Idiopathic CD4+T-cell lymphocytopenia associated with vitiligo

The syndrome of idiopathic CD4+ T lymphocytopenia (ICTL) is defined as the persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells/mm(3) or less than 20% of the total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. To date no known viral origin has been identified. ICTL has a variable clinical course ranging from patients with minimal symptoms to those who have died from opportunistic infections. We report a case of a 32-year-old white man with a long history of vitiligo that is associated with ICTL. He also had incidental psoriasis. The correlation between ICTL and autoimmune vitiligo suggests an aberration in the immune surveillance that leads to an abnormal response of CD4+ T lymphocytes in the host.     

Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype

Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the "S3-site" releases a C-terminal cytoplasmic fragment (Notch intracellular domain) that acts as the intracellular transduction molecule for Notch activation. Missense mutations in the presenilins cause familial Alzheimer's disease by augmenting the "gamma-secretase" cleavage of APP and overproducing one of the proteolytic derivatives, the Abeta peptide. Null mutations in PS1 inhibit both gamma-secretase cleavage of APP and S3-site cleavage of the Notch receptor. Mice lacking PS1 function have defective Notch signaling and die perinatally with severe skeletal and brain deformities. We report here that a genetic modifier on mouse distal chromosome 1, coinciding with the locus containing Nicastrin, influences presenilin-mediated Notch S3-site cleavage and the resultant Notch phenotype without affecting presenilin-mediated APP gamma-site cleavage. Two missense substitutions of residues conserved among vertebrates have been identified in nicastrin. These results indicate that Notch S3-site cleavage and APP gamma-site cleavage are distinct presenilin-dependent processes and support a functional interaction between nicastrin and presenilins in vertebrates. The dissociation of Notch S3-site and APP gamma-site cleavage activities will facilitate development of gamma-secretase inhibitors for treatment of Alzheimer's disease.     

Nitrogen assimilation and growth of wheat under elevated carbon dioxide

Simultaneous measurements of CO(2) and O(2) fluxes from wheat (Triticum aestivum) shoots indicated that short-term exposures to elevated CO(2) concentrations diverted photosynthetic reductant from NO(3)(-) or NO(2)(-) reduction to CO(2) fixation. With longer exposures to elevated CO(2), wheat leaves showed a diminished capacity for NO(3)(-) photoassimilation at any CO(2) concentration. Moreover, high bicarbonate levels impeded NO(2)(-) translocation into chloroplasts isolated from wheat or pea leaves. These results support the hypothesis that elevated CO(2) inhibits NO(3)(-) photoassimilation. Accordingly, when wheat plants received NO(3)(-) rather than NH(4)(+) as a nitrogen source, CO(2) enhancement of shoot growth halved and CO(2) inhibition of shoot protein doubled. This result will likely have major implications for the ability of wheat to use NO(3)(-) as a nitrogen source under elevated CO(2).     

Steep increase in HIV prevalence among tuberculosis patients in Ho Chi Minh City

In Vietnam the spread of HIV infection is thought to be limited. In 12 urban districts of Ho Chi Minh City representative samples of tuberculosis patients have undergone HIV testing since 1995. HIV prevalence increased steeply from 0.5% in 1995 to 4% in 2000, with a doubling time of approximately 21 months. This study highlights the need to intensify HIV/AIDS prevention and control in Vietnam.     

Fatal sepsis in an AIDS patient during therapy for Pneumocystis carinii pneumonia

The case of a patient with a newly diagnosed HIV infection and Pneumocystis carinii pneumonia is presented. Despite treatment with high-dose trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone with initial improvement, the patient acutely deteriorated with severe acidosis and died on the 4th day of hospitalization. Cryptococcus neoformans grew the next day in broncheoalveolar lavage (BAL) and blood culture. As simultaneous presence of more than one opportunistic infection can occur in these patients, systematic workup for other common opportunistic infections must be performed. Received: October 12, 2000 · Revision accepted: December 8, 2001 R. J. Piso (corresponding author)     

Accumulation of PN1 and PN3 sodium channels in painful human neuroma-evidence from immunocytochemistry

BACKGROUND: The axolemmal distribution and density of voltage-gated sodium channels largely determines the electrical excitability of sprouting neurites. Recent evidence suggests that accumulation of sodium channels at injured axonal tips may be responsible for ectopic axonal hyperexcitability and the resulting abnormal sensory phenomena of pain and paresthesias. For future improvement in pain management it is necessary to identify structurally significant generators of autorhythmicity. A first step in this regard will be to determine the predominant types of sodium channels in injured axons. The opportunity to test human specimens from painful and non-painful neuroma is of great value. METHODS: We employed immunocytochemical methods to investigate if two types of highly specific voltage-gated sodium channel subtypes could be detected in sections of human neuroma. FINDINGS: Both subtypes of sodium channels PN1 and PN3 accumulated abnormally in human neuromas. The immunoreactive pattern was more pronounced in painful neuromas. This is in contrast to previous reports that focused either on PN1 or PN3 as main generators of hyperexcitability induced pain. INTERPRETATION: Both, PN1 and PN3 seem to be involved in hyperexcitability induced pain. It can be expected that a variety of other highly specific voltage gated sodium channel subtypes will be detected in regenerating peripheral nerve in the near future, which contribute to the development of neuropathic pain states. Thus, in order to therapeutically control hyperexcitability induced neuropathic pain, it might be worthwhile to develop pharmaceuticals that can selectively block different sodium channel subtypes and subunits.A review of the role of sodium channels in neuropathic pain is implemented in the discussion.     

Intermediate term follow-up of calcaneal osteotomy and flexor digitorum longus transfer for treatment of posterior tibial tendon dysfunction

Twenty-three patients with stage II posterior tibial tendon dysfunction who had failed non-surgical therapy were treated with flexor digitorum longus transfer and calcaneal osteotomy. At latest follow-up averaging 35 +/- 7 months (range, 24 to 51 months), 22 patients (96%) were subjectively "better" or "much better." No patient had difficulty with shoe wear; however, four patients (17%) required routine orthotic use consisting of a molded shoe insert. AOFAS scores were available on 21 patients and improved from a preoperative mean of 50 +/- 14 (range, 27 to 85) to a postoperative mean of 89 +/- 10 (range, 70 to 100). Our experience, at an intermediate date follow-up is that calcaneal osteotomy and flexor digitorum longus transfer is a safe and effective form of treatment for stage II posterior tibial tendon dysfunction.