Toward an integrated multi-gigahertz ionizing particle diagnostic.

Needs arising at both current and future accelerator facilities call for the development of radiation-hardened position-sensing diagnostics that can operate with multi-GHz repetition rates. Such instruments are likely to also have applications in the diagnosis of rapid plasma behavior. Building on the recent work of our Advanced Accelerator Diagnostics Collaboration, we are exploring the development of integrated multi-GHz ionizing particle detection systems based on chemical-vapor deposition diamond sensors, with the initial goal of producing a quadrant detector that can determine the intensity and centroid position of a particle beam at a repetition rate between 5 and 10 GHz. Results from our initial high-speed characterization work are presented, including those from a single-channel sensor with a GHz response. Approaches to achieving multi-GHz (5-10 GHz) rate capability, including the design of a dedicated Application Specific Integrated Circuit and the use of 3D RF-solver computer aided design software, are presented and discussed in more detail. 3D RF simulations suggest clean pulses of duration less than 250 ps (FWHM less than 125 ps) can be achieved with the approaches developed by this work.

Use of diamond sensors for a high-flux, high-rate X-ray pass-through diagnostic.

X-ray free-electron lasers (XFELs) deliver pulses of coherent X-rays on the femtosecond time scale, with potentially high repetition rates. While XFELs provide high peak intensities, both the intensity and the centroid of the beam fluctuate strongly on a pulse-to-pulse basis, motivating high-rate beam diagnostics that operate over a large dynamic range. The fast drift velocity, low X-ray absorption and high radiation tolerance properties of chemical vapour deposition diamonds make these crystals a promising candidate material for developing a fast (multi-GHz) pass-through diagnostic for the next generation of XFELs. A new approach to the design of a diamond sensor signal path is presented, along with associated characterization studies performed in the XPP endstation of the LINAC Coherent Light Source (LCLS) at SLAC. Qualitative charge collection profiles (collected charge versus time) are presented and compared with those from a commercially available detector. Quantitative results on the charge collection efficiency and signal collection times are presented over a range of approximately four orders of magnitude in the generated electron-hole plasma density.

Reevaluation of the impact of a stringent low-iodine diet on ablation rates in radioiodine treatment of thyroid carcinoma.

Prior analyses of the impact of stringent, preablative low-iodine diets (LIDs) on ablation in patients with differentiated thyroid cancer postthyroidectomy are dated. We retrospectively reviewed first-time, short-term ablation rates for 44 LID patients and 50 patients following a regular diet (RD) who were verbally instructed to avoid salt, seafood, and multivitamins containing iodine. Patients who had undergone ablation were given between 100 and 200 mCi of 131I, depending on the presence of metastases. We found a 68.2% ablation rate for LID patients, compared to a 62.0% rate for RD patients, a nonsignificant difference (p = 0.53). We observed a dose-response relationship for both patient groups, with higher ablation rates corresponding to higher doses of radioiodine administered. We also measured iodine levels in spot urine samples from 7 matched LID patients and 7 matched RD adherents (healthy volunteers) prediet and postdiet as well as 39 healthy volunteers. LID patients had a lower mean urinary iodine level postdiet (173.9 microg/L; range, 45-1,217 microg/L; standard deviation [SD] = 127.7) than the RD patients (mean, 381.4 microg/L; range, 140-630 microg/L; SD = 196.3) or the 39 normal controls (444.0 microg/L; range, 50-1,690 microg/L; SD = 413.4). Whereas the LID lowered urinary iodine levels by 69.4% from prediet values, the RD reduced urinary iodine by 23.6%. Although differences in the reduction of urinary iodine levels between the LID and the RD were substantial, both groups experienced equivalent outcomes. The level of iodine in the American diet has progressively decreased, and may be much lower now than when prior LID studies were conducted. We suggest that prescribing a refined, less stringent diet that avoids high-iodine-containing foods would offer equivalent outcomes with increased patient convenience.

Changes in free amino acids in the hemolymph of giant freshwater prawn Macrobrachium rosenbergii exposed to varying salinities: relationship to osmoregulatory ability.

Changes in free amino acids (FAA) in the hemolymph of the giant freshwater prawn, Macrobrachium rosenbergii, were examined in individuals exposed to varying salinities for up to 1 week. In freshwater and under conditions of low salinity, total FAA concentrations were maintained between approximately 0.85 and 1 mM and did not exhibit changes in response to salinity exposure. Under high salinities, total FAA concentrations increased dramatically, reaching up to 2.1 mM depending on treatment. Examination of individual amino acid concentrations revealed that these increases were based on specific changes in glycine, arginine, alanine, proline and lysine. Among these, alanine showed the greatest increases, resulting in levels six-fold higher under high salinity than in freshwater and under low salinity. The other amino acid species showed increases of 2.5-fold compared to original values. These five FAAs in freshwater and under low salinity together occupied approximately 45% of total FAA contents and under high salinity comprised more than 70% of total FAA contents. These results suggest that specific hemolymph FAAs are involved in mediating response to salinity exposure in freshwater prawns.

Determination of amino acid sequence and site of mRNA expression of four vitellins in the giant freshwater prawn, Macrobrachium rosenbergii.

Four major yolk proteins, designated as vitellins (Vns) Macr-VnA, B, C, and D, were extracted from mature ovaries of Macrobrachium rosenbergii. These were purified to homogeneity by reversed-phase high performance liquid chromatography (HPLC) employing a unique separation system based on the hydrophobic properties of the Vn molecule. Using standard techniques of protein sequencing, more than 33 N-terminal and 57 internal amino acid residues were determined for each of the four Vns. The cDNA fragments encoding the four Vns were amplified by PCR using degenerate oligonucleotide primers derived from the N-terminal and internal amino acid sequences. These cDNA fragments were cloned, sequenced, and used as probes to examine the transcription of mRNAs encoding the four Vns. Significant accumulations of these mRNAs were observed in female hepatopancreas only, while mRNA expression was not detected in male hepatopancreas or any other female tissue including ovary, subepidermal adipose tissue, gill, and muscle. This is the first occasion in Crustacea in which multiple Vns were demonstrated to be synthesized simultaneously in a single tissue.

Characterization of Na/K-ATPase in Macrobrachium rosenbergii and the effects of changing salinity on enzymatic activity.

A ouabain-sensitive Na/K-ATPase kinetic assay system based on the hydrolysis of ATP and the oxidation of NADH was adapted in order to characterize enzymatic activity in gills and examine the effects of changing salinity in Macrobrachium rosenbergii. Maximum inhibition by ouabain occurred at a concentration of 1.4 mM, and the K(m) of the reaction was 0.2 mM. In a first experiment, animals were acclimated to freshwater, 1/3 seawater, 2/3 seawater and full seawater for up to 1 week. Na/K-ATPase activity in front gills was 1. 62+/-0.19 micromol ADP/mg protein per h in freshwater, and was seen to increase slightly in 1/3 seawater (1.88+/-0.19 micromol ADP/mg protein per h) and 2/3 seawater (2.09+/-0.24 micromol ADP/mg protein per h), decreasing slightly in full seawater (1.92+/-0.43 micromol ADP/mg protein per h); however, differences were not significant. Back gills showed slightly higher levels, and a similar pattern of Na/K-ATPase activity. In a second experiment, animals were acclimated to 1/3 seawater and 2/3 seawater, and then transferred to freshwater. However, no changes in activity were seen, indicating that exposure to dilute media did not effect enzymatic activity. Whereas Na/K-ATPase is important in osmoregulatory function in marine euryhaline crustaceans, it may not play a significant role in adaptation in freshwater crustaceans that inhabit a more narrow range of salinities.

Ethical issues in the delivery room: resuscitation of extremely low birth weight infants.

The neonatal team attending high-risk deliveries is often faced with difficult ethical decisions concerning aggressive cardiopulmonary resuscitation for infants of 22-24 weeks gestational age (GA). These decisions are often based on the ethical principles of beneficence, nonmaleficence, justice, futility, autonomy, quality of life, and best interests and legal rights of the infant. Three delivery room recommendations are discussed along with their legal and ethical considerations. The perinatal and neonatal intensive care nurse must understand the moral, ethical, legal, and professional responsibilities and their effect on her/his own judgment decisions. These, in turn, will affect the infants, their parents, and other colleagues.

Molecular Characterization of a cDNA Encoding Vitellogenin and Its Expression in the Hepatopancreas and Ovary during Vitellogenesis in the Kuruma Prawn, Penaeus japonicus.

In Crustacea, reproductive function and mechanisms regulating vitellogenesis have not been fully elucidated. This is due in great part to a lack of information concerning the biochemical nature of the vitellogenin molecule, the hemolymph precursor of yolk protein, vitellin, as well as the functional expression of the vitellogenin-encoding gene. We have therefore cloned a cDNA encoding vitellogenin in the kuruma prawn, Penaeus japonicus based on the N-terminal amino acid sequence of the 91 kDa subunit of vitellin. The open reading frame of this cDNA encoded 2,587 amino acid residues. This is the first investigation reporting a full-length cDNA and its corresponding amino acid sequence for vitellogenin in any crustacean species.Northern blot analysis and in situ hybridization have revealed that mRNA encoding vitellogenin was expressed in both the follicle cells in the ovary and the parenchymal cells in the hepatopancreas. In nonvitellogenic females, vitellogenin mRNA levels were negligible in both the ovary and hepatopancreas, but in vitellogenic females, levels were dramatically increased in both tissues. In the ovary, highest levels were observed during the early exogenous vitellogenic stage, and thereafter rapidly decreased, whereas in the hepatopancreas, high levels were maintained until the onset of the late vitellogenic stage. Differing profiles of vitellogenin mRNA levels in the ovary and hepatopancreas suggest that the contribution of these tissues to vitellogenin synthesis harbor separate and complementary roles during vitellogenesis.

Structural requirements for intracellular transport of pulmonary surfactant protein B (SP-B).

Human SP-B is synthesized by the alveolar Type II epithelial cell as a 381 amino acid preproprotein. The 79 residue mature SP-B peptide is extremely hydrophobic and flanked by propeptides of 200 and 102 amino acids at its NH2- and COOH-termini, respectively. The purpose of this study was to identify peptide domains of the SP-B proprotein necessary for trafficking of the mature peptide in the secretory pathway. To this end several constructs were generated, by subcloning the full length human SP-B (SP-B), COOH-terminally truncated SP-B (SP-B delta C, in which residues 201-381 were deleted), NH2-terminally deleted SP-B (SP-B delta N, in which residues 28-200 were deleted), NH2-terminal propeptide (SP-BN), mature SP-B (SP-BM) and COOH-terminal propeptide (SP-BC), into the mammalian expression vector pcDNA3. The resulting expression constructs were characterized by DNA sequencing and in vitro transcription/translation and subsequently transfected into Chinese hamster ovary cells. 48 h after transfection, cells were labeled with [35S]-met/cys and analyzed by immunoprecipitation, SDS-PAGE and autoradiography. Proteins encoded by SP-B, SP-B delta C, SP-BN and SP-BC constructs were secreted into media; in contrast, SP-B constructs lacking the NH2-terminal propeptide (SP-B delta N) remained in the endoplasmic reticulum (as assessed by endoglycosidase H sensitivity) and were rapidly degraded. We conclude that (1) 27 amino acids at the NH2-terminus of SP-B contain a functional signal peptide and (2) the NH2-terminal propeptide of the SP-B precursor is necessary and sufficient for intracellular trafficking of the mature peptide.

Inhibin is present in the corpus luteum of pseudopregnant rats and can interact with progesterone to inhibit resumption of estrous cycles.

The corpora lutea (CL) of ovaries of adult pseudopregnant (PSP) rats were stained by immunohistochemistry for inhibin alpha subunit using sheep alpha-chain1-27 antibody as a measure of inhibin content. Staining was light in estrous cycle CL (stage III), increased in Day 2 and Day 4 PSP CL and reached maximal density on day 6 PSP when both large cells and many small cells stained. Staining was decreased in CL from 8 and 10 day PSP. Granulosa cells of growing follicles showed light stain on days 8 and 10 of PSP. Adult female rats were treated for 5 days beginning at estrous cycle Stage III (cornified masses). In Experiment 1, three groups of rats were used: 1. implanted with 30mm progesterone capsules and injected with saline, 2. implanted with 30mm progesterone capsules and injected with 10 ng rh inhibin A daily, 3. implanted with empty capsules and injected with 10 ng rh inhibin A daily. Both groups of rats with progesterone implants had significantly slower return of cycling after removal of the capsules than did the rats injected with 10ng rh inhibin A alone. In Experiment 2, the same treatments were given except that 20ng of rh inhibin A (10ng 2x/day) was given to both inhibin treatment groups. Rats treated with progesterone and 20ng inhibin had a significantly slower return of cyclic activity (4.4 days) over that found in the other two treatment groups. We conclude that the absence of cyclic activity in PSP rats is possibly due to the secretion of both inhibin and progesterone by the CL.

Counseling the international traveler. Update '93.

The itinerary of international travelers will largely determine the amount of pretravel counseling, number of immunizations and type of malaria prophylaxis they will need. The countries visited are also the best predictor of traveler's diarrhea. Only yellow fever and cholera vaccines are required for entry into certain countries; the latter generally given only to satisfy entry requirements. Polio vaccine is important for some areas and is frequently neglected. For most malarious areas, chloroquine once per week is recommended. Mefloquine should be prescribed weekly for travelers going to chloroquine resistant malarious areas. Traveler's diarrhea is best prevented by avoiding high risk foods and beverages. Antibiotics, generally not recommended for prophylaxis, are very effective in treatment. Travelers should be reminded to advise physicians of their travel history during future medical encounters so that otherwise exotic tropical diseases, possibly contracted during travel, may be considered in diagnoses.

Thallium poisoning: an outbreak in Florida, 1988.

In October 1988, five of seven members of a Florida family were poisoned with thallium, constituting the largest outbreak of acute thallium poisoning in the United States since thallium was banned as a rodenticide in 1972. Three patients had an acute severe neuropathy with respiratory depression; one died. The other two had no symptoms. No cases were identified among nonhousehold relatives or friends, or in the community. Of the more than 100 environmental specimens collected at the family household and tested by atomic spectroscopy, three empty and four unopened glass soft drink bottles of the same lot number yielded thallium in a concentration fatal to humans. All family members who consumed the soft drink were poisoned (5/5) as compared with none of those who did not (0/2). Because poisoning was clustered to the family and police investigators provided evidence that the poisoning was deliberately targeted to the family, it was assumed that no other soft drink bottles contained thallium, and it was decided not to recall all soft drink bottles with the same lot number. A year later a neighbor of the family was arrested and convicted of the murder.

The protective effect of alcohol on the occurrence of epidemic oyster-borne hepatitis A.

Limited data indicate that drinking alcoholic beverages along with eating food contaminated with Shigella or Salmonella decreases the risk and/or the severity of illness. No such study has been reported following exposure to a viral pathogen. During an oyster-borne outbreak of hepatitis A, we studied the effect of ingestion of alcoholic beverages concomitant with consumption of contaminated oysters. The analysis was restricted to 51 cases and 33 controls who had consumed the implicated raw oysters. After controlling for potential confounders, we found a protective effect for beverages that have an alcohol concentration of greater than or equal to 10% (odds ratio = 0.1, 95% confidence interval = 0.02-0.9), but not for beverages with an alcohol concentration of less than 10% (odds ratio = 0.7, 95% confidence interval = 0.2-2.9).

A multistate outbreak of hepatitis A caused by the consumption of raw oysters.

BACKGROUND: In August 1988 we investigated a multistate outbreak of hepatitis A caused by Panama City, Florida, raw oysters. METHODS: Cases of hepatitis A (HA) with onset in July-August 1988 were identified among persons who ate seafoods harvested in the coastal waters of Panama City, Florida. We conducted a case-control study, using eating companions of case-patients, and calculated attack rate (AR) per 1000 dozen raw oysters served. Enzyme immunoassay (EIA) and a polymerase chain reaction (PCR) technique were performed on samples of raw shellfish obtained from Panama City coastal waters. RESULTS: Sixty-one case-patients were identified in five states: Alabama (23), Georgia (18), Florida (18), Tennessee (1), and Hawaii (1). We found an increased risk of HA for raw oyster eaters (odds ratio = 24.0; 95% confidence interval = 5.4-215.0; P less than .001). The AR of HA in seafood establishments was 1.9/1000 dozen raw oysters served. The EIA and PCR revealed HA virus antigen and nucleic acid in oysters from both unapproved and approved oyster beds, in confiscated illegally harvested oysters, and in scallops from an approved area. CONCLUSIONS: The monitoring of coastal waters and the enforcement of shellfish harvesting regulations were not adequate to protect raw oyster consumers. More emphasis should be placed on increasing public awareness of health hazards associated with eating raw shellfish.

Mycobacterium tuberculosis transmission in a health clinic.

Between January 1 and June 30, 1988, 30 (39.5%) of 76 staff members tested at a health clinic in Florida had positive tuberculin skin test reactions. This case-control study showed that people whose skin test converted were more likely than those whose skin test did not convert to have been present while patients were being treated with aerosolized pentamidine (odds ratio = 15.0; 95% confidence interval = 1.4 - 730.0) and to have worked on the first floor of the clinic (odds ratio = 9.3; 95% confidence interval = 1.1 - 420). The clinic building was poorly ventilated, and aerosolized pentamidine treatments were given in a room from which the air tended to flow into the hallway. Aerosolized pentamidine should be administered in a well-ventilated area from which the air is exhausted directly outside. All persons who are given such treatments should first be screened for tuberculosis. Use of trade names is for identification only and does not constitute endorsement by the Public Health Services or the U.S. Department of Health and Human Services.

Reversible accumulation of plant suspension cell cultures in g(1) phase and subsequent synchronous traverse of the cell cycle.

The induction of DNA synthesis in Datura innoxia Mill. cell cultures was determined by flow cytometry. A large fraction of the total population of cells traversed the cell cycle in synchrony when exposed to fresh medium. One hour after transfer to fresh medium, 37% of the cells were found in the process of DNA synthesis. After 24 hours of culture, 66% of the cells had accumulated in G(2) phase, and underwent cell division simultaneously. Only 10% of the cells remained in G(0) or G(1). Transfer of cells into a medium, 80% (v/v) of which was conditioned by a sister culture for 2 days, was adequate to inhibit this simultaneous traverse of the cell cycle. A large proportion of dividing cells could be arrested at the G(0) + G(1)/S boundary by exposure to 10 millimolar hydroxyurea (HU) for 12 to 24 hours. Inhibition of DNA synthesis by HU was reversible, and when resuspended into fresh culture medium synchronized cells resumed the cell cycle. Consequently, a large fraction of the cell population could be obtained in the G(2) phase. However, reversal of G(1) arrested cells was not complete and a fraction of cells did not initiate DNA synthesis. Seventy-four percent of the cells simultaneously reached 4C DNA content whereas the frequency of cells which remained in G(0) + G(1) phase was approximately 17%. Incorporation of radioactive precursors into DNA and proteins identified a population of nondividing cells which represents the fraction of cells in G(0). The frequency of cells entering G(0) was 11% at each generation. Our results indicate that almost 100% of the population of dividing cells synchronously traversed the cell cycle following suspension in fresh medium.

Ecdysteroid fluctuations during embryogenesis in the giant freshwater prawn, Macrobrachium rosenbergii.

Ecdysteroid levels during the embryogenesis of the giant freshwater prawn, Macrobrachium rosenbergii, were determined by radioimmunoassay and high-performance liquid chromatography. Ecdysteroids consisting of significant amounts of 20-hydroxyecdysone and high-polarity products (HPP) and lesser amounts of ecdysone and low-polarity products (LPP) were detected in mature ovaries and newly laid eggs. All ecdysteroid groups decreased gradually during the nauplius phase. With the formation of the compound eye and the appearance of the carapace and other body-like structures, marking morphogenesis to the zoeal stage, embryos showed the beginning of a continuous and dramatic increase in ecdysteroid concentrations sustained until larval hatchout. Ecdysteroid levels at hatchout were above 20-fold greater than ecdysteroid levels in newly laid eggs. More specifically, HPP and 20-hydroxyecdysone increased concomitantly, with a decrease in 20-hydroxyecdysone only at the end of the embryogenic period, while ecdysone and LPP levels remained low or undetectable. It may be postulated that the presence of ecdysteroids in ovaries and eggs represents a reserve of maternal ecdysteroids which are necessary at the commencement of embryonic development; with the differentiation of embryonic tissue capable of ecdysteroid synthesis, ecdysteroids increase rapidly to play a role in later embryonic development.