Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor

Urethral epithelial cells are invaded by Neisseria gonorrhoeae during gonococcal infection in men. To understand further the mechanisms of gonococcal entry into host cells, we used the primary human urethral epithelial cells (PHUECs) tissue culture system recently developed by our laboratory. These studies showed that human asialoglycoprotein receptor (ASGP-R) and the terminal lactosamine of lacto-N-neotetraose-expressing gonococcal lipooligosaccharide (LOS) play an important role in invasion of PHUECs. Microscopy studies showed that ASGP-R traffics to the cell surface after gonococcal challenge. Co-localization of ASGP-R with gonococci was observed. As ASGP-R-mediated endocytosis is clathrin dependent, clathrin localization in PHUECs was examined after infection. Infected PHUECs showed increased clathrin recruitment and co-localization of clathrin and gonococci. Preincubating PHUECs in 0.3 M sucrose or monodansylcadaverine (MDC), which both inhibit clathrin-coated pit formation, resulted in decreased invasion. N. gonorrhoeae strain 1291 produces a single LOS glycoform that terminates with Gal(beta1-4)Glc-Nac(beta1-3)Gal(beta1-4)Glc (lacto-N-neotetraose). Invasion assays showed that strain 1291 invades significantly more than four isogenic mutants expressing truncated LOS. Sialylation of strain 1291 LOS inhibited invasion significantly. Preincubation of PHUECs in asialofetuin (ASF), an ASGP-R ligand, significantly reduced invasion. A dose-response reduction in invasion was observed in PHUECs preincubated with increasing concentrations of NaOH-deacylated 1291 LOS. These studies indicated that an interaction between lacto-N-neotetraose-terminal LOS and ASGP-R allows gonococcal entry into PHUECs.

Primary aldosteronism: Are we diagnosing and operating on too few patients?

Many cases of potentially curable primary aldosteronism are currently likely to be diagnosed as essential hypertension unless screening tests based on suppression of renin are tarried out in all hypertensive patients. More than half of the patients with primary aldosteronism detected in this way have normal circulating potassium levels, so measurement of potassium is not enough to exclude primary aldosteronism. When primary aldosteronism is diagnosed, fewer than one-third of patients are suitable for surgery as initial treatment, but this still represents a significant percentage of hypertensive patients. After excluding glucocorticoid-suppressible primary aldosteronism, adrenal venous sampling is essential to detect unilateral production of aldosterone and diagnose angiotensin-responsive aldosterone-producing adenoma. One cannot rely on the computed tomography scan. If all hypertensive patients are screened for primary aldosteronism and the workup is continued methodically in those with a positive screening test, patients with unilateral overproduction of aldosterone who potentially can be cured surgically are not denied the possibility of cure.

Educating speech-language pathologists for a multicultural world

This paper presents critical elements and current needs in educating speech-language pathologists for a multicultural world. A proposed paradigm shift in clinical teaching using the UK model is also introduced. In addition, a case study on the American Speech Language Hearing Association's efforts in implementing the Multicultural Action Agenda by networking with the Asian Pacific Islander caucus is described. A survey of multicultural elements in programs in Australia and New Zealand is included. finally, suggestions for collaboration with those in established professional bodies to meet the increasing needs of a multicultural world are provided. copyright (C) 2001 S. Karger AG. Basel.

Subcortical brain mechanisms in speech and language

This paper reviews current research and contemporary theories of subcortical participation in the motor control of speech production and language processing. As a necessary precursor to the discussion of the functional roles of the basal ganglia and thalamus, the neuroanatomy of the basal ganglial-thalamocortical circuitry is described. Contemporary models of hypokinetic and hyperkinetic movement disorders based on recent neuroanatomical descriptions of the multi-segmented circuits that characterise basal ganglion anatomy are described. Reported effects of surgically induced lesions in the globus pallidus and thalamus on speech production are reviewed. In addition, contemporary models proposed to explain the possible contribution of various subcortical structures to language processing are described and discussed in the context of evidence gained from observation of the effects of circumscribed surgically induced lesions in the basal ganglia and thalamus on language function. The potential of studies based on examination of the speech/language outcomes of patients undergoing pallidotomy and thalamotomy to further inform the debate relating to the role of subcortical structures in speech motor control and language processing is highlighted. Copyright (C) 2001 S. Karger AG, Basel.

Taeniogonalos raymenti Carmean & Kimsey (Hymenoptera : Trigonalidae) reared as a hyperparasite of Sturmia convergens (Weidemann) (Diptera : Tachinidae), a primary parasite of Danaus plexippus (L.) (Lepidoptera : Nymphalidae)

Taeniogonalos raymenti is confirmed as a hyperparasitoid of the tachinid Sturmia convergens which parasitises larval Danaus plexippus. Trigonalids are indirect parasitoids and in this case we have direct evidence that wasp eggs must have been laid on the caterpillar's host plant. Asclepias fruticosa. before the secondary host, but not necessarily before the primary tachinid host, was present. Levels of hyperparasitism during our sampling period were very low at less than two percent.

Advances in the diagnosis of primary immunodeficiency disorders in childhood

Primary immunodeficiency disorders in childhood usually present as unusual, recurrent or severe infections, symptomatic infections with organisms of low pathogenicity, or as recognizable syndromes which are known to have associated immunological abnormalities. In many of the primary immunodeficiency disorders, there are known patterns of inheritance, and other family members may be affected. Some primary immunodeficiency disorders are relatively common, such as selective IgA deficiency, and often do not lead to major morbidity. Others, such as the severe combined immune deficiency syndromes, are relatively rare, and are fatal in early life if not recognized and treated early. Diagnosis of a primary immunodeficiency disorder depends on appropriate use of laboratory investigations. Often there will be abnormalities detected on a complete blood film and measurement of immunoglobulin isotypes. More complex investigations should be undertaken in conjunction with a paediatric immunology service. In recent years, many of the clinically defined primary immunodeficiency disorders have been shown to have associated specific gene defects. For some, this has led to the identification and characterization of defective or absent gene products. The consequences of this new knowledge are more accurate diagnosis, early diagnosis including antenatal diagnosis, detection of undiagnosed disease in other family members, and the potential for new therapies including gene or gene product therapy.

Primary Bartholin gland carcinoma: a report of seven cases

This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously published data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2000 was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively. All patients presented with a local swelling or a lump. Two had associated discharge and 2 had associated pain. Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the Bartholin gland. None of the patients with SCC developed recurrent disease. The patient with adenoid-cystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine cancer of the Bartholin gland was considered tumour-free after operation. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report, of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC.