[Calcification in nonfunctioning transplanted kidneys]. / Calcificación del injerto renal no funcionante.

Failed renal allografts often are left in situ in patients who revert to chronic dialysis therapy or who undergo retransplantation. These organs may be the site of massive calcification despite their lack of physiological function. Calcification of an endstage renal allograft is sometimes found incidentally. We report here two patients who developed extensive calcification of the renal graft, one was on chronic hemodialysis and the other had a second renal transplantation with normal renal function. The precise pathogenesis of calcification and the factors which determine its tissue localization are unclear. Factors postulated to promote the development of metastatic calcification include an elevated calcium phosphate product, severe secondary hyperparathyroidism, aluminium toxicity and duration of dialytic therapy. In some cases local factors related with the chronic inflammatory rejection process are probably involved as well. However, the exact relative contribution of these factors remains unresolved. Unless specific clinical indications are present, transplant nephrectomy is not necessary for calcified end-stage renal allografts.

[Hemoperfusion in the treatment of acute valproic acid intoxication]. / Tratamiento con hemoperfusión de la intoxicación aguda por ácido valproico.

Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. Valproic acid intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, pancytopenia, hemodynamic instability and death. The drug's relatively low molecular weight, small volume of distribution and saturable protein-binding render it potentially amenable to exracorporeal removal (hemodialysis, hemoperfusion or hemofiltration ), but published experience is scarce. We describe a case report involving valproic acid intoxication with ingestion of ethanol, who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of valproic acid was reduced with rapid lowering of valproic acid levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, charcoal hemoperfusion should be considered for serious valproic acid intoxication because free as well as bound drug fractions are eliminated via this technique.

Fluoroscopically guided vs modified traditional placement of tunneled hemodialysis catheters: clinical outcomes and cost analysis.

Tunneled cuffed internal jugular vein catheters are widely used to provide short to medium-term vascular access for hemodialysis. The NKF-K/DOQI guidelines state that fluoroscopy is mandatory for insertion of all cuffed dialysis catheters. The KDOQI recommendation makes it difficult for Nephrologists to perform this procedure without access to fluoroscopy. This results in unnecessary waiting times and the inappropriate use of acute, non-tunneled catheters. The purpose of this study is: 1) to compare the outcomes of fluoroscopically guided vs modified traditional catheter placement technique, and 2) to perform a cost analysis of the two techniques. We performed a retrospective investigation of 202 tunneled hemodialysis catheters performed at our tertiary care hospital. Procedural data were obtained from the University of Wisconsin Department of Medicine, Nephrology Section Interventional Nephrology procedural database. Patient demographics, laboratory tests were obtained from the University of Wisconsin Hospital electronic medical record (EMR). Logistic regression was used to evaluate the effect of blind vs fluoro-guided placement on clinical outcomes, corrected for side of procedure, age, gender, previous history of catheter placement, diabetes mellitus (DM), and pre-procedural coagulation parameters. Baseline characteristics of 'blind' vs fluoro-guided groups differed with respect to side of procedure and DM (91.0% vs 79.6%, p = 0.02 and 43.30% vs 58.40%, p = 0.02, respectively). Non-fluoroscopic placement of catheters was associated with a decreased odds ratio of immediate success (OR = 0.1298, CI = 0.02 - 0.71). No difference in major or minor bleeding complications was discovered between the blind vs fluoro-guided group. Cost analysis revealed that performing the non-fluoroscopic technique as the preferred initial procedure would represent a substantial reduction in total bills submitted to third-party payers, including Medicare.

[The patient and the crossing between Primary and Hospital care. Systematic review of trials for the implementation of tools for integration in Spain]. / El paciente y su travesía entre la atención primaria y la hospitalaria. Revisión sistemática de ensayos clínicos para la implementación de herramientas para la integración en España.

BACKGROUND: Health services are moving towards a complete integration to try and reduce fragmentation, increase efficiencies and improve health outcomes. Estimates the effectiveness in of different tools for integrated care in Spain. METHODS: We performed a systematic review of articles using MEDLINE (last search July31st, 2017). Randomized clinical trials reporting health outcomes of tools for integrated care used in Spain were included. Studies were appraised for quality using the Cochrane Risk of Bias assessment. RESULTS: Twenty studies met the criteria for the systematic review. Interventions included were hospital-at home (four studies, 455 patients), outpatient clinic by videoconference (three studies, 2438 patients), nurse navigator (four studies, 1051 patients), self-care improvement (four studies, 1291 patients), at-home health monitoring (three, 162), health apps (two, 225) and medical reconciliation (one, 172). Hospital-at-home, nurse navigator or self-care improvement reduced readmission rate in older patients, heart failure (HF) or chronic obstructive pulmonary disease (COPD). Self-care improvement and nurse navigator reduced mortality rate in HF. Hospital-at-home reduced hospital stay in COPD. Self-care improvement reduced outpatient visits in asthma patients. Outpatient video by videoconference reduced time to diagnosis and treatment in rural areas. The quality of the evidence ranged from low to very low for all the outcomes because it was based in double or triple downgraded randomized trials. CONCLUSION: The implementation of tools for integrated care in Spain improved some outcomes of relevance in patients with chronic conditions, although evidence is low. Self-care improvement stood out due to the improvements made.

Development and examination of an expectancy-based measure of test-taking motivation.

A 10-item multidimensional measure of test-taking motivation based on expectancy theory, the Valence, Instrumentality, Expectancy Motivation Scale (VIEMS), was developed using a student sample (N = 90) and tested using 2 samples of job applicants in a field setting (N = 296; N = 246). In Field Study 1, the VIEMS was related to test performance. Hierarchical regression analysis showed that the VIEMS explained variance in test score beyond a general measure of test motivation. In a second longitudinal field study, pretest and posttest perceptions of motivation were compared. Results indicated that expectancy was related to actual test performance, and perceived test performance accounted for variance in posttest reports of motivation after controlling for pretest levels of motivation. Test-taking motivation did not account for variance in test performance differences between African Americans and Whites in either field study.

[Surgery of portal hypertension. 12 years' experience]. / Cirugía de hipertensión portal. Experiencia de 12 años.

A retrospective study of 43 patients who were operated on for portal hypertension was performed (29 distal splenorenal shunts, 7 total portosystemic shunts, five Sugiura's operations and 2 splenectomies with gastric devascularization). Eighteen patients had recurrence of hemorrhage, 10 had ascitis and six encephalopathy. Thirteen of the 43 patients (seven Warren's operations, five Sugiura's and one mesocaval shunt) received postoperative sclerotherapy. The overall operative mortality was 34.8%. In the period 1977-1982, six of 20 patients (30%) died, and in 1983-1988 nine of 23 died (39.1%) (p greater than 0.05); so, we concluded that we must improve the perioperative care and that this kind of operations must be performed only by experienced surgeons.

[Cancer of the anal canal]. / Cáncer de canal anal.

Anal carcinoma is a rare malignant tumor, It occurs in only 0.02% of all malignant neoplasms. In Mexico, the incidence is of 1.5%, and only 0.18% belong to the anal canal. In recent years it has been reported an increased incidence of this tumor due to the association with the human papilloma virus in HIV positive patients. The most common histological forms are the epidermoid and the cloacogenic carcinomas. The most relevant prognostic factors are the size of the tumor and the presence of lymph node metastasis. Surgery has been the traditional form of treatment but the combined use of chemotherapy and radiotherapy seems to have the best results and surgery is reserved for local recurrences or palliation. A review of our experience at the National Institute of Cancer at Mexico city with the management of this tumor was performed. Thirty-four patients with the diagnosis of carcinoma of the anal canal were included of which none of them received previous treatment or have the diagnosis of AIDS. Patients were divided in four groups according to the form of treatment (surgery, radiation, and chemoradiation either with 5FU-MMC or 5FU and CDDP). The group that received chemotherapy with 5FU and CDDP combined with radiotherapy had the best results in terms of clinical response, survival and toxicity. The size of the tumor and the presence of lymph node metastasis are the prognostic factors that influence in survival: tumor smaller than 5 cm without lymph node metastasis have the best prognosis (p: 0.01 and p: 0.00004). Epidermoid carcinoma have a better prognosis than cloacogenic carcinoma (p: 0.07).

[Management of digestive system carcinoid tumors and carcinoid syndrome]. / Manejo del tumor carcinoide del aparato digestivo y del síndrome carcinoide.

INTRODUCTION: Carcinoid tumors are rare, most of the publications are case reports and the clinical series are uncommon. The quality of life and survival time of these patients depend on the adequate control of tumor growth and good palliation of their symptoms. AIMS: The purpose of this study is to inform epidemiological data and forms of management for these tumors and the Carcinoid Syndrome at the National Institute of Cancerology (INCan) at Mexico City in the last 15 years. METHODS: A retrospective review of the clinical records of patients diagnosed and treated at the INCan with carcinoid tumors from 1982 to 1997 was performed. RESULTS: The most common origin place was the gastrointestinal tract (GI), and the majority involved the right colon and the appendix. The longest survivors were patients with tumors originated in the appendix, tumors smaller than 2 cm or localized. At the time of diagnosis 47% of patients had metastatic disease that was also a poor prognostic factor. The experience in our hospital seem to support the use of interferon alone or in combination with octreotide or debulking surgery for the palliation of carcinoid syndrome. CONCLUSIONS: Carcinoid tumors are rare, and have a slow growth and less aggressive biological nature than noncarcinoid tumors. Treatment should be focused on trying to cure the small or localized lesions or to find the best palliative method for those symptomatic advanced lesions.

[Laparoscopic cholecystectomy at an oncologic center: a comparative analysis]. / La colecistectomía por laparoscopia en un centro oncológico: un análisis comparativo.

OBJECTIVE: To analyze and compare our results with open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) in patients with cancer. DESIGN: Case-control study. SETTING: An oncologic referral center in Mexico City. PATIENTS: All patients with previous treatment for cancer and indication for cholecystectomy who where referred in a 60-month period. They were divided into two groups. Group OC with operation performed in the former 30 months and group LC with operation performed in the later 30 months. RESULTS: Lower morbidity and mortality rates and less hospital stay were found in group LC (55 cases) as compared with group OC (50 cases). Conversion rate in group LC was 14%. This rate is higher in patients with previous surgeries in upper abdomen. There were no differences in morbidity and mortality in patients with previous abdominal surgeries or with diabetes. Patients with liver cirrhosis in group OC had higher morbidity and mortality. CONCLUSIONS: LC can be performed safely in patients with history of cancer, laparotomy or abdominal radiation therapy and should be considered as first choice for symptomatic gallstones. LC should be considered also in diabetes and liver cirrhosis. When previous surgery in the upper abdomen is found we recommend to insert the first trocar under direct vision of peritoneal cavity. In this case conversion rate is high.

[Indications and results of hepatic resection in benign and malignant tumors]. / Indicaciones y resultados de la resección hepática en tumores benignos y malignos.

OBJECTIVE: The authors analyze the indications and results in 75 consecutive liver resections. BACKGROUND: In recent years, the morbidity and mortality of this procedure have been reduced at specialized centers due to better control of intraoperative bleeding and improved perioperative management. METHODS: The clinical records of 72 patients who had a liver resection over a 4-year period were reviewed. RESULTS: Fifty-two were females and 23, males. Ages ranged between 15 and 88 years (X: 50 +/- 22 years). The indications for surgery were liver, secondary in 28, gallbladder or bile duct cancer in 17, benign liver tumors in 16, and primary malignant liver tumors in 14. Forty-seven major liver resections were performed and included 25 right hepatectomies, 13 left hepatectomies, five right trisegmentectomies, and four left trisegmentectomies. Additionally, 28 minor resections included 12 resections of the left lateral segment, nine bisegmentectomies, five segmentectomies and two resections of the caudate lobe. Operative time ranged from 60-540 min (X: 260 +/- 97 min); the mean operative bleeding was 1439 +/- 660 mL (range 20-5,000 mL). The pringle maneuver was used in 63 patients and ranged from 20-100 min (X: 42 +/- 25 min). Twenty-five patients presented complications (33%), the most frequent being hepatic failure, postoperative bleeding, ascitis and bilomas. Six patients died (8%) due to hepatic and multiorganic failure in four pneumonia and myocardial infarct in one, and systemic sepsis in the other. CONCLUSIONS: Liver resection is an excellent therapeutic alternative in patients with benign and malignant liver focal lesions.

[Laparoscopic partial hepatectomy. Report of the first case in Mexico]. / Hepatectomía parcial por laparoscopia. Informe del primer caso en México.

The authors report the case of a 47-year-old female patient referred to the Instituto Nacional de Cancerología with abdominal pain and a focal liver lesion in the left lateral segment. After a careful tumor work-up, a laparoscopic left lateral segmentectomy was performed. The postoperative course was uneventful and the patient was discharged at the 2nd postoperative day. Histologic examination revealed focal nodular hyperplasia. In a search of the literature we find this to be the first case treated by this approach in Mexico.

Longitudinal evaluation of health care utilization and costs during the first three years after a new diagnosis of fibromyalgia.

OBJECTIVE: To evaluate health care resource utilization and costs 1 year before and 3 years after a fibromyalgia (FM) diagnosis. METHODS: This retrospective cohort analysis used claims from Humana to identify newly diagnosed FM patients ≥18 years of age based on ≥2 medical claims for ICD-9 CM code 729.1 and 729.0 between June 1, 2002 and March 1, 2005. Prevalence of comorbidities, as well as utilization and costs of pharmacotherapy and health care services were examined for 12 months preceding (pre-diagnosis) and 36 months following (post-diagnosis) the date of first FM diagnosis. These periods were subdivided into 6-month blocks to better observe patterns of change. RESULTS: We identified 2613 FM patients who had a mean age at diagnosis of 58.5 ± 15.3 years and a mean Charlson Comorbidity Index of 0.48 ± 1.05. Of those, 73% were female. The use and costs of pain-related medications rose from pre-diagnosis and remained stable after the 6-month post-diagnosis period, while the use of non-pain-related medications steadily rose from pre-diagnosis to 3 years post-diagnosis. This increase was concomitant with an increase in the presence of conditions that may account for higher resource utilization. The use of recommended FM therapies (i.e., antidepressants and anticonvulsants) increased post-diagnosis but remained less common than other pain-related therapies. Total resource utilization and costs increased during the period up to 6 months after diagnosis. This increase was followed by a decline (7-12 months post-diagnosis), and plateau, with an increase during the final 6 months of the study period. Total mean per patient costs were $3481 for the 6-month post-diagnosis period, and $3588 for the final 6 months. Limitations include potential errors in coding and recording, and an inability of claims analyses to determine causality between resource utilization and the specific diagnosis of interest. CONCLUSIONS: An FM diagnosis was associated with increased utilization and pain-related medication cost up to the first 6 months post-diagnosis followed by stabilization over 3 years post-diagnosis. Less use of recommended therapies relative to other therapies suggests that further dissemination of treatment guidelines is needed. An increase in non-pain medications over the observation period accounted for the majority of pharmacy costs. These pharmacy costs may be related to an increasing prevalence of comorbid conditions.

Determinación de anticuerpos IGG anti-toxocara canis en estudiantes de Medicina / Determination of igg antibodies anti-toxocara canis in medical students

La Toxocariasis en una infección causada por el estadio larval de un nematodo del género Toxocara (con más frecuencia T. canis y rara vez T. cati), y es adquirida por ingestión de tierra y alimentos contaminados con huevos embrionados de dicho parásito provenientes de materia fecal animal. El objetivo fue determinar si la presencia del perro y el contacto frecuente con él representa un riesgo mayor para la infección en poblaciones sanas sin manifestaciones de síntomas clínicos de la enfermedad. Método: mediante el método de ELISA se determinaron los niveles de anticuerpos contra Toxocara canis, en dos poblaciones, una poseedora de perro (183 alumnos del tercer año de la carrera de medicina, de entre 21 y 23 años de edad, provenientes de todo el país, presentados voluntariamente para el estudio, con perro como mascota) y otra testigo (30 individuos aspirantes a policías, de entre 20 a 25 años de edad, que no poseen perro como mascota). Resultados: de las 183 muestras analizadas de la primera población (estudiantes de medicina), 25 resultaron positivas, lo que demuestra una prevalencia del 13,67 %. En los no poseedores de perro la prevalencia fue del 3,33 %. Conclusiones: si bien el porcentaje de positividad en ambas poblaciones fue bajo, se puede apreciar una mayor prevalencia de anticuerpos anti-Toxocara canis en los alumnos de medicina, lo que sugiere que el contacto permanente con el animal favorece la infección parasitaria. Por lo tanto, es de suma importancia educar a la población en cuanto al cuidado y control veterinario de su mascota, y extremar las medidas de higiene para evitar la propagación de ésta y otras parasitosis.

Toxocariasis in an infection caused by the larval stage of a nematode parasite, the Toxocara (T. canis more often and T. cati ,rarely), and it is acquired by ingestion of contaminated dirt or food by embryonated eggs of the parasite coming from animal feces. The aim was to determine whether the presence of a dog and frequent contact with it imply a greater risk for infection in healthy populations without evidence of clinical symptoms of the disease. Method: Using ELISA method, the levels of antibodies against Toxocara canis were determined in two populations: a group of dog owners (183 students in the third year of medical school, between 21 and 23 years old, from different areas of the country who voluntarily submitted for the study, with a dog as a pet) and a control group (30 would-be policemen, aged 20-25, who do not own a pet dog). Results: Out of the 183 samples analyzed from the first population (medical students), 25 were positive, showing a prevalence of 13.67%. In the population with no dogs, the prevalence was 3.33%. Conclusions: Although the percentage of positivity in both populations was low, a higher prevalence of Toxocara canis antibodies can be seen in the medical students, suggesting that contact with the animal favors parasitic infection. Therefore, it is extremely important to educate the population as regards care and veterinary control of pets, and to maximize hygiene measures to prevent the spread of this and other parasites.

Substrate specificity of CDC2 kinase from human HeLa cells as determined with synthetic peptides and molecular modeling.

A systematic study was undertaken in order to assess the substrate specificity of cyclin-B/cell division control protein kinase (CDC2) isolated from human HeLa cells, using 13-15 residue peptides with a central histone-like KKSPKK motif as a model. Replacement of the proline residue by any of the other 19 amino acids or D-proline drastically reduces or abolishes phosphorylation by CDC2. Changing the basic residues to Ala on either side of the -SP- structure differentially reduces phosphorylation. Molecular modeling and dynamics simulation indicated that the phosphorylation site of the peptide may have to adopt a turn-like conformation that will orientate the charged and hydrophobic residues so as to allow interaction with postulated binding surfaces within the CDC2 active site. It thus appears that, of the 20 coded amino acids, only proline can provide this conformation in short peptides. This is in agreement with the finding that sarcosine can replace proline in this respect (S. Ando et al. Biochem. Biophys. Res. Commun. 195, 837-843, 1993).

Loss of in vitro metal ion binding specificity in mutant copper-zinc superoxide dismutases associated with familial amyotrophic lateral sclerosis.

The presence of the copper ion at the active site of human wild type copper-zinc superoxide dismutase (CuZnSOD) is essential to its ability to catalyze the disproportionation of superoxide into dioxygen and hydrogen peroxide. Wild type CuZnSOD and several of the mutants associated with familial amyotrophic lateral sclerosis (FALS) (Ala(4) --> Val, Gly(93) --> Ala, and Leu(38) --> Val) were expressed in Saccharomyces cerevisiae. Purified metal-free (apoproteins) and various remetallated derivatives were analyzed by metal titrations monitored by UV-visible spectroscopy, histidine modification studies using diethylpyrocarbonate, and enzymatic activity measurements using pulse radiolysis. From these studies it was concluded that the FALS mutant CuZnSOD apoproteins, in direct contrast to the human wild type apoprotein, have lost their ability to partition and bind copper and zinc ions in their proper locations in vitro. Similar studies of the wild type and FALS mutant CuZnSOD holoenzymes in the "as isolated" metallation state showed abnormally low copper-to-zinc ratios, although all of the copper acquired was located at the native copper binding sites. Thus, the copper ions are properly directed to their native binding sites in vivo, presumably as a result of the action of the yeast copper chaperone Lys7p (yeast CCS). The loss of metal ion binding specificity of FALS mutant CuZnSODs in vitro may be related to their role in ALS.

Cobalt(2+) binding to human and tomato copper chaperone for superoxide dismutase: implications for the metal ion transfer mechanism.

The copper chaperone for superoxide dismutase (CCS) gene encodes a protein that is believed to deliver copper ions specifically to copper-zinc superoxide dismutase (CuZnSOD). CCS proteins from different organisms share high sequence homology and consist of three distinct domains; a CuZnSOD-like central domain 2 flanked by domains 1 and 3, which contain putative metal-binding motifs. We report deduced protein sequences from tomato and Arabidopsis, the first functional homologues of CCS identified in plants. We have purified recombinant human (hCCS) and tomato (tCCS) copper chaperone proteins, as well as a truncated version of tCCS containing only domains 2 and 3. Their cobalt(2+) binding properties in the presence and absence of mercury(2+) were characterized by UV-vis and circular dichroism spectroscopies and it was shown that hCCS has the ability to bind two spectroscopically distinct cobalt ions whereas tCCS binds only one. The cobalt binding site that is common to both hCCS and tCCS displayed spectroscopic characteristics of cobalt(2+) bound to four or three cysteine ligands. There are only four cysteine residues in tCCS, two in domain 1 and two in domain 3; all four are conserved in other CCS sequences including hCCS. Thus, an interaction between domain 1 and domain 3 is concluded, and it may be important in the copper chaperone mechanism of these proteins.

Detection of a new substrate-derived radical during inactivation of ribonucleotide reductase from Escherichia coli by gemcitabine 5'-diphosphate.

Ribonucleotide reductases (RNRs) play a central role in replication and repair by catalyzing the conversion of nucleotides to deoxynucleotides. Gemcitabine 5'-diphosphate (F2CDP), the nucleoside of which was recently approved by the FDA for treatment of pancreatic cancer, is a potent mechanism-based inhibitor of class I and II RNRs. Inactivation of the Eschericia coli class I RNR is accompanied by loss of two fluorides and one cytosine. This RNR is composed of two homodimeric subunits: R1 and R2. R1 is the site of nucleotide reduction, and R2 contains the essential diferric-tyrosyl radical cofactor. The mechanism of inactivation depends on the availability of reductant. In the presence of reductant [thioredoxin (TR)/thioredoxin reductase (TRR)/NADPH or dithiothreitol], inhibition results from R1 inactivation. In the absence of reductant with prereduced R1 and R2, inhibition results from loss of the essential tyrosyl radical in R2. The same result is obtained with C754S/C759S-R1 in the presence of TR/TRR/NADPH. In both cases, tyrosyl radical loss is accompanied by formation of a new stable radical (0.15-0.25 equiv/RNR). EPR studies in 2H2O, with [U-2H]R1, and examination of the microwave power saturation of the observed signal, indicate by process of elimination that this new radical is nucleotide-based. In contrast to all previously investigated 2'-substituted nucleotide inhibitors of RNR, inactivation is not accompanied by formation of a new protein-associated chromophore under any conditions. The requirement for reductant in the R1 inactivation pathway, the lack of chromophore on the protein, the loss of two fluoride ions, and the stoichiometry of the inactivation all suggest a unique mechanism of RNR inactivation not previously observed with other 2'-substituted nucleotide inhibitors of RNR. This unique mode of inactivation is proposed to be responsible for its observed clinical efficacy.

X-ray crystallographic and analytical ultracentrifugation analyses of truncated and full-length yeast copper chaperones for SOD (LYS7): a dimer-dimer model of LYS7-SOD association and copper delivery.

Copper-zinc superoxide dismutase (CuZnSOD) acquires its catalytic copper ion through interaction with another polypeptide termed the copper chaperone for SOD. Here, we combine X-ray crystallographic and analytical ultracentrifugation methods to characterize rigorously both truncated and full-length forms of apo-LYS7, the yeast copper chaperone for SOD. The 1.55 A crystal structure of LYS7 domain 2 alone (L7D2) was determined by multiple-isomorphous replacement (MIR) methods. The monomeric structure reveals an eight-stranded Greek key beta-barrel similar to that found in yeast CuZnSOD, but it is substantially elongated at one end where the loop regions of the beta-barrel come together to bind a calcium ion. In agreement with the crystal structure, sedimentation velocity experiments indicate that L7D2 is monomeric in solution under all conditions and concentrations that were tested. In contrast, sedimentation velocity and sedimentation equilibrium experiments show that full-length apo-LYS7 exists in a monomer-dimer equilibrium under nonreducing conditions. This equilibrium is shifted toward the dimer by approximately 1 order of magnitude in the presence of phosphate anion. Although the basis for the specificity of the LYS7-SOD interaction as well as the exact mechanism of copper insertion into SOD is unknown, it has been suggested that a monomer of LYS7 and a monomer of SOD may associate to form a heterodimer via L7D2. The data presented here, however, taken together with previously published crystallographic and analytical gel filtration data on full-length LYS7, suggest an alternative model wherein a dimer of LYS7 interacts with a dimer of yeast CuZnSOD. The advantages of the dimer-dimer model over the heterodimer model are enumerated.