Lipopolysaccharides from three phytopathogenic pseudomonads

The use of acetylated phenyl 1-seleno-beta-D-galactofuranoside as a glycosyl donor for the synthesis of protected D-Galf-beta-(1-->3)-alpha-D-Manp as its methyl or ethylthio glycoside has been demonstrated. Activation of the selenoglycoside over a thioglycoside acceptor by NIS/TfOH is extremely selective and gives the ethylthio disaccharide in 91% yield. The parent disaccharide is found as a terminal and branched unit in the lipopeptidophosphoglycan oligosaccharides of the protozoan Trypanosoma cruzi, the causative agent of Chagas' disease.     

Morphological and molecular processes of polyp formation in Apc(delta716) knockout mice

Mutations in the human adenomatous polyposis coli (APC) gene are responsible for not only familial adenomatous polyposis but also many sporadic cancers of the digestive tract. Using homologous recombination in embryonic stem cells, we recently constructed Apc gene knockout mice that contained a truncation mutation at codon 716 (Apc(delta716)). The heterozygous mice developed numerous intestinal polyps. All microadenomas dissected from nascent polyps had already lost the wild-type allele, indicating the loss of heterozygosity (M. Oshima et al., Proc. Natl. Acad. Sci. USA, 92: 4482-4486, 1995). We also demonstrated that cyclooxygenase 2 is induced in the polyps at an early stage and plays a key role in polyp development (M. Oshima et al., Cell 87: 803-809, 1996). We have analyzed the process of polyp development in these mice both at morphological and molecular levels. A small intestinal microadenoma is initiated as an outpocketing pouch in a single crypt and develops into the inner (lacteal) side of a neighboring villus forming a double-layer nascent polyp. The microadenoma then enlarges and gets folded inside the villus. When it fills the intravillous space, it expands downward and extends into adjoining villi, rather than rupturing into the intestinal lumen. During this course of development, the basement membrane remains intact, and the labeling index of the microadenoma cells is similar to that of the normal crypt epithelium. As in the crypt cells, neither transforming growth factor beta1 nor its receptor type II is expressed in the microadenoma cells. No hot spot mutations in the K-ras gene are found in the microadenoma tissue during these early stages of polyp development. Essentially, the same results have been obtained for the colonic polyps as well. These results suggest that early adenomas in the Apc(delta716) polyps are very similar to the normal proliferating cells of the crypt except for the lack of directed migration along the crypt-villus axis.     

Dietary fat intake and the risk of incident dementia in the Rotterdam Study

OBJECTIVE: To document prospectively variation in penile morphology and clinical findings in children. PATIENTS AND METHODS: The study comprised a consecutive sample of 468 boys whose consultation with a physician included a genital examination in a primary-care paediatric practice in rural northern Wisconsin. RESULTS: Circumcised boys under 3 years of age were significantly more likely to have a partially or completely covered glans, a reddened meatus, balanitis, or trapped epithelial debris, and less likely to have a fully exposed glans than were circumcised boys of 3 years or older. Among the 238 boys under 3 years, those circumcised were significantly more likely to have non-cosmetic problems, including coronal adhesions, trapped epithelial debris, a reddened meatus, preputial stenosis (phimosis) and balanitis, than were boys with a foreskin. Findings in the circumcised group under 3 years included: fully exposed glans (n = 78, 35.6%), partially covered glans (n = 67, 30.6%), adhesions (25.6%), completely covered glans (20.1%), entrapped desquamated epithelial debris (24.7%), reddened meatus (19.1%), balanitis (15.5%), and preputial stenosis (0.9%). Only two genital examinations in boys with foreskins revealed pertinent findings. Coronal adhesions develop in circumcised boys at 2-6 months of age and usually resolve by 24 months. The degree of skin covering the glans after neonatal circumcision peaks at 6 months of age. CONCLUSIONS: There are significant variations of appearance in circumcised boys; clinical findings are much more common in these boys than previously reported in retrospective studies. The circumcised penis requires more care than the intact penis during the first 3 years of life. Parents should be instructed to retract and clean any skin covering the glans in circumcised boys, to prevent adhesions forming and debris from accumulating. Penile inflammation (balanitis) may be more common in circumcised boys; preputial stenosis (phimosis) affects circumcised and intact boys with equal frequency. The revision of circumcision for purely cosmetic reasons should be discouraged on both medical and ethical grounds.     

Comparison of the Amplicor HIV-1 monitor test and the nucleic acid sequence-based amplification assay for quantitation of human immunodeficiency virus RNA in plasma, serum, and plasma subjected to freeze-thaw cycles

The Amplicor HIV-1 Monitor test was compared to the nucleic acid sequence-based amplification (Nasba) assay system for the quantitation of human immunodeficiency virus (HIV) RNA in three different types of clinical samples: plasma, serum, and plasma subjected to freeze-and-thaw cycles. Each assay detected HIV RNA in the same 73 (90%) of 81 samples tested, and the quantitative results obtained with the two assays were significantly correlated. Both assays detected higher RNA levels in patients with CD4+ cell counts lower than 200 cells/mm3 than in patients with CD4+ cell counts higher than 200 cells/mm3. In addition, RNA levels in plasma higher than 5 logs predicted higher numbers of clinical events than did RNA levels in plasma lower than 5 logs. Quantitation of HIV RNA in paired plasma and serum samples showed lower HIV RNA content in serum than in the paired plasma sample, with mean differences between HIV RNA contents of plasma and serum of 0.54 and 0.28 log RNA copy/ml by the Nasba assay and the Amplicor HIV-1 Monitor assay, respectively. No significant loss of HIV RNA was detected with either assay in plasma samples subjected to multiple freeze-and-thaw cycles. These studies demonstrate that the Nasba and Amplicor assays perform similarly with plasma and serum samples. Further, the results indicate that freeze-and-thaw cycles do not result in significant loss of detectable HIV RNA.     

Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist stimulation during lactation

To determine whether altered noradrenergic activation of the hypothalamo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine response to stress observed during lactation, the effect of intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg) was compared between virgin and lactating rats. Virgin rats showed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly elevated for more than 120 min, but lactating rats showed no significant increase in corticosterone levels. Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited comparable elevations in plasma PRL after methoxamine treatment. Arginine vasopressin messenger RNA expression within the parvocellular PVN was greater in the lactating animals than in the virgin controls, but methoxamine injection was without further effect. Studies performed on ovariectomized virgin rats and ovariectomized rats receiving estradiol or progesterone replacement failed to reproduce the attenuated HPA responses seen after methoxamine treatment, although methoxamine-induced PRL levels were greatly increased by estradiol, probably arising from an effect on hormone synthesis. In vitro electrophysiological recordings of PVN neurons in hypothalamic slices from proestrous virgin and lactating rats showed that 45-52% of neurons in both groups exhibited excitatory responses to 10(-4) M methoxamine, but there was a differential response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-regulation of alpha1-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activation of the HPA axis during lactation.     

Parvovirus B19 quiescence during the course of human immunodeficiency virus infection in persons with hemophilia

One hundred and seventy patients with major lower limb amputation (MLLA) presenting to The National Prosthetic-Orthotic Centre (NPOC) in Khartoum over a 1-year period were studied. There were 141 males and 29 females giving a M:F ratio of 4.9: 1.0, with mean age of 37 years (range 5-72 years). Forty-one patients (24%) underwent amputation of diabetic septic foot, 30 patients (17.6%) underwent amputation as a result of trauma from road traffic accidents and Madura foot, and war injuries accounted for 29 amputations (17%). One hundred and eleven patients had below knee amputation (BKA), 52 had above knee amputation (AKA) and seven patients had Syme's amputation. Diabetic amputees had higher rate of revisional surgery compared with others because of sepsis and/or flap necrosis. Stump pain was reported by amputees with excessive scarring of the stump and those with undue prominence of bony ends. There are two types of prostheses provided by the NPOC for both BKA and AKA: the peg leg and the conventional prostheses. The Syme's amputees were fitted with either simple hoof or articulated prostheses with solid ankle cushion heel (SACH). The peg leg consists of a leather lined side bearing metal socket connected to a rocker base by side steels. It is used by the country natives as it suits different weather and job conditions, particularly farming, and it can be repaired locally. The urban population use the conventional prostheses which is lighter in weight, can be put on and taken off easily and is cosmetically acceptable. However, these prostheses are more expensive and require frequent repair or replacement. The functional outcome of patient's rehabilitation with the prostheses was significantly affected by the level and indication of amputation. Those with BKA and those amputated because of trauma or Madura foot experienced better functional outcome compared with the diabetics, independent of age. 50% of patients with the AKA and 19% of those with BKA reported poor functional outcome. Surgeons should be more involved with the long-term evaluation of functional outcome in such patients, to offer help if feasible and to modify their technique for future procedures.     

Pitfalls in diagnosis of Lyme disease. What you need to know about serologic testing

Lyme disease can be difficult to recognize because not all patients have erythema migrans or other classic symptoms. Therefore, laboratory testing has become an important aid to clinical diagnosis. But the story doesn't end there-serologic testing presents another set of problems and concerns. Drs. Still and Ryan explain how aspects of the disease itself and various factors inherent in the available tests can affect laboratory results.     

Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes

In an unprecedented finding, Davis et al. [Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N. & Parker, W. D., Jr. (1997) Proc. Natl. Acad. Sci. USA 94, 4526-4531] used an unusual DNA isolation method to show that healthy adults harbor a specific population of mutated mitochondrial cytochrome c oxidase (COX) genes that coexist with normal mtDNAs. They reported that this heteroplasmic population was present at a level of 10-15% in the blood of normal individuals and at a significantly higher level (20-30%) in patients with sporadic Alzheimer's disease. We provide compelling evidence that the DNA isolation method employed resulted in the coamplification of authentic mtDNA-encoded COX genes together with highly similar COX-like sequences embedded in nuclear DNA ("mtDNA pseudogenes"). We conclude that the observed heteroplasmy is an artifact.     

Hepatitis C virus liver disease in women infected with contaminated anti-D immunoglobulin

The just-in-time (JIT) model originated in the manufacturing industry as a way to manage parts inventories process so that specific components could be made available at the appropriate times (that is, "just in time"). This JIT model can be applied to the management of clinical information inventories, so that clinicians can have more immediate access to the most current and relevant information at the time they most need it--when making clinical care decisions. The authors discuss traditional modes of managing clinical information, and then describe how a new, JIT model may be developed and implemented. They describe three modes of clinician-information interactions that a JIT model might employ, the scope of information that may be made available in a JIT model (global information or local, case-specific information), and the challenges posed by the implementation of such an information-access model. Finally, they discuss how JIT information access may change how physicians practice medicine, various ways JIT information may be delivered, and concerns about the trustworthiness of electronically published and accessed information resources.