Calcium is required for the expression of anthrax lethal toxin activity in the macrophagelike cell line J774A.1.

Anthrax lethal toxin, which consists of two separate proteins, protective antigen (Mr, 82,700) and lethal factor (Mr, approximately 83,000), is cytotoxic to the macrophagelike cell line J774A.1. Removal of calcium from the culture medium protected cells against the action of lethal toxin. Calcium depletion during the binding phase of intoxication afforded only partial protection. Further analysis showed that calcium removal caused some inhibition of protective antigen binding but that it had minimal effect on proteolytic conversion of protective antigen to the active 63-kilodalton fragment and that it had no effect on lethal factor binding. Cells to which lethal toxin had bound in the presence of calcium were protected when transferred to calcium-depleted culture medium, indicating a role for calcium at a postbinding stage. When ammonium chloride is present with lethal toxin, toxin accumulates in intracellular vesicles. Calcium-free medium protected these cells upon removal of the amine block, suggesting that calcium is also required at a step after internalization of lethal toxin. Calcium channel blockers inhibited 45Ca2+ uptake and protected cells against cytotoxicity. Calmodulin inhibitors also protected against the action of lethal toxin, suggesting involvement of calmodulin at a step during intoxication. We conclude that calcium is required at several steps in the intoxication of cells by anthrax lethal toxin.     

Bilateral granulocytic sarcoma (chloroma) of the breast in CML in blast crisis: a case report

A 35 year old lady was diagnosed as having chronic myeloid leukemia in May 1999 and thereafter started on chemotherapy. Three years later the patient presented with bilateral breast masses. FNAC from both the breast lesions showed leukemic infiltration (granulocytic sarcoma). The peripheral blood picture showed blastic transformation. Breast is an uncommon site for development of granulocytic sarcoma. We present this case because of its unusual location and bilateral nature.     

Primary malignant lymphoma of the breast

Primary malignant lymphomas of the breast (PBL) are uncommon constituting only 0.04 to 0.53% of malignant breast neoplasms. We wish to report the clinical, cytological and histologic findings of PBL diagnosed in a 52 years old female.     

New observations on carrying angle

Based on experiments on fresh cadaveric and accidentally amputated 8 upper limbs of children, study of ulnae for presence and absence of non articular strip on the trochlear notch, measurements of carrying angle, length of forearm bones, pronation-supination, height and weight in 2250 infants, children and adults of various age groups and clinical observations on 800 cases of injuries around elbow many new facts have been observed about the development of the carrying angle and its significance in the etiopathogenesis of various types of fractures seen around the elbow. The carrying angle develops in response to pronation of the forearm and is dependent on length of the forearm bones. Lesser the length of forearm bones greater is the carrying angle. So the carrying angle is more in shorter persons as compared to taller persons. It is abduction at the shoulder and not the carrying angle which keeps the swinging upper limbs away from the side of the pelvis during walking. Carrying angle is not a secondary sex character. The type of fracture a child sustains after fall on outstretched hand is also determined by the value of the carrying angle. A new type of fracture hitherto undescribed in the literature, T-Y fracture of the distal humeral epiphysis is also reported.     

Visual evoked responses in ethambutol induced optic neuritis

Pattern evoked responses were recorded in 46 patients of tuberculosis on ethambutol and 16 healthy subjects. Deterioration in visual acuity was documented in two patients (4.3%). P100 latency was delayed in 16 cases (34.8%), while in 12 patients (26.1%) both latency and amplitude were affected. A cut off latency value of > or = 140 ms was associated with ophthalmological findings. The incidence of subclinical toxicity as detected by visual evoked response (VER) was higher in older subjects, patients on higher doses of ethambutol (> or = 20 mg/kg/day) and longer duration of treatment. Of two cases with objective ocular signs, one who reported for follow up after two months had recovered completely after stopping ethambutol. Recording of VER is an extremely useful objective test for subclinical optic nerve damage.     

Case of double superior vena cava

A 23-year-old male patient who had no history of any previous medical illness was noted to have a widened mediastinum on chest X-ray undertaken as part of a routine medical evaluation. A computer tomographic (CT) scan confirmed the widened mediastinum to be due to a double superior vena cava (SVC). No further investigations were undertaken. The patient was noted to be well when re-assessed 3 years later.     

Cytokines: the yin and yang of vitiligo pathogenesis

Introduction: Dysregulation of melanocyte function is associated with vitiligo, an idiopathic autoimmune hypopigmentary skin disorder, caused by the selective destruction of melanocytes. Cytokines, the key mediators of immune response, which are pivotal in maintaining immune homeostasis, are crucial in vitiligo pathogenesis. Several studies indicate that there is an imbalance between pro- and anti-inflammatory cytokines in the skin and serum of vitiligo patients.

Areas covered: In this comprehensive review, we have summarized the correlation of cytokine imbalance and vitiligo pathogenesis, its role in melanocyte biology, and its impact on vitiligo treatment. We have integrated various published reports on the levels of major cytokines from skin and serum samples of vitiligo patients. We have also discussed the role of endoplasmic reticulum and oxidative stress on cytokine imbalance and vice versa leading to destruction of melanocytes.

Expert commentary: The review reflects that dysregulation of cytokines is multifactorial, ranging from genetic predisposition to altered protein expression relevant to vitiligo pathogenesis. We emphasize that cytokine imbalance in systemic and skin microenvironment plays a crucial role in vitiligo pathogenesis and has promising potential as therapeutic targets for vitiligo.