Stimulation of DNA synthesis by rat plasma following in vivo treatment with three liver mitogens.

The present study was undertaken to determine the effect of two different types of liver cell proliferative stimuli, namely compensatory regeneration and direct hyperplasia on DNA synthesis of normal and preneoplastic isolated hepatocytes. Platelet-poor plasma (PPP) isolated from male Wistar rats treated with three different hepato-mitogens, lead nitrate (LN), cyproterone acetate (CPA) and ethylene dibromide (EDB), or subjected to surgical partial hepatectomy (PH), was tested for its ability to stimulate DNA synthesis in normal and preneoplastic hepatocytes in primary cultures. Induction of DNA synthesis was detected as early as 30 min after CPA, EDB and PH administration and persisted up to 5 days after the LN administration. In addition, hepatocytes isolated from preneoplastic liver nodules were also able to respond in culture to the DNA synthesis stimulus induced by these factors.     

5-Azacytidine potentiates initiation induced by carcinogens in rat liver

To test the validity of the hypothesis that hypomethylationof DNA plays an important role in the initiation of carcinogenicprocess, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNAmethylation, was given to rats during the phase of repair synthesisinduced by the three carcinogens, benzo[a]-pyrene (200 mg/kg),N-methyl-N-nltrosourea (60 mg/kg) and 1,2-dimethylhydrazine(1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liverwere assayed as the -glutamyltransferase (-GT) positive fociformed following a 2-week selection regimen consisting of dietary0.02% 2-acetylaminofluorene coupled with a necrogenic dose ofCCl₄. The results obtained indicate that with all three carcinogens,administration of 5-AzC during repair synthesis increased theincidence of initiated hepatocytes, for example 10–20foci/cm² in 5-AzC and carcinogen-treated rats compared with3–5 foci/cm² in rats treated with carcinogen only. Administrationof [³H]-5-azadeoxycytidine during the repair synthesis inducedby 1,2-DMH further showed that 0.019 mol% of cytosine residuesin DNA were substituted by the analogue, indicating that incorporationof 5-AzC occurs during repair synthesis. In the absence of thecarcinogen, 5-AzC given after a two thirds partial hepatectomy,when its incorporation should be maximum, failed to induce any-GT positive foci. The results suggest that hypomethylationof DNA per se may not be sufficient for initiation. Perhapstwo events might be necessary for initiation, the first causedby the carcinogen and a second involving hypomethylation ofDNA.     

Proliferating cell nuclear antigen expression and the progression of cervical intraepithelial neoplasia

Cell proliferation is an important biological aspect of a tumor cell population which can affect clinical outcome. In addition to other well established clinical and histopathological prognostic criteria? cell kinetic data have significant predictive value. This study evaluates the proliferative activity of benign, premalignant and malignant cervical tissue by analyzing the expression of the proliferating cell nuclear antigen (PCNA). PCNA is a 36 kD nuclear protein associated with the cell cycle and is directly involved in DNA synthesis during cell proliferation. A total of 122 subjects were included in the study. This included 30 benign tissue samples, 30 low grade lesions (CIN 1), 30 high grade lesions (CIN 2/3) and 32 invasive squamous carcinomas. There was significant difference in PCNA index between benign and high grade lesions as well as benign and invasive cancer. The percentage of PCNA positive cells were significantly higher in invasive carcinoma when compared with non malignant lesions. Moreover, there was also good correlation between increasing histological abnormality and PCNA expression. These results suggest that cell proliferation index as detected by PCNA expression may be useful in the evaluation of alterations in cell kinetics of various grades of cervical lesions. Such data could also possibly help explain the biological behaviour of these lesions and be useful in planning of radiotherapy for invasive cervical cancer.     

Effects of long-term administration of androgens and estrogen on rhesus monkey prostate: possible induction of benign prostatic hyperplasia

Rhesus monkeys were used to investigate the role of androgenic steroids and estradiol in the induction of hyperplastic changes in stromal and glandular prostate tissues. Adult male rhesus monkeys were procured from the wild and, after routine quarantine procedures, were randomly divided into 5 groups of 5 animals each. Gluteus maximus muscles were injected with 2.5 mg of androstenedione (Group II), 2.5 mg of dihydrotestosterone (DHT) or 0.25 mg of estradiol (Group II), 2.5 mg androstanediol (Diol; Group IV), or Diol in combination with 0.25 mg of estradiol (Group V). Group I consisted of untreated controls. Animals were injected with steroids 3 times a week for 2 years. Treatment with androstenedione (Group II) resulted in stromal hyperplasia in the caudal lobe and an increase in epithelial cell height in all zones except in the central zone of the caudal lobe. In monkeys treated with DHT and estradiol (Group III), stromal hyperplasia in both lobes, a decrease in tubular size, and degranulation and vacuolation of epithelial cells were noticed. Injection of Diol alone (Group IV) or in combination with estradiol (Group V) resulted in a widening of stroma in the central and peripheral zones of cranial and caudal lobes, whereas the tubular size decreased. Diol also induced epithelial cell hypercellularity in the central and peripheral zones of the caudal lobe and in the peripheral zone of the cranial lobe. Prostate-specific antigen levels in Group IV animals gradually increased from 6 months of treatment and were maximal after 18 months of injections. Serum estradiol levels increased to detectable levels in all groups except Group IV. Serum testosterone levels decreased to very low or undetectable levels in all groups, whereas prostate-specific acid phosphatase increased in all treated groups. Prolactin levels were elevated in all treated groups except in animals injected with androstenedione. These results indicate that repeated long-term injections of androstenedione or DHT and estradiol induced stromal hyperplasia, which may be an estrogen-related effect. Androstanediol-induced hypercellularity and stratification of glandular epithelium is comparable to human prostatic intraepithelial neoplasia. These results also suggest that the rhesus monkey is a suitable animal model for experimental induction of prostate diseases.     

Child with Abdominal Pain

Abdominal pain is one of the common symptoms reported by children in urgent care clinics. While most children tend to have self-limiting conditions, the treating pediatrician should watch out for underlying serious causes like intestinal obstruction and perforation peritonitis, which require immediate referral to an emergency department (ED). Abdominal pain may be secondary to surgical or non-surgical causes, and will differ as per the age of the child. The common etiologies for abdominal pain presenting to an urgent care clinic are acute gastro-enteritis, constipation and functional abdominal pain; however, a variety of extra-abdominal conditions may also present as abdominal pain. Meticulous history taking and physical examination are the best tools for diagnosis, while investigations have a limited role in treating benign etiologies.     

Direct immunofluorescence in cutaneous vesiculobullous lesions

Direct Immunofluorescence (DIF) is invaluable in the diagnosis of cutaneous vesiculobullous lesions (VBL). It is limited by technical factors and disease nature. 1) To record the sensitivity of DIF in VBL 2) To correlate DIF with clinical, histologic findings and analyse discrepancies. Material and Methods: A retrospective study of 100 DIFs on suspected VBL of skin. DIF, histology and clinical data were reviewed. 73/100 cases showed DIF patterns concordant with clinical/histologic diagnosis. The sensitivity of DIF was 88% in Pemphigus group (39/ 44), 82% in Bullous Pemphigoid (BP) (23/28), and 20% in Dermatitis Herpetiformis (DH) (1/5).18 cases of histologically proven VBL were negative and of these, 4 had no epidermis. The remaining 9 cases were discordant with clinical/histologic features, including 4 BP and 5 DH, whose histology was non-specific and will be discussed in detail. One case of DH showed an aberrant vasculitic pattern. DIF is of great value in the diagnosis of VBL, specially in clinical/histologic dilemmas. In DH, neither biopsy nor DIF were very useful and response to therapy was the standard. Sampling errors contributed to false negative results. Proper selection of cases and judicious use are mandatory to optimize its' utility.     

Genetic Diversity,Population Structure and Correlation Study in Moringa oleifera Lam. Using ISSR and SRAP Markers

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Moringa oleifera Lam. is promoted in homestead gardens and is extensively cultivated as an affordable...     

Intraventricular gliosarcoma with dual sarcomatous differentiation: A unique case

Gliosarcoma, a variant of isocitrate dehydrogenase‐wildtype glioblastoma, is largely a lobar surfacing neoplasm often with dural attachment. In this biphasic neoplasm, the sarcomatous component usually takes the form of fibrosarcoma or malignant fibrous histiocytoma. Heterologous sarcomatous differentiation is a rare phenomenon. Here, we present a case of gliosarcoma with liposarcomatous and myosarcomatous differentiation in a 68‐year‐old man which was purely intraventricular. This is the first report of such a morphologic pattern in this location. Varied histological components with their immunohistochemical profile are discussed. Of note was the presence of a p53 negative giant cell glioblastoma component, as was the expression in the rest of the tumor.