Re-examine the transfusion transmitted risk of SARS-CoV-2 virus during a major COVID-19 outbreak in 2022.

INTRODUCTION: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors. MATERIALS AND METHODS: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants. RESULTS: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA. DISCUSSION: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness.

Control of hospital endemicity of multiple-drug-resistant Acinetobacter baumannii ST457 with directly observed hand hygiene.

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.

Validation of the Cambridge Prospective Memory Test (Hong Kong Chinese version) for people with stroke.

This study aimed to develop and evaluate a Hong Kong Chinese version of the Cambridge Prospective Memory Test (CAMPROMPT-HKCV). Thirty-three subjects at least one year post-stroke participated in the study. They were simultaneously rated on version A of the CAMPROMPT-HKCV by two testers to establish its internal consistency and inter-rater reliability. Raters used the parallel versions of the test (A and B), in rating 10 patients within 2 weeks to establish the parallel form reliability. Another 10 were also assessed on the same day using both version A of the CAMPROMPT-HKCV and the Rivermead Behavioural Memory Test-Chinese version (RBMT-CV) to establish concurrent validity. A new group of 40 stroke patients and 44 healthy controls was recruited to establish its sensitivity and specificity. Results indicated that test-retest reliability on time-based, event-based and total scores, and inter-rater reliability for versions A and B of the test were high. Cronbach's alpha of the event-based score was higher than that of the time-based score. The reliability and concurrent validity of the parallel forms were established. There was a significant difference in performance on CAMPROMPT-HKCV (version A) between the stroke group and the healthy control group. ROC analysis showed that the ability of the cut-off CAMPROMPT-HKCV (total score) to differentiate PM problems was 20.5 (out of 36) with sensitivity at 95.5% and specificity at 55.9%. Further study in developing stratified norms across different age groups in Chinese-speaking stroke patients is recommended.

Assessing the use of a smartphone app to teach eye screening to opticians.

INTRODUCTION: Torch-light Eye Screening Test (TEST) is a simple eye screening technique designed for use by opticians to look for common anterior segment eye conditions. The TEACHES-Learning Electronic Module (TEACHES-LEM) is an e-learning platform that was developed to teach opticians to perform TEST. The objective of this study was to compare the effectiveness of TEACHES-LEM with face-to-face training (F2FT) in the training and assessment of knowledge among opticians. METHODS: Participants were randomly assigned in this experimental study to receive either the intervention group ((TEACHES-LEM, n = 60) or the control group (F2FT, n = 57). The conceptual knowledge of TEST was assessed with a 20-item clinical scenario-based multiple choice question (MCQ) test before and after teaching (immediately post-teaching and 1-month post-teaching). The MCQ test was developed by three ophthalmologists to give face validity. RESULTS: The pre-teaching test scores (TS), indicating prior knowledge, were comparable in both groups (10.02 ± 2.79 versus 10.40 ± 4.17, p = 0.563, independent t test). The mean immediate post teaching score for TEACHES-LEM was 13.3 ± 4.01 versus 12.3 ± 3.29 in the F2FT group (p = 0.170, independent t test). The mean post 1-month teaching score for TEACHES-LEM and F2FT groups were also comparable, 14.5 ± 4.19 versus 13.4 ± 3.90 respectively (p = 0.295, independent t test), indicating non-inferiority of TEACHES to F2FT. CONCLUSION: The TEACHES-LEM e-learning tool is as effective as F2FT in teaching opticians to perform TEST. It is an alternative to face-to-face teaching in delivering knowledge and assessment. The obviation for physical contact will make it a useful teaching tool during the COVID-19 pandemic period.

Human enterovirus 71 and hand, foot and mouth disease.

Hand, foot and mouth disease (HFMD) is generally a benign febrile exanthematous childhood disease caused by human enteroviruses. The route of transmission is postulated to be faeco-oral in developing areas but attributed more to respiratory droplet in developed areas. Transmission is facilitated by the prolonged environmental survival of these viruses and their greater resistance to biocides. Serious outbreaks with neurological and cardiopulmonary complications caused by human enterovirus 71 (HEV-71) seem to be commoner in the Asian Pacific region than elsewhere in the world. This geographical predilection is unexplained but could be related to the frequency of intra- and inter-typic genetic recombinations of the virus, the host populations' genetic predisposition, environmental hygiene, and standard of healthcare. Vaccine development could be hampered by the general mildness of the illness and rapid genetic evolution of the virus. Antivirals are not readily available; the role of intravenous immunoglobulin in the treatment of serious complications should be investigated. Monitoring of this disease and its epidemiology in the densely populated Asia Pacific epicentre is important for the detection of emerging epidemics due to enteroviruses.

Insulin binding to cultured human fibroblasts increases with normal and precocious aging.

Specific and nonspecific [125I]insulin binding and concentration of unlabeled hormone producing 50 percent competition with 1.0 nanomolar [125I]insulin for specific binding sites correlated positively with age of fibroblast donors. Cells from four children with precocious aging--three with progeria and one with Rothmund syndrome-resembled those from the chronologically old.

Quaternary structure of the insulin-insulin receptor complex.

The three-dimensional (3D) structure of the intrinsically dimeric insulin receptor bound to its ligand, insulin, was determined by electron cryomicroscopy. Gold-labeled insulin served to locate the insulin-binding domain. The 3D structure was then fitted with available known high-resolution domain substructures to obtain a detailed contiguous model for this heterotetrameric transmembrane receptor. The 3D reconstruction indicates that the two alpha subunits jointly participate in insulin binding and that the kinase domains in the two beta subunits are in a juxtaposition that permits autophosphorylation of tyrosine residues in the first step of insulin receptor activation.

Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study.

OBJECTIVES: To determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection. METHODS: This prospective cohort study was conducted during the 2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG™ Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel. RESULTS: A total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04). CONCLUSIONS: Respiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study.

OBJECTIVES: Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva. METHODS: This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated. RESULTS: Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776-0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%-96.2%) and 100% (97.3%-100%), respectively, for saliva, and were 96.1% (88.9%-99.2%) and 98.5% (94.7%-99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA. CONCLUSIONS: Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.

Evaluation of the molecular Xpert Xpress Flu/RSV assay vs. Alere i Influenza A & B assay for rapid detection of influenza viruses.

A new FDA-approved Xpert Xpress Flu/RSV assay has been released for rapid influenza virus detection. We collected 134 nasopharyngeal specimens to compare the diagnostic performance of the Xpert assay and the Alere i Influenza A & B assay for influenza A and B virus detection. The Xpert assay demonstrated 100% and 96.3% sensitivity to influenza A and influenza B virus respectively. Its specificity was 100% for both viruses. The Alere i assay demonstrated slightly lower sensitivity but similar specificity to the Xpert Xpress assay. Although the Xpert assay (30 min) required longer processing time than the Alere assay (15 min), the handling procedure of the Alere assay was more complicated than the Xpert assay. As the GenXpert system has higher throughput than the Alere system, it is more suitable for hospital clinical laboratories. Overall, the new Xpert Xpress Flu/RSV assay is a reliable and useful tool for rapid influenza detection.

High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells.

We studied the nature of insulin receptor binding in MCF-7 breast cancer cells. In both intact cells and solubilized receptor preparations, high-affinity insulin binding was seen. However, unlabeled insulin-like growth factor-I (IGF-I) was five-fold more potent in inhibiting 125I-insulin binding than insulin itself. With monoclonal antibodies to the insulin receptor, 30% of 125I-insulin binding was inhibited. In contrast when alpha-IR3, a monoclonal antibody that recognizes typical IGF-I receptor, was employed over 60% of 125I-insulin binding was inhibited. The B29-MAB-125I-insulin photoprobe was then cross-linked to MCF-7 membranes. Cross-linking was inhibited by both unlabeled insulin and IGF-I. Further, the B29-MAB-125I-insulin photoprobe cross-linked to MCF-7 membranes was strongly immunoprecipitated by alpha-IR3. Employing sequential affinity chromatography with insulin-Affi-gel followed by insulin receptor monoclonal antibody agarose, atypical insulin binding activity was separated from insulin receptor binding activity. This atypical receptor had intrinsic tyrosine kinase activity. Both insulin and IGF-I stimulated the phosphorylation of the receptor's beta subunit. In MCF-7 cells both IGF-I and insulin stimulated [3H]thymidine incorporation; alpha-IR3 blocked all of the IGF-I effect but only 50-60% of the insulin effect. This study demonstrates in MCF-7 cells that, in addition to typical insulin and IGF-I receptors, there is another receptor that binds both insulin and IGF-I with high affinity.

Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates.

This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.

Structure of the insulin receptor of rat adipocytes. The three interconvertible redox forms.

Isolated intact rat adipocytes were photoaffinity labeled with radioactive and photoreactive N alpha B1-monoazidobenzoyl insulin (B1-MABI) or N epsilon B29-monoazidobenzoyl insulin (B29-MABI). Polyacrylamide gel electrophoresis of the labeled plasma membranes solubilized in sodium dodecyl sulfate revealed the specific labeling of three receptor species of 380 kDa, 300 kDa, and 230 kDa. Reduction of each species individually produced the subunits of 130 kDa, 90 kDa, and 40 kDa. Exposure of the adipocytes or plasma membranes after photolabeling to sulfhydryl alkylating agents such as N-ethylmaleimide or p-chloromercuriphenylsulfonate resulted in the appearance of the receptor quantitatively in the 380-kDa form. The effect of the sulfhydryl reagent was concentration dependent and in the case of p-chloromercuriphenylsulfonate the three receptor species reappeared when high concentrations of the reagent were used. Incubation of the adipocytes with low concentrations of dithiothreitol before photolabeling reduced these receptors to discrete lower-molecular-weight forms. In addition, an 85-kDa subunit was now photolabeled by B1-MABI. This subunit was demonstrated to be different from the 90-kDa subunit normally labeled by B29-MABI. We conclude that on the cell surface of the adipocyte, there is one molecular-weight form of insulin receptor of 380 kDa composed of one 130-kDa, one 90-kDa, one 85-kDa, and two 40-kDa subunits. The 300 kDa and 230 kDa are partially reduced forms of the 380-kDa species. We further postulate that a membrane factor or factors sensitive to sulfhydryl alkylating reagents may be involved in the partial reduction and oxidation of these three redox receptor species. The distribution of these redox receptor species may be related to the cellular or tissue sensitivity to insulin.

Biosynthesis of glucagon (IRG3500) in canine gastric mucosa.

The canine gastric mucosa has previously been shown to contain considerable amounts of a polypeptide with the immunologic and physicochemical characteristics and biologic activity of glucagon (IRG3500). Using mucosal pieces that remained viable for at least 8 h, we have demonstrated that IRG3500 is synthesized in this extrapancreatic tissue. Gel filtration and electrophoresis of extracts of mucosal pieces incubated with 3H-tryptophan, 3H-leucine, or 35S-methionine revealed small amounts of labeled, newly synthesized gastric IRG3500. No labeling of gastric IRG3500 was observed when the mucosa was incubated with 3H-proline, an amino acid not found in glucagon, in the presence of cycloheximide, or in isolated rat hepatocytes. Small amounts of newly synthesized IRG3500 were specifically immunoprecipitated by C-terminally directed glucagon antiserum gamma globulins. The rate of gastric IRG3500 biosynthesis in vitro was apparently unchanged in mucosal pieces from pancreatectomized dogs and unaffected by increased glucose or glucose lack during incubations. Thus we have provided evidence that a hormone of the endocrine pancreas can be synthesized in extrapancreatic tissues.

Measurement and partial characterization of immunoreactive glucagon in gastrointestinal tissues of dogs.

We have reported previously that increasing amounts of immunoreactive glucagon (IRG), measured by four specific antisera, appeared in plasma of depancreatized insulin-deficient dogs. It was therefore concluded that pancreatectomy was not accompanied by glucagon deficiency in the dog, but instead excessive amounts of extrapancreatic IRG could contribute to the diabetic syndrome. In order to locate the source of extrapancreatic glucagon, tissue extracts were assayed with anti-glucagon sera 30-K and K-44, which cross-react minimally with crude gut extracts. IRG was detected in all gastrointestinal tissues and in the salivary glands, but not in extracts of liver, kidney, brain, heart atrium, and adenohypophysis. Immunologic dilution curves of extracts from all gastrointestinal tissues were parallel to those of the pure pancreatic glucagon standard, and both antisera (30-K and K-44) measured the same concentrations. The highest concentration of gastrointestinal IRG was found in the fundus and corpus of the stomach. Presence of IRG in gastrointestinal tissues of depancreatized dogs indicates that gastrointestinal cells can not only secrete but also store large amounts of IRG. Extracts of mucosa of stomach fundus were further purified by gel filtration on Biogel P-30 columns. The immunoreactivity in the eluate was assayed by 30-K and a strongly crossreacting antibody, K-4023. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was found to contain the largest amount of IRG and the highest specific immunoreactivity (IRG/protein concentration). This fraction showed also the highest activity in a glucagon-receptor assay system. Disc gel electrophoresis in the presence of urea resolved this fraction into three immunoreactive components, one of which was identical to pancreatic glucagon in its electrophoretic mobility. It appears, therefore, that mucosa of the upper stomach in the dog contains a polypeptide similar to pancreatic glucagon. We conclude that (a) hyperglucagonemia in the dog can result from excessive secretion of IRG not only by the pancreatic alpha cells but also by cells of the gastrointestinal tract; (b) the highest IRG concentration was found in fundus and corpus of the stomach and lower concentrations throughout the gastrointestinal tract; (c) the IRG component in the stomach displayed immunologic and physical properties similar to pancreatic glucagon.

Direct demonstration of insulin receptor internalization. A quantitative electron microscopic study of covalently bound 125I-photoreactive insulin incubated with isolated hepatocytes.

When 125I-insulin is incubated with isolated rodent hepatocytes at 37 degrees C, the ligand initially binds to the plasma membrane of the cell and is subsequently internalized by adsorptive endocytosis. To confirm directly that the insulin receptor is internalized with the ligand, we covalently linked photoreactive 125I-N sigma B29 (azidobenzoyl) insulin to its specific hepatocyte receptor and followed its fate by quantitative electron microscopic autoradiography. We found that the covalently linked photoreactive insulin is internalized by the cell in fashion analogous to the internalization of ordinary 125I-insulin, indicating that, at least under these conditions, the insulin receptor is internalized with the ligand.

Lagophthalmos in enophthalmic eyes.

AIMS: To report a case series of enophthalmic patients with lagophthalmos. METHODS: A retrospective review of the electronic medical records at a tertiary health care centre of all patients with the diagnoses of "enophthalmos" and "lagophthalmos". Patients who had a history of diseases (such as Graves' orbitopathy), trauma or surgery of the orbit and eyelid were excluded. Enophthalmos was defined as exophthalmometric reading of 14 mm or less in both eyes. RESULTS: Seven patients (14 eyes) with bilateral enophthalmos were found to have concomitant lagophthalmos. All patients had deep superior sulci bilaterally. The upper eyelids were seen to be severely retro-placed behind the superior orbital rim. The extraocular motilities were full with no focal neurological deficit. The orbicularis oculi function was normal with no facial paralysis. The orbits were soft on retropulsion and no facial asymmetry was noted. The mean exophthalmolmetry reading measured 12.6 (SD 1.1) mm. The lagophthalmos varied from 1-5 mm. One patient (one eye) with 3 mm lagophthalmos developed a corneal ulcer and was treated with topical antibiotics and gold weight placement in the upper eyelid. CONCLUSION: Enophthalmic patients with deep superior sulci and retro-placed upper eyelids may present with lagophthalmos and exposure keratopathy.

Deletion of residues 485-599 from the human insulin receptor abolishes antireceptor antibody binding and influences tyrosine kinase activation.

We have studied insulin and antireceptor antibody binding to mutated human insulin receptors deleted of residues 485-599 in the alpha-subunit by site-directed mutagenesis. Both normal and mutated receptors were expressed in rat HTC hepatoma cells. Cells expressing either the normal receptor or the mutated receptor retained the ability to bind insulin. In contrast to the normal receptor, however, the mutated receptor failed to interact with antireceptor alpha-subunit antibodies. The inability of the mutated receptor to interact with various antireceptor antibodies was further documented by photoaffinity labeling studies. In intact HTC cells expressing mutated receptors, basal insulin receptor tyrosine autophosphorylation was 2-fold elevated when compared to cells expressing normal receptors. In these cells, however, the response of this function to insulin was blunted. When receptors were isolated from these cells and assayed for both autophosphorylation and phosphotransferase activities toward the synthetic substrate poly(Glu, Tyr), the response to insulin was also blunted. To study the ability of the mutated receptor to transmembrane signal, insulin stimulation of S6 kinase activity was measured. In cells with mutated receptors, in concert with the insulin receptor kinase data, basal S6 kinase activity was elevated, and the response to insulin was blunted. The data suggest, therefore, that residues 485-599 in the alpha-subunit of the insulin receptor are critical for antireceptor antibody binding, but not for insulin binding. Moreover, these data suggest that residues 485-599 contain a regulatory domain for insulin regulation of receptor beta-subunit functions.

Functional characterization of hybrid receptors composed of a truncated insulin receptor and wild type insulin-like growth factor 1 or insulin receptors.

To assess the characteristics of hybrid receptors composed of one kinase-inactive alpha beta-insulin half-receptor and one endogenous alpha beta-insulin-like growth factor 1 (IGF-1) or insulin half-receptor, a cell line expressing an insulin receptor truncated by 365 amino acids (HIR delta 978) was studied, which lacks most of the cytoplasmic beta-subunit. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis under nonreducing conditions revealed four distinct receptor species: endogenous receptors, the more rapidly migrating HIR delta 978 homodimer, and two intermediate species representing HIR delta 978/IGF-1 hybrid receptors and HIR delta 978/IR hybrid receptors. In vivo ligand-binding affinity of the hybrid receptors was studied by receptor-ligand cross-linking, and the delta 978/IGF-1R hybrid receptor was found to have a high affinity for IGF-1, whereas its affinity for insulin was low. Autophosphorylation studies of lectin-purified receptors revealed that neither the HIR delta 978 holoreceptor nor the hybrid receptors underwent autophosphorylation in response to either ligand, despite the presence of intact IGF-1 or insulin half-receptors in the hybrids. Neither hybrid receptor underwent ligand-induced endocytosis, as assessed with the bioactive photoaffinity probes B2(2-nitro-4-azidophenylacetyl)-des-PheB1-insulin and N-epsilon B28-monoazidobenzoyl-IGF-1. In conclusion, the HIR delta 978/IGF-1R hybrid receptor has a high in vivo affinity for IGF-1 but not for insulin. Neither the delta 978/IGF-1R nor the delta 978/IR hybrids undergo autophosphorylation or ligand-induced endocytosis in response to either ligand, indicating that intramolecular trans-, rather than cis-, signal transduction is important in mediating autophosphorylation and endocytosis.