Effects of Alzheimer's disease and Lewy body disease on subcortical atrophy.

BACKGROUND AND PURPOSE: Subcortical structures are affected by neurodegeneration in Alzheimer's disease (AD) and Lewy body disease (LBD). Although the co-occurrence of AD and LBD pathologies and their possible interaction have been reported, the effect of AD and LBD on subcortical structures remains unknown. The effects of AD and LBD on subcortical atrophy and their relationship with cognitive dysfunction were investigated. METHODS: The cross-sectional study recruited 42 patients with pure AD related cognitive impairment (ADCI), 30 patients with pure LBD related cognitive impairment (LBCI), 58 patients with mixed ADCI and LBCI, and 29 normal subjects. A general linear model was used to compare subcortical volume and shape amongst the groups, to investigate the independent and interaction effects of ADCI and LBCI on subcortical shape and volume, and to analyze the relationship between subcortical volume and cognitive dysfunction in each group. RESULTS: Alzheimer's disease related cognitive impairment and LBCI were independently associated with subcortical atrophies in the hippocampus and amygdala and in the hippocampus and putamen respectively, but their interaction effect was not significant. Compared to the control group, the pure LBCI group exhibited additional local atrophies in the amygdala, caudate and thalamus. Subcortical atrophies correlated differently with cognitive dysfunction according to the underlying causes of cognitive dysfunction. CONCLUSIONS: The patterns of subcortical atrophies and their correlation with cognitive dysfunction differ according to the underlying AD, LBD or concomitant AD and LBD.

Racial disparities after stoma construction in colorectal surgery.

AIM: Racial disparities are under-recognized among patients undergoing colorectal surgery. The purpose of this study was to determine the complication rates and surgical outcomes stratified by race and ethnicity among patients undergoing colorectal surgery with intestinal stoma creation. METHOD: The ACS NSQIP database from 2013 to 2016 was used. Colon, rectum and small bowel cases requiring intestinal stoma creation were selected. Both African-American and other groups of minority patients were compared with Caucasian patients using a complex multivariable analysis model. Primary outcomes of interest were complication rates, mortality and extended hospital length of stay. RESULTS: The study included 38 088 admissions. After multivariable analysis, African-American patients still had a prolonged length of hospital stay and higher complication rates. Other minorities also had a prolonged length of hospital stay and higher complication rates. CONCLUSIONS: Both African-American and other groups of minority patients requiring an ostomy suffer significantly higher postoperative complication rates and a prolonged hospital length of stay, even after comorbidity adjustment. Access to care, socioeconomic status and comorbid disease management are all important factors for minority patients who undergo colorectal surgery requiring intestinal stoma construction.

Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery.

Stress-inducible Hsp72 is a potential biomarker to track risk of exertional heat illness during exercise/environmental stress. Characterization of extracellular (eHsp72) vs cellular Hsp72 (iHsp72) responses is required to define the appropriate use of Hsp72 as a reliable biomarker. In each of four repeat visits, participants (n = 6 men, 4 trials; total n = 24): (a) passively dehydrated overnight, (b) exercised (2 h) with no fluid in a hot, humid environmental chamber, (c) rested and rehydrated (1 h), (d) maximally exercised for 0.5 h, and (e) returned after 24 h of at-home recovery and rehydration. We measured rectal temperature, hydration status (% body mass loss, urine markers, serum osmolality), and Hsp72 (ELISA, flow cytometry. eHsp72 (circulating) and iHsp72 (CD3+ PBMCs) correlated (P < 0.05) with markers of heat, exercise, and dehydration stresses. eHsp72 immediately post-exercise (>15% above baseline, P < 0.05) decreased back to baseline levels by 1 h post-exercise, but iHsp72 expression continued to rise and remained elevated 24 h post-exercise (~2.5-fold baseline, P < 0.05). These data suggest that in addition to the classic physiological biomarkers of exercise heat stress, using cellular Hsp72 as an indicator of lasting effects of stress into recovery may be most appropriate for determining long-term effects of stress on risk for exertional heat illness.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

BACKGROUND AND OBJECTIVES: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. MATERIALS AND METHODS: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. RESULTS: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. CONCLUSIONS: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

Effects of poor maternal diet during gestation are detected in F2 offspring.

Poor maternal nutrition of F0 ewes impairs F1 offspring growth, with minimal differences in glucose tolerance or select metabolic circulating factors, and independent of differences in residual feed intake (RFI). To determine if poor maternal nutrition in F0 ewes alters F2 offspring growth, circulating leptin, feed efficiency, or glucose tolerance, F0 ewes (n = 46) pregnant with twins were fed 100% (control), 60% (restricted), or 140% (over) of National Research Council requirements from days 30 ±â€…0.02 of gestation until parturition. At 16 to 19 mo of age, female F1 (n = 36) offspring were bred to generate F2 offspring [CON-F2 (n = 12 ewes; 6 rams), RES-F2 (n = 7 ewes; 13 rams), or OVER-F2 (n = 13 ewes; 9 rams) corresponding to diets of the granddam (F0)]. Lamb body weights (BW) and blood samples were collected weekly from days 0 to 28 and every 14 d until day 252 of age. Circulating leptin was measured in serum at days 0, 7, 14, 56, 210, and 252. An intravenous glucose tolerance test was performed at days 133 ±â€…0.28. At days 167 ±â€…0.33, individual daily intake was recorded over a 77-d feeding period to determine RFI. Rams were euthanized at days 285 ±â€…0.93, and body morphometrics, loin eye area (LEA), back fat thickness, and organ weights were collected and bone mineral density (BMD) and length were determined in the right hind leg. During gestation, OVER-F1 ewes tended to be 8.6% smaller than CON-F1 ewes (P ≤ 0.06). F2 offspring were of similar BW from birth to day 70 (P ≥ 0.20). However, from days 84 to 252, RES-F2 offspring tended to be 7.3% smaller than CON-F2 (P ≤ 0.10). Granddam diet did not influence F2 ram body morphometrics, organ or muscle weights, LEA, adipose deposition, or leg BMD (P ≥ 0.84). RES-F2 (-0.20) and CON-F2 (-0.45) rams tended to be more feed efficient than CON-F2 ewes (0.31; P ≤ 0.08). No effects of granddam diet were observed on glucose or insulin average or baseline concentrations, area under the curve, first-phase response, or ratio (P ≥ 0.52). However, CON-F2 rams (297 mg/dL ±â€…16.5) had a greater glucose peak compared with RES-F2 rams (239 mg/dL ±â€…11.2; P = 0.05). Peak insulin concentrations were not influenced by granddam diet (P = 0.75). At d 56, RES-F2 and OVER-F2 offspring had 53.5% and 61.8% less leptin compared with CON-F2 offspring, respectively (P ≤ 0.02). These data indicate that poor maternal nutrition impacts offspring growth into the second generation with minimal impacts on offspring RFI, glucose tolerance, and circulating leptin.

A Single Dose of Ibuprofen Impacts IL-10 Response to 164-km Road Cycling in the Heat.

Purpose: The purpose was to determine the effect of a single-dose prophylactic ibuprofen use before a 164-km road cycling event in high ambient temperature on the circulating cytokine and leukocyte responses. Methods: Twenty-three men (53 ± 8 y, 172.0 ± 22.0 cm, 85.1 ± 12.8 kg, 19.6 ± 4.4% body fat) completed a 164-km self-paced recreational road cycling event in a hot, humid, sunny environment (WBGT = 29.0 ± 2.9°C) after consuming 600 mg of ibuprofen (n = 13) or a placebo (n = 10). Blood samples were obtained one to two hours before (PRE) and immediately after (POST) the event, and analyzed for concentrations of circulating cytokines interleukins (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, GM-CSF, IFN-γ, and TNF-α and leukocytes (total leukocytes, granulocytes, monocytes, and lymphocytes). Results: Event completion time was 400.2 ± 74.8 min. Concentrations of all cytokines (except IL-1ß, IL-2, IL-5, IL-12, GM-CSF, and IFN-γ) and of all leukocyte subsets increased from PRE to POST. Ibuprofen ingestion attenuated the increase in IL-10 (86% increase with Ibuprofen; 270% increase with placebo). Conclusions: Consuming 600 mg of Ibuprofen prior to a 164-km road cycling event in a hot-humid environment attenuates exercise-induced increases in the concentration of the anti-inflammatory cytokine IL-10, but does not alter the effect of the exercise event on concentrations of other circulating cytokines or leukocyte subset concentrations.

Knowledge of pet-related zoonotic diseases and pet care in Hong Kong, a heavily crowded urban setting.

BACKGROUND: With the rapid expansion of pet animal populations worldwide, pet-related zoonotic diseases are becoming an important issue in public health. Hong Kong (HK), located in southern China, is one of the most crowded urban centres in the world. The population of pets, especially exotic pets, in HK has grown significantly in recent decades, potentially elevating the risk of pet-related zoonotic diseases. However, no studies have been conducted to explore the knowledge of HK public towards pet-related zoonotic diseases and animal husbandry practices. OBJECTIVES: To evaluate the level of awareness among the HK public of pet-related zoonotic diseases and their understanding of proper animal husbandry practices. METHODS: The study was carried out in HK from June-August 2019 using both online and paper versions of a questionnaire. A total of 362 completed questionnaires (74.3% return rate) were collected and the responses analysed. RESULTS: Sixty percent of the participants were current or past pet owners or planned on becoming pet owners in the coming 2 years, irrespective of their income or size of their living space. Among the participants, pet owners (including those who planned pet ownership) had a relatively higher level of awareness of pet-related zoonotic disease. However, the overall awareness of zoonotic diseases among both pet and non-pet owners was low with a knowledge score of <50%. A similar trend was observed for knowledge about proper animal husbandry practices. CONCLUSIONS: This study showed that the HK public was generally not familiar with pet-related zoonotic diseases and proper pet care. These knowledge gaps could potentially increase the risk of disease transmission. Further studies focusing on specific pet species and on people of different social-economic backgrounds are needed to provide future direction of efforts to reduce the risk of pet-related zoonotic diseases and to enhance pet-related animal and human welfare.

Single-incision vs straight laparoscopic segmental colectomy: a case-controlled study.

PURPOSE: Single-incision laparoscopic surgery is gaining momentum in general surgery but it is essentially unstudied for laparoscopic colectomy. The aim of our study was to compare outcomes for single-incision laparoscopic colectomy with laparoscopic-assisted colectomy. METHODS: Patients undergoing laparoscopic colectomy were prospectively entered into an institutional review board-approved database. Those that underwent single-incision laparoscopic colectomy were case matched for sex, age, disease, surgery, body mass index, previous surgeries, and surgeon with patients undergoing LAC. RESULTS: Twenty-nine single-incision laparoscopic segmental colectomies were performed for polyps (4), adenocarcinoma (12), diverticulitis (6), and Crohn's disease (7) and were case matched to laparoscopic-assisted colectomy for the same indications. Mean body mass index was 28.8 ± 3 kg/m². Operative time was longer for single-incision laparoscopic colectomy (134.4 ± 40 vs 103.8 ± 54 min; P = .0002). Four single-incision laparoscopic colectomies were converted to LAC requiring either one extra port (2) or 2 extra ports (2), and there was one conversion to laparotomy. Extraction scar length (millimeters) was similar (38 ± 6.0 vs 45 ± 6.2; P = .746). Postoperative morbidity (5/29 vs 7/29; P = .284) and length of stay (day) (3.7 ± 1.1 vs 3.9 ± 1.1; P = .445) were similar between groups. CONCLUSIONS: Single-incision laparoscopic colectomy is feasible and safe but takes more time than laparoscopic-assisted colectomy. Although results approximate those for laparoscopic-assisted colectomy, an additional learning curve is involved, and extra incisions are sometimes required. Single-incision laparoscopic colectomy requires further prospective validation so that the cost of the device can be justified by an improved clinical outcome.

The integrin alpha 6 beta 4 is a laminin receptor.

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as by A9, a beta 4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha 6 beta 4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha 6 beta 4 integrin does not bind to collagen-Sepharose, but the alpha 2 beta 1 integrin does bind. Clone A cells do not express alpha 6 beta 1 as evidenced by the following observations: (a) no beta 1 integrin is detected in beta 1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha 6 beta 1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta 4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha 6 beta 4 integrin and that this integrin can function as a laminin receptor independently of alpha 6 beta 1.

Specific chromosome defect associated with human small-cell lung cancer; deletion 3p(14-23).

A specific, acquired chromosomal abnormality (deletion 3p) has been found in at least one chromosome 3 in 100 percent of the metaphases in 12 of 12 cell lines cultured from human small-cell lung cancer tissue and in 2-day tumor culture specimens from three patients. Analysis of the shortest region of overlap shows the deletion to be 3p(14-23). This specific change was not seen in five of five lung cancer cell lines other than small-cell lung cancer or in two lymphoblastoid lines cultured from cells of small-cell lung cancer patients whose tumors had the 3p deletion.

Living-donor Liver Retransplantation Using the Vessels of the Previous Allograft by Means of Intragraft Dissection.

Retransplantation with the use of a living-donor graft can be the only therapeutic option for patients with irreversible graft failure, especially in regions with limited access to deceased donors, but it can be technically demanding because of severe adhesion around the hepatic hilum and inferior vena cava. We introduce an effective and safe technique to overcome this challenge for right-lobe living-donor liver retransplantation by using the vessels of the previous right liver allograft with the use of intragraft dissection. The technique was used in 2 critically ill patients undergoing the graft failure. The operative times were 360 and 410 minutes. The recipients were discharged on days 18 and 25 with normal liver function. One postoperative complication occurred 3 months after retransplantation: biliary leakage, corrected with the use of percutaneous transhepatic biliary drainage. Both patients were alive with a functioning allograft at last follow-up of >3 years. Intragraft dissection to use the vessels of the previous right-liver allograft can be a useful technique and should be considered for right-lobe living-donor liver retransplantation.

The scabrous protein can act as an extracellular antagonist of notch signaling in the Drosophila wing.

Notch (N) is a receptor for signals that inhibit neural precursor specification [1-6]. As N and its ligand Delta (DI) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with nonneural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling in response to DI, but inhibits N signaling in response to Serrate (Ser), which encodes a ligand that is structurally similar to DI. Dorsal expression of Fng protein localizes N signaling to the dorsoventral (DV) wing margin [9-11]. The secreted protein Scabrous (Sca) is a candidate for modulation of N in neural cells. Mutations at the scabrous (sca) locus alter the locations where precursor cells form in the peripheral nervous system [12,13]. Unlike fringe, sca mutations act cell non-autonomously [12]. Here, we report that targeted misexpression of Sca during wing development inhibited N signaling, blocking expression of all N target genes. Sca reduced N activation in response to DI more than in response to Ser. Ligand-independent signaling by overexpression of N protein, or by expression of activated truncated N molecules, was not inhibited by Sca. Our results indicate that Sca can act on N to reduce its availability for paracrine and autocrine interactions with DI and Ser, and can act as an antagonist of N signaling.

The scabrous gene encodes a secreted glycoprotein dimer and regulates proneural development in Drosophila eyes.

R8 photoreceptor cells play a primary role in the differentiation of Drosophila eyes. In scabrous (sca) mutants, the pattern of R8 photoreceptor differentiation is altered. The sca gene is predicted to encode a secreted protein related in part to fibrinogen and tenascins. Using expression in Drosophila Schneider cells, we showed that sca encoded a dimeric glycoprotein which was secreted and found in soluble form in the tissue culture medium. The sca protein contained both N- and O-linked carbohydrates and interacted with heparin. This Schneider cell protein was similar to protein detected in embryos. We showed that sca mutations, along with conditional alleles of Notch (N) and Delta (Dl), each affected the pattern of cells expressing atonal (ato), the proneural gene required for R8 differentiation. In normal development, about 1 cell in 20 differentiates into an R8 cell; in the others, ato is repressed. N and Dl were required to repress ato in the vicinity of R8 cells, whereas sca had effects over several cell diameters. Certain antibodies detected uptake of sca protein several cells away from its source. The overall growth factor-like structure of sca protein, its solubility, and its range of effects in vivo are consistent with a diffusible role that complements mechanisms involving direct cell contact. We propose that as the morphogenic furrow advances, cell secreting sca protein control the pattern of the next ommatidial column.

Optical frequency domain imaging with a rapidly swept laser in the 815-870 nm range.

Optical frequency domain imaging (OFDI) in the 800-nm biological imaging window is demonstrated by using a novel wavelength-swept laser source. The laser output is tuned continuously from 815 to 870 nm at a 43.2-kHz repetition rate with 7-mW average power. Axial resolution of 10-mum in biological tissue and peak sensitivity of 96 dB are achieved. In vivo imaging of Xenopus laevis is demonstrated with an acquisition speed of 84 frames per second (512 axial lines per frame). This new imaging technique may prove useful in comprehensive retinal screening for medical diagnosis and contrast-agent-based imaging for biological investigations.

High-speed imaging of human retina in vivo with swept-source optical coherence tomography.

We present the first demonstration of human retinal imaging in vivo using optical frequency domain imaging (OFDI) in the 800-nm range. With 460-muW incident power on the eye, the sensitivity is 91 dB at maximum and >85 dB over 2-mm depth range. The axial resolution is 13 mum in air. We acquired images of retina at 43,200 depth profiles per second and a continuous acquisition speed of 84 frames/s (512 A-lines per frame) could be maintained over more than 2 seconds.

Serial cytogenetic studies of nonendemic Burkitt's lymphoma cell lines.

Cytogenetic study of nonendemic Burkitt's lymphoma (BL) cell lines showed a translocation of chromosomes #8 and #14, t(8;14), present in 16 of the 18 lines examined. Serial cytogenetic studies of nine of these lines showed the t(8;14) to be stable and present in all cells examined. Although many other chromosome aberrations were present, they did not demonstrate the stability or the pervasiveness of the t(8;14). The significance of these results and previously reported cytogenetic studies on the etiology of BL was discussed.

Mutant lines of guinea pig L2C leukemia. II. Comparative cytogenetic studies and banding analyses of normal and leukemic karyotypes.

Chromosomes of normal guinea pig (strain 2) cells and of cell lines dervied from a spontaneously arising leukemia were analyzed in detail. All cell lines studied, LG-L2C, GH-L2-C, BZ-LC, and EN-L2C, contained one M1 marker and two X chromosomes, in addition to other chromosome abnormalities specific for each cell line. The presence of the M1 marker and the two X chromosomes confirmed that all of these leukemic cell lines are derived from one ancestral line. Comparison of the chromosome markers and immunologic characteristics of these lines revealed that possibly the gene involved in the determination of C3 receptor sites is located on the terminal portion of the long arm of chromosome No. 2, but no other correlations could be made.

Direct cytogenetic studies by needle aspiration of Burkitt's lymphoma in Ghana, West Africa.

With the use of a needle aspiration technique for obtaining tumor material, the direct karyotype of Burkitt's lymphoma cells was examined from 15 Ghanaian patients. The 14q+ chromosome (in addition to other chromosomal abnormalities) was present in 8 (57%) of the 14 patients; 6 of these 8 patients had t(8;14) (q24;q32). One of the remaining 2 patients had a #8 chromosome deleted, whereas the second had 2 normal-appearing #8 chromosomes. Other numerical and structural abnormalities were frequent. No correlation between type or frequency of abnormality and clinical status or survival was found. Within cells of the same tumor aspirate, the karyotype abnormalities were generally similar. In 3 patients, karyotypes from two separate tumor sites (abdomen-bone marrow, 2 cases; right maxilla-left mandible, 1 case) showed identical markers. The same marker was seen in specimens from the initial and second relapse abdominal tumors of 1 patient. The similarity of chromosomal markers from two sites or in serial studies further supports the concept that African Burkitt's lymphoma is a disease of monoclonal origin.

Collagenase secretion by human breast neoplasms: a clinicopathologic investigation.

Evidence is presented that biopsy specimens from fibroadenomas, benign cystic lesions, and carcinomas of the human breast can produce in organ culture a neutral protease capable of digesting type I collagen. This enzyme activity, measured with the use of a radioactive release assay, was characterized as true vertebrate collagenase and occurred in both active and latent (requiring trypsin activation) forms. For the two types of benign breast lesion studied, collagenase secretion was significantly higher from fibroadenomas than from benign cystic tissue. Breast carcinomas, however, exhibited a wide quantitative spectrum of collagenase secretion, encompassing the extremes observed for the benign lesions and showing no correlation with histologic type. These results, while providing a plausible mechanism for the marked collagen degradation seen in disseminating neoplasms, demonstrate that high collagenase secretory activity is not pathognomonic of invasive behavior. The findings, however, indicate disordered regulation of collagenase activity in malignant tumors.