The Massachusetts Mental Health/Substance Abuse managed care program: The providers' view

This paper reviews the differential impacts of the Massachusetts Mental Health/Substance Abuse Program from the viewpoints of the providers. The program is a state wide managed care system, providing services for adult and children's mental health and substance abuse care. Interviews found that even though the severity of illness of most clients in the program was greater than before managed care, most providers believed that the quality of care and access to services for these clients was the same or better than before managed care. Providers' concerns about the future suggested that savings in a managed care program primarily occur in its initial stages and that future reductions have the potential for negative impacts upon clients and providers.Funding for this study was provided by the Massachusetts Division of Medical Assistance (James O. Michel, Director of the Mental Health/Substance Abuse Program.)     

The Importance of Surface Charge in the Optimization of Antigen–Adjuvant Interactions

The adsorptive behavior of the recombinant malarial antigens R32tet32, R32NS181 and NS181V20 to aluminum hydroxide and aluminum phosphate gels was studied as a function of pH and buffer ions. The Plasmodium falciparum antigen, R32NS181, and the P. vivax antigen, NS181V20, with isoelectric points (pI) of 5.9 and 5.5, respectively, adsorbed readily to the positively charged boehmite form of aluminum hydroxide gel. These two antigens displayed reversible, linear adsorption behavior in the pH range 5–9, with maximal adsorption observed at the lowest pH studied. The addition of acetate buffer ions had little effect on adsorption, while the presence of phosphate decreased adsorption for R32NS181 and NS181V20 by 25 and 40% respectively. The adsorptive behavior of these two antigens with the negatively charged adjuvant, aluminum phosphate, was markedly decreased. The converse situation was observed with the R32tet32 antigen, whose pI is estimated to be 12.8. There was minimal interaction of this antigen with aluminum hydroxide gel except in the presence of phosphate counter ions and significant, nonreversible adsorption with aluminum phosphate gel. Enhanced adsorption of R32tet32 to aluminum hydroxide gel in the presence of phosphate is suggested to be the result of a covalent bond between a surface aluminum and a phosphate anion that modifies the surface charge of the aluminum hydroxide gel. These results indicate that the role of complementary surface charges, both for the ionization state of the protein and for the aluminum adjuvants, is the key in optimizing conditions for significant antigen-adjuvant interactions.     

Mutations in human breast cancer: an overview

Studies of mammary tumorigenesis in mice infected with the mouse mammary tumor virus and in certain strains of transgenic mice with an activated oncogene have provided strong evidence that multiple mutations contribute to the initiation and progression of malignancies in the breast. The increasing availability of recombinant DNA probes that detect various proto-oncogenes, growth factor genes, and growth factor receptor genes, as well as restriction fragment length polymorphisms in the human population, have made possible a molecular approach for the identification of frequently occurring mutations in primary human breast tumor DNA. The aim of studies using this molecular approach has been to investigate whether specific mutations are highly associated with various clinical parameters, including disease prognosis. Eight mutations have been identified, including amplification of c-myc, c-erbB2, and int-2, as well as loss of heterozygosity on five chromosomes (1q, 3p, 11p, 13q, and 17p). Loss of heterozygosity is thought to unmask recessive mutations of tumor-suppressor genes. In some studies, amplification of either c-myc, c-erbB2, or int-2 has been found to have a significant association with high risk of relapse or poor survival. The current status of these mutations as potentially useful prognostic indicators for the management of the disease is controversial and points to the need for further research in this area.     

Molecular cloning and complete sequence determination of RNA genome of human rhinovirus type 14.

The genomic RNA of human rhinovirus type 14 was cloned in Escherichia coli and the complete nucleotide sequence was determined. The RNA genome is 7212 nucleotides long. A single large open reading frame of 6536 nucleotides was identified, which starts at nucleotide 678 and ends 47 nucleotides from the 3' end of the RNA genome. Comparisons of the specified proteins with those of other picornaviruses showed a striking homology (44-65%) between rhinovirus and poliovirus. The rhinovirus genomic RNA is rich in adenosine (32.1%) and strongly favors an adenosine or uridine in the third position of codons. The predicted map locations of all the rhinovirus structural and non-structural proteins and their proposed proteolytic cleavage sites are described.     

Steric control of CO binding in a totally synthetic heme protein model

A family of totally synthetic models for the carbon monoxide adducts of heme proteins has been synthesized and applied to the elucidation of the role of steric effects in the relative detoxification of carbon monoxide. The complexes are designed such that a sheltered void of controllable dimensions encompasses the CO binding site. Systematic variations in the available space for the iron-bound CO produce a wide range of equilibrium binding constants (K_CO). An x-ray structure determination of a CO adduct complex having a crowded CO site reveals that the Fe—CO linkage is bent, and further, the distortion involves both displacement of the Fe—C vector from the normal to the N₄ plane and bending of the Fe—C—O angle.     

Prevention of blindness after blepharoplasty

As reported in the medical literature, approximately 68 patients have been blinded by complications of the blepharoplasty procedure. All cases have been associated with intraoperative or postoperative orbital hemorrhage. Those factors which will help blepharoplasty surgeons reduce the occurrence of orbital hemorrhage and subsequent blindness are reviewed.     

Cholesterol esterification and Niemann-Pick disease: an approach to identifying the defect in fibroblasts

Fibroblasts from 13 patients with the clinical phenotype of type IIS, Niemann-Pick disease were evaluated for their ability to incorporate oleic acid into cholesterol esters via an LDL responsive mechanism. Eight patients displayed a severe deficiency (less than 8% of normal) of cholesterol ester (CE) synthesis while a clinically less affected group displayed intermediate levels (36% of normal) of synthetic capacity with no detectable overlap between these groups and the control range. There was no deficiency in cholesterol ester production in fibroblasts from a patient with Zellweger's disease, a disorder characterized by altered peroxisomes and abnormal peroxisomal cholesterol metabolism, while in I-cell disease, characterized by a primary deficiency of a phosphotransferase which results in altered targeting of lysosomal hydrolases, it was reduced to 25% of the control level. To further implicate lysosomal proteins in the etiology of type IIS, Niemann-Pick disease we measured the effect of correction (conditioned) medium, and the lysosomotropic agent, NH4Cl on cholesterol ester synthesis in fibroblasts. NH4Cl completely inhibited incorporation into CE by normal cells, thus mimicking the CE defect in type IIS, Niemann-Pick cells. Conditioned medium had no effect on incorporation into CE synthesis but medium conditioned in the presence of 10 mM NH4Cl stimulated incorporation into CE in the control but not in Niemann-Pick cells. When Niemann-Pick cells cultured in the presence of NH4Cl were challenged to synthesize CE in the absence of NH4Cl, a significant enhancement of CE synthesis was noted in representative cell lines from both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)