Imaging frozen, hydrated acrosomal bundle from Limulus sperm at 7 A resolution with a 400 kV electron cryomicroscope

Actin and scruin are present in a highly ordered array in the acrosomal bundle from Limulus sperm. Frozen, hydrated acrosomal bundle can be imaged in a 400 kV electron cryomicroscope using the spot-scan technique. Quantitative analysis of the h0l projection images shows diffraction data beyond 7 A.     

Experimental validation of radiopharmaceutical absorbed dose to mineralized bone tissue

Therapeutic and palliative uses of bone-seeking radiopharmaceuticals are undergoing clinical trials for human subjects. Radiation dosimetry for these applications is based on the Medical Internal Radiation Dosimetry (MIRD) schema. An experimental method for dosimetry of bone tissue based on electron paramagnetic resonance (EPR) spectrometry is described. Preliminary results for beagle bone exposed to radiopharmaceuticals under clinical conditions have indicated that the EPR dose measurements give approximately the calculated dose, but suggest that the dose distribution may be non-uniform.     

Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS

The highly conserved and mutationally intolerant retroviral zinc finger motif of the HIV-1 nucleocapsid protein (NC) is an attractive target for drug therapy due to its participation in multiple stages of the viral replication cycle. A literature search identified cystamine, thiamine disulfide, and disulfiram as compounds that have been shown to inhibit HIV-1 replication by poorly defined mechanisms and that have electrophilic functional groups that might react with the metal-coordinating sulfur atoms of the retroviral zinc fingers and cause zinc ejection. 1H NMR studies reveal that these compounds readily eject zinc from synthetic peptides with sequences corresponding to the HIV-1 NC zinc fingers, as well as from the intact HIV-1 NC protein. In contrast, the reduced forms of disulfiram and cystamine, diethyl dithiocarbamate and cysteamine, respectively, were found to be ineffective at zinc ejection, although cysteamine formed a transient complex with the zinc fingers. Studies with HIV-1-infected human T-cells and monocyte/macrophage cultures revealed that cystamine and cysteamine possess significant antiviral properties at nontoxic concentrations, which warrant their consideration as therapeutically useful anti-HIV agents.     

Stabilization of pelvic ring disruptions

Pelvic ring disruptions are challenging management problems for the orthopedic surgeon. Early hemorrhage, permanent nerve injury, and late pain caused by residual pelvic deformity are some of the many complicating factors. A variety of treatment alternatives are available to stabilize the disrupted pelvic ring. Each technique has inherent advantages and problems.     

Detection of occult disease in tissue donors by routine autopsy

A particular pigmentary disorder develops on the skin of Chinese children. The lesions are composed of whitish macules and patches arranged in linear bands on the extremities unilaterally. Histologically these lesions are hypopigmented chronic dermatitis. Although the lesions are arranged in a lichen striatus pattern, they differ clinically from lichen striatus by the absence of papules and plaques. These cases may represent a new entity. The differential diagnosis includes lichen striatus, vitiligo, piebaldism, nevus depigmentosus, and hypomelanosis of Ito. The differences between the disorder presented here and those of different diagnosis are discussed.     

Cocaine impairs follicular phase pulsatile gonadotropin secretion in rhesus monkeys

BACKGROUND: Ménière's disease is a medical condition that involves hearing loss, tinnitus and attacks of vertigo. The attacks can be severely disabling with nausea, dizziness, and aural sensations. METHOD: Three scales assessing the correlates of vertigo attacks in Ménière's disease were developed and completed by 514 subjects diagnosed with the disease. The three scales measured were somatic sensations (SOM), psychological state (PSYCHOL), and situational characteristics (SIT) associated with an attack. RESULTS: Psychometric properties of the three scales were investigated showing Cronbach's alphas of 0.76, 0.80, and 0.62 for the three scales respectively. The results on the scales were related to disease progression. Principal components factor analyses showed that the SOM scale could be divided into two subscales: dizziness/vertigo/anxiety and sensations in the ear. The PSYCHOL scale showed an energy/awareness factor and a negative emotional state factor. The SIT scale, finally, showed two factors: environmental disturbances and stressful conditions. CONCLUSIONS: Knowledge of somatic, psychological and situational premonitory characteristics of attacks in Ménière's disease could lead to improved therapy and counselling.     

Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia

The etiology of the selective neuronal death that occurs in Huntington's disease (HD) is unknown. Several lines of evidence implicate the involvement of energetic defects and oxidative damage in the disease process, including a recent study that demonstrated an interaction between huntingtin protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using spectrophotometric assays in postmortem brain tissue, we found evidence of impaired oxidative phosphorylation enzyme activities restricted to the basal ganglia in HD brain, while enzyme activities were unaltered in three regions relatively spared by HD pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase-corrected complex II-III activity was markedly reduced in both HD caudate (-29%) and putamen (-67%), and complex IV activity was reduced in HD putamen (-62%). Complex I and GAPDH activities were unaltered in all regions examined. We also measured levels of the oxidative damage product 8-hydroxydeoxyguanosine (OH8dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH8dG levels were significantly increased in HD caudate. Cytosolic SOD activity was slightly reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity was unaltered in these regions. These results further support a role for metabolic dysfunction and oxidative damage in the pathogenesis of HD.