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Biomedical subjects

H Han

Publications and source records attributed to H Han.

At least 55 records · Page 3Linked to original sources
PubMed1999

Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by abnormal lipoprotein deposition in the glomeruli, dysbetalipoproteinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although the plasma cholesterol and triglyceride levels were normal, the levels of intermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/dl (0.336 mmol/l; 4.2+/-2.9 mg/dl, mean +/- SD, in 12 normolipidemic controls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual apo E phenotype (E1/3). Apo E genotyping using DNA digested by a restriction enzyme (HhaI) identified a 66-bp fragment which was not seen with any of the common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141-143). This novel mutation involves the region of the apo E molecule known to be critically involved in binding to its receptor, and this may well transform the apo E molecule, an inefficient ligand, to its receptor(s). How this mutations causes glomerular damage remains to be determined.

Apolipoproteins E↗
PubMed1999

Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients.

The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, >/=6 months posttransplantation) renal transplant recipients (RTRs) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid. There are no controlled data evaluating the comparative efficacy of supraphysiological versus standard multivitamin dose folic acid supplementation in reducing fasting total homocysteine (tHcy) levels among RTRs. We block-randomized 60 chronic, stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid at either 2.4 (group 1), 0.4 (ie, standard multivitamin dose) (group 2), or 0.0 (group 3) mg/d. All 60 study participants also received 50 mg/d vitamin B(6) and 0.4 mg/d vitamin B(12). The mean percent reductions (+/-SEM) in fasting tHcy were as follows: group 1, 32.3+/-2.4%; group 2, 23.4+/-2.3%; and group 3, 19.1+/-2.3%. ANCOVA accounting for the pretreatment matching and adjusted for pretreatment levels of fasting tHcy, folate, and albumin; change in creatinine during the study; and cyclosporine A use revealed significant overall group differences (P=0.005) and significant differences between groups 1 and 2 (P=0. 038) and groups 1 and 3 (P=0.001), but not between groups 2 and 3 (P=0.153). Moreover, a chi(2) analysis of participants with pretreatment tHcy levels >/=15 micromol/L (n=29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels <12 micromol/L: group 1, 5 of 10 (50%); group 2, 1 of 11 (9%); and group 3, 0 of 8 (0%) (P=0.016; test of trend P=0. 007). We conclude that a supraphysiological dose of folic acid is superior to standard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs.

Adult↗
PubMed1999

Compound heterozygosity for an apolipoprotein A1 gene promoter mutation and a structural nonsense mutation with apolipoprotein A1 deficiency.

Apolipoprotein (apo) A1 plays a central role in the metabolism of HDL. We describe a novel genetic variant of the apoA1 gene identified in a patient with low concentrations of plasma HDL cholesterol. The proband, a 12-year-old Japanese boy, exhibited markedly low levels of both plasma apoA1 and HDL cholesterol. Genomic DNA sequencing of apoA1 genes of the patient showed a compound heterozygosity for an A to C substitution at 27 bp upstream of the transcription start site of 1 apoA1 allele, and a C to T substitution in another allele at residue 84 resulting in aberrant termination. The point mutation at nucleotide position -27 changed ATAAATA of the putative TATA box signal sequence to ATACATA. In addition to this mutation, the patient was heterozygous for a G to A substitution at position -75. Immunoblotting of an isoelectric focusing electrophoresis gel of the proband's plasma showed a trace amount of normal apoA1. No measurable plasma apoA1 and HDL cholesterol in a patient with homozygosity for nonsense mutation at residue 84 has been reported previously. To determine the effects of substitution either at position -27 or -75, plasmids containing the 5'-flanking region of the human apoA1 promoter fused to the CAT reporter gene were constructed and transfected in HepG2 cells. A construct with the A to C substitution at position -27 showed 41. 8+/-4.2%, and G to A substitution at position -75 showed 72.8+/-15. 2% (means+/-SD, n=3) of CAT activities, compared with the wild-type promoter sequence. A construct with the double substitutions at positions -27 and -75 showed only 22.8+/-1.3% (mean+/-SD, n=3) activity relative to the wild type. Our patient is the first case with a TATA box mutation etiologically related to lipoprotein disorders.

Apolipoprotein A-I↗
PubMed1999

A novel mutant, ApoA-I nichinan (Glu235-->0), is associated with low HDL cholesterol levels and decreased cholesterol efflux from cells.

A novel variant of apolipoprotein (apo) A-I associated with low high density lipoprotein (HDL) cholesterolemia has been identified in a Japanese family during screening for apoA-I variants by isoelectric focusing (IEF) gel analysis. ApoA-I (Glu235-->0) Nichinan was caused by a 3-bp deletion of nucleotides 1998 through 2000 in exon 4 of the apoA-I gene. Four subjects in the family were heterozygous carriers for this mutation; the mean plasma concentrations of apoA-I and HDL cholesterol of affected family members were 30% and 32% lower, respectively, than those of unaffected family members. There were no differences in the levels of very low density lipoprotein and low density lipoprotein cholesterol, triglycerides, and other apolipoproteins between the carriers and the noncarrier family members. In the proband, plasma lecithin:cholesterol acyltransferase activity was normal. Functional consequences of the mutation were examined by expressing the mutated and wild-type proapoA-I cDNAs in Escherichia coli. Cholesterol efflux to recombinant proapoA-I Nichinan from mouse peritoneal macrophages loaded with [3H]cholesterol-labeled acetylated low density lipoprotein was decreased by 54% when compared that of normal recombinant proapoA-I. In vivo turnover studies in normal rabbits demonstrated that the recombinant proapoA-I Nichinan was rapidly cleared (22% faster) compared with normal recombinant proapoA-I. We conclude that apoA-I (Glu235-->0) Nichinan induced a critical structural change in the carboxyl-terminal domain of apoA-I for cellular cholesterol efflux and increased the catabolism of apoA-I, resulting in low HDL cholesterol levels.

Adolescent↗
PubMed1999

Role of the tyrosine kinase pyk2 in the integrin-dependent activation of human neutrophils by TNF.

Secretion of inflammatory products from neutrophils can be induced by a combination of signals from ligated integrins and receptors for soluble, physiological agonists such as TNF. Here we identify pyk2 in primary human neutrophils; localize it to focal adhesions and podosomes; and demonstrate its tyrosine phosphorylation, activation, and association with paxillin during stimulation of adherent cells by TNF. Tyrphostin A9 emerged as the most potent and selective of 51 tyrosine kinase inhibitors tested against the TNF-induced respiratory burst. Tyrphostin A9 inhibited TNF-induced tyrosine phosphorylation of pyk2 without blocking the cells' bactericidal activity. Wortmannin, an inhibitor of phosphatidylinositol-3-kinase, potently blocked the TNF-induced respiratory burst and selectively inhibited tyrosine phosphorylation of pyk2. Thus, pyk2 appears to play an essential role in the ability of neutrophils to integrate signals from beta(2) integrins and TNF receptors.

Androstadienes↗
PubMed1999

The mandibular foramen: an anatomic study and its relevance to the sagittal ramus osteotomy.

The sagittal split ramus osteotomy is the most commonly used procedure to reposition the mandible surgically. Because it is more technically difficult and associated with a higher incidence of complications compared with other mandibular osteotomies, thorough knowledge of the anatomy of the mandibular ramus is a prerequisite. Anatomic measurements related to the mandibular foramen were obtained from 57 formalin-preserved non-Asian hemimandibles. As shown in previous reports, great variability was noted in the position of the mandibular foramen. However, these studies utilized Asian mandibles with a clear discrepancy in key anatomic measurements in comparison with the authors' data. This brings into question the validity of these earlier studies when applying their data to non-Asian groups. The "fade-out" point of the internal oblique ridge was found not to be a reliable anatomic reference for placement of the horizontal osteotomy along the medial ramus. Thus, familiarity with the described relationships of the mandibular foramen will assist in performing properly a sagittal split of the ramus and will reduce the chance for an unfavorable split.

Adult↗
PubMed1998

Overexpression of the sarcolemmal calcium pump in the myocardium of transgenic rats.

The plasma membrane calmodulin-dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na+/Ca2+ exchanger. We approached the question of the physiological function of the calcium pump using a transgenic "gain of function" model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the L-type Ca2+ current, or fast [Ca2+]i transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 micromol/L phenylephrine. A 1.4-fold- and 2.0-fold-higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the alpha- and beta-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of alpha- and beta-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca2+-pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction.

Animals↗
PubMed1998

NMR-Based model of a telomerase-inhibiting compound bound to G-quadruplex DNA.

The single-stranded (TTAGGG)n tail of human telomeric DNA is known to form stable G-quadruplex structures. Optimal telomerase activity requires the nonfolded single-stranded form of the primer, and stabilization of the G-quadruplex form is known to interfere with telomerase binding. We have identified 3,4,9, 10-perylenetetracarboxylic diimide-based ligands as potent inhibitors of human telomerase by using a primer extension assay that does not use PCR-based amplification of the telomerase primer extension products. A set of NMR titrations of the ligand into solutions of G-quadruplexes using various oligonucleotides related to human telomeric DNA showed strong and specific binding of the ligand to the G-quadruplex. The exchange rate between bound and free DNA forms is slow on the NMR time scale and allows the unequivocal determination of the binding site and mode of binding. In the case of the 5'-TTAGGG sequence, the ligand-DNA complex consists of two quadruplexes oriented in a tail-to-tail manner with the ligand sandwiched between terminal G4 planes. Longer telomeric sequences, such as TTAGGGTT, TTAGGGTTA, and TAGGGTTA, form 1:1 ligand-quadruplex complexes with the ligand bound at the GT step by a threading intercalation mode. On the basis of 2D NOESY data, a model of the latter complex has been derived that is consistent with the available experimental data. The determination of the solution structure of this telomerase inhibitor bound to telomeric quadruplex DNA should help in the design of new anticancer agents with a unique and novel mechanism of action.

Anthracenes↗
PubMed1998

Investigations of azapeptides as mimetics of Leu-enkephalin.

Solution syntheses of azapeptide pentamers 2, 3, and 4 were accomplished. The binding affinity of these azapeptides and azatide 1 were examined in the context of monoclonal antibody 3-E7 known to strongly bind the [Leu5]enkephalin sequence.

Enkephalin, Leucine↗
PubMed1998

Inhibition of TCR/CD3-mediated signaling by a mutant of the hematopoietically expressed G16 GTP-binding protein.

We have investigated the role of the hematopoietically expressed G16 GTP-binding protein on T cell activation. We constructed transfectants of Jurkat T cells that express a function-deficient mutant of G alpha 16 predicted to prevent activation of this G protein. Upon stimulation with anti-CD3 epsilon antibodies, mutant G alpha 16 transfectants display a profound defect in the production of IL-2 and IL-10, as well as in the expression of CD69. In contrast, the phorbol 12-myristate 13-acetate (PMA)-induced IL-10 production and CD69 expression, and the ionomycin plus PMA-induced IL-2 production are not affected. Consistent with the reduction in cytokine production is the inhibition of early signaling events in the mutant G alpha 16-expressing cells. There are significant reductions in anti-epsilon-induced tyrosine phosphorylation of zeta, epsilon, ZAP-70, and phospholipase C gamma 1, as well as in intracellular Ca2+ mobilization. In accordance with the effects on tyrosine phosphorylation is the reduction of TCR/CD3-mediated Fyn and Lck activities in G alpha 16 mutant cells. Even though the mechanism through which the G alpha 16 mutant mediates inhibition of T cell activation is not known, the data suggest a model where G proteins become activated upon TCR/CD3 engagement and regulate the activation of tyrosine kinases and subsequent downstream signaling events that lead to the activation of cytokine genes.

Alanine↗
PubMed1998

5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter.

PURPOSE: General use of nucleoside analogues in the treatment of viral infections and cancer is often limited by poor oral absorption. Valacyclovir, a water soluble amino acid ester prodrug of acyclovir has been reported to increase the oral bioavailability of acyclovir but its absorption mechanism is unknown. This study characterized the intestinal absorption mechanism of 5' -amino acid ester prodrugs of the antiviral drugs and examined the potential of amino acid esters as an effective strategy for improving oral drug absorption. METHODS: Acyclovir (ACV) and Zidovudine (AZT) were selected as the different sugar-modified nucleoside antiviral agents and synthesized to L-valyl esters of ACV and AZT (L-Val-ACV and L-Val-AZT), D-valyl ester of ACV (D-Val-ACV) and glycly ester of ACV (Gly-ACV). The intestinal absorption mechanism of these 5' -amino acid ester prodrugs was characterized in three different experimental systems; in situ rat perfusion model, CHO/hPEPT1 cells and Caco-2 cells. RESULTS: Testing 5' -amino acid ester prodrugs of acyclovir and AZT, we found that the prodrugs increased the intestinal permeability of the parent nucleoside analogue 3- to 10-fold. The dose- dependent permeation enhancement was selective for L-amino acid esters. Competitive inhibition studies in rats and in CHO cells transfected with the human peptide transporter, hPEPT1, demonstrated that membrane transport of the prodrugs was mediated predominantly by the PEPT1 H+/dipeptide cotransporter even though these prodrugs did not possess a peptide bond. Finally, transport studies in Caco-2 cells confirmed that the 5' - amino acid ester prodrugs enhanced the transcellular transport of the parent drug. CONCLUSIONS: This study demonstrates that L-amino acid-nucleoside chimeras can serve as prodrugs to enhance intestinal absorption via the PEPT1 transporter, providing a novel strategy for improving oral therapy of nucleoside drugs.

Acyclovir↗
PubMed1998

Active domains of human papillomavirus type 11 E1 protein for origin replication.

Viral proteins E1 and E2 are essential for transient human papillomavirus (HPV) DNA replication. E1 is a multifunctional protein which can bind DNA and complex with E2, has ATPase and helicase activities, and interacts with DNA polymerase alpha-primase. E2 is a transactivator-repressor protein, playing an important role in replication and transcriptional regulation. A series of deletion mutants of HPV-11 E1 were constructed and tested in functional assays to define those domains of HPV-11 E1 which are important for binding to the origin DNA and E2. The domain of HPV-11 E1 involved in binding to the origin was located between aa 186 and 649, and that for binding to E2 was between aa 346 and 649. Since E1 binds to the origin more efficiently in the presence of E2, we also mapped the DNA binding domain of E1 in the presence of E2, and found that when binding was enhanced, the region of E1 involved in binding was similar to that observed with E1 alone. The same deletion mutation constructs of E1 were subcloned into an expression vector for use in transient replication assays to study the effect of the deletions on the replication of the origin DNA in vivo and the data suggest that the C-terminal domain contains important functions for replication.

Binding Sites↗
PubMed1998

LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein.

The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with RBP-J. Differential splicing gave rise to two transcripts of the KyoT gene, KyoT1 and KyoT2, that encoded proteins with four and two LIM domains, respectively. With differential splicing resulting in deletion of an exon, KyoT2 lacked two LIM domains from the C terminus and had a frameshift in the last exon, creating the RBP-J-binding region in the C terminus. KyoT1 had a negligible level of interaction with RBP-J. Strong expression of KyoT mRNAs was detected in skeletal muscle and lung, with a predominance of KyoT1 mRNA. When expressed in F9 embryonal carcinoma cells, KyoT1 and KyoT2 were localized in the cytoplasm and the nucleus, respectively. The binding site of KyoT2 on RBP-J overlaps those of EBNA2 and Notchl but is distinct from that of Hairless, the negative regulator of RBP-J-mediated transcription in Drosophila. KyoT2 but not KyoT1 repressed the RBP-J-mediated transcriptional activation by EBNA2 and Notch1 by competing with them for binding to RBP-J and by dislocating RBP-J from DNA. KyoT2 is a novel negative regulatory molecule for RBP-J-mediated transcription in mammalian systems.

Amino Acid Sequence↗
PubMed1998

A novel homozygous missense mutation in the apo A-I gene with apo A-I deficiency.

We analyzed the genetic defect in a 67-year-old Japanese male patient with apolipoprotein (apo) A-I and high density lipoprotein (HDL) deficiencies, corneal opacities, and coronary artery disease. The plasma concentrations of apoA-I and HDL cholesterol were 2.9 to 7.3 mg/dL and 0.08 to 0.19 mmol/L, respectively. The lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate were <40% of normal control values. LCAT mass was 550% of normal control. Sequence analysis of polymerase chain reaction-amplified DNA of the proband's apoA-I gene showed a homozygous T-to-A transition resulting in the substitution of Val 156 with Glu (apoA-I Oita). Direct sequencing of samples obtained from other family members showed that the brother was homozygous, whereas the son was a heterozygous carrier of apoA-I Oita. The heterozygote for apo A-I Oita showed nearly 60% of normal apoA-I and normal HDL cholesterol levels. In vivo turnover studies in rabbits demonstrated that the variant apoA-I was rapidly cleared from plasma compared with normal human apoA-I. Our data suggest that the Val156Glu substitution is associated with apoA-I and HDL deficiency, partial LCAT deficiency, and corneal opacities and that Val156 of apoA-I may play an important role in apoA-I function.

Aged↗
PubMed1997

Cloning of P2XM, a novel human P2X receptor gene regulated by p53.

Through cloning of functional p53-binding sites (p53-tagged sites) from the human genome, we isolated a novel gene inducible by wild-type p53. Its cDNA sequence contained an open reading frame encoding a 431-amino acid peptide that showed a significant homology with members of the P2X family. This protein also revealed a similarity to RP-2, a gene activated in thymocytes undergoing programmed cell death. Northern blot analysis showed that it was expressed predominantly in skeletal muscle. Hence, we designated the gene P2XM (P2X specifically expressed in skeletal muscle). P2XM was localized to chromosomal band 22q11, where frequent loss of heterozygosity has been observed in rhabdoid tumors. Although we detected no genetic alteration in the coding sequences, one of four rhabdomyosarcoma cell lines examined had completely lost expression of this gene. Furthermore, a minor splice variant lacking a part of exon 1 that would encode residues corresponding to transmembrane domain M1 was relatively more abundant in two of seven sarcoma cell lines, one of which was derived from a rhabdomyosarcoma, and the other was derived from an osteosarcoma. The results suggest that P2XM may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and that its altered expression may be involved in the development of some sarcomas.

Alternative Splicing↗
PubMed1997

Redox-regulated signaling by lactosylceramide in the proliferation of human aortic smooth muscle cells.

Previously, our laboratory reported that lactosylceramide (LacCer) stimulated human aortic smooth muscle cell proliferation via specific activation of p44 mitogen-activated protein kinase (MAPK) in the p21(ras)/Raf-1/MEK2 pathway and induced expression of the transcription factor c-fos downstream to the p44 MAPK signaling cascade (Bhunia A. K., Han, H., Snowden, A., and Chatterjee S. (1996) J. Biol. Chem. 271, 10660-10666). In the present study, we explored the role of free oxygen radicals in LacCer-mediated induction of cell proliferation. Superoxide levels were measured by the lucigenin chemiluminescence method, MAPK activity was measured by immunocomplex kinase assays, and Western blot analysis and c-fos expression were measured by Northern blot assay. We found that LacCer (10 microM) stimulates endogenous superoxide production (7-fold compared with control) in human aortic smooth muscle cells specifically by activating membrane-associated NADPH oxidase, but not NADH or xanthine oxidase. This process was inhibited by an inhibitor of NADPH oxidase, diphenylene iodonium (DPI), and by antioxidants, N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate. NAC and DPI both abrogated individual steps in the signaling pathway leading to cell proliferation. For example, the p21(ras).GTP loading, p44 MAPK activity, and induction of transcription factor c-fos all were inhibited by NAC and DPI as well as an antioxidant pyrrolidine dithiocarbamate or reduced glutathione (GSH). In contrast, depletion of GSH by L-buthionine (S, R)-sulfoximine up-regulated the above described signaling cascade. In sum, LacCer, by virtue of activating NADPH oxidase, produces superoxide (a redox stress signaling molecule), which mediates cell proliferation via activation of the kinase cascade. Our findings may explain the potential role of LacCer in the pathogenesis of atherosclerosis involving the proliferation of aortic smooth muscle cells.

Acetylcysteine↗
PubMed1997

Palliation of AIDS-related primary lymphoma of the brain: observations from a multi-institutional database.

PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. METHODS: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha-beta value of 10. RESULTS: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS > or = 70 vs. KPS < or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management program that includes cranial irradiation. Young patients with excellent performance status are most likely to respond to treatment. The delivery of higher biologically effective doses of irradiation also may increase the probability of achieving a palliative response.

Acquired Immunodeficiency Syndrome↗