An example of almost universally observable vector fields on P(R)

Using methods of dynamical systems, we construct examples of smooth, almost universally observable vector fields on the projective 1-space. These vector fields are non-linear, non-autonomous and their time dependence is almost periodic.     

Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized neuropathologically by chromatolysis, Bunina bodies, hyaline inclusions, skein-like inclusions and axonal spheroids. Aluminum, a known neurotoxin, is the cause of dialysis encephalopathy and is considered to be a causative agent in high incidence foci of ALS in the western Pacific. We have developed an experimental model of motor neuron degeneration in New Zealand white rabbits using chronic low-dose intracisternal administration of aluminum and compared the clinical and neuropathological changes to those of human ALS. Aluminum-inoculated rabbits developed progressive hyperreflexia, hypertonia, limb splaying, gait impairment, muscle wasting, hindlimb paralysis and impaired tonic immobility responses without overt encephalopathic features over a 14-month period. Examination of spinal cords from these animals demonstrated the frequent occurrence and progressive development of anterior horn cell lesions that included small, round, argentophilic perikaryal inclusions similar to hyaline inclusions seen in human ALS. Other inclusions were more condensed and eosinophilic, while still others had neurofibrillary tangle-like morphologies. Axonal spheroids and neuritic thickenings were also prominent and were identical to those seen in human ALS. We believe that the similar and progressive development of neuropathological changes observed in the chronic aluminum-intoxication model, compared to human ALS, warrants further study to aid in understanding the cellular and molecular mechanisms of human motor neuron disease.     

Design of an IV Formulation of an Unstable Prodrug Candidate for Prostate Cancer Treatment: Solution Chemistry of N-(glutaryl-hyp-ala-ser-cyclohexylglycyl-gln-ser-leu)-doxorubicin

ABSTRACT

The chemical degradation of N-(glutaryl-hyp-ala-ser-cyclohexylglycyl-gln-ser-leu)-doxorubicin (henceforth referred to as doxorubicin peptide conjugate 1) was studied in buffered aqueous solution. The pH-rate profile of degradation shows that the doxorubicin conjugate is most stable between pH 5 and 6. The dependence of log k_obsd on pH in acidic medium is characteristic of specific acid-catalysis of the sugar hemiaminal of 1 (as in the case of doxorubicin). Isolation of degradates and structural determination shows that the degradation at lower pH values yields the water-insoluble aglycone doxorubicinone, supporting the mechanism of acid-catalyzed loss of the amino sugar. At pH higher than 5, a more complicated degradation pattern is observed, including the loss of the amino sugar and the aromatization of the saturated ring to give 7,8-dehydro-9,10-desacetyldoxorubicinone as one of the major products. Around the pH of maximum stability in solution, the rate of degradation of 1 is significantly greater than that for doxorubicin, which rules out the formulation of a room temperature solution product with a sufficiently long shelflife for market use. Design of a stable lyophilized formulation for sterile reconstitution based on the physicochemical properties of 1 is described.     

CCR5 chemokine receptor genotype frequencies among Puerto Rican HIV-1-seropositive individuals

Some individuals remain uninfected by human immunodeficiency virus type 1 (HIV-1), despite multiple sexual contacts with subjects with confirmed HIV-1 infection. Several studies have confirmed that individuals who are homozygous for a 32 base pair (bp) deletion mutation in the chemokine receptor gene CCR5, designated as delta 32/ delta 32, are protected against HIV-1 infection. Heterozygotes of the same chemokine receptor deletion mutation are, however, not protected from acquiring HIV-1 infection but seemingly have slower progression to acquired immunodeficiency syndromes (AIDS). Genotype frequencies of the delta 32 CCR5 mutation vary markedly among different ethnic groups; heterozygosity is found in approximately 15% of Caucasians, about 5-7% of Hispanics and African Americans and 1% or less of Asians. The ethnic background of Puerto Ricans is highly complex and usually includes admixture of Caucasian, Caribbean Indian and African traits to a varying extent. This study was conducted to examine the frequencies of the delta 32 CCR5 mutation among Puerto Ricans who are infected with HIV-1. Samples were received from different geographical regions of the island. Of 377 samples tested, 94.2% were wild type (non-deletion mutant) homozygotes, 5.8% were delta 32 CCR5 heterozygotes, and none were delta 32 CCR5 homozygotes. The incidence of CCR5 delta 32/w heterozygous mutation among Puerto Ricans seems to be somewhat lower than what was reported with US Hispanics. Some age and gender associated bias of the mutation frequency were observed with the study population, the reason for which is unclear at present.     

Design of an i.v. formulation of an unstable prodrug candidate for prostate cancer treatment: solution chemistry of N-(glutaryl-hyp-ala-ser-cyclohexylglycyl-gln-ser-leu)-doxorubicin

The chemical degradation of N-(glutaryl-hyp-ala-ser-cyclohexylglycyl-gln-ser-leu)-doxorubicin (henceforth referred to as doxorubicin peptide conjugate 1) was studied in buffered aqueous solution. The pH-rate profile of degradation shows that the doxorubicin conjugate is most stable between pH 5 and 6. The dependence of log k_obsd on pH in acidic medium is characteristic of specific acid-catalysis of the sugar hemiaminal of 1 (as in the case of doxorubicin). Isolation of degradates and structural determination shows that the degradation at lower pH values yields the water-insoluble aglycone doxorubicinone, supporting the mechanism of acid-catalyzed loss of the amino sugar. At pH higher than 5, a more complicated degradation pattern is observed, including the loss of the amino sugar and the aromatization of the saturated ring to give 7,8-dehydro-9,10-desacetyldoxorubicinone as one of the major products. Around the pH of maximum stability in solution, the rate of degradation of 1 is significantly greater than that for doxorubicin, which rules out the formulation of a room temperature solution product with a sufficiently long shelflife for market use. Design of a stable lyophilized formulation for sterile reconstitution based on the physicochemical properties of 1 is described.     

Gradual loss of IgG antibodies against GB virus C/hepatitis G virus in a patient with AIDS

GB virus C/hepatitis G virus (GBV-C/HGV) is a positive-sense, single-stranded RNA virus belonging to the family Flaviviridae and is distantly related to hepatitis C virus (HCV). GBV-C/HGV can be transmitted by the parenteral and the sexual route. Among individuals infected with human immunodeficiency virus type 1 (HIV-1) by the sexual route, we and others have demonstrated a high prevalence of GBV-C/HGV infection. Recently, Woolley and colleagues reported that AIDS patients co-infected with GBV-C/HGV had a significantly lower mean CD4 cell count than AIDS patients without GBV-C/HGV infection, suggesting that GBV-C/HGV antibody may be lost with progression to AIDS. To our knowledge no data are available on the loss of antibody against GBV-C/HGV in AIDS patients. We now report on an HIV-infected patient who exhibited gradual loss of IgG antibodies against GBV-C/HGV, as well as HCV, with progression of HIV disease.     

Application of Lipase from Marine Bacteria Bacillus sonorensis as an Additive in Detergent Formulation

The efficacy of lipase (triacylglycerol acylhydrolases EC 3.1.1.3) as a detergent additive from a newly isolated marine halophilic bacteria Bacillus sonorensis from marine clams Paphia malabarica collected in the Kalbadevi Estuary, Mumbai, has been assessed and reported. In terms of activity and stability, the lipase exhibited maximum activity in alkaline conditions and was observed to be stable over a temperature range from room temperature to 60 °C. The activity of the lipase increased in the presence of surfactants and detergents. Due to these properties of the lipase from marine bacteria, it was used as an additive in detergents to study its efficiency at corn oil removal from fabrics. The washing studies indicated that the efficiency of corn oil removal from the cotton fabrics increased by 20 % when lipase was incorporated in the detergent as compared to the treatment with detergent alone. The lipase was also capable of removing corn oil from natural as well as synthetic fabrics dyed with a respective, preferred class of dyes.