation and oxygen deprivation. Sporulation has been demonstrated in a number of different bacteria but Mycobacterium spp. have been considered to be non-sporulating bacteria. We recently provided evidence that Mycobacterium marinum and likely also Mycobacterium bovis bacillus Calmette–Guérin can form spores. Mycobacterial spores were detected in old cultures and our findings suggest that sporulation might be an adaptation of lifestyle for mycobacteria under stress. Here we will discuss our current understanding of growth, cell division, and sporulation in mycobacteria

Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity

The thymus is sexually differentiated organ providing microenvironment for T-cell precursor differentiation/maturation in the major histocompatibility complex-restricted self-tolerant T cells. With increasing age, the thymus undergoes involution leading to the decline in efficacy of thymopoiesis. Noradrenaline from thymic nerve fibers and "(nor) adrenergic" cells is involved in the regulation of thymopoiesis. In rodents, noradrenaline concentration in thymus and adrenoceptor (AR) expression on thymic cells depend on sex and age. These differences are suggested to be implicated in the development of sexual diergism and the age-related decline in thymopoiesis. The programming of both thymic sexual differentiation and its involution occurs during the critical early perinatal period and may be reprogrammed during peripubertal development. The thymic (re) programming is critically dependent on circulating levels of gonadal steroids. Although the underlying molecular mechanisms have not yet been elucidated fully, it is assumed that the gonadal steroid action during the critical perinatal/peripubertal developmental periods leads to long-lasting changes in the efficacy of thymopoiesis partly through (re) programming of "(nor) adrenergic" cell networks and AR expression on thymic cells

The mycobacterial cell cycle

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Laparoscopic excision of hepatoduodenal ligament cyst

Hepatoduodenal ligament cysts are rare. These may be confused with hepatic cysts even on advanced investigative modalities like Computerized tomography scanning or Magnetic Resonance Imaging. Diagnosis is often an intraoperative surprise. Laparoscopic treatment of such hepatoduodenal cysts is not described in available medical literature. We report one such case treated laparoscopicall

Epidemiology and outcomes of nasopharyngeal carcinoma: Experience from a regional cancer center in Southern India

Context: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer with significant geographical variation. There are limited data on epidemiology and outcomes of NPC reported from Southern India. Settings and Design: Retrospective analysis. Materials and Methods: We analyzed our hospital data between January 2005 and December 2011 with NPC and analyzed their demographic parameters and outcomes with therapy. Results: A total 143 cases of NPC were identified. Median age at presentation was 35 years with male predominance. Majority (84%) of the cases had the WHO Type 3 histology. Nodal metastasis at presentation was seen in 90% of the cases, majority being bilateral. Distant metastasis was seen in 16% of the cases, most commonly at bone, lung, and liver. Concurrent chemoradiation with weekly cisplatin was offered to 84.7% of localized disease while 80% of these also received adjuvant chemotherapy. Complete remission and partial remission were achieved in 66.1% and 15.2% of the cases, respectively. Weekly cisplatin was well tolerated with Grade 3–4 toxicity seen in 22% of cases. At a median follow-up of 20 months, 2-year progression-free survival and overall survival were 67.2% and 79.5%, respectively. Statistical Analysis Used: SPSS software version 20. Conclusion: NPC is a rare head and neck malignancy in Southern India, presenting with advanced stage and more propensity to distant metastasis. It has good outcomes to concurrent chemoradiation with weekly schedule of cisplatin being well-tolerated regime. Further prospective studies to test this schedule and other novel agents in this potentially curable malignancy are warranted

Outcome of young adults with chronic myeloid leukemia treated with upfront imatinib: A single institutional experience

Background: Young adult patients with malignancy are a distinct group of the population. In addition to their ailment, psychosocial issues including fertility issues should be addressed. Chronic myeloid leukemia (CML) is a disease of the elderly population. The outcome with imatinib in young population is not known. Aim: To study the clinical profile and outcome of young patients newly diagnosed with CML on imatinib and to compare with those of elderly population in a tertiary cancer center. Materials and Methods: 369 patients with newly diagnosed CML were included in the study. Patients belonging to the age group of 20–39 years were used as the study group and those who were more than 40 years were used as controls. Both the groups were treated with imatinib. They were followed up for a period of 3 years. Milestones in terms of achieving hematological, cytogenetic and molecular responses were noted. Toxicity profile of the imatinib and the compliance of the patients were also recorded. Results: A total of 173 patients were in the study group and 196 patients were in the control group. Rates of achieving a hematological response at 3 months (94.2% vs. 93%), the complete cytogenetic response at 12 months (68% vs. 61%) and major molecular response at 18 months (72.2% vs. 67.6%) were among the study group and control group, respectively. None of them were statistically significant. Three years event free survival among the study group and the control group was (85.2% vs. 83.4%) respectively; however, the difference did not reach statistical significant value. Conclusion: This study shows that the outcome of young adults with CML is comparable to those of the elderly people with imatinib both in terms of response rates and survival

Prognostic significance of bone only metastasis compared to visceral metastasis in patients with carcinoma cervix treated with platinum-based chemotherapy

Context: Carcinoma cervix is a leading cause of cancer in Indian females where 15%–60% of the cases eventually metastasize. Bone only metastasis is rare, and data on its response and survival with systemic therapy as compared to other visceral metastasis are limited. Settings and Design: The study design was a retrospective analysis. Materials and Methods: We retrospectively analyzed our data between May 2013 and April 2015 to identify the cases of bone only metastasis and visceral metastasis and tried to analyze their outcomes with paclitaxel- and carboplatin-based chemotherapy and bisphosphonates (for bone metastasis only). Results: Totally, 12 cases with bone only metastasis (Group 1) and 43 cases with visceral metastasis (Group 2) were identified. Most common sites of bone metastasis were vertebrae (66.67%) and pelvis (25%) while that of visceral metastasis was liver (44.18%) and lung (34.88%). Only 33.33% and 34.88% of cases in Group 1 and Group 2, respectively, could complete all six cycles of chemotherapy. Overall, response rates were 41.67% and 30.32% in Group 1 and Group 2, respectively. Median progression-free survival and overall survival (OS) were 10 months and 14 months, respectively, in Group 1 as compared to 4 months and 9 months, respectively, in Group 2. The difference in survival was statistically significant. Statistical Analysis Used: It was carried out by SPSS software version 20. Conclusion: Bone only metastasis is a rare and distinct entity with favorable outcomes as compared to visceral metastasis. However, disease remains aggressive and poor OS emphasizing the need of further research