The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

MQW wavelength-tunable DBR lasers with monolithically integrated external cavity electroabsorption modulators with low-driving voltages fabricated by selective-area MOCVD

The design and operation of multiple-quantum-well (MQW) wavelength-tunable distributed Bragg reflector (DBR) InGaAs QW lasers with nonabsorbing gratings and monolithically integrated external cavity electroabsorption modulators fabricated by selective-area MOCVD are presented. Uncoated devices exhibit CW threshold currents as low as 10.5 mA with slope efficiencies of 0.21 W/A from the laser facet. Wavelength tuning of 7 nm is obtained by injection current heating of the DBR section. These devices also exhibit extinction ratios of 18 dB from the modulator facet at a low modulator bias of 1 V, when measured with a broad-area detector. When coupled to a singlemode fiber, these devices exhibited high extinction ratios of 40 dB at a modulator bias of 1.25 V.     

Applications of ultrashort pulse propagation in Bragg gratings forwavelength-division multiplexing and code-division multiple access

We discuss theoretical and experimental studies on the propagation of ultrashort pulses through fiber Bragg gratings. We also consider several applications in optical communications to be found by combining ultrashort pulses and fiber Bragg gratings: a multiwavelength source for wavelength-division-multiplexed systems and a means for implementing optical code-division multiple access     

Optical characterization of low-temperature-grown GaAs forultrafast all-optical switching devices

Low-temperature-grown GaAs (LT-GaAs) is a promising material for all-optical switching devices due to its outstanding optical characteristics. In this paper, we outline a simplified model we have developed to describe the dynamics of the carriers in this material. We also report the results of a series of measurements that we have performed to characterize the optical properties of the material. Specifically, we present the first measurements of the two-photon absorption coefficient and the refractive index changes as a function of the growth and annealing temperatures in LT-GaAs. Finally, we show how our model can be used to optimize the material for applications in all-optical switching     

Modeling Spin-Dependent Transport in InAs/GaSb/AlSb Resonant Tunneling Structures

The Rashba effect resonant tunneling diode is a candidate for achieving spin polarizing under zero magnetic field using only conventional non-magnetic III–V semiconductor heterostructures. We point out the challenges involved based on simple arguments, and offer strategies for overcoming these difficulties. We present modeling results that demonstrate the benefits of the InAs/GaSb/AlSb-based asymmetric resonant interband tunneling diode (a-RITD) for spin filtering applications.     

Pulmonary and allergy subspecialty care in adults with asthma. Treatment, use of services, and health outcomes

This study examined the relationship of several maternal variables to the duration of exclusive breast-feeding and the total duration of breast-feeding, along with attitudes, perceptions, and beliefs about breast-feeding among women living in poor neighborhoods of Managua, Nicaragua. The field work was carried out in December 1992 and January 1993 using qualitative and quantitative methods. A structured questionnaire was administered in interviews with 556 mothers of children under 12 months of age, and meetings of four directed discussion groups were held, in which a total of 20 women participated. At one week of age, almost all the children of the mothers who were surveyed had been breast-fed, but only 45% had been exclusively breast-fed. At 12 weeks old, 30% were already completely weaned. The discussion groups revealed the coexistence of positive opinions about both breast-feeding and bottle-feeding. However, exclusive breast-feeding was considered harmful for the mother, and breast milk was not thought to be sufficient nourishment for the child. Previous experience was strongly related to the duration of exclusive breast-feeding and to total breast-feeding duration. Attitudes, social support, and work situation were important factors influencing the total length of time women breast-fed a child. In general, the results obtained through the interviews and in the discussion groups were in agreement and showed that the elements needed to promote exclusive breast-feeding were social support, a favorable community environment, and policies that dealt with problems faced by working mothers. The complementary research methods were useful for obtaining information about the relative importance of different factors that determine the duration of breast-feeding and for understanding that practice in greater depth from the mother's point of view.     

Immunohistochemical and molecular characterization of the rat 11 beta-hydroxysteroid dehydrogenase type II enzyme

Mineralocorticoid action is facilitated by 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2), which metabolizes glucocorticoids and allows aldosterone to bind to the nonselective mineralocorticoid receptor. We have recently demonstrated the presence of the 11 beta HSD2 protein in a wide range of human epithelia, suggesting that it is the sole isoform endowing specificity in man. In the present study we have used an immunopurified polyclonal antibody (RAH23) raised against a C-terminal peptide derived from the cloned rat 11 beta HSD2 protein to perform immunohistochemical and molecular analysis in rat tissues. In frozen sections of rat kidney, strong staining was seen with the RAH23 antibody in the distal tubule; weaker staining was observed in the thick ascending loop of Henle and the medullary and papillary collecting ducts. Punctate cortical staining was observed in the fetus at 20 days gestation and in 8-day-old rats, with a noticeable increase in the staining pattern at 16 days of age. The kidney did not attain the adult pattern of staining until 28 days of age. Epithelia of ileum and colon also stained with RAH23, as did excretory ducts of the submandibular gland. Intrahepatic and excretory bile ducts displayed strong immunoreactivity in the epithelial lining. Rat adrenal glands showed evidence of the 11 beta HSD2 antigen in the zona fasciculata and zona reticularis, but not in the zona glomerulosa or medulla. Western blot analysis with the RAH23 antibody revealed strong bands in the kidney, colon, adrenal gland, and submandibular gland at 40 kDa, colinear with the migration of the cloned 11 beta HSD2 enzyme. A band of medium intensity was also seen at this size in the pancreas, whereas a band of moderate intensity was seen in the bile duct, and weaker bands were noticed in the stomach, small intestine, and liver, with a diffuse band at 36-42 kDa in the prostate. Strong bands were seen in the pancreas and prostate at 78 kDa, with weaker signals in the colon, adrenal, stomach, and bile duct. A number of tissues also displayed multiple bands at about 30 kDa. Enzymatic assays on tissue homogenates showed extensive conversion of corticosterone to its 11-dehydro product in an NAD-dependent manner in the submandibular gland, adrenal gland, and kidney, but not in the pancreas or prostate. This study confirms the ubiquitous presence of 11 beta HSD2 in sodium-transporting epithelia, demonstrates the high level of 11 beta HSD2 protein and enzyme activity in the rat adrenal, and suggests a possible role for the enzyme in the biliary system. Further studies are required to determine the relevance of the various molecular species to the activity, latency, and processing of the enzyme.