Inhibition of proprotein convertases abrogates processing of the middle eastern respiratory syndrome coronavirus spike protein in infected cells but does not reduce viral infectivity.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated.

Chlamydia psittaci inclusion membrane protein IncB associates with host protein Snapin.

Chlamydia (C.) psittaci, the causative agent of psittacosis in birds and humans, is the most important zoonotic pathogen of the family Chlamydiaceae. During a unique developmental cycle of this obligate intracellular pathogen, the infectious elementary body gains access to the susceptible host cell, where it transforms into the replicative reticulate body.

TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein.

The type II transmembrane serine proteases TMPRSS2 and HAT can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion. In addition, these proteases cleave the viral receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), and it was proposed that ACE2 cleavage augments viral infectivity. However, no mechanistic insights into this process were obtained and the relevance of ACE2 cleavage for SARS-CoV S protein (SARS-S) activation has not been determined.

Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.

The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear.

TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium.

Infection with human coronavirus 229E (HCoV-229E) is associated with the common cold and may result in pneumonia in immunocompromised patients. The viral spike (S) protein is incorporated into the viral envelope and mediates infectious entry of HCoV-229E into host cells, a process that depends on the activation of the S-protein by host cell proteases. However, the proteases responsible for HCoV-229E activation are incompletely defined.

The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies.

The novel human coronavirus EMC (hCoV-EMC), which recently emerged in Saudi Arabia, is highly pathogenic and could pose a significant threat to public health. The elucidation of hCoV-EMC interactions with host cells is critical to our understanding of the pathogenesis of this virus and to the identification of targets for antiviral intervention. Here we investigated the viral and cellular determinants governing hCoV-EMC entry into host cells.

Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts.

The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract.

The utility of the forced oscillation technique in assessing bronchodilator responsiveness in patients with asthma.

Objective: To address the utility of the forced oscillation technique (FOT) in assessing bronchodilator responsiveness compared with forced expiratory volume in 1s (FEV(1)).

Methods: This is a retrospective analysis of consecutive 126 patients with a clinical history of asthma without any other lung diseases at a pulmonary function testing laboratory. The following measurements were obtained three times each, before and after two doses of pirbuterol 0.

Nontuberculous mycobacterial infection of the central nervous system in patients with AIDS.

Infections due to nontuberculous mycobacteria (NTM) are especially common in patients with AIDS. Meningitis due to NTM, however, is rare. A search for CSF cultures positive for NTM over the past 11 years at our hospital yielded 16 cases.

Cardiopulmonary responses to continuous positive airway pressure in acute asthma.

The effects of nasal continuous positive airway pressure (CPAP) on expiratory flow, arterial blood gas tensions, cardiovascular status, and dyspnea were studied in 21 patients with acute asthma. Therapy consisted of the following CPAP sequence: 30 minutes at 5 cm H2O, 20 minutes at 0 cm H2O, 30 minutes at 7.5 cm H2O, and 20 minutes at 0 cm H2O.

Drug-resistant tuberculosis in an urban population including patients at risk for human immunodeficiency virus infection.

In the past 5 yr, an increased incidence of tuberculosis has been noted in the United States. Simultaneously, the population infected with human immunodeficiency virus-type I (HIV-I) and the number of cases of acquired immunodeficiency syndrome (AIDS) have increased. Selected areas of the United States have also reported increases in the frequency of drug-resistant isolates of Mycobacterium tuberculosis.

Pleural tuberculosis in patients with and without AIDS.

We retrospectively reviewed the records of 71 patients to determine the epidemiologic and clinical features of pleural tuberculosis in patients with and without AIDS and compared the composition of pleural fluid in these two groups of patients. By age, race, sex, and country of birth, the 21 AIDS and 50 non-AIDS patients with pleural tuberculosis were comparable. However, the AIDS patients were more likely to be intravenous drug abusers than the non-AIDS patients (15/21 vs 6/50, p less than .

Hypertrophic osteoarthropathy associated with Pneumocystis carinii pneumonia in AIDS.

Hypertrophic osteoarthropathy (HOA) is a systemic disorder primarily affecting the bones, joints, and soft tissues and developing in association with another disease process. Acute pyogenic pulmonary processes (empyema, lung abscess) are occasionally accompanied by transient HOA, but reversible HOA has not previously been reported in the setting of PCP in AIDS.

Reversible pulmonary uptake and hypertrophic pulmonary osteoarthropathic distribution of technetium-99m methylene diphosphonate in a case of Pneumocystis carinii pneumonia.

Diffuse pulmonary deposition of [99mTc]methylene diphosphonate (MDP) as well as abnormalities characteristic of hypertrophic pulmonary osteoarthropathy have been observed in a patient with Pneumocystis carinii pneumonia (PCP). The findings of the bone scan together with those in the corresponding scintigraphy, and roentgenograms of the chest and skeletal structures are presented. Parallel reversal of [67Ga]citrate and [99mTc]MDP pulmonary uptake with specific treatment for and clinical resolution of PCP implies a causal relationship.

Management of tuberculous pericarditis.

The cases of 17 patients with tuberculous pericarditis were reviewed. Thirteen patients had effusive pericarditis, and 10 had surgical drainage of the effusion. No deaths were due to pericardial tamponade; this appears to be related to earlier recognition of major pericardial effusions by echocardiography.

Nonbronchoscopic lung lavage for diagnosis of opportunistic infection in AIDS.

Thirty patients known to have or suspected of having acquired immunodeficiency syndrome (AIDS) were evaluated for opportunistic pulmonary infection using a double lumen lavage catheter (DLL). Lavage specimens obtained were cytocentrifuged and initially stained by the Papanicolaou technique as a means of rapid evaluation for Pneumocystis carinii. If no opportunistic organism was identified, the patient underwent further diagnostic investigations.

Value of bronchoalveolar lavage in the diagnosis of pulmonary infection in acquired immune deficiency syndrome.

Seventy five patients with pulmonary disease and suspected acquired immune deficiency syndrome (AIDS) underwent fibreoptic bronchoscopy with bronchoalveolar lavage. Of 54 cases of Pneumocystis carinii pneumonia, 53 (98%) were diagnosed by bronchoalveolar lavage. Complications were recorded in 12 instances and included pneumothorax in two and transient increase in fever and hypoxaemia in the remainder.

Cytologic diagnosis of Pneumocystis carinii infection by bronchoalveolar lavage in acquired immune deficiency syndrome.

Twenty-six patients with pulmonary infiltrates and suspected acquired immune deficiency syndrome (AIDS) underwent 29 fiberoptic bronchoscopies, including bronchoalveolar lavage. Seventeen of the 18 patients (94.4%) shown to have Pneumocystis carinii pneumonia were diagnosed by examination of the bronchoalveolar lavage specimen.

Mortality in sarcoidosis. A changing pattern of the causes of death.

Forty-one deaths occurred among 1,090 patients with the clinical diagnosis of sarcoidosis between 1960 and 1977. Thirteen patients died of causes unrelated to sarcoidosis, whereas death was related to sarcoidosis in 28 patients (68%). The most prevalent lesion leading to death was advanced pulmonary involvement (22/28 patients or 78%) with various late complications: cardiorespiratory failure, gram-negative pneumonias, fungal infections.

Pulmonary sarcoidosis: roentgenographic, functional, and pathologic correlations.

Discrepancies were observed between functional (PFT), chest roentgenographic, and open lung biopsy findings (granulomata, interstitial pneumonitis, angiitis, and fibrosis) in 81 patients with clinical diagnosis of sarcoidosis. A combination of normal PFT and Type 1 roentgenographic findings (hilar lymphadenopathy) was associated with minimal lung lesions without fibrosis. Type 1 findings alone did not preclude extensive lesions or fibrosis.

Double-blind, controlled study of clemastine fumarate, chlorpheniramine and placebo in the symptomatic treatment of seasonal allergic rhinitis in desensitized and nondesensitized patients.

In double-blind trials clemastine fumarate 2.68 mg. chlorpheniramine 4 mg and placebo were randomly assigned to two groups of patients with seasonal allergic rhinitis.

Double-blind, controlled study of clemastine fumarate, chlorpheniramine and placebo in patients with seasonal allergic rhinitis.

A whole body plethysmograph (body box) equipped with a flow meter (see Figure 1) was used for objective quantification of the effects of single doses of clemastine fumarate 2.68 mg, chlorpheniramine 4 mg and placebo in a double-blind study of 48 patients with seasonal allergic rhinitis. This technique offers an objective means of assessing drug effects on nasal congestion and obstruction.

A comparative study of subcutaneously administered terbutaline and epinephrine in the treatment of acute bronchial asthma.

Terbutaline, a new bronchodilator drug reported to have selective affinity for beta 2-adrenergic receptors, was compared with epinephrine in the treatment of 49 adult subjects with acute bronchial asthma. Under double-blind conditions, 24 subjects received 1.0 mg of terbutaline sulfate, and 25 subjects received 0.