The influence of host tissue on M. gallisepticum vlhA gene expression.

Mycoplasma gallisepticum, a significant poultry pathogen, has evolved rapidly in its new passerine host since its first reported isolation from house finches in the US in 1994. In poultry, M. gallisepticum infects the upper respiratory tract, causing tracheal mucosal thickening and inflammation, in addition to inflammation of the reproductive tract. However, in house finches M. gallisepticum primarily causes inflammation of the conjunctiva. Given that different tissues are primarily affected by the same pathogen in different hosts, we have compared the early changes in gene expression of the phase-variable lipoproteins (vlhA) gene family of M. gallisepticum collected directly from target tissues in both hosts. Previous data have demonstrated that vlhA genes may be related to virulence, exhibiting changes in expression in a non-stochastic, temporal progression and we hypothesize that this may be influenced by differences in the target host tissue. If this is true, we would expect M. gallisepticum to display a different vlhA gene expression pattern in the chicken trachea compared to its expression pattern in house finch conjunctiva. Here we report significant differences in vlhA gene expression patterns between M. gallisepticum collected from chicken tracheas compared to those collected from house finch conjunctiva. While many of the predominant vlhA genes expressed in the input population showed an increase in expression in the chicken trachea at day one postinfection, those same vlhA genes decreased in expression in the house finch. These data suggest that discrete suites of vlhA genes may be involved in M. gallisepticum pathogenesis and tropism for unique tissues in two disparate avian hosts.

Transcriptional and Pathological Host Responses to Coinfection with Virulent or Attenuated Mycoplasma gallisepticum and Low-Pathogenic Avian Influenza A Virus in Chickens.

The avian pathogen Mycoplasma gallisepticum, the etiological agent of chronic respiratory disease in chickens, exhibits enhanced pathogenesis in the presence of a copathogen such as low-pathogenic avian influenza virus (LPAIV). To further investigate the intricacies of this copathogenesis, chickens were monoinfected or coinfected with either virulent M. gallisepticum strain Rlow or LPAIV H3N8 (A/duck/Ukraine/1963), with assessment of tracheal histopathology, pathogen load, and transcriptomic host responses to infection by RNA sequencing. Chickens coinfected with M. gallisepticum Rlow followed by LPAIV H3N8 exhibited significantly more severe tracheal lesions and mucosal thickening than chickens infected with LPAIV H3N8 alone and greater viral loads than chickens infected first with H3N8 and subsequently with M. gallisepticum Rlow Recovery of live M. gallisepticum was significantly higher in chickens infected first with LPAIV H3N8 and then with M. gallisepticum Rlow, compared to chickens given a mock infection followed by M. gallisepticum Rlow The transcriptional responses to monoinfection and coinfection with M. gallisepticum and LPAIV highlighted the involvement of differential expression of genes such as Toll-like receptor 15, Toll-like receptor 21, and matrix metallopeptidase 1. Pathway and gene ontology analyses of these differentially expressed genes suggest that coinfection with virulent M. gallisepticum and LPAIV induces decreases in the expression of genes related to ciliary activity in vivo and alters multiple immune-related signaling cascades. These data aid in the understanding of the relationship between M. gallisepticum and LPAIV during copathogenesis in the natural host and may contribute to further understanding of copathogen infections of humans and other animals.

Variable Lipoprotein Hemagglutinin A Gene (vlhA) Expression in Variant Mycoplasma gallisepticum Strains In Vivo.

Mycoplasma gallisepticum, the primary etiologic agent of chronic respiratory disease, is a significant poultry pathogen, causing severe inflammation and leading to economic losses worldwide. Immunodominant proteins encoded by the variable lipoprotein and hemagglutinin (vlhA) gene family are thought to be important for M. gallisepticum-host interaction, pathogenesis, and immune evasion, but their exact role remains unknown. Previous work has demonstrated that vlhA phase variation is dynamic throughout the earliest stages of infection, with vlhA 3.03 being the predominant vlhA expressed during the initial infection, and that the pattern of dominant vlhA expression may be nonrandom and regulated by previously unrecognized mechanisms. To further investigate this gene family, we assessed the vlhA profile of two well-characterized vaccine strains, GT5 and Mg7, a vlhA 3.03 mutant strain, and an M. gallisepticum population expressing an alternative immunodominant vlhA Here, we report that two M. gallisepticum vaccine strains show different vlhA profiles over the first 2 days of infection compared to that of wild-type Rlow, while the population expressing an alternative immunodominant vlhA gene reverted to a profile indistinguishable from that of wild-type Rlow Additionally, we observed a slight shift in the vlhA gene expression profile but no reduction in virulence in a vlhA 3.03 mutant. Taken together, these data further support the hypothesis that M. gallisepticum vlhA genes change in a nonstochastic temporal progression of expression and that vlhA 3.03, while preferred, is not required for virulence. Collectively, these data may be important in elucidating mechanisms of colonization and overall pathogenesis of M. gallisepticum.

The mitochondrial pharmacogenomics of haplogroup T: MTND2*LHON4917G and antiretroviral therapy-associated peripheral neuropathy.

Peripheral neuropathy (PN) due to mitochondrial injury complicates HIV therapy with some nucleoside reverse transcriptase inhibitors (NRTIs). Variation in the mitochondrial genome may influence susceptibility to NRTI toxicities. Two non-synonymous mitochondrial DNA polymorphisms, MTND1*LHON4216C (4216C) and MTND2*LHON4917G (4917G) were characterized in HIV-infected participants exposed to NRTIs in a randomized clinical trial. Among 250 self-identified white, non-Hispanic participants, symptomatic PN (> or = grade 1) developed in 70 (28%). Both 4216C (odds ratio (OR)=1.98 (95% confidence interval (CI) 1.05-3.75); P=0.04) and 4917G (OR=2.93 (95% CI 1.25-6.89); P=0.01) were more frequent in PN cases. These two polymorphisms remained independently associated with PN after adjusting for age, baseline CD4 count, plasma HIV RNA level, and NRTI randomization arm; 4216C (OR=2.0 (95% CI 1.1-4.0) P=0.04) and 4917G (OR=5.5 (95% CI 1.6-18.7) P<0.01). When 4917G individuals were excluded from the analysis, the association with 4216C was no longer seen. The mitochondrial 4917G polymorphism may increase susceptibility to NRTI-associated PN.

An outbreak of hepatitis B associated with jet injections in a weight reduction clinic.

From January 1984 through November 1985, 31 clinical cases of hepatitis B occurred among attendees of a weight reduction clinic (clinic 1). Before the onset of illness, each case-patient had received a series of injections of human chorionic gonadotropin administered by jet injectors at clinic 1. Clinical history, risk factor assessment, serologic evaluation, and review of clinic injection records were obtained on 287 (84%) of 341 persons who had attended clinic 1 in the first 6 months of 1985. Of this cohort, 21% (60/287) had evidence of acute infection with hepatitis B virus (either documented clinical cases or antibody to hepatitis B core antigen, IgM positive). Of persons who had been given human chorionic gonadotropin at the clinic during the period studied, 24% (57/239) of those receiving human chorionic gonadotropin only by jet injector experienced acute hepatitis B virus infection. None of the 22 persons who had received injections only by syringe experienced hepatitis B virus infection. Stopping the use of the jet injectors on July 2, 1985, at clinic 1, was associated with the termination of this outbreak. This investigation demonstrated that jet injectors can become contaminated with hepatitis B virus and then may be vehicles for its transmission.

The early diagnosis of splenic abscess.

Five cases of splenic abscess seen between 1970 and 1984 are reviewed. The predisposing factors included preceding pyogenic infection, sickle cell disease, and contiguous disease in the pancreas. Abdominal pain and fever were the most frequent presenting symptoms. The most common physical finding was left upper quadrant (LUQ) abdominal tenderness. All patients were treated with splenectomy. In one patient percutaneous drainage was attempted prior to splenectomy but failed. The mortality rate was 20 per cent. Radiologic procedures developed in the last ten years make possible the early diagnosis and treatment of splenic abscess. The treatment of choice remains antibiotics followed by splenectomy.

The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog.

Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value.

Fine needle aspiration in the diagnosis and management of solid breast lesions.

Follow-up data were obtained for 449 fine needle aspirations of solid breast masses from January 1979 through December 1980. The accuracy with which a concordant benign or malignant diagnosis was made was 92 percent. There was a 9.6 percent false-negative rate and a 0.9 percent false-positive rate. Emphasis was placed on the utility of fine-needle aspiration for assessing patients with chronic fibrocystic disease. In 104 cases, patients with a benign cytologic report were followed clinically for 12 months or more. There was a 1.7 percent false-negative rate in this group of patients. We stress that a biopsy should be immediately performed on any worrisome mass, despite the repeatedly negative results of fine needle aspiration. Guidelines for the prevention of false-negative and unsatisfactory cytologic reports have been presented herein. We believe that by careful clinical assessment of the mass, careful performance of the procedure, and close follow-up of the patient, the number of inaccurate fine needle aspirations can be kept at a minimum.

Surgical diseases of the breast during pregnancy.

Physicians caring for women with diseases of the breast are well aware of the time lost before many patients consult their physicians. Nowhere is this more apparent than when a breast mass is associated with gestation or lactation. Enlargement of the breast tends to obscure parenchymal masses. Those that are found are too readily attributed to normal hypertrophy, abscess, or resolving fibrocystic disease. In this review we have attempted to focus on the earlier diagnosis and treatment of breast masses in pregnancy. Prompt needle aspiration will elucidate the solid or cystic nature of a mass. A simple cyst or a galactocele can be diagnosed by the fluid obtained. Solid lesions can be further investigated by fine-needle aspiration for cytologic study. Cytologically equivocal lesions should be subjected to excisional biopsy using local anesthesia. Cancerous lesions occurring during pregnancy should be treated promptly by mastectomy. The outlook for these patients, if treated before metastases occur, is comparable to that for nonpregnant patients. Pregnancy need not be terminated unless disseminated cancer is present and chemotherapy is necessary on an urgent basis.

Cardiotonic activity of milrinone, a new and potent cardiac bipyridine, on the normal and failing heart of experimental animals.

Milrinone (Win 47203) is a potent cardiac bipyridine with inotropic and vasodilator properties. Its effects were studied in anesthetized and unanesthetized dogs and in isolated cardiac tissues from guinea pigs. In the anesthetized dog, the intravenous injection of milrinone (0.01-0.1 mg/kg) increased cardiac contractile force (CF) (23 +/- 6.1 to 87 +/- 8.9%), maximum left ventricular pressure development (24 +/- 5.8 to 119 +/- 16.1%), and cardiac output (16 +/- 4.5 to 33 +/- 8.9%), with less than a 30% increase in heart rate (HR). Significant decreases in systolic and diastolic blood pressures were seen at 0.3-3 mg/kg i.v. Oral doses of milrinone (0.1-1.0 mg/kg), in unanesthetized dogs, increased cardiac CF by 35 +/- 7.0 to 99 +/- 17.0%, with a maximum increase in HR of 40 +/- 7.1% and no significant change in blood pressure. Milrinone was effective in the presence of ouabain and dopamine without enhancing their arrhythmogenic properties. It was also effective in reversing propranolol-, verapamil-, or pentobarbital-induced heart failure. The inotropic response does not seem to involve the stimulation of the autonomic receptors, the release of endogenous catecholamines, histamine, or prostaglandins, or the inhibition of Na+,K+-adenosine triphosphatase. Milrinone is an inhibitor or cardiac adenosine 3',5'-monophosphate (cAMP) phosphodiesterase, with resultant increases in cardiac cAMP levels. However, the time course for this increase does not seem to correspond to the increase in muscle developed tension, and, therefore, it is unlikely to be responsible for the initiation of the inotropic response. Milrinone is a potent cardioactive agent which should be beneficial in the treatment of acute and chronic congestive heart failure.

Influenza A/USSR/77 (H1N1) on a university campus.

An extensive outbreak of influenza caused by A/USSR/77 (H1N1) virus occurred in February, 1978, at the University of Maryland, College Park, Maryland, and the outbreak was studied by virus isolation, serology, clinical questionnaire and outpatient chart review. Among students who returned questionnaires, clinical attack rates were extraordinarily high (73.2% of those less than or equal to 23 years of age and 45.7% for those greater than 23 years (p less than 0.001)), and rates were higher in students who lived on campus (p less than 0.05). Employing the criterion of hemagglutination inhibition titer greater than or equal to 16, 89.8% of those less than or equal to 23 years of age had evidence of infection by March, 1978. Illness was generally mild, and no complications were reported. The extent and rapid spread of this outbreak suggested that only immunoprophylaxis or rapidly acting control measures such as chemoprophylaxis would be effective in this institutional setting with a highly susceptible population.

Fatal paralytic ileus complicating phenothiazine therapy.

The occurrence of fatal paralytic ileus with peritonitis in a patient receiving phenothiazines and an antiparkinsonian agent is described. Although sporadic reports of this complication have appeared, it has not been emphasized in the literature. Only by being alert to this problem can one hope to achieve earlier diagnosis and begin prompt and appropriate treatment.