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Background:  The ability of Staphylococcus aureus to form biofilmsâ€"architectural complexes that cause chronic and recalcitrant infectionsâ€"along with its notorious variant, methicillin-resistant Staphylococcus aureus (MRSA), leads to multidrug-resistant (MDR) infections that are challenging to treat with antibiotics. This cross-sectional study investigated the prevalence of S. aureus infections in Kanti Children’s Hospital and characterized the antibiograms of MDR, MRSA, and biofilm-forming strains, along with their coexistence., Methods:  S. aureus strains were isolated and identified from clinical samples and tested for antibiograms following standard microbiology guidelines. MDR strains were non-susceptible to at least one agent in three antimicrobial categories, whereas MRSA strains were cefoxitin-resistant. The microtiter plate method was used to detect biofilms. Statistical analyses were performed using SPSS version 17.0., Results:  S. aureus was detected in 9.0% (11.4-6.6%, 95% Confidence Interval) of 543 samples, primarily from pus (79.6%, 39/49). Children aged 1 to <3 years most commonly contracted infections (30.6%, 15/49), and males (67.4%, 33/49) had twice as many infections as females (32.7%, 16/49). As high as 84.7% (83/98) of strains were penicillin-resistant, while 18.4% (27/147) were aminoglycoside-resistant. MDR accounted for 79.6% (39/49) of all S. aureus infections, while MRSA and biofilm-formers accounted for 67.6% (33/49) and 24.5% (12/49), respectively. Fluoroquinolone resistance in non-MDR-MRSA-biofilm-formers, MDR-MRSA, MDR-biofilm-formers, and MRSA-biofilm-formers was 31.3%, 46.8%, 58.3%, and 60.0%, respectively, while aminoglycoside resistance was 0%, 32.3%, 50.0%, and 45.0%, and penicillin resistance was 87.5%, 85.5%, 100.0%, and 100.0%., Conclusions:  MDR-isolates and MRSA caused nearly four-fifths of S. aureus infections. Compared to MDR and MRSA strains, biofilm-formers triggered higher levels of antimicrobial resistance.

Background: A bibliometric analysis was performed to map the current status and development trends in medical research in Nepal. It aims to visualize research hotspots within this field and provide effective guidance for future research directions., Methods: A systematic search of the Scopus database was performed to identify high-cited papers (HCPs) on medical research in Nepal between January 1, 1994, and December 31, 2023. Bibliometrics techniques were applied to analyze the publication dates, countries, institutions, journals, authors, and research hotspots. Statistical analysis and visualization were carried output by MS-Excel and VOSviewer software., Results: A total of 326 HCPs were identified that have received 100 to 10719 citations and registered 223.05 Citations Per Paper (CPP). The 47.54% and 95.40% share of the 326 HCPs have received external funding support and are involved in international collaboration, respectively. The 15892 (417 from Nepal) authors, affiliated to 12830 (177 from Nepal) organizations and published in 138 journals participated in 326 HCPs from Nepal. USA (60.45% share) and India. (51.45% share) were the most collaborative countries, while Spain (1609.15 CPP) and Mexico (1597.08 CPP) made the largest citation impact in collaboration with Nepal. C.L. Ranabhat (n=27) and B. Sathian (n=26) were the most productive authors, while D. Acharya (3652.29 and 16.5), and S. Bhattarai (2880.11 and 13.01) registered the highest citation impact (CPP and RCI). Tribhuvan University, Kathmandu (n=72) and Nepal Health Research Council, Kathmandu (n=34) were the most productive organizations, while Kathmandu University (3652.29 and 16.5) and Nepal Academy of Science and Technology, Lalitpur (2941.67 and 13.29) registered the highest citation impact (CPP and RCI). The Lancet (n=75) and British Medical Journal (n=11) were the most productive journals, while The Lancet Neurology (1749.5 CPP), and The Lancet (1371.13 CPP) registered the highest average citations impact. B. Basnyat has the most citation as first author in health and medical research., Conclusions: The present study offers an overview of research characteristics and trends of medical research output in Nepal. It identifies main contributors, core journals, and significant subject topics. The study hopes to assist researchers and practitioners in comprehending the development and trends of medical research in Nepal and discovering potential directions for future research.

Hospital-acquired infections, including surgical site infections (SSIs), pose a concerning challenge because of the growing resistance to multiple drugs, largely influenced by extensive prophylactic antimicrobial therapy. Although SSIs are well documented in advanced hospitals in developed nations, their prevalence and bacterial profiles are inadequately reported in low- and middle-income nations such as Nepal. This retrospective cohort study explored the prevalence of orthopaedic SSIs in relation to bacterial etiology and antimicrobial resistance. We examined the surgical and bacteriological records of patients suffering SSIs (clean or clean-contaminated wounds) within a month of their surgical procedures between January 2020 and June 2022 at the National Trauma Center, Kathmandu, Nepal. The prevalence of orthopaedic SSIs among hospital-visiting patients was 31.2% (448/1,438; 95% CI: 28.8-33.5). There were 341 (76.1%) males and 361 (80.6%) adults with SSIs. Knee/joint infections (n = 141, 31.5%) were predominant. An SSI typically occurs 7 days after surgery. Enterobacterales were dominated by Escherichia coli (n = 54, 40.9%), whereas nonfermenters gram-positive cocci (GPC) were dominated by Pseudomonas aeruginosa (n = 69, 81.2%) and Staphylococcus aureus (n = 216, 93.5%), respectively. Enterobacterales, nonfermenters, and GPC exhibited penicillin resistance at 74.5%, 29.8%, and 65.1%, respectively, whereas cephalosporin resistance was exhibited at 48.3%, 57.1%, and 49.6%; fluoroquinolone resistance at 25.9%, 40.5%, and 25.7%; and aminoglycoside resistance at 21.5%, 43.2%, and 17.3%. One-third of orthopaedic surgeries resulted in SSIs, mainly caused by S. aureus. Fluoroquinolones and aminoglycosides were moderately effective in treating bacterial SSIs, whereas penicillins and cephalosporins were the least effective. Nonfermenters exhibited higher antimicrobial resistance compared with Enterobacterales and GPC.

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Introduction: In orthopaedic practice, injuries to the anterior cruciate ligaments occur almost on an epidemic scale, yet it continues to be of interest in orthopaedic surgery whether semitendinosus or gracilis hamstring autografts can be used for better anterior cruciate ligament reconstruction. This study aimed to determine the prevalence of anterior cruciate ligament reconstruction using semitendinosus tendon autografts among paramilitary patients undergoing arthroscopic surgery in a tertiary care centre., Methods: This descriptive cross-sectional study was conducted among paramilitary individuals who had knee injuries and were admitted between 6 february 2020 and 26 January 2022 for arthroscopic surgery after obtaining ethical approval from the Institutional Review Committee. Demographic details and the mode of injury were obtained from the patients. The treating orthopaedic surgeons evaluated the pre- and post-analysis Lysholm Knee Score and Lysholm Knee Scale based on the patient's response. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval., Results: Among 166 patients, anterior cruciate ligament reconstruction using a semitendinosus tendon autograft was done in 58 (34.94%) (27.69-42.19, 95% Confidence Interval). Most of the patients in the pre-analysis had mild/periodic limp issues 52 (89.66%), followed by instability during athletics or other severe exertion 43 (74.14%)., Conclusions: The prevalence of anterior cruciate ligament injuries in our study is higher than other studies done in similar settings., Keywords: anterior cruciate ligament; grafts; semitendinosus tendon.

Introduction: Orthopedic fractures caused by chronic metabolic bone disease, overuse, or road traffic accidents are among the most significant burdens on society. Furthermore, a growing number of people undergoing arthroplasty and an increase in life expectancy seem to contribute to an increase in orthopaedic fractures. However, research on orthopaedic fracture prevalence or types has been scarce in low- and middle-income countries, including Nepal. The objective of this study was to find out the prevalence of orthopaedic fractures among patients attending a tertiary care centre., Methods: A descriptive cross-sectional study among patients attending a tertiary care centre was conducted between 19 May and 18 November 2023 during which date from 1 January to 30 December 2021 were collected from the hospital records. Ethical approval was obtained from the Institutional Review Committee. A convenience sampling method was used. Point estimate was calculated at a 95% Confidence Interval., Results: Among 7609 people, 2518 (33.09%) (12.97-10.55, 95% Confidence Interval) had orthopaedic fractures. A total of 1925 (76.45%) were males. There were 339 (95.49%) fractures associated with two-wheelers and 307 (86.48%) with four-wheelers. There were 1387 (55.08%) soft tissue injuries, 198 (7.86%) skull injuries, and 116 (4.61%) facial injuries. Additionally, there were 73 (2.90%) fractures of the femur, 71 (2.82%) fractures of the phalanx, and 70 (2.78%) fractures of the clavicle., Conclusions: The prevalence of orthopaedic fractures was found to be higher than in other studies done in similar settings., Keywords: bone fracture; orthopedics; prevalence; tertiary care centre.

Introduction: Driving under the influence is one of the most significant risk factors for road traffic accidents, leading to severe and multiple orthopaedic injuries. The aim of this study was to find out the prevalence of driving under the influence of alcohol among road traffic accident patients presenting to a tertiary care centre., Methods: A descriptive cross-sectional study was conducted on patients involved in road traffic accidents presenting to a tertiary care centre. Data from 10 January 2020 to 9 December 2021 were collected between 22 July 2023 to 22 August 2023 from the hospital records after receiving ethical approval from the Institutional Review Committee. Patients who had road traffic accidents and were diagnosed with fractures were included in the study. Patients with incomplete hospital records were excluded from the study. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval., Results: Among 2,519 patients, 307 (12.19%) (10.91-13.47, 95% Confidence Interval) were driving under the influence of alcohol when involved in a road traffic accident. Out of 307 patients, 305 (99.35%) accidents involved two-wheelers. A total of 118 (38.44%) patients suffered soft tissue injuries, while 47 (15.31%) sustained head injuries, and 28 (9.12%) sustained facial injuries., Conclusions: The prevalence of driving under the influence of alcohol among road traffic accident patients presenting to a tertiary care centre was similar to other studies done in similar settings., Keywords: accidents; alcohol consumption; bone; Nepal; trauma.

Introduction: Vitamin D deficiency is a global health issue affecting billions of people. Its deficiency results in abnormal homeostasis of calcium and phosphorous levels in an individual and results in reduced bone mineral density, which further makes them more prone to develop osteogenic disorders, such as fractures. The aim of this study is to find out the prevalence of vitamin D deficiency among patients visiting the outpatient departments in a tertiary care centre., Methods: This was a descriptive cross-sectional study done among 582 patients visiting outpatient departments in a tertiary care centre between January 1, 2019 and July 31, 2020. The study was approved by the Institutional Review Committee (Reference number: 076/077/17) of a tertiary care centre. A convenience sampling method was used. Patients' demographic detail and serum vitamin D level were determined. Data were collected retrospectively from hospital records and analysis was performed using the Statistical Package for the Social Sciences software version 17.0. Point estimate at 95% Confidence Interval was calculated along with frequency, the proportion for binary data, and mean with standard deviation for continuous data., Results: Among 582 patients enrolled in this study, 328 (56.35%) (52.32-60.38 at 95% Confidence Interval) patients were vitamin D deficient. Vitamin D deficiency was found in 238 (72.56%) females and 257 (78.35%) aged 16 to 59 years. Finally, there were 102 (31.09%) cases of vitamin D deficiency over the winter season., Conclusions: The prevalence of serum vitamin D deficiency in the current study was lower when compared to similar studies done in similar settings and similar to the prevalence from international literature., Keywords: deficient; prevalence; vitamin D.

Introduction: Osteonecrosis of femoral head is a disease affecting young individuals and often occurs in bilateral hips. The purpose of this study is to find out the prevalence of single stage simultaneous core decompression for Ficat stage I and II bilateral femoral head osteonecrosis among total hip surgeries done in a tertiary care center., Methods: A descriptive cross-sectional study was conducted at a tertiary care trauma centre from April 2017 and March 2020. Ethical approval was obtained from the Institutional Review Committee prior to data collection (Reference no: 673/2077/78). Convenience sampling was done. Patients undergoing hip surgeries were included in the study. Patients with missing data were excluded. Patients operated upto Ficat Stage IIb femoral head osteonecrosis were followed up. Data was analysed using the Statistical Package for Social Sciences version 22.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data., Results: Out of 916 patients who underwent hip surgeries, 12 (1.31%) (0.57-2.04 at 95% Confidence Interval) underwent single stage simultaneous core decompression. Idiopathic cause in 6 (50%) and prolonged corticosteroid usage in 4 (33.33%) were the leading causes. Twelve (50%) of the treated hips were in Ficat stage IIa. At the end of one year, of the 11 patients who followed up, 12 (54.5%) hips had a good Harris hip outcome., Conclusions: Our study showed that a small proportion of hip surgeries were single stage simultaneous bilateral core decompression for osteonecrosis of femoral head in our setting. Our findings were similar to studies done internationally with a very low complication rate.

Introduction: Communication is an important aspect of the medical profession. Doctor-patient communication plays a significant role in health care delivery. This study aims to find outpatient department patient satisfaction in doctor-patient communication in a tertiary care hospital in Kathmandu, Nepal., Methods: A descriptive cross-sectional study was conducted in the outpatient department of a tertiary care hospital in Kathmandu, Nepal in the month of August 2019. Validated questionnaire of Patient Satisfaction Questionnaire, consisting of 80 items, originally developed by Willis H. Ware and his colleagues were used and distributed to the patient in the outpatient department of the hospital. Their satisfaction level for doctor-patient communication was assessed on a five-point scale. The questionnaire was distributed randomly to the patient attending the hospital outpatient department during one month period., Results: Out of the total participants, 420 (96%) at 95% CI (95.07±96.93) respondents reported that they were satisfied regarding communication with their doctors. Among the patients, 109 (24.0%) visited the department of medicine followed by obstetrics and gynaecology 85 (19.4%)., Conclusions: The majority of participants were found to be satisfied with the doctor-patient communication. While this study has shown that the communication in the doctor-patient relationship was seen to be satisfactory, this might not show the generalized picture of the country. We should also think of ways to further improve the communication in our hospitals.

Introduction: Orthopedic conditions includes a range of condition varying from traumatic injuries, congenital anomalies, chronic back pain, arthritis, rheumatologic conditions, and other. Length of hospital stay is determined by a number of factors such as symptom severity, patient co morbidity and hospital availability. Our study aims to study the length of hospital stay of the patients admitted in a provincial hospital., Methods: A descriptive cross-sectional study was conducted in Seti Provincial Hospital in the month of January among 800 cases. The record of each orthopedic cases admitted in the hospital was retrospectively collected from the medical record section after receiving ethical approval from Institutional Review Committee of Seti Provincial Hospital. Whole sampling technique was used. Data were analyzed by Statistical Package for the Social Sciences version 20. The descriptive statistical analysis was done., Results: The average length of hospital stay was 2.87 days with the maximum length of the stay of 10 days and the minimum stay of zero days (discharged on the same day). Forearm bone fracture was the main reason for admission in the hospital 325 (40.62%)., Conclusions: Length of the hospital stay was found to shorter than the previous study done in similar settings.

Context: CVOID-19 induced significant economic and social disruptions in India. Rural households, including smallholders, were affected by loss in migrant income, livelihood and farm and non-farm incomes. During this lockdown, the Indian government enacted several emergency legislations to provide direct and indirect relief to workers and households. India's COVID-19 social assistance package, namely, PM-GKY, announced in March 2020, was designed to provide immediate relief to the vulnerable population. The PM-GKY provided cash direct benefit transfers (DBT) and in-kind supports (IKS) through existing schemes., Objectives: This study examines the impact of India's government assistance package (known as Pradhan Mantri Garib Kalyan Yojana or PM-GKY), announced immediately after the COVID-19 lockdown, on the procurement of agricultural inputs for the upcoming farming season., Methods: The study uses a quasi-experimental method and survey data from 1,789 smallholder households in three northern Indian states (Rajasthan, Madhya Pradesh, and Uttar Pradesh)., Results: The result suggests that the fungibility of funds received under the government transfer package was significant in alleviating credit constraints and increasing agricultural investments in agricultural inputs. The farmers who received benefits from the PM-GKY scheme spent significantly more on the procurement of seeds, fertilizers, and pesticides., Conclusions: The disbursement of cash transfers in the three states showed that emergency relief packages had reached the vulnerable sections of Indian society. Overall, 89-94% of households benefited from direct cash transfers. Perhaps lower transaction costs, minimal leakages, and immediate delivery make a strong case for direct cash transfers. The above advantages facilitate the provision of relief to a large proportion of vulnerable sections of Indian society in a short period., Competing Interests: We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (© 2021 The Author(s).)

Although the COVID-19 pandemic resulted in about a 24% decline in India's GDP during the April-June 2020 quarter, the nation's agricultural sector, somewhat surprisingly, seems to have done remarkably well. This paper examines whether the public transfer program Pradhan Mantri Garib Kalyan Yojana (PMGKY), announced immediately after the lockdown, benefited farmers in dealing with the COVID shock. Overall, 95% of the smallholders received support from at least one of PMGKY's four components. Direct cash transfers had significantly more impact than in-kind transfer schemes. The result shows that farmers receiving cash transfers under PM-KISAN, one component of PMGKY, were more likely to invest in buying seeds. In contrast, farmers receiving cash transfers under PM-UY, another piece of PMGKY, were more likely to invest in fertilizer and pesticides. Finally, smallholders who received benefits from all four components of PMGKY were more likely to invest in purchasing seeds, fertilizer, and pesticides. Findings suggest the fungibility of public cash transfers from the recent PMGKY scheme is significant in alleviating credit constraints and increasing future investments in modern inputs., (© 2021 Agricultural and Applied Economics Association.)

Introduction: Supracondylar fractures of humerus are the most common elbow fractures in children consisting of about 15% of all pediatric fractures and more than half of all elbow fractures. A high incidence of nerve injures, and vascular injuries make this fracture a serious injury. Our study aims to study on the clinical and demographic pattern of pediatric supracondylar fracture cases presenting in the hospital retrospectively., Methods: We conducted a descriptive cross-sectional study in Seti Provincial Hospital in the month of December. The data from the medical record section was retrospectively collected. A whole sampling technique was used. The descriptive statistical analysis was done., Results: Seven hundred cases were studied, among which the most common age group was found to be 5-10 410 (58.57%). Most of the cases presented in the emergency department 513 (73.28%), and the most common time of presentation was from 3 AM to 6 AM 170 (24.28%)., Conclusions: Supracondylar fracture cases presented as a common injury among pediatric population. It was presented as an emergency more than general cases.

Introduction: The growing prevalence of diabetes mellitus (DM) is a critical threat for global health, including in Nepal, especially in Kathmandu District, where diabetic patients are increasing in hospitals catastrophically. This study tends to assess the prevalence rate of type 2 diabetes among admitted patients visiting a hospital in Kathmandu., Methods: An electronic chart review was done to assess the prevalence of type 2 diabetes in Nepal Police hospital, Kathmandu, Nepal. Ethical approval was taken from the Nepal Health Research Council. Considering eligibility criteria, 8631 cases from 4 May 2018 to 31 August 2020 were observed. The calculated sample size was 500. However, all diabetic cases, i.e., 576, were processed and analyzed using Python and later visualized using MS Excel., Results: The overall prevalence rate of type 2 diabetes was 6.67%. The prevalence rate was seen higher among males (7.5%). Similarly, a high prevalence rate was seen among 64-73 years, i.e., 15.10%., Conclusions: The findings showed a high prevalence rate of type 2 diabetes. Older age groups are at high risk. Urgent public health interventions including lifestyle modification measures are required to reduce the extra burden of type 2 diabetes.

Calcitonin gene-related peptide (CGRP) has been implicated in acute migraine pathogenesis. In an effort to identify novel CGRP receptor antagonists for the treatment of migraine, we have discovered thiazolidinone 49, a potent (Ki=30 pM, IC50=1 nM), orally bioavailable, CNS-penetrant CGRP antagonist with good pharmacokinetic properties., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Activation-induced cytidine deaminase (AID) is an enzyme essential for the generation of Ab diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. In this study, we report that small interfering RNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by CTLs. AID silencing did not decrease the mutation frequencies of tumor Ag gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells, and upregulation of CD200 was shown to be in favor of tumor eradication by CTLs. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID-positive tumors.

An 11-year-old Nepalese male child presented with history of recurrent abrupt episodes of syncope for the last one year. There was no family history of sudden death at a young age in his family. ECG at base-line revealed an isorhythmic AV dissociation with a heart rate of 50 bpm and a normal QTc. Echocardiography of the heart was normal. His 24 hour holter study revealed frequent VPC's and episodes of polymorphic ventricular tachycardia. Exercise stress test provoked a polymorphic VT. On EP study, sinus node recovery time (SNRT) was prolonged and ventricular tachycardia (VT) was induced on Isoproterenol infusion. He was treated with a permanent pacemaker and beta-blocker.

Despite negative selection in the thymus, significant numbers of autoreactive T cells still escape to the periphery and cause autoimmune diseases when immune regulation goes awry. It is largely unknown how these T cells escape clonal deletion. In this study, we report that CD24 deficiency caused deletion of autoreactive T cells that normally escape negative selection. Restoration of CD24 expression on T cells alone did not prevent autoreactive T cells from deletion; bone marrow chimera experiments suggest that CD24 on radio-resistant stromal cells is necessary for preventing deletion of autoreactive T cells. CD24 deficiency abrogated the development of experimental autoimmune encephalomyelitis in transgenic mice with a TCR specific for a pathogenic autoantigen. The role of CD24 in negative selection provides a novel explanation for its control of genetic susceptibility to autoimmune diseases in mice and humans.

CD24 is a cell surface glycoprotein that is expressed on both immune cells and cells of the CNS. We have previously shown that CD24 is required for the induction of experimental autoimmune encephalomyelitis (EAE), an experimental model for the human disease multiple sclerosis (MS). The development of EAE requires CD24 expression on both T cells and non-T host cells in the CNS. To understand the role of CD24 on the resident cells in the CNS during EAE development, we created CD24 bone marrow chimeras and transgenic mice in which CD24 expression was under the control of a glial fibrillary acidic protein promotor (AstroCD24TG mice). We showed that mice lacking CD24 expression on the CNS resident cells developed a mild form of EAE; in contrast, mice with overexpression of CD24 in the CNS developed severe EAE. Compared with nontransgenic mice, the CNS of AstroCD24TG mice had higher expression of cytokine genes such as IL-17 and demyelination-associated marker P8; the CNS of AstroCD24TG mice accumulated higher numbers of Th17 and total CD4+ T cells, whereas CD4+ T cells underwent more proliferation during EAE development. Expression of CD24 in CD24-deficient astrocytes also enhanced their costimulatory activity to myelin oligodendrocyte glycoprotein-specific, TCR-transgenic 2D2 T cells. Thus, CD24 on the resident cells in the CNS enhances EAE development via costimulation of encephalitogenic T cells. Because CD24 is increased drastically on resident cells in the CNS during EAE, our data have important implications for CD24-targeted therapy of MS.

Cytokine-induced killer (CIK) cells are ex vivo, expanded T cells with proven anticancer activity in vitro and in vivo. However, their functional properties with the exception of their cancer cell-killing activity are largely unclear. Here, we show that CIK T cells recognize dendritic cells (DC), and although mature DC (mDC) induce CIK T cells to produce IFN-gamma, immature DC (iDC) are killed selectively by them. Moreover, CIK T cell activation by mDC and their destruction of iDC are independent of the TCR. The cytotoxicity of CIK T cells to iDC is perforin-dependent. Our data have revealed an important regulatory role of CIK cells.

Tumor evasion of T-cell immunity remains a significant obstacle to adoptive T-cell therapy. It is unknown whether the mode of immune evasion is dictated by the cancer cells or by the tumor antigens. Taking advantage of the fact that multiple lineages of tumor cells share the tumor antigen P1A, we adoptively transferred transgenic T cells specific for P1A (P1CTL) into mice with established P1A-expressing tumors, including mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Although P1CTL conferred partial protection, tumors recurred in almost all mice. Analysis of the status of the tumor antigen revealed that all J558 tumors underwent antigenic drift whereas all P815 tumors experienced antigenic loss. Interestingly, although Meth A cells are capable of both antigenic loss and antigenic drift, the majority of recurrent Meth A tumors retained P1A antigen. The ability of Meth A to induce apoptosis of P1CTL in vivo alleviated the need for antigenic drift and antigenic loss. Our data showed that, in spite of their shared tumor antigen, different lineages of cancer cells use different mechanisms to evade T-cell therapy.

[reaction: see text] The TiCl4-mediated reaction of an ester with benzoyl chloride results in high yields of the alpha-benzoylated ester. Diazo transfer of the benzoylated ester utilizing p-acetoamidobenzenesulfonyl azide affords the alpha-diazo ester in good yield. Using this simplified procedure, it is easy to prepare gram quantities of alpha-diazo esters.

In the development of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), autoreactive T cells must be activated and clonally expand in the lymphoid organs, and then migrate into the central nervous system (CNS) where they undergo further activation. It is unclear whether the autoreactive T cells further expand in the CNS and if so, what interactions are required for this process. We have demonstrated previously that expression by the host cells of the heat-stable antigen (CD24), which was recently identified as a genetic modifier for MS, is essential for their susceptibility to EAE. Here we show that CD24 is essential for local clonal expansion and persistence of T cells after their migration into the CNS, and that expression of CD24 on either hematopoietic cells or nonhematopoietic antigen-presenting cells in the recipient is sufficient to confer susceptibility to EAE.

The preparation and Rh-mediated cyclization of the alpha-diazoester 1 are outlined, and its utility in determining the elements that contribute to the reactivity of the intermediate Rh-carbenoid is presented. The rate of disappearance of diazo ester 1 catalyzed by several representative Rh(II) complexes was determined. The observed relative rate constants for the reaction of the Rh(II) complexes with 1 varied over a range of >10(7). The reactivity of the Rh-carbenoid intermediate was explored using the ratio of the sum of (3 + 4 + 5) to 2 (cyclization vs elimination), the ratio of 3 to the sum of (4 + 5) (chemoselectivity), and the ratio of 4 to 5 (diastereoselectivity). It is striking that these four measures of reactivity were found to be independent of each other.

The preparation of alkenyl cyclopropanes 1 with a variety of common organic functionalities is reported. These substrates were subjected to the Fe(CO)(5)-mediated carbonylation process under a CO atmosphere, leading to the formation of 2,5-disubstituted cyclohexenones 2, important intermediates for target-directed synthesis.