Touch imprint cytology of axillary lymph nodes after neoadjuvant chemotherapy in patients with breast carcinoma

BACKGROUND: Neoadjuvant chemotherapy (NC) reportedly downstages axilla in approximately one-third of patients with locally advanced breast carcinoma (LABC). Postchemotherapy axillary lymph node status is an important prognostic factor. In the current study, the authors evaluated the reliability of touch imprint cytology (TIC) in detecting axillary lymph node metastasis after NC and identified chemotherapy-induced changes that may influence this assessment. METHODS: Thirty-three patients with LABC were studied. Seventeen patients had received chemotherapy before surgery (NC group) and 16 patients had not (non-NC group). Touch imprints were made from either the largest axillary lymph node (in 13 patients from the NC group and 16 patients from the non-NC) or the sentinel lymph node (in 4 patients from the NC group). Imprints from the NC group were evaluated for metastasis and were correlated with histopathology. Touch imprints from both groups were compared for cellularity, tumor load, necrosis/degeneration, and histiocytes. RESULTS: Cytologic evaluation for metastasis was 100% concordant with histopathology in all 17 patients from the NC group (9 positive results [53%] and 8 negative results [47%]). The presence of few tumor cells in sparsely cellular imprints that exhibited necrosis (two patients) and the presence of only degenerating/necrotic tumor cells (two patients) were two cytologic patterns unique to post-NC imprints that may have influenced their accurate assessment. CONCLUSIONS: TIC was found to be reliable for the intraoperative evaluation of axillary lymph node metastasis after NC. However, a careful examination is warranted in sparsely cellular imprints, because there is the possibility of overlooking a small group of tumor cells. To the authors' knowledge, the significance of finding extensive necrosis in axillary lymph nodes after NC is not known and may be investigated.     

Seasonal prevalence of Culex vishnui subgroup,the major vectors of Japanese encephalitis virus in an endemic district of Andhra Pradesh,India

Seasonal prevalence of members of the Culex vishnui subgroup, the major vectors of Japanese encephalitis virus (JE) in an endemic district of Andhra Pradesh, was investigated. Approximately 15,500 mosquitoes belonging to 2 genera and 5 species were collected by indoor-resting collections. The predominant species were found to be from the Cx. vishnui subgroup, which comprised 42.6% of the total collection, followed by Anopheles subpictus (40.4%), An. hyrcanus (12.8%), Cx. gelidus (3.5%), and An. barbirostris (0.8%). Mosquitoes of the Cx. vishnui subgroup were collected throughout the year, and densities of females ranged from 2.3/man-hour in January 1999 to 26.0/man-hour in December 1999. Ninety-three cases of Japanese encephalitis (27 confirmed serologically) were reported, mainly during the monsoon months of November and December. A significant positive correlation between densities of mosquitoes of the Cx. vishnui subgroup and occurrence of Japanese encephalitis cases (r = 0.765, P < 0.01) was observed. The factors responsible for transmission of JE in the endemic district are discussed.     

Scavenger receptor-mediated delivery of muramyl dipeptide activates antitumor efficacy of macrophages by enhanced secretion of tumor-suppressive cytokines

We showed that muramyl dipeptide (MDP) conjugated to maleylated bovine serum albumin (MBSA) was internalized by macrophages (Mphi) through scavenger receptor (SCR)-mediated endocytosis, which leads to 50-fold higher cytotoxic activity against non-Mphi tumor cells compared with that elicited by free MDP-treated Mphi. The enhanced cytotoxic effect of MBSA-MDP was found to be a result of higher secretion of interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO) because the addition of antibodies directed against IL-1, IL-6, or TNF-alpha in combination with Mphi cultures totally abrogated the tumoricidal activity of MBSA-MDP. It is interesting to note that MBSA-MDP triggers the secretion of IL-12, whereas IL-10, a Mphi suppressor cytokine, could be detected only on free MDP treatment. The cytotoxic activity of MBSA-MDP was inhibited by indomethacin, indicating a regulatory role for prostaglandin E2 (PGE2). Efficient SCR-mediated intracellular delivery of MDP leading to elimination of cancer cells suggests the immunotherapeutic potential of this approach for treatment of neoplasia.     

Capsid Protein-Encoding (P1) Sequence of Foot and Mouth Disease Virus Type Asia 1 Ind 63/72

Variations in the amino acid sequence of Foot-and-Mouth Disease Virus (FMDV) structural proteins are the basis for the antigenic diversity of the virus. Majority of antigenic sites for the virus neutralization are present on VP1, the major immunogenic protein. However, a few conformational epitopes are present on the structural proteins VP2 and VP3. The nucleotide sequence encoding all the four structural proteins (P1 region) of FMDV type Asia 1 Ind 63/72 was determined. The nucleotide and the deduced amino acid sequence of P1 of Asia 1 of Indian strain was compared with that of Asia 1 Israel strain. Differences were observed at 284 (14%) nucleotide positions resulting in 69 (10%) amino acid changes. The variation in the derived amino acid sequence is the highest in VP1 (14.4%) followed by VP2 (10%), VP3 (6.4%) and VP4 (3%). Deletion of two amino acids, which was observed in the case of Indian strain as well as in Israel strain indicated that these deletions are specific for type Asia 1. The P1 sequence was also compared with the corresponding region of the other serotypes O1K, A12, C1 and SAT-1. The sequence has been submitted to EMBL data bank, under accession number Y09949.     

Structure-function relationships of icosahedral plant viruses

Summary X-ray diffraction studies on single crystals of a few viruses have led to the elucidation of their three dimensional structure at near atomic resolution. Both the tertiary structure of the coat protein subunit and the quaternary organization of the icosahedral capsid in these viruses are remarkably similar. These studies have led to a critical re-examination of the structural principles in the architecture of isometric viruses and suggestions of alternative mechanisms of assembly. Apart from their role in the assembly of the virus particle, the coat proteins of certian viruses have been shown to inhibit the replication of the cognate RNA leading to cross-protection. The coat protein amino acid sequence and the genomic sequence of several spherical plant RNA viruses have been determined in the last decade. Experimental data on the mechanisms of uncoating, gene expression and replication of several classes of viruses have also become available. The function of the non-structural proteins of some viruses have been determined. This rapid progress has provided a wealth of information on several key steps in the life cycle of RNA viruses. The function of the viral coat protein, capsid architecture, assembly and disassembly and replication of isometric RNA plant viruses are discussed in the light of this accumulated knowledge.     

Clinical epidemiology of bancroftian filariasis: effect of age and gender

A cross-sectional survey was used to determine the prevalence of disease (n = 6493) and microfilaraemia (n = 24,946) due to Wuchereria bancrofti in Pondicherry, south India. The total disease attributable to filariasis was significantly higher in males (13.67%) than females (2.26%), due to the occurrence of hydrocele in males. While the prevalence of chronic signs was clearly age-dependent in both sexes, that of acute signs was independent of age. Thus the age and gender structure of the survey sample will crucially influence apparent prevalence. Examination of the gender differences in the point prevalence of disease in 12 areas of India showed a significant relationship between occurrence of disease and gender, but this relationship did not significantly differ between northern and southern Indian populations. The study suggested that the failure to appreciate the importance of age and gender in disease prevalence has led to misconception about disease patterns in India.     

Impact of different housing structures on filarial transmission in rural areas of southern India

The aim of the present investigation was to assess the filarial transmission levels in houses of different structure in rural areas of Andhra Pradesh, India. During this study, ecologically-similar households were selected for entomological study. The per-man-hour density (PMHD), infection and infectivity rates, were recorded in different ranges ie, 16.1 to 77.6, 0-31.2% and 0-5.6%, respectively.     

Management of Inflammatory Tracheoesophageal Adhesions During Transhiatal Esophagectomy

Purpose: Mediastinal adhesions, caused by the transerosal spread of disease, inflammatory diseases, or preoperative chemoradiotherapy, can result in diffi-culties and major complications during transhiatal esophagectomy (THE). However, few studies have specifically addressed the incidence and management of inflammatory adhesions encountered during THE. Methods: We retrospectively analyzed the operative details and postoperative outcome of 70 patients who underwent THE between 1998 and 2000. Patients with inflammatory tracheoesophageal adhesions were identified and their operative records were reviewed for operative findings, intraoperative management, morbidity, and mortality. Patients with upper thoracic esophageal tumors and direct tumor spread to the airways were excluded from the analysis. Results: Eight (11.4%) of the 70 patients had inflammatory adhesions and esophagectomy was possible in 7 of these 8 patients. Due to poor pulmonary status, one patient required conversion to the trnsthoracic approach, but the other six were managed transhiatally. Three patients underwent subtotal esophagectomy, the esophagectomy was completed by the inversion extraction technique in two, one required extended transhiatal dissection, and esophagectomy could not be completed in one due to dense inseparable adhesions between the trachea and esophagus. There was no major airway injury or bleeding. Conclusions: Inflammatory tracheoesophageal adhesions may be encountered in patients undergoing THE in developing countries. Thus, an awareness of the possibility of these adhesions and suitable modifications of the operating procedures are necessary to prevent major complications. Received: November 5, 2001 / Accepted: September 3, 2002 Reprint requests to: N.K. Shukla     

Oral administration of the citrus coumarin,isopimpinellin, blocks DNA adduct formation and skin tumor initiation by 7,12-dimethylbenz[a]anthracene in SENCAR mice

The current study was designed to evaluate the effects of oral administration of the citrus coumarin, isopimpinellin, on skin tumor initiation by topically applied benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA). To evaluate the effects of orally administered isopimpinellin on skin tumor initiation by B[a]P and DMBA, its effects on DNA adduct formation were first evaluated. Female SENCAR mice were pre-treated twice with corn oil, or isopimpinellin (70 mg/kg body wt per os) at 24 h and 2 h prior to topical treatment with B[a]P or DMBA. Another citrus coumarin, imperatorin, was also included in these experiments for comparison. Orally administered isopimpinellin and imperatorin significantly inhibited B[a]P-DNA adduct formation by 37 and 26%, respectively. Imperatorin also blocked DMBA-DNA adduct formation by 43%. In a second dose-response study, orally administered isopimpinellin (35, 70 and 150 mg/kg) blocked DMBA-DNA adduct formation by 23, 56 and 69%, respectively. For the tumor study, mice were pretreated orally with corn oil or isopimpinellin at 24 and 2 h prior to initiation with DMBA, and 2 weeks later promotion began with 12-O-tetradecanoylphorbol-13-acetate (TPA). Isopimpinellin significantly reduced the mean number of papillomas per mouse by 49, 73 and 78% compared to corn oil controls at 30, 70 and 150 mg/kg body wt, respectively. Orally administered isopimpinellin also significantly reduced the percentage of mice with papillomas at the highest dose tested (150 mg/kg). The effectiveness of isopimpinellin given topically over a broad dose range against DMBA tumor initiation was also evaluated for comparison. As part of this study, several parameters of systemic toxicity were evaluated following oral dosing with isopimpinellin and imperatorin. Mice were treated orally with corn oil, isopimpinellin or imperatorin (35, 70 and 150 mg/kg body wt per os) once daily for four consecutive days, killed at 24 h after the last dose, and livers, lungs, and kidneys evaluated histologically. In addition, urinary parameters of nephrotoxicity, blood parameters of liver and kidney function, and thrombin clotting time were assayed. No significant changes in blood clotting, or renal or hepatic function were observed. There was, however, a significant increase in liver wt accompanied by cytoplasmic vacuolation of hepatocytes. There were no histopathological changes in lungs or kidneys. Overall, these data indicate that isopimpinellin (and imperatorin) have chemopreventive effects when administered orally on skin tumor initiation by DMBA.