Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane

Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption-treated antisera per microgram IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals.     

The biological characteristics and chemosensitivity of anaplastic thyroid carcinoma transplanted into nude mice

Three xenografts established from three patients with anaplastic thyroid carcinoma were investigated for their biological characteristics and chemosensitivity. The histological and immunohistochemical findings of these tumors were almost the same as those of the original tumors. Although the growth rate of each xenograft was constant, the tumor doubling time varied from 4.8 per 9.0 days, and the labeling indexes, determined using bromodeoxyuridine pulse labeling, varied from 11.4 to 25.1 per cent. The chemosensitivity tests were performed according to the Battelle Columbus Laboratories Protocol, with adriamycin, cyclophosphamide, cisplatin, mitomycin C and tegafur administered intraperitoneally to tumor-bearing nude mice in maximum tolerable doses. Tumors with slower growth rates tended to be sensitive to more drugs. Furthermore, cyclophosphamide showed antitumor effects against all the tumors tested. Although previous treatments of the original tumors may have affected the results, our results suggest that a more suitable chemotherapy for anaplastic thyroid carcinoma could be developed.     

Long-term storage effects on canine osteochondral allografts.

We have studied long-term (to 60 days) effects of 4 degrees C storage in culture media on the histologic, mechanical, and chemical properties of the cartilage from osteochondral shell allografts from the dog. The structural integrity of the cartilage matrix was intact up to 60 days of storage, for the mechanical properties represented by the aggregate modulus and apparent permeability remained normal. These data are supported by normal safranin-O staining as well as normal glycosaminoglycan content and total collagen concentration. However, chondrocyte viability, as assessed by 35SO4 uptake and hematoxylin and eosin preparations, decreased dramatically with time. We believe that the longer storage to 60 days is not indicated, unless conditions can be modified to maintain cell viability.     

Book Reviews Editor

INLANDER, CHARLES B., LEVIN, LOWELL B., AND WEINER, E.D. Medicine on Trial: The Appalling Story of Medical Ineptitude and the Arrogance that Overlooks It.     

Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels

The authors examined the effect of topical application of agents known to increase cyclic nucleotide levels on tear secretion by accessory lacrimal gland tissue in their rabbit model for keratoconjunctivitis sicca (KCS). Tear secretion was studied by changes in tear film osmolarity and tear volume caused by application of the agents relative to application of isotonic buffer solution alone. A decrease in tear film osmolarity or increase in tear volume was interpreted as an increase in tear secretion. Irritative stimulation was distinguished from pharmacologic stimulation by the prior use of topical proparacaine. The following agents significantly decreased tear film osmolarity and increased tear volume: vasoactive intestinal peptide (2 X 10(-8) to 2 X 10(-6) M); three pro-opiomelanocortin fragments alpha-, beta-, and gamma-melanocyte stimulating hormone at 10(-4), 10(-3), and 10(-3) M, respectively; the permeable cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) analogs 8-Br cAMP (0.3-3.0 X 10(-3) M) and 8-Br cGMP (1.0-10.0 X 10(-3) M); and the cyclic nucleotide phosphodiesterase inhibitor 1-isobutyl-3-methyl xanthine (0.3-3.0 X 10(-3) M). Forskolin (2 X 10(-4) M), which activates the catalytic subunits of adenyl cyclase, increased tear volume significantly. Secretin, adrenocorticotropic hormone, and pilocarpine were ineffective. The authors conclude that agents that increase either cAMP or cGMP levels pharmacologically stimulated tear secretion when applied topically to rabbit eyes with surgically induced KCS.     

Effects of ethylene glycol on hepatic microsomal cytochrome P-450

The effect of ethylene glycol on rat hepatic microsomal cytochrome P-450 was studied in vitro and in vivo. The destruction of cytochrome P-450 was not seen in vitro. The addition of 1 mM NADPH also did not change. When ethylene glycol was added to drinking water at a concentration of 1.0% for 7 days, there was no change in the contents of microsomal protein, cytochrome P-450, b5 and heme. While NADPH-cytochrome C reductase activity of the exposed group did not change, NADH-ferricyanide reductase activity increased significantly.     

Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis

The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.     

Destructive ocular myiasis in a noncompromised host

A case of destructive ocular myiasis resulting in complete loss of the globe in two days time is documented. To the best of our knowledge this is the first report of such a severe involvement in a healthy and non-compromised host. Mechanical removal and good local hygiene helped heal the wound. The larvae were isolated to be that of Chrysomyia bezziana (screwworm fly). This is possibly the first report of destructive ocular myiasis caused by Chrysomyia bezziana from the Indian subcontinent and the second in world literature. Infestation of human eyes with larvae of flies (myiasis) has been reported. Serious consequences of destructive myiasis are seen in emaciated and diseased patients. Only one report of total destruction of the globe by maggots of Chrysomyia bezziana exists in the literature. As in previous communications, the patient in this report had no predisposing factors both systemic and local. We here in document a case of orbital myiasis leading to rapid destruction of the globe within two days in a healthy and a non-compromised patient.