Giant axonal neuropathy: central abnormalities demonstrated by evoked potentials

Previous studies of giant axonal neuropathy have reported clinical and pathological findings that indicate involvement of the central nervous system. We studied 3 boys with giant axonal neuropathy, who were 14 to 16 years of age, using auditory, visual, and somatosensory evoked potentials. Absence of waveforms and prolongation of peak and interwave latencies were found. Abnormalities were noted in all modalities. The auditory brainstem evoked response in particular indicated a significant increase in brainstem conduction time. These studies add clinical neurophysiological confirmation of the central nervous system involvement in this disorder and may also provide a means of quantitative evaluation of its progression.     

The simultaneous determination of cerebrospinal fluid and plasma adenosine deaminase activity as a diagnostic aid in tuberculous meningitis

The simultaneous determination of cerebrospinal fluid (CSF) and plasma adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in tuberculous meningitis (TBM). CSF and plasma ADA activity were determined in four groups of patients: (i) a 'no meningitis' group of 174 children investigated for possible meningitis, but found to be uninfected; (ii) an aseptic meningitis group of 40 children; (iii) a bacterial meningitis group of 31 children; and (iv) a TBM group of 27 patients (24 children and 3 adults). CSF ADA alone was determined in a further 23 children with aseptic meningitis, 19 with bacterial meningitis and 13 children and 7 adults with TBM. Both the CSF/plasma ADA ratio and the absolute CSF ADA activity were raised in TBM (mean values 0,24 and 12,61 U/I respectively) and bacterial meningitis (mean values 0,59 and 15,43 U/I respectively), but not in the aseptic meningitis group (mean values 0,06 and 2,00 U/I) or the 'no meningitis' group (mean values 0,04 and 1,51 U/I). Both values will distinguish TBM from aseptic meningitis, but do not appear to hold any marked advantages over conventional CSF criteria in the diagnosis of TBM.     

Role of membrane N-linked oligosaccharides in host cell interaction with invasive forms of Trypanosoma cruzi

The removal of N-linked oligosaccharides by peptide-N4-[N-acetyl-beta-glucoseaminyl]asparagine amidase (previously known as aspartoglycosylamine amidohydrolase and abbreviated N-glycanase) from the surface of blood or insect-transmissible forms of Trypanosoma cruzi markedly increased the capacity of these organisms to associate with (i.e., bind and penetrate) either mouse peritoneal macrophages or rat heart myoblasts. This effect was evidenced by a significant elevation in both the percentage of infected host cells and the average number of parasites per 100 cells. Conversely, N-glycanase treatment of either host cell markedly reduced both parameters to levels significantly below those obtained with cells mock treated with medium alone. The N-glycanase effect on the parasites was inhibited by heat inactivation of the enzyme or by the presence of fetuin, an N-glycanase substrate. The enhanced capacity of N-glycanase-treated T. cruzi to engage the host cells started to subside 2 h after the treatment, indicating the reversibility of the effect. The decreased reactivity of N-glycanase-treated macrophages or myoblasts with T. cruzi suggests that N-linked oligosaccharides on these host cells are involved in the initial phase of the cell infection process. Instead, because T. cruzi interacted more effectively with host cells after treatment with N-glycanase, parasite surface N-linked oligosaccharides would seem to interfere with the association.     

Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists

The resolution of three 2-substituted derivatives of idazoxan is described. The enantiomers show large separations in activity in a variety of in vitro and in vivo tests, and the active isomers are all potent and selective antagonists at the alpha 2-adrenoreceptor. The significance of these results in relation to those published on the enantiomers of idazoxan and to those on optically active alpha 2-adrenoreceptor agonists is discussed.     

Synthesis of estradiol haptens

Synthesis of Estradiol Haptens Two estradiol haptens, 4-(3β,17β-dihydroxyestran-7α-yl)butanoic acid ( 9 ) and 7α-(4-aminobutyl)-3β,17β-estradiols ( 13 ), were prepared from 19-nortestosterone by partial synthesis. The binding activity for the cytosol estrogen receptor was determined by competition against [³H]-estradiol; at a concentration of 2×10^?7mol/l, compound 9 displaces 50% of [³H]-estradiol. Attached to AH-Sepharose 4B compound 9 allows the cytosol estrogen receptor from calf uterus to be concentrated 1800-fold by affinity chromatography.     

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer

Summary Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30–37.5 mg/m² IV QW. In responding patients drug was given QOW after 4–6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m² depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.