Secretory immunoglobulin A in tears: functions and changes during contact lens wear

Introduction : Secretory immunoglobulin A (sIgA) is the predominant immunoglobulin in tears. The role of sIgA in defending the eye against pathogens has not been established clearly. There have been conflicting reports about the effect of contact lens wear on the concentration of sIgA in tears. This study was conducted to elucidate the role of sIgA in ocular defence and to determine the effect of contact lens wear on sIgA concentration. Methods : Tears were collected from contact lens wearers and non-wearers using microcapillary tubes. The concentration of sIgA was evaluated using an in-house ELISA. The specificity of sIgA to a strain of P. aeruginosa was examined using a fluorescent assay and the ability of neutrophils to phagocytose sIgA coated bacteria were assessed by plate counts. Results : Tears contained sIgA that reacted to P. aeruginosa. P. aeruginosa coated with sIgA was phagocytosed by the neutrophils. The level of sIgA and the level of sIgA specific to P. aeruginosa in the tears of contact lens wearers were significantly reduced. Conclusions : These results indicate that contact lens wear significantly alters the level of sIgA in tears which may lead to changes in the ability of the ocular surface to defend itself against potential pathogens.     

Meningitis in Hong Kong children, with special reference to the infrequency of haemophilus and meningococcal infection

Objective: To study the epidemiologic and aetiologic features of meningitis in children in Hong Kong.
Methodology: A retrospective study of 85 children resident in the New Territory East region of Hong Kong admitted to a teaching Hospital because of meningitis during a 9 year period.
Results: Mycobacterium tuberculosis was the most common aetiological agent accounting for 13 cases (15.3%). Other bacteria accounted for 41 cases (48%); among these one fifth were caused by Haemophilus influenzae type b. The overall admission rates for tuberculous meningitis in Chinese children were 0.76/100 000 (95% CI 0.25-1.78) and 0.42/100 000 (CI 0.19-0.8) per year, respectively, for under 5 year olds and under 15 year olds. The overall annual incidence rates of bacterial meningitis other than tuberculous were 5.2/100 000 (CI 3.72-7.43) and 1.6/100 000 (CI 1.14-2.29) for Chinese children under 5 years and under 15 years, respectively. The annual incidence of H. influenzae meningitis in Chinese children under 5 years old was low at 1.1/100 000 (0.43-2.2). All five cases of meningococcal meningitis were in Vietnamese children (under 5 years of age incidence: 13.0/100 000 per year, CI 4.2-30.3). There were no cases of meningococcal meningitis in Chinese children during the 9 year period.
Conclusion: M. tuberculosis was the most common aetiological agent of meningitis in Hong Kong children. The incidence of haemophilus or meningococcal meningitis was very low.     

Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis

One hundred and eight patients with cystic fibrosis were investigated over one year to determine whether an association existed between rhinovirus or other respiratory virus infection and clinical status. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), Shwachman score, Chrispin-Norman chest radiograph score, and percentage weight for height were recorded at the beginning and end of the study; days of intravenous antibiotics were noted. Nasopharyngeal aspirates were taken for viral studies during respiratory exacerbations. Serum was collected at enrollment and 2-6 weeks after each respiratory exacerbation. One hundred and fifty seven exacerbations occurred in 76 patients. Respiratory virus infection was detected in 44 exacerbations and rhinovirus was present in 16% (25/157) of exacerbations. Patients with one or more respiratory virus infections were compared with those who had none. When all respiratory virus infections were considered, patients had a significantly greater deterioration in Shwachman score and received significantly more days of intravenous antibiotics. When rhinovirus was considered separately, patients received significantly more days of intravenous antibiotics, but showed no deterioration in clinical status. However, patients infected with another respiratory virus had a significant decline in FEV1, with trends towards significance for decline in FVC and Shwachman score.     

Spontaneous intracranial hypotension: A study of six cases with MR findings and literature review

Spontaneous intracranial hypotension is clinically characterized by orthostatic headache and other symptoms caused by low cerebrospinal fluid pressure due to leakage of cerebrospinal fluid from dural punctures or other medical causes. The other symptoms are mainly due to traction of the cranial and spinal nerves owing to descent of the brain caused by low cerebrospinal fluid pressure. Magnetic resonance imaging is very useful in the diagnosis because of its characteristic findings. We describe the MRI findings in six cases that had variable clinical presentation.     

Sperm-induced oocyte activation in the rhesus monkey: nuclear and cytoplasmic changes following intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI) has increased the potential of the assisted reproductive technologies to propagate mammalian species and has provided an opportunity for research into cell cycle control and the mechanisms involved in sperm-induced oocyte activation. We have investigated the efficacy of ICSI in the rhesus monkey, the mechanism of fertilization following sperm injection and the cytoskeletal rearrangement that occurs upon oocyte activation. These studies were conducted on mature, and to a lesser extent, immature oocytes. Ejaculated spermatozoa, washed, capacitated and activated before immobilization, were injected into oocytes using conventional ICSI methodology. Sperm injection into mature oocytes induced oocyte activation (19/22; 86%) and pronuclear formation. In contrast, sham- injected oocytes did not activate readily (2/16; 13%). To localize oocyte activation factor(s), spermatozoa were separated mechanically into heads and tails which were then injected individually into mature oocytes. Activation occurred in 87% (20/23) of oocytes receiving heads. After tail injection, a single microtubule aster was nucleated and one pronucleus (PN) was seen in four of 21 oocytes. Intracytoplasmic injection of sperm extract (SE) resulted in oocyte activation at a significantly higher rate than occurred following sham injection (76 versus 13%). Sperm-induced oocyte activation was also evaluated in immature metaphase (MI) oocytes; activation occurred in 46% (12/26) of cases; however, only 8% of the activated oocytes exhibited 2 PN. Finally, beta-tubulin localization in untreated and taxol-treated oocytes was established as a marker for cytoplasmic changes associated with oocyte activation. These results are consistent with the hypothesis that spermatozoa contain an oocyte activating factor(s) which is primarily localized in the sperm head. Moreover, an activation response is limited to mature oocytes and is accompanied by cytoskeletal changes analogous to those seen following conventional fertilization.      

The mouse SCA2 gene: cDNA sequence, alternative splicing and protein expression

Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinucleotide repeat located in the coding region of the human SCA2 gene. Sequence analysis revealed that SCA2 is a novel gene of unknown function. In order to provide insights into the molecular mechanisms of pathogenesis of SCA2 and to identify conserved domains, we isolated and characterized the mouse homolog of the SCA2 gene. Sequence and amino acid analysis revealed 89% identity at the nucleotide and 91% identity at the amino acid level. However, there was no extended polyglutamine tract in the mouse SCA2 cDNA, suggesting that the normal function of SCA2 is not dependent on this domain. Northern blot analysis of different mouse tissues indicated that the mouse SCA2 gene was expressed in most tissues, but at varying levels. Alternative splicing seen in human SCA2 was conserved in the mouse. By northern blot analysis, SCA2 was expressed during embryogenesis as early as day 8 of gestation (E8). Immunohistochemical staining using affinity-purified antibodies demonstrated that ataxin 2 was expressed in the cytoplasm of Purkinje cells as well as in other neurons of the CNS.      

Initiation of periovulatory events in gonadotrophin-stimulated macaques with varying doses of recombinant human chorionic gonadotrophin

During in-vitro fertilization (IVF) cycles, a large bolus of human chorionic gonadotrophin (HCG) is used to induce periovulatory events, but the efficacy of lower doses is undefined. Following follicular stimulation in rhesus monkeys, oocyte nuclear maturation, IVF, granulosa cell luteinization and corpus luteum function were compared after injection of 100, 300 or 1000 IU recombinant HCG or 1000 IU urinary HCG. Bioactive HCG rose to peak concentrations within 2 h that were proportional to the dose administered (100 < 300 < 1000 IU, recombinant HCG = urinary HCG). The duration of surge values (>100 ng/ml) was also dose-dependent (0 h, 100 IU; 24 h, 300 IU; >48 h, 1000 IU, recombinant and urinary HCG). While the proportions of oocytes resuming meiosis and undergoing IVF were similar among groups, fewer animals yielded fertilizable oocytes following 100 and 300 IU (five of nine) compared to 1000 IU recombinant and urinary HCG (nine of 10). Peak values of serum progesterone in the luteal phase were similar, but declined 2 days earlier after 100 and 300 IU relative to 1000 IU recombinant and urinary HCG. Thus, 3-10 fold lower doses of HCG elicit low amplitude surges of short duration that induce periovulatory events such as re-initiation of oocyte meiosis and granulosa cell luteinization. However, oocyte fertilization and luteal function may optimally require surges of higher amplitude and longer duration similar to those produced by standard doses of 1000 IU recombinant or urinary HCG.      

Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC)

Focal non-epidermolytic palmoplantar keratoderma (PPK or palmoplantar ectodermal dysplasia type III) is associated with oesophageal cancer in three families: two large pedigrees located in Liverpool, UK and in the midwestern American states and one smaller family from Germany. In these families, the PPK is inherited as autosomal dominant and has a late onset, usually manifesting between 7 and 8 years of age. The disease is characterised by thickening of the pressure areas of the soles, but is not restricted to the feet and also presents with oral leukokeratosis and follicular hyperkeratosis. The disease locus [previously termed the "tylosis oesophageal cancer gene' (TOC) locus] has been mapped to 17q23-qter by linkage analysis. This region is located telomeric to the keratin 16 gene, in which mutations have been identified in focal PPK families who show no increased cancer risk. We describe the close mapping of this locus to the interval between AFMb054zf9 and D17S1603 using haplotype analysis of additional Genethon markers in the region and show that although the American family is unlikely to be related to either of the other two, the UK and German pedigrees may share a common descent. This work provides a basis for positional cloning and candidate gene analysis in order to identify a gene that may be involved in familial oesophageal cancer.