Increased occurrence of free immunoglobulin light chains in cerebrospinal fluid and serum in human immunodeficiency virus-1 infection

The presence of free immunoglobulin light chains (FLCs) in the cerebrospinal fluid (CSF) and sera of patients with human immunodeficiency virus-1 (HIV-1) infection, multiple sclerosis (MS), and neurologically healthy control individuals was investigated by paying special attention to ensure that only truly free light chains would be detected. The FLCs were extracted by specifically binding them to Sepharose-coupled anti-FLC monoclonal antibodies, and thereafter they were electrophoresed and immunoblotted with monoclonal antibodies to both light chain (LC) isotypes. A frequent occurrence of kappa and lambda FLCs was found in both CSF and sera of HIV-1 infected patients. In HIV-1 infection and in MS, the frequency of FLCs of the CSF was equal. In healthy controls, only occasional weak FLCs were observed in either CSF or serum. FLC bands of the CSF from patients with HIV-1 infection tended to be more intensive than those of the appropriately diluted sera. Both intrathecal synthesis of FLCs and their transudation from sera through the impaired blood-brain barrier (BBB) may contribute to this. Increasing severity of general HIV-1 infection was accompanied by an increase of FLC intensity in sera. A qualitative demonstration of FLC in the CSF may be meaningful only in the absence of altered BBB function.     

A role for decorin in cutaneous wound healing and angiogenesis

Decorin is known to influence tissue tensile strength and cellular phenotype. Therefore, decorin is likely to have an impact on tissue repair, including cutaneous wound healing. In this study, cutaneous healing of both excisional and incisional full‐thickness dermal wounds was studied in decorin‐deficient (Dcn^?/?) animals. A statistically significant delay in excisional wound healing in the Dcn^?/? mice occurred at 4 and 10 days postwounding and, in incisional wounds at 4, 10, and 18 days when compared with wild‐type (Dcn^?/?) controls. Fibrovascular invasion into polyvinylalcohol sponges was significantly increased by day 18 in Dcn^?/? mice relative to Dcn^+/+ mice. The 18‐day sponge implants in the Dcn^?/? mice showed a marked accumulation of biglycan when compared with the corresponding implants in Dcn^+/+ mice. Thus, regulated production of decorin may serve as an excellent therapeutic approach for modifying impaired wound healing and harmful foreign body reactions.     

The αvβ6 integrin plays a role in compromised epidermal wound healing

The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.     

Bone Mineral Density in the Proximal Femur and Contralateral Knee After Total Knee Arthroplasty

Osteoarthrosis (OA) is often associated with pain and disability, which are relieved after total knee arthroplasty (TKA), but the nature of bone changes associated with OA is controversial. We examined preoperative hip and contralateral knee bone mineral density (BMD) in patients requiring TKA and monitored the BMD changes postoperatively. Sixty-nine patients, scheduled to have TKA for osteoarthrotic knees, had both hips and contralateral knee BMD measured by dual-energy X-ray absorptiometry (DXA) at the time of operation (baseline) and at 1 yr after operation. X-rays of the knee joints were also taken to evaluate the severity of OA. Preoperatively, 27% and 38% of the patients had total hip BMD Z-score more than 1 SD in the operated side and contralateral hips, respectively. In all regions of interest (ROI), the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side (p < 0.0005-0.019). The severity of OA was not associated with BMD. During 1-yr follow-up, the postoperative knee status and the physical activity of the patients (AKS score) improved. However, neither the hip nor the nonoperated knee BMDs increased. Knee OA is associated with significantly lower BMD values in the affected side compared with the contralateral hip, and these levels remained similar or decreased during a 1-yr follow-up. We conclude that improved mobility after TKA does not improve the effects of preoperative disuse-associated bone loss in the short term.     

Effect of totally absorbable implant volume on wound infection rate: Study of 2500 operated fractures, osteotomies, and ligament injuries

Between November 1984 and January 1994 in our department, a total of 2500 patients were treated with totally absorbable internal fixation devices. We studied these patients and analyzed results with regard to the volume of the absorbable implants and the development of wound infection. Of the 2500 patients 2044 were trauma patients and 456 were operated on for orthopedic disease. In 1466 patients treated with implants made of self-reinforced polyglycolic acid (SR-PGA) only, the patients who developed wound infection had a higher implant volume (P=0.07) than those who did not; this difference was close to statistical significance. In the 446 patients who received only implants made of self-reinforced poly-l-lactic acid (SR-PLLA), the 5 who developed wound infection had a mean implant volume more than three times that of the non-infected patients (P=0.01). We found that in the patients treated with the earlier SR-PGA implants, which contained a green staining material, there was no correlation between implant volume and incidence of wound infections. On the other hand, both the non-stained SR-PGA implants, which have been in clinical use since 1989, and the SR-PLLA implants, seem to be more predictable in terms of wound infections. We believe that this difference, is largely due to the lower level of tissue reactions with these newer implants.     

Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.     

Stability of European Anti-D Immunoglobulin Preparations

The stability of 18 batches of anti-D immunoglobulin preparations from 7 European manufacturers was studied over 28-day incubation at +37 degrees C and 3-year storage at +4 degrees C. The mean loss of activity after 28 days at +37 degrees C was 12.3 +/- 8.2%, and after 3 years at +4 degrees C 15.2 +/- 9.5%. The correlation coefficient of the loss of activity between these two storages was r = 0.61, p less than 0.05 indicating that short-term incubation can be used to evaluate the shelf life stability of anti-D activity. In general, measurements of IgG fragments or activities of plasmin, plasminogen, or prekallikrein activator were not valuable in predicting the stability of anti-D activity due to the fact that the preparation of each manufacturer has its own unique pattern of enzymes and inhibitors. The anti-D immunoglobulin preparations contained up to at least 7 plasma proteins in addition to IgG. All preparations contained factor B, most of them alpha 2-macroglobulin, alpha 1-antitrypsin, albumin, and alpha 2-HS glycoprotein, alpha-Lysozyme was present in 7, and ceruloplasmin in 2 preparations. Neither purity nor impurity correlated with stability.     

Serotonin 5-HT2C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments.

Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT2C receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT2C receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT2C receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20 mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20 mg/kg) increased the maximal PI hydrolysis response by 40%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT2C receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT2C receptors. Thus, functional 5-HT2C receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration.     

Terminal deletion of chromosome 4p (4p16.3) shows a breakpoint between loci linked to Huntington disease

A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus. © 1992 Wiley-Liss, Inc.