Spondylolysis after posterior decompression of the lumbar spine: 35 patients followed for 3-9 years

Radiographs were examined in 35 patients who had had posterior decompression without fusion of the lumbar spine. Spondylolysis was found in 10 patients. Segmental range of motion, degree of vertebral slippage and width of decompression were analyzed by radiography. There was greater vertebral slippage after surgery in patients with postoperative spondylolysis than in those without spondylolysis. We conclude that excessive bony decompression may cause postoperative spondylolysis.     

Responsiveness of human gastric tumors implanted in nude mice to clinically equivalent doses of various antitumor agents

To reproduce clinical effects of various antitumor agents in the human tumor/nude mouse model, we investigated the responsiveness of 11 lines of human gastric tumor xenografts to doses of the agents pharmacokinetically equivalent to the respective clinical doses, which we designated the "rational dose" (RD). We found that the response rates to mitomycin C, 3-[(4-amino-2-methyl-5-pyrimidinyl]methyl-1-[2-chloroethyl]-1- nitrosourea (ACNU), adriamycin, 5-fluorouracil were 18%, and that to vinblastine was 30%; on the other hand, those to vincristine, methotrexate, and cyclophosphamide were poor. In contrast, in our previous study using the maximum tolerated doses, response rates to mitomycin C, ACNU, and vinblastine were as high as 64-82%, and those to adriamycin and 5-fluorouracil were 18%. When these results were compared with the clinical response rates of gastric tumors, as a whole, the results with RD's exhibited much better coincidence with the clinical data in terms of relative therapeutic potency, indicating the validity of the use of clinically equivalent doses instead of maximum tolerated doses in the human tumor model.     

Changes in ultrastructure of hepatocytes and liver test results before,during, and after treatment with interferon-β in patients with HBeAg-positive chronic active hepatitis

We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon- from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3×10⁶ to 6×10⁶ units of interferon- was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P<0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P<0.01) and at the third day (P<0.01) to the second week (P<0.05) of treatment, respectively. These results suggest that interferon- injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.     

Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea-pigs in vivo

BACKGROUND: Indoor formaldehyde (FA) might worsen allergies and be an underlying factor for the increasing incidence and severity of asthma; the exact mechanism, however, remains unclear. OBJECTIVE: The present study examined the effects of repeated exposure to FA on methacholine- and antigen-induced bronchoconstriction in guinea-pigs in vivo. METHODS: First, non-sensitized guinea-pigs were transnasally treated with 0.1 or 1.0% FA or saline three times a week for 6 weeks, and increasing concentrations of methacholine (50, 100, and 200 microg/mL) were inhaled at 5-min intervals. Second, guinea-pigs pre-treated with transnasal administration of FA or saline using the same protocol were passively sensitized with anti-ovalbumin (OA) serum 7 days before antigen challenge. Third, guinea-pigs were actively sensitized with OA and pre-treated with transnasal administration of FA or saline using the same protocol. The lateral pressure of the tracheal tube (Pao) was measured under anesthesia and artificial ventilation. RESULTS: The antigen-induced increase in Pao in actively sensitized guinea-pigs was significantly potentiated by FA exposure in a dose-dependent manner. The dose-response curve of the methacholine-induced increase in Pao in non-sensitized guinea-pigs or of the antigen-induced increase in Pao in passively sensitized guinea-pigs was not altered by FA exposure. Transnasal administration of FA significantly increased the serum anti-OA homocytotropic antibody titre (IgG) as measured by the passive cutaneous anaphylaxis reaction in actively sensitized guinea-pigs. CONCLUSION: The results suggest that repeated exposure to FA worsens allergic bronchoconstriction through enhancing antigen sensitization.     

Relationship between HLA-D and in vitro and in vivo responsiveness to Candida allergen.

In vitro reaction to Candida allergen was studied in 100 normal healthy Japanese and related to HLA. A significant association was found between the low responder group (< 7,000 c.p.m.) and HLA-B15 and the high responder group (> 7,000 c.p.m.) and HLA-B7, as well as Dwl. Four HLA-D homozygote cells of types HLA-Dwl and DHO, were tested; these fitted in the high responder group. HLA-DYT and DEn fitted into the low responder group. Responsiveness to Candida allergen corresponded to skin test (r = 0.884, P < 0.01). From these results, in vitro lymphocyte reaction to Candida allergen and skin tests showed close correlation and an association with HLA antigens, HLA-D in particular.     

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.     

Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the human matrix Gla protein (MGP) locus

Matrix Gla protein (MGP) is an 84-residue, vitamin K-dependent protein expressed by chondrocytes and vascular smooth muscle cells, and is a potent regulator of calcium deposition in cartilage and arterial wall. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human MGP gene. This polymorphism will be useful in genetic studies of arteriosclerosis and osteoporosis. Received: November 5, 1997 / Accepted November 27, 1997     

Electron Microscopic Studies on IgA Nephropathy

We carried out electron microscopic studies on renal tissues from 9 patients with IgA nephropathy. Electron dense deposits were present in the mesangial area in all cases, subendothelial deposits in 4, and subepithelial deposits in only one. In basement membrane, segmental swelling and rarefaction of basement membrane substance were observed. In some cases the degenerated basement membrane substance protruded through the dilated endothelial fenestration into capillary lumina. Focal splitting, attenuation, mouse eaten appearance, and herniation of basement membrane were seen in a high incidence. Mesangial cells possessed well developed rough endoplasmic reticulums and polysomes. In the peripheral areas of mesangial cell cytoplasm, there was accumulation of electron dense substance and this was occasionally continuously present in the mesangial matrix. There was segmental swelling of endothelial cell cytoplasm, resulting in loss of fenestration. Epithelial cells had well developed rough endoplasmic reticulums and polysomes. Segmental foot process fusion was seen, and these processes, regardless of fusion, became electron denser in the area close to the basement membrane. Multivesiculated bodies were present in all cases in the epithelial cells and in 7 cases in the endothelial cells. Spherical microparticles were present in 3 cases in the urinary space or between the basement membrane and the epithelial cells.