Trends of insecticide resistance monitoring in mainland Tanzania, 2004-2020.

BACKGROUND: Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020. METHODS: The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed. RESULTS: Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites. CONCLUSIONS: Anopheles gambiae Tanzania's major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.

Improvements in malaria surveillance through the electronic Integrated Disease Surveillance and Response (eIDSR) system in mainland Tanzania, 2013-2021.

BACKGROUND: Tanzania has made remarkable progress in reducing malaria burden and aims to transition from malaria control to sub-national elimination. In 2013, electronic weekly and monthly reporting platforms using the District Health Information System 2 (DHIS2) were introduced. Weekly reporting was implemented through the mobile phone-based Integrated Disease Surveillance and Response (eIDSR) platform and progressively scaled-up from 67 to 7471 (100%) public and private health facilities between 2013 and 2020. This study describes the roll-out and large-scale implementation of eIDSR and compares the consistency between weekly eIDSR and monthly DHIS2 malaria indicator data reporting, including an assessment of its usefulness for malaria outbreak detection and case-based surveillance (CBS) in low transmission areas. METHODS: The indicators included in the analysis were number of patients tested for malaria, number of confirmed malaria cases, and clinical cases (treated presumptively for malaria). The analysis described the time trends of reporting, testing, test positivity, and malaria cases between 2013 and 2021. For both weekly eIDSR and monthly DHIS2 data, comparisons of annual reporting completeness, malaria cases and annualized incidence were performed for 2020 and 2021; additionally, comparisons were stratified by malaria epidemiological strata (parasite prevalence: very low < 1%, low 1 ≤ 5%, moderate 5 ≤ 30%, and high > 30%). RESULTS: Weekly eIDSR reporting completeness steadily improved over time, with completeness being 90.2% in 2020 and 93.9% in 2021; conversely, monthly DHIS2 reporting completeness was 98.9% and 98.7% in 2020 and 2021, respectively. Weekly eIDSR reporting completeness and timeliness were highest in the very low epidemiological stratum. Annualized malaria incidence as reported by weekly eIDSR was 17.5% and 12.4% lower than reported by monthly DHIS2 in 2020 and 2021; for both 2020 and 2021, annualized incidence was similar across weekly and monthly data in the very low stratum. CONCLUSION: The concurrence of annualized weekly eIDSR and monthly DHIS2 reporting completeness, malaria cases and incidence in very low strata suggests that eIDSR could be useful tool for early outbreak detection, and the eIDSR platform could reliably be expanded by adding more indicators and modules for CBS in the very low epidemiological stratum.

Risk factors associated with malaria infection identified through reactive case detection in Zanzibar, 2012-2019.

BACKGROUND: Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar. METHODS: Surveillance data from Zanzibar's Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level. RESULTS: A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3-39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3-2.8) and living in Unguja (OR = 1.2; 95% CI 1.0-1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7-0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7-0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7-0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6-0.8). CONCLUSIONS: The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5-14 years and travellers are needed.

UX007 for the treatment of long chain-fatty acid oxidation disorders: Safety and efficacy in children and adults following 24weeks of treatment.

BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) lead to accumulation of high concentrations of potentially toxic fatty acid intermediates. Newborn screening and early intervention have reduced mortality, but most patients continue to experience frequent hospitalizations and significant morbidity despite treatment. The deficient energy state can cause serious liver, muscle, and heart disease, and may be associated with an increased risk of sudden death. Triheptanoin is a medium odd-chain fatty acid. Anaplerotic metabolites of triheptanoin have the potential to replace deficient tricarboxylic acid (TCA) cycle intermediates, resulting in net glucose production as a novel energy source for the treatment of LC-FAOD. STUDY DESIGN: A single-arm, open-label, multicenter Phase 2 safety and efficacy study evaluated patients with severe LC-FAOD evidenced by ongoing related musculoskeletal, cardiac, and/or hepatic events despite treatment. After a four-week run-in on current regimen, investigational triheptanoin (UX007) was titrated to a target dose of 25-35% of total daily caloric intake. Patients were evaluated on several age/condition-eligible endpoints, including submaximal exercise tests to assess muscle function/endurance (12-minute walk test; 12MWT) and exercise tolerance (cycle ergometry), and health related quality of life (HR-QoL). Results through 24weeks of treatment are presented; total study duration is 78weeks. RESULTS: Twenty-nine patients (0.8 to 58years) were enrolled; most qualified based on severe musculoskeletal disease. Twenty-five patients (86%) completed the 24-week treatment period. At Week 18, eligible patients (n=8) demonstrated a 28% increase (LS mean=+181.9 meters; p=0.087) from baseline (673.4meters) in 12MWT distance. At Week 24, eligible patients (n=7) showed a 60% increase in watts generated (LS mean=+409.3W; p=0.149) over baseline (744.6W) for the exercise tolerance test. Improvements in exercise tests were supported by significant improvements from baseline in the adult (n=5) self-reported SF-12v2 physical component summary score (LS mean=+8.9; p<0.001). No difference from baseline was seen in pediatric parent-reported (n=5) scores (SF-10) at Week 24. Eighteen patients (62%) had treatment-related adverse events, predominantly gastrointestinal (55%), mild-to-moderate in severity, similar to that seen with prior treatment with medium chain triglyceride (MCT) oil. One patient experienced a treatment-related serious adverse event of gastroenteritis. One patient discontinued from study due to diarrhea of moderate severity; the majority of patients (25/29; 86%) elected to continue treatment in the extension period. CONCLUSIONS: In patients with severe LC-FAOD, UX007 interim study results demonstrated improved exercise endurance and tolerance, and were associated with positive changes in self-reported HR-QoL.

Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials.

BACKGROUND: This analysis was carried out to evaluate the long-term survival of patients with metastatic melanoma who received ipilimumab, a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte antigen-4, in clinical trials. PATIENTS AND METHODS: Patients received ipilimumab in one of three completed phase II clinical trials (CA184-008, CA184-022, and CA184-007). Previously treated patients were enrolled in all studies, and treatment-naïve patients were also included in study CA184-007. Patients received ipilimumab at a dose of 10 mg/kg in studies CA184-008 and CA184-007, and at doses of 0.3, 3, or 10 mg/kg in study CA184-022. Ipilimumab was given every 3 weeks for four doses, and eligible patients could receive ipilimumab maintenance therapy every 12 weeks. In study CA184-022, patients could cross over to be retreated with ipilimumab at 10 mg/kg upon disease progression. Ongoing survival follow-up is conducted in a companion study, CA184-025. RESULTS: Four-year survival rates [95% confidence interval (95% CI)] for previously treated patients who received ipilimumab at 0.3, 3, or 10 mg/kg were 13.8% [6.1-22.5], 18.2% [9.5-27.6], and 19.7% [13.4-26.5] to 28.4% [13.9-44.2], respectively. In treatment-naïve patients who received ipilimumab at 10 mg/kg, 4-year survival rates were 37.7% [18.6-57.4] to 49.5% [23.8-75.4]. CONCLUSIONS: These results demonstrate durable survival in a significant proportion of patients with metastatic melanoma who received ipilimumab therapy.

Spatiotemporal dynamics of malaria in Zanzibar, 2015-2020.

BACKGROUND: Despite high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. OBJECTIVE: The aims of the study were to (1) assess the spatiotemporal dynamics of malaria in Zanzibar between 2015 and 2020 and (2) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting. METHODS: In this study, we analysed data routinely collected by Zanzibar's Malaria Case Notification (MCN) system. The system collects sociodemographic and epidemiological data from all malaria cases. Cases are passively detected at health facilities (ie, primary index cases) and through case follow-up and reactive case detection (ie, secondary cases). Analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons. RESULTS: From 1 January 2015 to 30 April 2020, the MCN system reported 22 686 index cases. Number of cases reported showed a declining trends from 2015 to 2016, followed by an increase from 2017 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed up index cases was approximately 70% for all years. Out of 387 shehias, 79 (20.4%) were identified as malaria hotspots in any given year; these hotspots reported 52% of all index cases during the study period. Of the 79 hotspot shehias, 12 were hotspots in more than 4 years, that is, considered temporally stable, reporting 14.5% of all index cases. CONCLUSIONS: Our findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006. Analyses identified hotspots, some of which were stable across multiple years. Malaria efforts should progress from a universal intervention coverage approach to an approach that is more tailored to a select number of hotspot shehias.

How Real-Time Case-Based Malaria Surveillance Helps Zanzibar Get a Step Closer to Malaria Elimination: Description of Operational Platform and Resources.

Testing and treating asymptomatic populations have the potential to reduce the population's parasite reservoir and reduce malaria transmission. Zanzibar's malaria case notification (MCN) platform collects detailed sociodemographic and epidemiological data from all confirmed malaria cases to inform programmatic decision-making. We describe the design and operationalization process of the platform and other malaria surveillance resources that are enabling Zanzibar's progress toward malaria elimination.The MCN platform consists of an interactive short message service (SMS) system for case notification, a software application for Android mobile devices, a visual question set and workflow manager, a back-end database server, and a web browser-based application for data analytics, configuration, and management. Malaria case data were collected from August 2012 to December 2021 and reported via SMS from all public and private health facilities to a central database and then to district malaria surveillance officers' mobile devices. Data included patient names, shehia (administrative area), and date of diagnosis, enabling officers to track patients, ideally within 24 hours of reporting. Patients' household members were tested for malaria using conventional rapid diagnostic tests (RDTs). Treatment using artemisinin-based combination therapy was provided for persons testing positive.Between 2012 and 2021, a total of 48,899 index malaria cases were confirmed at health facilities, 22,152 (45.3%) within 24 hours of reporting; 41,886 (85.7%) cases were fully investigated and followed up to the household level. A total of 111,811 additional household members were tested with RDTs, of whom 10,602 (9.5%) were malaria positive.The MCN platform reports malaria case data in near real time, enabling prompt follow-up of index cases and prompt testing and treatment of members in index case households. Along with routine testing and treatment and other preventive interventions, the MCN platform is foundational to the programmatic efforts in further reducing malaria and ultimately eliminating autochthonous malaria transmission in Zanzibar.

Feasibility of vesicoamniotic shunt insertion in an inanimate model: comparison of fetoscopic and ultrasound-guided techniques.

OBJECTIVES: To determine the feasibility of fetoscopic vesicoamniotic shunt insertion (F-VASI) in an inanimate model and to compare F-VASI to ultrasound (US)-guided VASI (US-VASI) with respect to accuracy of shunt placement and overall success rate. METHODS: An inanimate second-trimester fetus with a replaceable bladder balloon was suspended in a pressurized water tank and localized with US. Fetal position was randomized, the operator was blinded and a 5-Fr Harrison Shunt® decompressed the bladder in both groups. Thirty shunt insertions were performed per group. RESULTS: Procedure time was longer for F-VASI (15.0 vs. 2.8 min, p < 0.05), although it decreased with practice. F-VASI and US-VASI were similar for adequate depth of insertion (27/30 vs. 27/30, p = 1.0), placement within 1 cm of midline (27/30 vs. 25/30, p = 0.42), bladder puncture (28/30 vs. 28/30, p = 1.0), and overall success rate (27/30 vs. 23/30, p = 0.3). CONCLUSIONS: F-VASI is feasible in an inanimate model. Overall success rate was similar between the groups, although procedure time was longer for F-VASI. Further study is required to determine whether shunt migration is decreased with F-VASI.

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.

BACKGROUND: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). RESULTS: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. CONCLUSION: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.

Ultrastructural studies of radiation-induced chromosome damage.

The fine structure of radiation-induced chromosomal aberrations in Potorous tridactylis (rat kangaroo) cells was examined in situ by electron microscopy. The observations on the structure of terminal deletions (acentric fragments), anaphase bridges and "gaps," sidearm bridges, and specialized regions, such as the nucleolus organizer, are discussed in detail. Conclusions based on these observations are the following: (a) damage is physically expressed only at anaphase; (b) a gap region is composed of two subunits, each of which is about 800-1000 A in diameter and may correspond to a half-chromatid structure; (c) the ends of acentric fragments are structurally similar to normal chromosome ends, except where the break occurs in a specific region such as the secondary constriction; (d) at metaphase the fragment and the main portion of the chromosome move as a single unit to the equator, and the two units are disconnected only at the onset of anaphase; (e) sidearm bridges appear to be exchanges, involving a subchromatid unit. The interpretation of this evidence is consistent with the hypothesis that the chromosome is a multistranded structure.

Breakdown and assembly of polyribosomes in synchronized Chinese hamster cells.

Polyribosomes were absent in metaphase Chinese hamster cells and were reassembled after mitosis. This assembly correlated temporally with formation of nuclear membrane and decondensation of chromatin, accounted for a threefold increased rate of protein synthesis, and occurred independently of de novo RNA synthesis, that is, it utilized preexisting messenger RNA.

Radiosensitization of X chromosome of Chinese hamster cells related to incorporation of 5-bromodeoxyuridine.

Selective incorporation of 5-bromodeoxyuridine into the late replicating arm of the X chromosome of Chinese hamister cells cultured in vitro caused a selective radiosensization of the arm to ionizing radiation. Radiation damage was observed as chromosomal aberrations, and incorporation was studied by using tritiated 5-bromodeoxyuridine.

Cytotoxic antibody in normal human serums reactive with tumor cells from acute lymphocytic leukemia.

Serums showing complement-dependent cytotoxic reactions to acute lymphocytic leukemia cells were detected in three normal unimmunized subjects. These serums were reactive with tumor cells from 514 (514 tested) acute lymphocytic leukemia patients, and three (12 tested) patients with acute myelocytic leukemia; they did not react with tumor cells from patients with acute monocytic leukemia (two tested), with chronic lymphocytic leukemia (two tested) or with leukolymphosarcoma (two tested); nor did they react with normal lymphocytes from 52 different donors. These reactive serums appear to recognize antigens primarily associated with acute lymphocytic leukemia.

Evaluating Response Time in Zanzibar's Malaria Elimination Case-Based Surveillance-Response System.

As countries transition toward malaria elimination, malaria programs rely on surveillance-response systems, which are often supported by web- and mobile phone-based reporting tools. Such surveillance-response systems are interventions for elimination, making it important to determine if they are operating optimally. A metric to measure this by is timeliness. This study used a mixed-methods approach to investigate the response time of Zanzibar's malaria elimination surveillance-response system, Malaria Case Notification (MCN). MCN conducts both passive and reactive case detection, supported by a mobile phone-based reporting tool called Coconut Surveillance. Using data obtained from RTI International and the Zanzibar Malaria Elimination Program (ZAMEP), analysis of summary statistics was conducted to investigate the association of response time with geography, and time series techniques were used to investigate trends in response time and its association with the number of reported cases. Results indicated that response time varied by the district in Zanzibar (0.6-6.05 days) and that it was not associated with calendar time or the number of reported cases. Survey responses and focus groups with a cadre of health workers, district malaria surveillance officers, shed light on operational challenges faced during case investigation, such as incomplete health records and transportation issues, which stem from deficiencies in aspects of ZAMEP's program management. These findings illustrate that timely response for malaria elimination depends on effective program management, despite the automation of web-based or mobile phone-based tools. For surveillance-response systems to work optimally, malaria programs should ensure that optimal management practices are in place.

An unreported variation of the cervical vagus nerve: anatomical and histological observations.

Variations involving the cervical portion of the vagus nerve are seemingly very rare. We report an adult male found to harbour a right cervical vagus nerve that crossed anterior to the right common carotid artery to terminate in the lateral aspect of the thyroid gland. A very small continuation of this nerve was found to continue distally into the thorax. Histologically, this part of the vagus nerve did not contain ganglion or other cell bodies. There were no heterologous inclusions (thyroid, parathyroid, thymus, salivary gland or branchial cleft remnants) present. Although grossly there was a connection into the thyroid gland, this was not observed histologically. No signs of trauma were found to the ipsilateral neck region. We hypothesise that this variation is due to entanglement between the thyroid gland and cervical vagus nerve during development. This rare variation might be considered by the clinician who operates in the cervical region or interprets imaging of the neck. To our knowledge, a vagus nerve with the above described morphology has not been described.

Influence of renal insufficiency on levels of serum ribonuclease in patients with multiple myeloma.

Serum RNase levels were measured in 34 patients with multiple myeloma and compared with 51 normal controls and 28 non-myeloma patients on chronic hemodialysis. Nineteen of the myeloma patinets with creatinine clearance (CCr) greater than 50 ml/minute had mean serum RNase levels that were statistically indistinguishable from those of the normal controls. The 15 myeloma patinets with CCr less than 50 ml/minute had mean RNase levels much higher than normal controls or myeloma patients with normal renal function. Patients without myeloma but on hemodialysis for chronic renal failure of varied etiologies had markedly elevated serum RNase levels. A strong correlation between RNase levels and renal insufficiency, as measured by CCr, has thus been demonstrated. In addition, case histories of 5 representative myeloma patients were analyzed in greater detail; they illustrated the rise and fall of RNase levels as a function of the status of their renal insufficiency, regardless of the extent of the underlying myeloma. We concluded that the serum RNase level was an indicator of renal function, and was not a biomarker either for the presence or extent of the plasma cell tumor.

Chronic lymphocytic leukemia and acquired disorders affecting the immune system: a case-control study.

The relationship of a number of subacute or chronic infectious diseases, connective tissue or autoimmune disorders, allergic conditions, and surgical excision of lymphoid tissue with chronic lymphocytic leukemia (CLL) was examined in a case-control study involving 342 cases and 342 matched controls. In both analyses of all matched pairs and those pairs in which both subjects were respondents, no statistically significant association was found between a history of subacute viral infections or subacute and chronic bacterial infections and CLL. Connective tissue or autoimmune disorders also were found not to be associated with CLL. Examination of the association between several allergic conditions and CLL suggested a protective effect as did a "dose-response" analysis, although none of the individual disorders showed a statistically significant relationship; however, a test for linear trend was significant (P = .04). Similarly, examination of the relationship between surgical excision of lymphoid tissue in several anatomic locations and CLL showed a protective effect, statistically significant for tonsillectomy-adenoidectomy (odds ratio = 0.69; 95% confidence interval = 0.48, 0.98). A statistically significant negative dose-response relationship, substantiating the protectiveness of the effect, was found.

The effect of adriamycin on cell cycle progression and DNA replication in chinese hamster ovary cells.

Administration of[3H]aflatoxin B2 (2,3-dihydroaflatoxin B1)(AFB2) to male rats resulted in levels of hepatic DNA- and ribosomal (r)RNA-aflatoxin adducts that were about 1% of those for rats given [3H]aflatoxin B1(AFB1). The levels of hepatic protein-aflatoxin adducts were 35 to70% as great for AFB2-treated as compared to AFB1-treated rats...

The significance of DNA damage in the cell cycle sensitivity of Chinese hamster ovary cells to bleomycin.

Chinese hamster ovary cells have been treated with bleomycin at various stages in the cell cycle. Mitotic cells, which exhibit least survival, show the greatest amount of DNA strand breakage and a marked inhibition of DNA replication in the subsequent S phase. Strand-rejoining experiments suggest that this is primarily due to differences in the amount of damage produced in the DNA but does not exclude the possibility that cells at the various cell stages also differ in their ability to repair this damage. DNA breakage also occurs in cells incubated in bleomycin at 4 degrees.

Temporary disappearance ("eclipse") of LPC-1 plasmacytoma M component synthesis following tumor cell transfer.

The early phase of LPC-1 plasmacytoma development was studied by in vivo labeling with [6-14C]arginine using its M component (immunoglobulin G 2a,kappa) as marker. At a time when M component was not detected or faint by protein staining of electrophoretograms, significant labeling of M component was detectable by autoradiography. Labeling of the M component was fairly constant for the first 10 hr but was markedly decreased from Days 1 to 7. Nadir (0 to 3% of initial 30-min value) was observed on Day 3. Recovery of M component labeling to the 30-min level was complete by Day 13. This period of marked reduction or "eclipse" in newly synthesized M component was shortened by 2 days when mice were pretreated with pristane or cyclophosphamide prior to tumor cell transfer. The eclipse period was also 2 days shorter in athymic BALB/c-nu/nu mice than in normal BALB/c mice. The eclipse period corresponds to the classical "lag" following tumor cell transfer before tumor growth can be detected by conventional methods. The sensitivity of the [6-14C]arginine pulse permits the in vivo detection of small numbers of tumor cells (as few as 10(6) cells) over the early time periods after cell transfer. Modification of eclipse by manipulating host and/or tumor cells may elucidate the accompanying cellular and biochemical events.