Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants; a number are carcinogenic. Metabolic polymorphisms may modulate susceptibility to PAH-induced DNA damage and carcinogenesis. This study investigates the relationship between PAH-DNA adduct levels (in maternal and newborn WBCs) and two polymorphisms: (a) an MspI RFLP in the 3' noncoding region of cytochrome P4501A1 (CYP1A1); and (b) an A-->G transition in nucleotide 313 of glutathione S-transferase P1 (GSTP1), resulting in an ile105val substitution. CYP1A1 catalyzes the bioactivation of PAH; the CYP1A1 MspI RFLP has been associated with cancer of the lung. GSTP1 catalyzes the detoxification of PAH; the val allele has greater catalytic efficiency toward PAH diol epoxides. The study involves 160 mothers and their newborns from Poland. Regression models controlled for maternal smoking and other confounders. No association was seen between maternal adduct levels and either polymorphism, separately or combined. However, adduct levels were higher among newborns with the CYP1A1 MspI restriction site (heterozygotes and homozygotes combined) compared with newborns lacking the restriction site (P = 0.06). Adducts were higher among GSTP1 ile/val and ile/ile newborns compared with GSTP1 val/val newborns (P = 0.08). Adduct levels were 4-fold higher among GSTP1 ile/ile newborns having the CYP1A1 restriction site compared with GSTP1 val/val newborns who lacked the CYP1A1 restriction site (P = 0.04). This study demonstrates a significant combined effect of phase I and phase II polymorphisms on DNA damage from PAHs in fetal tissues. It illustrates the importance of considering interindividual variation in assessing risks of transplacental exposure to PAHs.     

The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue.

A major goal in molecular epidemiology is to identify preventable environmental risk factors and susceptible subpopulations. In a hospital-based molecular epidemiological case-control study of breast cancer, we investigated the relationship between DNA damage from exposure to polycyclic aromatic hydrocarbons (PAHs) and susceptibility attributable to inherited deletion of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1). Prior to breast surgery, women (n = 227) were enrolled and interviewed and donated a blood sample. PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples retrieved from pathology blocks, and GSTM1 genotype was determined by PCR using WBC DNA. The GSTM1 analysis included 95 cases and 87 benign breast disease controls. GSTM1 genotype was not associated with breast cancer case-control status (odds ratio = 0.73; 95% confidence interval, 0.37-1.44). However, the GSTM1 null genotype predicted PAH-DNA adduct levels in malignant (beta = 0.407; P = 0.003) and nonmalignant (beta = 0.243; P = 0.05) breast tissue from cases. This relationship was not seen in tissue from controls (beta = 0.095; P = 0.341). When tissue from controls was compared with tumor tissue from cases, there was a significant case-control difference in PAH-DNA adduct levels among women who were GSTM1 null. There was no such case-control difference among women who were homozygous or heterozygous for GSTM1. There was an interaction between GSTM1 and case-control status on adduct levels in breast tissue (P = 0.002). The results suggest that genetic susceptibility to the formation of PAH-DNA adducts in breast tissue may play a role in breast cancer development.     

Unusual findings in the inguinal canal: a report of four cases

Masses in the inguinal canal other than hernias are rare occurrences, and their preoperative diagnosis requires a high index of suspicion. A soft, partly reducible groin mass in a 3-month-old boy proved to be a cystic lymphangioma within the inguinal canal. A 15-month-old female who presented with an irreducible inguinal mass was found to have a neuroblastoma metastasis in the groin. An irreducible groin mass in a 6-year-old female proved to be an inguinal canal epidermal inclusion cyst. A 14-year-old female presented with a painful groin swelling that represented an incarcerated hemorrhagic ovarian cyst. An awareness of the wide spectrum of entities other than the standard bowel, testicle, and ovary in the inguinal canal can help to identify uncommon pathologies preoperatively. Accepted: 6 January 1998     

Metabolism of 4′-thio-β- -arabinofuranosylcytosine in CEM cells

Because of the excellent in vivo activity of 4′-thio-β- -arabinofuranosylcytosine (T-araC) against a variety of human solid tumors, we have studied its metabolism in CEM cells to determine how the biochemical pharmacology of this compound differs from that of β- -arabinofuranosylcytosine (araC). Although there were many quantitative differences in the metabolism of T-araC and araC, the basic mechanism of action of T-araC was similar to that of araC: it was phosphorylated to T-araC-5′-triphosphate (T-araCTP) and inhibited DNA synthesis. The major differences between these two compounds were: (i) T-araC was phosphorylated to active metabolites at 1% the rate of araC; (ii) T-araCTP was 10- to 20-fold more potent as an inhibitor of DNA synthesis than was the 5′-triphosphate of araC (araCTP); (iii) the half-life of T-araCTP was twice that of araCTP; (iv) the catalytic efficiency of T-araC with cytidine deaminase was 10% that of araC; and (v) the 5′-monophosphate of araC was a better substrate for deoxycytidine 5′-monophosphate deaminase than was the 5′-monophosphate of T-araC. Of these differences in the metabolism of these two compounds, we propose that the prolonged retention of T-araCTP is a major factor contributing to the activity of T-araC against solid tumors. The data in this study represent another example of how relatively small structural changes in nucleoside analogs can profoundly affect the biochemical activity.     

Basaloid squamous carcinoma metastatic to renal-cell carcinoma: Fine-needle aspiration cytology of tumor-to-tumor metastasis

We describe an unusual case of a basaloid squamous-cell carcinoma (BSCC) of the tonsil in a 56-yr-old man that metastasized to a primary renal-cell carcinoma (RCC) and the lung. The diagnosis of the second primary, the RCC, was based on fine-needle aspiration (FNA) cytology. A subsequent nephrectomy specimen revealed BSCC metastatic to RCC, clear-cell type. Retrospective analysis of the FNA of the renal mass revealed classic RCC morphology and, in addition, another cytologically distinctive pattern characterized by occasional sheets of cohesive neoplastic cells with hyperchromatic nuclei and nuclear molding representative of BSCC. The cytologic features of a subsequent FNA of the lung were characteristic of metastatic BSCC. Our retrospective analysis of cytologic material from the renal mass underscores the importance of raising the possibility of tumor-to-tumor metastasis when distinctly different morphologic features are seen in an otherwise typical cytology of a neoplasm in patients with an already known or suspected second primary. To our knowledge, this case report is the first one documenting metastasis of BSCC to RCC. Diagn. Cytopathol. 1997;17:379–382. © 1997 Wiley-Liss, Inc.     

Salt intake and salt‐reduction strategies in South Asia: From evidence to action

The World Health Organization recommends salt reduction as a cost‐effective intervention to prevent noncommunicable diseases. Salt‐reduction interventions are best tailored to the local context, taking into consideration the varying baseline salt‐intake levels, population''s knowledge, attitude, and behaviors. Fundamental to reduction programs is the source of dietary salt‐intake. In South Asian countries, there is a paucity of such baseline evidence around factors that contribute to community salt intake. Upon reviewing the electronic literature databases and government websites through March 31, 2021, we summarized dietary salt intake levels and aimed to identify major sources of sodium in the diet. Information on the current salt reduction strategies in eight South Asian countries were summarized, namely Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. One hundred twelve publications (out of identified 640) met our inclusion‐exclusion criteria for full text review. Twenty‐one studies were included in the review. Quality of the included studies was assessed using the US National Heart, Lung, and Blood Institute assessment tool. The primary result revealed that mean salt intake of South Asian countries was approximately twice (10 g/day) compared to WHO recommended intake (< 5 g/day). The significant proportion of salt intake is derived from salt additions during cooking and/or discretionary use at table. In most South Asian countries, there is limited data on population sodium intake based on 24‐h urinary methods and sources of dietary salt in diet. While salt reduction initiatives have been proposed in these countries, they are yet to be fully implemented and evaluated. Proven salt reduction strategies in high‐income countries could possibly be replicated in South Asian countries; however, further community‐health promotion studies are necessary to test the effectiveness and scalability of those strategies in the local context.     

Ultrastructural studies of neuronal correlates of the pubertal reaugmentation of hypothalamic gonadotropin-releasing hormone (GnRH) release in the rhesus monkey (Macaca mulatta)

This study tested the hypothesis that puberty in primates is triggered by a remodeling of synaptic inputs and/or glial coverage of hypothalamic gonadotropin releasing hormone (GnRH) neurons. Male rhesus monkeys were prepubertally castrated at 16 months of age and were killed and perfused either 1 month later (n = 4, juvenile group) or at 30 months of age, shortly after initiation of the pubertal increase in pulsatile GnRH release (n = 4, adult group). Hypothalami were sectioned, immunocytochemically stained for GnRH, and processed for electron microscopy. Cross-sectional profiles of 77 GnRH cells from the medial basal hypothalamus (MBH) and the region of the organum vasculosum of the lamina terminalis (OVLT) were compared between the two developmental stages. GnRH cell and nucleolus size in the two groups were the same. The percentage of GnRH perikaryal membrane occupied by synaptic density in the MBH of juveniles was significantly greater (P < 0.05) than that of adults. Differences in the percentage of GnRH perikaryal membrane occupied by synaptic density were not observed in the OVLT nor on GnRH dendrites in either brain region. Qualitative analysis, based on synaptic vesicle shape, failed to reveal developmental differences in putatively excitatory or inhibitory synapses on GnRH cells. The degree of glial ensheathment of GnRH neurons did not change significantly during the two developmental stages. These findings provide ultrastructural evidence for the view that, in primates, neuronal plasticity, and specifically a decrease in synaptic input to GnRH perikarya, may underlie the initiation of the pubertal mode of release of this neuropeptide, and therefore, the onset of puberty in these species. J. Comp. Neurol. 385:71–82, 1997. © 1997 Wiley-Liss, Inc.     

The 21st Annual Meeting of the Rocky Mountain Virology Association

Nestled within the Rocky Mountain National Forest, 114 scientists and students gathered at Colorado State University’s Mountain Campus for this year’s 21st annual Rocky Mountain National Virology Association meeting. This 3-day retreat consisted of 31 talks and 30 poster presentations discussing advances in research pertaining to viral and prion diseases. The keynote address provided a timely discussion on zoonotic coronaviruses, lessons learned, and the path forward towards predicting, preparing, and preventing future viral disease outbreaks. Other invited speakers discussed advances in SARS-CoV-2 surveillance, molecular interactions involved in flavivirus genome assembly, evaluation of ethnomedicines for their efficacy against infectious diseases, multi-omic analyses to define risk factors associated with long COVID, the role that interferon lambda plays in control of viral pathogenesis, cell-fusion-dependent pathogenesis of varicella zoster virus, and advances in the development of a vaccine platform against prion diseases. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations.     

A worthy technique for transcanal drilling during endoscopic ear surgery

ObjectiveTo evaluate the necessity and effectiveness of a preplanned technique for drilling during transcanal endoscopic ear surgery.MethodsStudy design: Retrospective case series study from June 2011 to June 2015. Setting: Private tertiary care hospital. Patients: Eighty-five ears of 78 patients, age ranging from 9 to 57 years underwent transcanal endoscopic drilling for various types of pathology in their middle and external ear. Interventions: Application of a preplanned technique for transcanal drilling in endoscopic ear surgery that involved short timed drilling with use of intermittent irrigation and suction. Every events of the procedure were done one after another with the single hand of the surgeon. An attachment providing protecting sheath around rotating burr was used during each time of drilling. Main outcomes measure: Efficacy of such drilling technique in single handed endoscopic ear surgery. Presence of any postoperative thermal injury of facial nerve and any lacerated injury of skin of external ear.ResultsThis preplanned technique was found suitable for transcanal endoscopic drilling with the single hand of the surgeon. Postoperative facial nerve palsy or laceration of skin of external ear was not noted in any patient.ConclusionAfter using the present technique, transcanal endoscopic drilling could be done easily and safely with single hand of the surgeon.     

Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies. Although most MERS-CoV isolates had similar stability and pathogenicity in our experiments, the camel-derived isolate C/KSA/13 had reduced surface stability, and another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that although betacoronaviruses might have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the need for continual global viral surveillance.