Permanent Bilateral Vision Loss in Eclamptic Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) classically consists of reversible vasogenic oedema in the posterior circulation territories, which is reversible both clinically and radiologically in the majority of patients after the control of hypertension. The authors describe a 27-year-old eclamptic patient with PRES in accelerated hypertension who revealed permanent vision loss associated with bilateral Purtscher retinopathy. One of the two competing theories that explain vasogenic brain oedema in PRES is excessive autoregulation leading to the dilation of cerebral arterial vessels, particularly in the occipito-parietal vasculatures. Dysfunction of endothelial cells that results in constriction of vessels has also been hypothesised as a cause of PRES. The concurrence of bilateral vaso-occlusive retinopathy and PRES supports the hypothesis that vasoconstriction is a more plausible mechanism of vasogenic oedema in PRES.     

Polybenzimidazole/Nafion hybrid membrane with improved chemical stability for vanadium redox flow battery application

In order to increase the chemical stability of polybenzimidazole (PBI) membrane against the highly oxidizing environment of a vanadium redox flow battery (VRFB), PBI/Nafion hybrid membrane was developed by spray coating a Nafion ionomer onto one surface of the PBI membrane. The acid–base interaction between the sulfonic acid of the Nafion and the benzimidazole of the PBI created a stable interfacial adhesion between the Nafion layer and the PBI layer. The hybrid membrane showed an area resistance of 0.269 Ω cm² and a very low vanadium permeability of 1.95 × 10⁻⁹ cm² min⁻¹. The Nafion layer protected the PBI from chemical degradation under accelerated oxidizing conditions of 1 M VO₂⁺/5 M H₂SO₄, and this was subsequently examined in spectroscopic analysis. In the VRFB single cell performance test, the cell with the hybrid membrane showed better energy efficiency than the Nafion cell with 92.66% at 40 mA cm⁻² and 78.1% at 100 mA cm⁻² with no delamination observed between the Nafion layer and the PBI layer after the test was completed.

Novel polybenzimidazole (PBI)/Nafion hybrid membranes for the VRFB are made by spray coating a Nafion layer to protect PBI from chemical degradation.     

Variation and heritability of Hb F and F-cells among beta-thalassemia heterozygotes in Hong Kong

Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults.     

High incidence of pulmonary tuberculosis in the non-HIV infected immunocompromised patients in Hong Kong

In areas where tuberculosis is endemic, clinicians managing immunocompromised patients (ICP) are confronted with the possibility of Mycobacterium tuberculosis as a pathogen. To determine the incidence and clinical pattern of, the diagnostic approach to, and potential therapeutic implications of pulmonary tuberculosis in this patient population, we reviewed 62 non-HIV infected ICP in Hong Kong who had bronchoscopy because of pulmonary infiltrates. Pulmonary tuberculosis was the second most common cause after bacterial infections. Clinical and radiographic presentations of 12 patients with tuberculosis were nonspecific. Flexible bronchoscopy for tuberculosis carried a diagnostic sensitivity of 91.7 percent. We conclude that for the non-HIV infected ICP from areas where tuberculosis is endemic: M tuberculosis should be suspected as the pathogen; radiographic findings are diagnostically not helpful; FB is a sensitive diagnostic test for tuberculosis and in smear-negative cases where tuberculosis is suspected, initiation of empiric anti-tuberculosis therapy should be considered while awaiting culture results.     

Echocardiography as a tool for determining the incidence of congenital heart disease in newborn babies: a pilot study in Hong Kong

We studied, with echocardiography as the main tool, the incidence of congenital heart disease in newborn babies in Hong Kong. The population examined was the 20,928 babies who were born alive in the Prince of Wales Hospital from January 1987 to December 1989. All had a thorough physical examination by a paediatrician after birth, and an estimated 95% of the babies who were discharged from hospital received another routine physical examination at one of the five local Maternal and Child Health Centres within two months of birth. All babies with either suspected congenital heart disease or multiple congenital abnormalities were referred to the paediatric cardiologists in the Prince of Wales Hospital for further cardiovascular assessment that included echocardiographic examination. In all, 492 babies had Doppler and cross-sectional echocardiographic studies. Various abnormalities of the cardiovascular system were diagnosed in 216 babies. Almost all the babies who died within two months of life underwent autopsy. This proved the presence of congenital cardiac malformations in 15 babies, of whom 10 had correct echocardiographic diagnoses during life. One had a patent arterial duct which was missed by the echocardiography. The other four babies did not have echocardiographic examination while alive, either because of early death or absence of clinical suspicion. In total, congenital cardiac malformations were confirmed in 221 babies by echocardiographic examination and autopsy. Excluding 82 premature babies with patency of the arterial duct, and 6 babies with transient tricuspid regurgitation, there were 133 cases of structural cardiac malformation in the studied population, giving an incidence of 6.35 per thousand live births.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rising asthma mortality in young males in Hong Kong, 1976-85

The trend in asthma mortality in Hong Kong was estimated from published statistics for the years 1976-85. To avoid coding errors in death certifications, only asthma deaths in the age group 5-34 years were analysed. Mortality rose annually by an average of 10.5% in male (P less than 0.02), but not female asthmatics. Such an increase was not due to a change in coding as a result of the revision of the International Classification of Diseases in 1979, or an exchange of diagnostic labelling from other respiratory diseases. The exact causes for the increase in asthma mortality have yet to be determined.     

The origin recognition complex is dispensable for endoreplication in Drosophila

The origin recognition complex (ORC) is an essential component of the prereplication complex (pre-RC) in mitotic cell cycles. The role of ORC as a foundation to assemble the pre-RC is conserved from yeast to human. Furthermore, in metazoans ORC plays a key role in determining the timing of replication initiation and origin usage. In this report we have produced and analyzed a Drosophila orc1 allele to investigate the roles of ORC1 in three different modes of DNA replication during development. As expected, ORC1 is essential for mitotic replication and proliferation in brains and imaginal discs, as well as for gene amplification in ovarian follicle cells. Surprisingly, however, ORC1 is not required for endoreplication. Decreased cell number in orc1 mutant salivary glands is consistent with the idea that undetectable levels of maternal ORC1 during embryogenesis fail to support further proliferation. Nevertheless, these cells begin endoreplicating normally and reach a final ploidy of >1000C in the absence of zygotic synthesis of ORC1. The dispensability of ORC is further supported by an examination of other ORC members, whereas Double-parked protein/Cdt1 and minichromosome maintenance proteins are apparently essential for endoreplication, implying that some aspects of initiation are shared among the three modes of DNA replication. This study provides insight into the physiologic roles of ORC during metazoan development and proposes that DNA replication initiation is governed differently in mitotic and endocycles.     

A tumor necrosis factor alpha- and interleukin 6-inducible protein that interacts with the small subunit of DNA polymerase delta and proliferating cell nuclear antigen

A cDNA encoding a protein of 36 kDa, polymerase delta-interacting protein 1 (PDIP1), that interacts with the small subunit (p50) of DNA polymerase delta (pol delta) was identified in a two-hybrid screen of a HepG2 cDNA library by using p50 as bait. The interaction of PDIP1 with p50 was confirmed by pull-down assays, and a similar assay was used to demonstrate that PDIP1 interacts directly with the proliferating cell nuclear antigen (PCNA). PCNA and p50 bound to PDIP1 simultaneously, and PDIP1 stimulated pol delta activity in vitro in the presence, but not the absence, of PCNA, suggesting that PDIP1 also interacts functionally with both p50 and PCNA. Subcellular localization studies demonstrated that PDIP1 is a nuclear protein that colocalizes with PCNA at replication foci. A putative PCNA-binding motif was identified within the C terminus of PDIP1, and a synthetic peptide containing this PCNA-binding motif was shown to bind PCNA by far-Western analysis. Northern analysis demonstrated that PDIP1 mRNA is present in a wide variety of human tissues. PDIP1 was found to be highly homologous to a previously identified protein, B12 [Wolf, F. W., Marks, R. M., Sarma. V., Byers, M. G., Katz, R. W., Shows, T. B. & Dixit, V. M. (1992) J. Biol. Chem. 267, 1317-1326], one of the early response genes induced by tumor necrosis factor alpha. PDIP1 synthesis can also be induced by tumor necrosis factor alpha and by IL-6, cytokines essential for liver regeneration after loss of hepatic tissue. It is suggested that PDIP1 provides a link between cytokine activation and DNA replication in liver as well as in other tissues.     

Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation

One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8⁺ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8⁺ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.