Lipooligosaccharide of Campylobacter jejuni prevents myelin-specific enteral tolerance to autoimmune neuritis--a potential mechanism in Guillain-Barre syndrome?

Campylobacter jejuni-induced enteritis is the most common infection preceding Guillain-Barre syndrome (GBS), an immune-mediated polyradiculoneuritis. The acute autoimmune attack is thought to be based on C. jejuni antigens which may mimick antigens of the peripheral nervous system. Additional pathomechanisms, like disturbance of natural T cell immunoregulation by C. jejuni, have not been evaluated so far. In experimental autoimmune neuritis (EAN), a T lymphocyte-mediated animal model of human GBS, tolerance to myelin-derived autoantigens can be induced by oral feeding of the respective antigen. Here we investigated whether the lipooligosaccharide (LOS) fraction of C. jejuni may directly alter immunologic tolerance through gastrointestinal pathways. While EAN, actively induced by immunization with bovine peripheral nerve myelin could be ameliorated by precedent feeding of myelin, feeding of C. jejuni LOS along with the myelin antigen not only prevented the tolerizing effects of oral myelin but even accelerated the onset of overt EAN and augmented the myelin-specific B cell response. These findings provide evidence that LOS of C. jejuni, as produced in the gut during C. jejuni-induced enteritis, can disturb natural tolerance to definite proteins which may be or may mimic peripheral nerve antigens. In human patients this may be one of the potential mechanisms to explain why C. jejuni enteritis is a common trigger of GBS.     

Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy

Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.     

Detection of T suppressor cells in patients with organ allografts

Specific immunosuppression of host's immune response to donor HLA antigens has been a major goal to clinical transplantation. Recent evidence has been accumulating to show that a distinct population of T cells expressing the CD8(+) CD28(-) phenotype display suppressor function and inhibit Th activation and proliferation by modulating the APC function. To assess the presence of Ts in transplant recipient's circulation, we have developed a flow cytometry method that measures the expression of costimulatory molecules on donor APC exposed to recipient Th and Ts. Our results demonstrate that quantitation of the capacity of CD8(+) CD28(-) T cells from patient circulation to suppress the activation of costimulatory molecules (CD80, CD86) on donor APC offers a reliable tool for monitoring specific immunosuppression against the graft in solid organ transplantation.     

PCR-RFLP based molecular typing of enteroviruses isolated from patients with aseptic meningitis in Korea

Summary.  We have evaluated PCR–RFLP as a practical method for rapid typing of enteroviruses causing aseptic meningitis in Korea. Through blind examination of 80 clinical isolates from patients with aseptic meningitis, we have compared the results of conventional serotyping with PCR–RFLP based genotyping, which was developed for this study. Among the 80 case isolates, which had been previously typed by routine neutralization test, only 42 cases (52.5%) were matched with typing by PCR–RFLP. The result clearly demonstrated that the enterovirus serotype does not coincide with the genotype. Therefore, the classification of enteroviruses by genotyping with PCR–RFLP, although rapid and simple, may be complicated by regional or seasonal differences. However, the PCR–RFLP method developed in this study is applicable to the epidemiological study of enteroviruses when regional or seasonal differences exist, and is useful in identifying the source of an infection. Received August 6, 2001; accepted April 15, 2002 Published online July 10, 2002     

Regulation of L-carnitine metabolism in Escherichia coli

The metabolization of L-carnitine was studied using whole cells of Escherichia coli 044 K74. It showed features of an epigenetical control. L-carnitine and crotonobetaine were able to induce the carnitine-reducing system. Oxygen and nitrate as electron acceptors, gamma-butyrobetaine as final product of carnitine transformation in E. coli as well as glucose repress the carnitine metabolization. Other betaines and structurally related compounds did not show any effect neither as inductors nor as repressors.     

Hematological indices and the prevalence of anemia in an elderly Chinese population

Hematological indices were determined in a group of 427 elderly Chinese subjects over 60 years old; reference ranges were established after excluding subjects with hemoglobinopathies or diseases giving rise to anemia and those with values less or greater than 3 SD from the mean. The values were similar to those for elderly Caucasians. All the red cell indices were significantly higher in men than women, possibly reflecting the influence of androgens on bone marrow function. Previously reported age-related decline in hemoglobin, red cell count and hematocrit from studies of all age groups was not seen in men or women above age 60 years, but a fall in platelet count with age, which had not been previously reported, was observed. There were no age-related changes in any other indices. Reference ranges were lower for Hb, MCV, and MCH in men and women, compared to those derived from a study of Chinese of all age groups. The prevalence of anemia due to disease and hemoglobinpathies in this population was 6.4% in men and 6.3% in women.     

Chronic intracranial pressure monitoring by telemetry: Clinical experience

Intracranial pressure (ICP) monitoring is a critical measure for avoiding severe brain dysfunction or brain death by directing supportive therapy so as to prevent ICP increase severe enough to reduce cerebral blood perfusion. Such situations occur with brain swelling, increased cerebral vascular volume, and increase in cerebrospinal fluid (CSF) volume. Causes include ischemic stroke, subarachnoid bleeding, brain contusion, encephalitis (as in Reye's syndrome), and hydrocephalus from meningitis or neoplasm. When several days of ICP monitoring can direct resolution of the pressure crisis, the invasive direct connection of an intracranial sensor with external recording device carries only minimal infection risk. Prolonged ICP monitoring for weeks or months demands telemetry and becomes desirable in a number of chronic disease problems including both congenital and acquired hydrocephalus where enlarged and pressurized cerebral ventricles develop with reduced absorption of continuously secreted CSF. Although the primary disturbance in CSF circulation can remain incurable, its palliation by valve-regulated CSF diversions or shunting can restore normal brain function and in infants permit normal brain development. Missing this goal can result from failure to maintain a sufficiently normal pattern of CSF dynamics and ICP. Monitoring of the CSF pressure fluctuations transmitted through an intraventricular catheter provides the most accurate record of ICP pulsations. Therefore, a pressure sensing module can be “T'd” into an existing shunt system in continuity with the already placed ventricular tube. The capacity to monitor ICP accurately by telemetry was first established in dogs made hydrocephalic to assure free CSF pulse through a ventricular catheter (1,2,3, 4,5). The subsequent use of ICP monitoring by telemetry in three patients will be described.     

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.     

Ocular colobomata, cardiac defect, and other anomalies: a study of seven cases including two sibs.

An association of ocular colobomata and congenital heart disease was observed in seven patients. Two of these were maternal half sisters whose mother also had ocular colobomata. All the patients had normal karyotypes. There was a high incidence of other associated abnormalities involving the central nervous, skeletal, and urogenital systems. Discovery of an ocular coloboma should alert the clinician to search for other abnormalities.     

Calmodulin content in human prolactin-secreting pituitary adenoma: an inverse relationship to serum prolactin levels

Calmodulin content was evaluated in 3 prolactin-secreting pituitary adenomas (prolactinoma) and 3 normal anterior pituitary glands. The calmodulin content in the normal anterior pituitary tissue was quite consistent, 3.32 +/- 0.016 micrograms/mg protein. In contrast, calmodulin content varied almost 4-fold in the prolactinoma tissue (10.97, 8.50 and 3.00 micrograms/mg protein). Preoperative serum prolactin levels varied inversely with the prolactinoma calmodulin content (125, 257 and 3526 ng/ml, respectively). This study reveals that prolactinoma calmodulin content differs from normal, although it is not uniformly elevated as in other transformed tissues and that elevation of prolactinoma calmodulin content does not positively correlate with serum prolactin levels.