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In the present study, the microbial source for potent lactase producers was explored to supplement the lactase intolerant individuals. Dairy effluent was screened for lactase producing bacteria by conventional microbiological methods. Among the positive isolates, one isolate VUVD001 was found to be a strong producer of lactase enzyme and this strain identified by 16S rDNA analysis. The lactase producing bacterium is identified as Bacillus subtilis by biochemical and 16S rDNA analysis. The VUVD001 strain found to survive in a temperature range of 20–55 °C, pH range of 5–8 and a salt concentration up to 8%. Further, the partially purified enzyme preparation was tested by zymogram analysis for activity testing using x-gal and the enzyme activity of cell free supernatant was estimated to be 15.10 U/ml at 37 °C, 4% NaCl and pH of 7.0. Our finding reports a new isolate Bacillus subtilis VUVD001 strain which can be used as potential strain for commercial production of lactase. Keywords: Lactase, Bacillus subtilis, ortho-nitrophenyl-β-galactoside (ONPG), X-gal, 16S rDNA

A person presented with multiple gunshot injury. Chest x-ray & CT whole body trauma protocol was done which showed multiples pellets of bullet in abdomen and one bullet in elbow according to entry wound. There was an entry wound without any bullet in left maxillofacial region however there was no exit wound. A bullet was noticed in tracheobronchial tree. There was no pneumothorax any signs of chest trauma or any pneumomediastinum. It is assumed that the bullet first hit the left cheek (maxilla) and lost its momentum. As the patient lost consciousness and had a fall leading to inhalation (aspiration) of bullet in the airway. As per ballistic experts it was basically a jacketed metallic bullet. As bullet moved in airway, the outer metallic core reached the trachea near carina and the soft metallic core slipped more distally to right main bronchus and bronchus intermedius. While inspection the outer metallic capsule was seen in trachea just above carina which was hollow and was gently removed with the help of foreign body forceps. The core was removed with dormia basket without any mucosal tear. The favorable outcome can be attributed as patient had no lung contusion or chest trauma and bullet was inhaled which was not very old. The evolution of bronchoscopy started with rigid one but the fibreoptic bronchoscopy (FOB) has revolutionized the pulmonary interventions. The FOB can be used with minimal traumas under local anesthesia resulting in markedly reduced morbidity and mortality.

Background: Imaging is a key diagnostic modality for suspected invasive pulmonary or sinus fungal disease and may help to direct testing and treatment. Fungal diagnostic guidelines have been developed and emphasize the role of imaging in this setting. We review and summarize evidence regarding imaging for fungal pulmonary and sinus disease (in particular invasive aspergillosis, mucormycosis and pneumocystosis) in immunocompromised patients., Objectives: We reviewed data on imaging modalities and findings used for diagnosis of invasive fungal pulmonary and sinus disease., Sources: References for this review were identified by searches of PubMed, Google Scholar, Embase and Web of Science through 1 April 1 2023., Content: Computed tomography imaging is the method of choice for the evaluation of suspected lung or sinus fungal disease. Although no computed tomography radiologic pattern is pathognomonic of pulmonary invasive fungal disease (IFD) the halo sign firstly suggests an angio-invasive pulmonary aspergillosis while the Reversed Halo Sign is more suggestive of pulmonary mucormycosis in an appropriate clinical setting. The air crescent sign is uncommon, occurring in the later stages of invasive aspergillosis in neutropenic patients. In contrast, new cavitary lesions should suggest IFD in moderately immunocompromised patients. Regarding sinus site, bony erosion, peri-antral fat or septal ulceration are reasonably predictive of IFD., Implications: Imaging assessment of the lung and sinuses is an important component of the diagnostic work-up and management of IFD in immunocompromised patients. However, radiological features signs have sensitivity and specificity that often vary according to underlying disease states. Periodic review of imaging studies and diagnostic guidelines characterizing imaging findings may help clinicians to consider fungal infections in clinical care thereby leading to an earlier confirmation and treatment of IFD., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Although trauma is one of the most significant areas of study in paleopathology, most studies focus on fractures of single anatomical elements. Paleopathological research on regional trauma, such as of the thorax, is rare. This paper explores the causes, complications, and consequences of adult thoracic trauma using clinical data in order to inform paleopathological research., Materials and Methods: Trends in paleopathological thoracic trauma literature were assessed by evaluating publications from Bioarchaeology International, International Journal of Osteoarchaeology, International Journal of Paleopathology, and American Journal of Biological Anthropology. Clinical publications on thoracic trauma throughout time were also assessed through a PubMed search, and modern prevalence data was found through trauma databases such as the National Trauma Databank., Results: Consideration of thoracic trauma involving concomitant injuries is a recent trend in clinical literature and patient care, but paleopathological research on thoracic trauma has been limited. Since thoracic fractures tend to occur in conjunction with other injuries, assessing them together is critical to the interpretation of trauma in the past., Conclusions: Clinical research into thoracic fractures and concomitant injuries provides valuable data for paleopathological research. Evaluating the likelihood and consequences of concomitant injury in skeletal remains provides a more robust understanding of trauma in the past and its impact on past lifeways., Significance: This paper provides a review of current clinical and paleopathological literature on thoracic trauma and demonstrates the importance of moving beyond the analysis of fractures or trauma of single anatomical elements., Limitations: Thoracic bones are often taphonomically altered and differentially preserved leading to difficulty in identifying and interpreting fractures., Suggestions for Further Research: Practical application of the data presented here to archaeological samples will help to advance paleopathological understandings of thoracic trauma., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Purpose: A videolaryngoscope has been recommended for intubation in the COVID-19 scenario but the videolaryngoscope providing optimal intubation conditions is not ascertained. We compared KingVision channelled blade with a non-Channelled videolaryngoscope for intubation times in a simulated COVID-19 intubation scenario by both anaesthesiologists and non-anaesthesiologists., Methods: This prospective randomised cross over mannequin study was conducted in a skill training lab. 25 anaesthesiologists and 25 non-anaesthesiologists donned in standard personal protective equipment performed 100 intubations with KingVision and Tuoren videolaryngoscopes in a mannequin covered with a transparent plastic sheet. The total intubation time, percentage of glottic opening scores, first attempt success rates were assessed., Results: The mean difference in intubation times in anaesthesiologists and non-anaesthesiologist less with KingVision videolaryngoscope (21.1s; 95% CI 9.6-32.6s vs. 35.9s; 95% CI 24.4-47.4 s; P = 0.001). Percentage of glottic opening score was significantly better with KingVision by non-anaesthesiologists (60; IQR 42.5 to 75 vs. 70; IQR 50 to 100; P = 0.019). KingVision provided superior first attempt success rate in non-anaesthesiologists (84% vs. 61.9%; P = 0.02) and anaesthesiologists (96% vs. 76%; P = 0.12)., Conclusion: KingVision channelled videolaryngoscope provided faster intubation times, glottic views and first attempt success rates in a simulated COVID-19 scenario in manikins and might be preferred over videolaryngoscopes with non-channelled blade. The findings need to be further verified in humans., Trial Registration: ctri.nic.in identifier: REF/2020/05/033338., Competing Interests: None., (© 2021 Elsevier Ltd. All rights reserved.)

With the advent of direct-acting antiviral agents, there has been a rapid rise in hepatitis C virus-infected (HCV+) heart transplantation. We aimed to understand local and regional differences in utilization and allocation of HCV+ hearts. Using United Network for Organ Sharing (UNOS) de-identified data from January 1, 2016 to September 30, 2019 we compared trends in the utilization rates (hearts transplanted/donors recovered) of HCV-uninfected (HCV-) to those of HCV+ nonviremic (HCV-NV) and viremic (HCV-V) hearts nationally and by UNOS region. We also evaluated allocation rates (hearts successfully allocated/donors recovered) by organ procurement organization (OPO). We found that (1) in 2019, national utilization rates for HCV-NV and HCV-V hearts were the same as HCV- hearts (27.6% for HCV-NV, 30.9 for HCV-V, and 31.7% for HCV-, P = .277); (2) utilization rates of HCV-NV hearts were low in regions 3 and 4 and of HCV-V hearts in regions 3, 4, and 8 even in the contemporary period since 2018; and (3) there was marked variability in allocation of HCV+ hearts at the OPO level even within the same UNOS region. We conclude that despite national strides in the utilization of HCV+ hearts for transplantation, more aggressive allocation of HCV+ hearts at the OPO level may still significantly affect the organ shortage., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

β-glucosidase hydrolyzes the β-1,4 linkage of cellobiose, a product generated from the action of endoglucanase and cellobiohydrolase on cellulose, and generates glucose. Accumulated glucose during saccharification leads to product inhibition of β-glucosidase, which in turn cause an accumulation of cellobiose and inhibition of other cellulolytic enzymes. Thus, glucose tolerant and active β-glucosidase is required for the efficient saccharification of biomass. O08324 is a glucose tolerant β-glucosidase isolated from archaeon Thermococcus sp. which shows no loss in enzyme specific activity in the presence of up to 4 M glucose and is active at 78 °C. Since O08324 has such high glucose tolerance, knowing the rationale for glucose tolerance will be helpful in engineering glucose tolerant β-glucosidase. In the present study, we designed mutations at eleven sites across the gatekeeper, aglycone, and glycone region. Based on the kinetic studies of O08324 mutants, the gatekeeper residues at positions 160, 166, 167, 168, and the aglycone binding residue 156 were identified to play a role in glucose inhibition. However, only residues at the tunnel entrance, and not all gatekeeper residues contribute to glucose tolerance. This study sheds some light on the unusual glucose tolerance of O08321 archaeal GH1 β-glucosidase., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Today, clinicians and researchers believe that mood disorders in children and adolescents remain one of the most under diagnosed mental health problems. Mood disorders in adolescents also put them at risk for other conditions that may persist long after the initial episodes of depression are resolved. In our study we have assessed the mood state spectrum of a person over the time and validated the same by correlating with salivary cortisol, psychologist assessment results., Methods and Materials: Images from the training dataset are classified according to one among the nine emotions. The Images that are classified accordingly are taken as training set and a suitable convolutional neural network is trained/retrained for this data. The mean values predicted moods are considered as input for another model that predicts higher the stress level., Results: With the inception v3 trained for 1,00,000 times with the data set that's close to 12,000 images classified accordingly to the nine emotion classes as specified by psychologist the model was able to obtain 78.4% of testing accuracy while with the near perfect training accuracy., Conclusion: The mood analysis was conclusively helpful in the estimation of the negative emotion parameter as close to the values that are obtained by with Depression, Anxiety and stress scale (DASS21) the mood analysis. The salivary cortisol as unbiased variable correlating with DASS 21 score could have a potential uses in early detection of mood disorder and correction. This platform will be helping the subject as a early mood screening tool., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the present study, we have designed and synthesized indole derivatives by coalescing the indole nucleus with chromene carbonitrile and dihydropyridine nucleus. Two compounds 5c and 6d were selected from series I and II after sequential combinatorial library generation, docking, absorption, distribution, metabolism and excretion (ADME) filtering, anti-proliferative activity, cytotoxicity, and ER-α competitor assay kit by utilizing estrogen receptor-α (ER-α) dominant T47D BC cells line and PBMCs (Peripheral Blood Mononuclear Cells). Cell imaging experiment suggested that both the compounds successfully cross cellular biomembrane and accumulate in nuclear, cytoplasmic and plasma membrane region. Semiquantitative RT-PCR and Western blotting experiments further supported that both compounds reduced the expression of mRNA and receptor protein of ER-α, thereby preventing downstream transactivation and signaling pathway in T47D cells line. Current findings imply that 5c and 6d represent novel ER-α antagonists and may be used in the development of chemotherapy for the management of BC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate the effect of different types of exercise on left ventricular (LV) geometry in a large group of female and male athletes., Background: Studies assessing cardiac adaptation in female and male athletes indicate that female athletes reveal smaller increases in LV wall thickness and cavity size compared with male athletes. However, data on sex-specific changes in LV geometry in athletes are scarce., Methods: A total of 1,083 healthy, elite, white athletes (41% female; mean age 21.8 ± 5.7 years) assessed with electrocardiogram and echocardiogram were considered. LV geometry was classified into 4 groups according to relative wall thickness (RWT) and left ventricular mass (LVM) as per European and American Society of Echocardiography guidelines: normal (normal LVM/normal RWT), concentric hypertrophy (increased LVM/increased RWT), eccentric hypertrophy (increased LVM/normal RWT), and concentric remodeling (normal LVM/increased RWT)., Results: Athletes were engaged in 40 different sporting disciplines with similar participation rates with respect to the type of exercise between females and males. Females exhibited lower LVM (83 ± 17 g/m 2 vs. 101 ± 21 g/m 2 ; p < 0.001) and RWT (0.35 ± 0.05 vs. 0.36 ± 0.05; p < 0.001) compared with male athletes. Females also demonstrated lower absolute LV dimensions (49 ± 4 mm vs. 54 ± 5 mm; p < 0.001) but following correction for body surface area, the indexed LV dimensions were greater in females (28.6 ± 2.7 mm/m 2 vs. 27.2 ± 2.7 mm/m 2 ; p < 0.001). Most athletes showed normal LV geometry. A greater proportion of females competing in dynamic sport exhibited eccentric hypertrophy compared with males (22% vs. 14%; p < 0.001). In this subgroup only 4% of females compared with 15% of males demonstrated concentric hypertrophy/remodeling (p < 0.001)., Conclusions: Highly trained athletes generally show normal LV geometry; however, female athletes participating in dynamic sport often exhibit eccentric hypertrophy. Although concentric remodeling or hypertrophy in male athletes engaged in dynamic sport is relatively common, it is rare in female athletes and may be a marker of disease in a symptomatic athlete., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Inoculation with live sporozoites under prophylactic antimalarial cover (CPS-immunization) represents an alternate approach to develop sterile, reproducible, and long-term protection against malaria. Here, we have employed arteether (ART), a semi synthetic derivative of artemisinin to explore its potential as a chemoprophylaxis candidate in CPS approach and systematically compared the protective potential of arteether with mefloquine, azithromycin and primaquine. Blood stage patency and quantitative RT-PCR of liver stage parasite load were monitored as primary key end-points for protection against malaria challenge infection. For this purpose, sequential exposures of Plasmodium yoelii sporozoites under prophylactic treatment with arteether (ART), mefloquine (MFQ), azithromycin (AZ) or primaquine (PQ) was conducted in experimental Swiss mice. Our results show that during the first three sequential exposures (1st, 2nd and 3rd challenge) no marked difference in the blood stage patency was observed between control and CPS-ART group. However, delayed patency was recorded following 4th sporozoite challenge and mice enjoyed sterile protection after 5th sporozoite challenge. A similar response was observed in CPS-MFQ group, whereas earlier protection was recorded in CPS-AZ group i.e., after 4th sprozoite challenge. However, mice under PQ cover did not show any protection/delay in patency even after five sequential sporozoite inoculations, possibly due to inhibition of liver stage development. Furthermore, protection acquired by CPS-immunization is stage-specific as the protected mice remained susceptible to challenge with blood stage parasites. In short, the present study demonstrates that sporozoite administration under ART, MFQ or AZ treatment confers strong protection against subsequent sporozoite infection and the acquired response is dependent on the presence of liver stage parasites., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Regular intensive participation in sport results in electrical and structural alterations within the heart that can manifest on the surface electrocardiogram (ECG). In addition to the actual sporting discipline and the volume and intensity of exercise being performed, other factors play a role in the development of certain ECG patterns including sex, age, and ethnicity. In some instances, large male endurance athletes and those of African or Afro-Caribbean origin (black athletes), might exhibit ECG patterns that overlap with those seen in patients with cardiomyopathy and channelopathies, which are recognized causes of exercise-related sudden cardiac death. The ability to distinguish accurately between benign physiological electrical alterations and pathological ECG changes is crucial to prevent the unnecessary termination of an athlete's career and to minimize the risk of sudden death. Several recommendations currently exist to aid the physician in the interpretation of the athlete's ECG. In this review we discuss which ECG patterns can safely be considered benign as opposed to those that should prompt the physician to consider cardiac pathology., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Regular intensive exercise is associated with a constellation of several structural and functional adaptations within the heart that permit the generation of a large and sustained increase in cardiac output and/or increase in blood pressure. The magnitude with which these markers of physiological remodeling manifest on the surface electrocardiogram is governed by several factors and some athletes show electrical and structural changes that overlap with those observed in cardiomyopathy and in ion channel diseases, which are recognized causes of sudden cardiac death in young athletes. This article provides a critical appraisal of the athlete's ECG., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Plasmodium parasite utilizes superoxide dismutase family proteins to limit the toxicity of reactive oxygen species, such as produced through hemoglobin degradation. These proteins play an important role in parasite survival during intra-erythrocytic phase. We have identified, and biochemically characterized a putative iron dependent superoxide dismutase from rodent malaria parasite Plasmodium vinckei (PvSOD1). The recombinant PvSOD1 protein was purified to homogeneity through a combination of affinity and gel filtration chromatography. Crosslinking, Native-PAGE and FPLC gel filtration analyses documented that PvSOD1 exists as a dimer in solution, a common feature shared by other Fe-SODs. PvSOD1 is cytosolic in localization and its expression is comparatively higher during trophozoite as compared to that of ring and schizont stages. Enzymatic activity of recombinant PvSOD1 was validated using conventional zymogram analyses and xanthine-xanthine oxidase system. Under optimal conditions, PvSOD1 was highly active and catalyzed the dismutation of superoxide radicals. Furthermore, PvSOD1 showed activity over a broad range of pH and temperature. Inhibition studies suggested that PvSOD1 was inactivated by hydrogen peroxide, and peroxynitrite, but not by cyanide and azide. Since, PvSOD1 plays a central role in oxidative defense mechanism, therefore, characterization of PvSOD1 will be exploited in the screening of new superoxide dismutase inhibitors for their antimalarial activity., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Helicases catalyze the opening of nucleic acid duplexes and are implicated in many nucleic acid metabolic cellular processes that require single stranded DNA or reorganization of RNA structure. Previously we have reported that Plasmodium falciparum genome contains a number of DEAD box helicases. In the present study we report the cloning, expression and characterization of one of the novel members of DEAD box family from P. falciparum. Our results indicate that it is a homologue of Has1p from yeast and it contains DNA and RNA unwinding, nucleic acid-dependent ATPase and RNA binding activities. This enzyme can utilize all the nucleosidetriphosphates (NTPs) and deoxy nucleosidetriphosphates (dNTPs) for its unwinding activity. Using a truncated derivative of this protein we further report that the N-terminal region of the protein is essentially required for its activity. These studies suggest that besides the conserved helicase domain the highly variable N-terminal region also contributes in the activity of the protein.

Maternal night blindness is common during pregnancy in many developing countries. Previous studies have demonstrated important consequences of maternal night blindness during pregnancy on the health of the mother and newborn infant. We compared birthweight, 6-mo infant mortality, morbidity, and growth among infants of women who did and did not report a history of night blindness from a community-based, randomized trial of newborn vitamin A supplementation in south India. Birthweight was measured within 72 h of delivery. Infants were followed until 6 mo of age for mortality and morbidity was assessed at household visits every 2 wk. Anthropometry was assessed at 6 mo of age. A total of 12,829 live-born infants were included, 680 of whom were infants of mothers with night blindness during the index pregnancy. Maternal night blindness was associated with an increased risk of low birthweight in a dose-dependent fashion based on birthweight cut-offs: <2500 g, adjusted relative risk (RR) = 1.13 (95% CI = 1.01, 1.26); <2000 g, adjusted RR = 1.70 (95% CI = 1.27, 2.26); <1500 g, adjusted RR = 3.38 (95% CI = 1.18, 6.33); with an increased risk of diarrhea (adjusted RR = 1.16, 95% CI = 1.03, 1.30), dysentery (adjusted RR = 1.25, 95% CI = 1.03, 1.53), acute respiratory illness (adjusted RR = 1.32, 95% CI = 1.21, 1.44), and poor growth at 6 mo; underweight (adjusted RR = 1.14, 95% CI = 1.02, 1.26), stunting (adjusted RR = 1.19, 95% CI = 1.05, 1.34). Maternal night blindness was not associated with 6-mo infant mortality or wasting at 6 mo. This study demonstrates that there are important consequences to the infant of maternal vitamin A deficiency during pregnancy.

Vitamin A supplementation reduces mortality in young children in areas of endemic vitamin A deficiency. However, it has no impact on the incidence of common morbidities. This discrepancy has been explained by an impact on case fatality, although with the exception of hospitalized measles cases, there is little direct evidence to support this hypothesis. We assessed the impact of newborn dosing with vitamin A on the incidence and case fatality of common childhood morbidities in early infancy in a community-based, randomized trial in South India. Morbidity for each day in the previous 2 wk was assessed for the first 6 mo of life. A total of 11,619 live-born infants were enrolled and randomized to receive either 48,000 IU (50.4 micromol retinol) of oral vitamin A or placebo following delivery. There was no difference between treatment groups in the incidence of acute or chronic diarrhea, dysentery, or fever but a small increased incidence of acute respiratory illness (ARI). Case fatality for diarrhea and fever were significantly reduced in the vitamin A group compared with placebo (relative case fatality [95% CI] of 0.50 [0.27, 0.90] and 0.60 [0.40, 0.88], respectively). There was a trend in reduction of case fatality for various definitions of ARI, but the evidence for this effect was modest. Survival analysis among those with morbid episodes confirmed the case fatality analysis. This trial demonstrated that the reduction in overall mortality due to newborn vitamin A dosing was driven primarily by a reduction in case fatality among infants.

Objective: To determine the incidence of acute-onset postcataract endophthalmitis, identify risk factors, and determine clinical outcomes in a tertiary eye care center in South India., Design: Retrospective, interventional, observational case series., Participants: All patients who underwent cataract extraction from January 2002 to December 2003 at Aravind Eye Hospital, Madurai., Methods: The records of patients with acute endophthalmitis after cataract surgery were reviewed., Main Outcome Measures: Acute-onset postcataract endophthalmitis, incidence rates, risk factors, organisms cultured, and visual acuity outcomes after treatment., Results: During the study period, 36072 cataract surgeries were performed; these included 22294 cases of phacoemulsification and 9503 cases of extracapsular cataract extraction. A total of 19 eyes developed acute endophthalmitis after cataract surgery (average 2-year incidence, 0.05%). Ten cases were culture positive (average 2-year incidence, 0.03%). In multivariate analysis, increased risk of endophthalmitis was associated with intraoperative complications, such as posterior capsular rent and vitreous loss (relative risk [RR], 6.57; 95% confidence interval [CI], 1.5-28.5; P = 0.05) for all endophthalmitis cases, age >60 years for culture-positive endophthalmitis cases (RR, 6; 95% CI, 0.7-47.8; P = 0.04), and an extracapsular cataract extraction technique for culture-positive endophthalmitis cases (RR, 4.9; 95% CI, 1.2-19.3; P = 0.001). After follow-up of 37 days, 5 (29.41%) of the 17 patients achieved a best-corrected visual acuity (BCVA) of 20/40, and the remaining 7 (32.3%) had a BCVA better than 20/200. Of the culture-positive cases, Nocardia species was the most common organism isolated, accounting for more than half of these cases (6/10 [60%])., Conclusions: This study found the incidence of acute postoperative endophthalmitis after cataract surgery to be 0.05%. Extracapsular cataract extraction technique and the occurrence of intraoperative complications are major risk factors for developing endophthalmitis. Visual outcome after endophthalmitis was generally poor. Nocardia is a lesser-known but virulent organism causing endophthalmitis, the management of which still poses a therapeutic dilemma.

The pluripotent human embryonal carcinoma (EC) cell line NTERA-2 provides a useful tool for investigating cell differentiation in a way that is pertinent to the development of the early human embryo. The major immediate early (MIE) gene of human cytomegalovirus (HCMV), which is not transcribed in undifferentiated NTERA-2 EC cells but is transcribed in their differentiated derivatives, offers a model with which to study the developmental regulation of gene activity during the differentiation of these cells. We have investigated the regulatory activity of the cAMP response elements (CRE) and the activation protein (AP1) site found within several repeated 19-base-pair (bp) elements from the HCMV MIE promoter, and the developmental regulation of nuclear DNA-binding factors that interact with these sites. The 19-bp CRE but not the AP1 site is responsive to cAMP in undifferentiated NTERA-2 EC and its activity is enhanced upon differentiation. Nuclear proteins of the CREB, Fos, and Jun families bind to these sites, but, surprisingly, their levels only show limited regulation during NTERA-2 differentiation. This contrasts with results obtained with murine EC cells. However, additional and apparently novel proteins with molecular weights between 80,000 and 90,000, and binding specificities for both CRE and AP1 sites, were detected in undifferentiated EC cells. The activity of these proteins decreased markedly after differentiation, indicating their involvement in negative regulation of the CRE/AP1-like site in undifferentiated EC cells. This suggests novel members able to interact via leucine zippers with other members of the Jun-Fos-CREB family of DNA binding proteins that are also involved in this regulation.

Infectious molecular clones of the human immunodeficiency virus (HIV) have been very important tools for the analysis of regulatory gene functions and the study of differential cell tropism. We have cloned and characterized a proviral sequence of HIVmn from mn strain infected H9 cells. This clone, called KP1, was found to be infectious for different cell lines and human peripheral blood lymphocytes (PBL). KP1 proviral DNA was detected in HUT-78 cells and human PBL by polymerase chain reaction (PCR) analysis after infection of these cells with cell-free supernatants from KP1 transfected human rhabdomyosarcoma (RD) cells. To the best of our knowledge, this is the first report of an infectious molecular clone of HIVmn which is a representative of one of the most prevalent strains of HIV-1 in North America and Europe. Biologically active clones of a broadly antigenic strain such as HIVmn will be extremely useful in therapeutic approaches for AIDS.

Thirty patients with acute rheumatic fever, and 20 with inactive rheumatic heart disease were studied in order to determine parameters which differentiate the two groups. Subcutaneous nodules developed following the subcutaneous injection of autologous blood in 16 of 26 patients with rheumatic fever but in none of the 20 with inactive rheumatic heart disease (P = 0.00001). Myocardial reactive antibodies were found in 14 of 30 patients with rheumatic fever, and in 4 of 20 with inactive rheumatic heart disease (P = 0.0505). Significantly higher values of IgG (P less than 0.001), IgA (P less than 0.01), C3 (P less than 0.001) and C4 (P less than 0.001) were observed in rheumatic fever patients. There was no significant difference in IgM levels. A combination of three variables (artificial subcutaneous nodules, IgA, and C3) had a sensitivity of 87% and a specificity of 100% for rheumatic fever. A combination of two variables (artificial subcutaneous nodules and IgA) had a sensitivity of 84% and a specificity of 100% for rheumatic fever.

In a prospective controlled study the anti-infective properties of breast-milk were evaluated in 70 high-risk low-birth-weight infants. 32 babies (group I) were given fresh expressed breast-milk during the day and milk formula at night. 38 infants (group II) received only milk formula and served as controls. The two groups were matched for other factors that could influence the occurrence of infection. The incidence of infections was significantly less (p < 0.01) in babies who received breast-milk.

We used v-rasKi, v-bas, Ras-l, v-mos and v-abl DNA fragments as probes to detect homologous sequences in genomic DNA from a variety of fungi. Cellular homologs were identified in most of them and the number of related fragments detected varied with the probe used. In addition, we found that some onc gene homologs were linked to actin-related sequences.

Supplementary formula feeds inhibited the protective effect of expressed raw and pasteurised human milk in 226 high-risk neonates in a randomised controlled trial. The infection rate in the group given pasteurised human milk and formula (33%) was significantly higher than the rates in the groups given raw human milk (10.5%), pasteurised human milk (14.3%), and raw human milk and formula (16%). This accords with the impressions that some of the association of infection with artificial feeding is partly attributable to the lack of the protective effect of human milk. Heating expressed human milk to 62.5 degrees C for 30 min significantly reduces its protective effect.

Blood specimens from patients with rheumatic heart disease in both India and New Mexico were typed for the presence of B cell alloantigen 883 by use of a mouse monoclonal antibody with identical specificity to the original 883 human alloantiserum. Strong relative segregation was recorded for 883 positive B cell typing in patients with rheumatic heart disease in both geographic locations as compared with that in normal unaffected controls. In patients with acute rheumatic fever, studies of actual B-lymphocyte membrane binding by anti-883 monoclonal antibody and sonicated group A streptococcal membrane antigens showed separate but contiguous localization on isolated cell surfaces. Although physically distinct, 883 B cell alloantigen and sonicated group A streptococcal membrane antigens moved together in cell capping studies after incubation at 37 degrees C. These findings reaffirm the apparent close association between 883 B cell alloantigen and rheumatic heart disease. They also demonstrate that the B cell alloantigen 883 itself is physically distinct from but very close to sites on antigen-reactive B cells actually binding to group A streptococcal membrane antigens.