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Measurement of free kappa and lambda chains in serum and the significance of their ratio in patients with multiple myeloma.

An inhibition enzyme-linked immunoassay technique using commercially available antibodies has been developed for the quantitation of both kappa and lambda light chains in the serum of patients with B-cell malignancies. Assay conditions were selected to enable measurement of free light chains in the concentration range between 0.1 and 20 mg/l. The normal range for free lambda chains in serum was found to be 0.4-4.2 mg/l and for free kappa chains it was 1.6-15.2 mg/l. At diagnosis the serum of most patients with multiple myeloma contained increased levels of the malignant free light chain and in some cases there was also elevation of the non-malignant light chain. The absolute level of the malignant light chain at diagnosis did not correlate with survival nor with laboratory parameters such as IgM or creatinine. A correlation with beta 2 M and serum paraprotein levels was evident only in cases of IgA myeloma. Although the absolute level of free serum light chain had no value as a prognostic indicator, the ratio of kappa:lambda chains closely followed the clinical assessment of disease status, being near the normal range (1.2-9.1) in plateau phase or stable disease. During periods of progressive disease this ratio ranged from 19 to 460 (n = 14) in patients with kappa myeloma, and 0.0013-0.14 (n = 9) in patients with lambda myeloma. Determination of the ratio of free light chains in the serum may allow effective monitoring and earlier warning of disease progression in patients with multiple myeloma.

Enzyme-Linked Immunosorbent Assay↗

Role of ocular matrix metalloproteinases in peripheral ulcerative keratitis.

AIM: Peripheral ulcerative keratitis (PUK) is an ocular manifestation of rheumatoid arthritis and other similar systemic diseases. The purpose of this inquiry was to investigate the involvement of matrix metalloproteinases (MMPs) in the induction and/or maintenance of PUK. METHODS: Substrate gel electrophoresis was used to characterise the MMP activities secreted by primary cultures of keratocytes derived from normal and perforated pathological corneal specimens, and those present in tears of normal subjects and patients with PUK. Substrate specificity and the in vivo activity status of the secreted MMPs was assessed by SDS-polyacrylamide gel electrophoresis of standard collagens incubated in the presence or absence of the various enzyme preparations. RESULTS: In addition to MMP-2 of M(r) 66,000, cultured keratocytes derived from perforated corneas of patients with PUK abnormally produce the MMP-2 of apparent M(r) 62,000. Other MMPs and in particular MMP-9 of M(r) 92,000, also occur in the tears of these patients. Their visualisation on substrate polyacrylamide gels correlated with clinical manifestations of disease activity; during periods of disease quiescence they were barely detectable. The steroid prednisolone, frequently used in systemic therapy, had no effect on the in vitro activity of MMP-2, or on its production by cultured corneal keratocytes. Although the in vitro activity of MMP-2 was inhibited by both Cu(2+) and Zn(2+), Cu(2+) apparently induced the keratocytes to produce activated enzyme and Zn(2+) irreversibly inhibited their production of MMP-2. CONCLUSION: Overexpression of corneal MMP-2 and tear film MMP-9 are characteristic features of patients with PUK and their activation may be a crucial facet of disease initiation or progression. Although effective in systemic therapy for PUK, prednisolone had no direct control over corneal MMP-2 production or activity. Zn(2+) on the other hand inhibited both MMP-2 production and MMP-2 activity and may, therefore, be of therapeutic value if suitably formulated and used in conjunction with systemic steroid treatment.

Copper↗

Photoreceptor cell rescue at early and late RPE-cell transplantation periods during retinal disease in RCS dystrophic rats.

Normal retinal pigment epithelial (RPE) cells were transplanted into retinas of Royal College of Surgeons (RCS) dystrophic rats at different stages of the retinal disease process. RPE-cell transplantation at 10, 17 and 26 days resulted in rescue of photoreceptor cells, such that at 4 months the outer nuclear layer (ONL) was 8-10 cells in thickness as shown in retinas of age-matched control rats. Of these transplantation times, day 17 appeared to affect the best rescue of photoreceptor cells. Nongrafted retinas of 4 month-old RCS dystrophic rats exhibited scattered PRC's, most prevalent in the peripheral retina. In addition, a small, but significant increase in the ONL thickness was detected in vehicle-injected retinas (sham control) of 17 day-old RCS dystrophic rats at 2 months; however, at 3 months, the ONL thickness was reduced to control levels. A normal distribution of (Na+ + K+)-ATPase immunostain was demonstrated beneath grafted RPE cells in retinas of 4 month-old RCS dystrophic rats. Dense immunostaining was shown along rescued photoreceptor cell inner segments (IS), within the inner (IPL) and outer (OPL) plexiform layers and on plasmalemma of cell bodies in the inner nuclear layer (INL). In nongrafted retinas of age-matched RCS dystrophic rats, immunostaining for (Na+ + K+)-ATPase was observed only in the INL and IPL. Under RPE-cells transplants in retinas of 4 month-old RCS dystrophic rats, opsin immunostaining was detected along both rescued photoreceptor cell inner and outer (OS) segments and on plasmalemma of ONL cell bodies. However, immunostaining for opsin was restricted to a debris zone in nongrafted retinas of age-matched RCS dystrophic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The panmictic nature of Neisseria meningitidis serogroup B during a period of endemic disease in Canada.

Three hundred and one (301) strains of Neisseria meningitidis serogroup B, isolated from patients with meningococcal disease during the years 1994-1996, were subjected to multilocus enzyme electrophoresis, serotyping, and serosubtyping. Based on the analyses of 14 enzyme loci, 177 electrophoretic types (ETs) were identified. Of these, 136 were represented by single isolates and 41 were represented by multiple isolates (range 2-31). The mean genetic diversity for isolates was 0.444 and for ETs was 0.440. The index of association (I(A)) between loci was 0.530 +/- 0.08 for isolates and 0.256 +/- 0.10 for ETs. Cluster analysis revealed the presence of 39 lineages each represented by a single ET or clusters of ETs. The most common serotypes were 4, 15, and 14 and accounted for 84 (28.0%), 53 (17.6%), and 32 (10.6%) of the isolates, respectively, and were dispersed amongst 46 ETs (1-122), 35 ETs (3-165), and 26 ETs (18-76), respectively. The 109 (36.6%) nontypable (NT) isolates were amongst 74 ETs (6-177). The mean genetic diversity for serotypes 4, 15, and 14 and NT isolates was 0.368, 0.371, 0.343, and 0.442, respectively, and for ETs was 0.363, 0.354, 0.397, and 0.440, respectively. Combinations of serotypes and serosubtypes (number of isolates) that occurred most frequently were 4:P1.14 (17), 14:P1.16 (16), NT:P1.16 (16), 15:P1.16 (13), and NT:P1.13 (13). The majority of group B disease in Canada during 1994-1996 was caused by meningococci of considerable genetic diversity, and reflects a situation of endemic disease. However, the results also indicate that organisms belonging to the ET-5 complex, which has been responsible for outbreaks of group B disease globally for several decades, have been introduced into the country.

Alleles↗

[Gas exchange disorders and their correction during the acute period of burn disease].

The criteria of early respiratory therapy in patients with isolated and combined thermal burns are accurately defined and the efficiency of such therapy is evaluated. Early respiratory therapy in the form of forced or assisted ventilation of the lungs stabilizes hemodynamics, improves oxygen transport and consumption, and eventually improves the results of treatment in patients with isolated and combined thermal burns.

Acute Disease↗

[Minimally invasive technologies in the treatment of severe forms of acute pancreatitis at various periods of the disease].

The choice of the optimum technique of the sanitation procedure in treatment of acute necrotizing pancreatitis (ANP) is now one of the most disputable problems. Clinical estimation of the efficiency of various operative techniques of treatment of ANP at various stages of disease has been made. In the aseptic phase laparoscopic decompression of the pancreas is indicated when the patient has evident hemorrhagic parapancreatitis. In the phase of septic sequestration of ANP the optimum method of minimally invasive surgical intervention is considered to be minilaparotomy which is expedient for abscesses of small volume, lipid abscesses of any volume with the minimal content of necrotizing tissues as the first step of sanitation in critical patient. High quantity of the necrotizing tissues in the zone of the destructive focus requires traditional laparotomy of the abscess under conditions of preventive maintenance of the endotoxic shock.

Humans↗