Tubulo-interstitial nephritis (TIN) with no glomerular lesions, distal renal tubular acidosis and asteatosis cutis in a patient with systemic lupus erythematosus (SLE): a case report]

We report a 28-year-old woman with systemic lupus erythematosus (SLE) who showed tubulo-interstitial nephritis (TIN) without any glomerular changes. In 1990, she was admitted to our hospital, complaining of anorexia, vomiting and persistent high fever. Laboratory findings showed proteinuria, pancytopenia, hypocomplementemia and positive for antinuclear antibody, anti-DNA antibody, anti-Sm antibody, anti-SSA antibody and anti-SSB antibody. We made a diagnosis of SLE. Furthermore, distal renal tubular acidosis and asteatosis cutis were revealed. The diagnosis of Sj?gren's syndrome was not made. We treated with high-dose prednisolone (60mg/day) and achieved improvement of symptoms and laboratory data. Open renal biopsy showed TIN without any glomerular changes. Predominant TIN is very rare in SLE. We discussed its pathogenesis and relation to the renal lesions of Sj?gren's syndrome.     

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through, an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrorcyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern. blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.     

Familial Juvenile Nephronophthisis in Two Siblings — Histological Findings at an Early Stage —

We present two female siblings with familial juvenile nephronophthisis (FJN) which was diagnosed at the early stage of renal failure. Diagnosis was made during the investigation of anemia in case 1 and by a subsequent family survey in case 2. Most patients with FJN are not identified until the terminal stage of renal failure and such cases have rarely been reported in Japan. Case 2 had a reduction in the maximum urinary concentration ability but no azotemia, and among the FJN patients reported in Japan so far she has the least advanced renal disease. Histological examination of the renal biopsy in case 1 showed typical findings of FJN, such as thickening and lamination of the tubular basement membrane (TBM), interstitial fibrosis, and round cell infiltration of the interstitium. In case 2, renal biopsy revealed an irregular marked thickening of the TBM with trivial interstitial changes and a normal glomerular appearance. The histology of these two cases suggests that the TBM may be the primary site affected in FJN.     

Recent Advances in Molecular Genetics of Colorectal Cancer

APC gene and mismatch repair genes. The role of these genes in colorectal carcinogenesis has been studied intensively. The adenoma–carcinoma sequence was initially proposed by Vogelstein, and the multistep carcinogenesis theory is now well accepted. The various functions of the APC gene have been elucidated. APC genes are considered to play a role in shedding of the epithelial cells into the lumen. The mechanism behind formation of a unicryptal adenoma is now better understood. Adenoma formation is a monoclonal event with two hits of the APC gene. There is no zonal extension of the proliferative zone in the background colonic mucosa of FAP patients. In addition to the adenoma–carcinoma sequence, there seem to be various carcinogenetic pathways in the development of colorectal cancer. A depressed type of early cancer was recently found by the use of magnifying endoscopy. The incidence of K- ras mutation was extremely low in this group of early cancers. Some of the minute cancers show the p53 mutation before the occurrence of APC mutation. Cancers of microsatellite mutator phenotype show exaggerated genomic instability at simple repeat sequences, such as TGFβRII. These genes may play a suppressor role in a p53 independent pathway of colorectal carcinogenesis. We are now in an exciting era of this progressing field of science. This genetic information may be more widely applicable clinically in the near future (e.g., for presymptomatic diagnosis, selection of patients for the most appropriate treatments, and assessment of malignant potential).     

Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance

Background: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.     

Selective blood-tumor barrier disruption by leukotrienes.

The authors have previously reported that intracarotid infusion of 5 micrograms leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the tumors was observed at the 0.5-microgram LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min).     

Extracardiac Direct Total Cavopulmonary Connection

We report a successful extracardiac direct total cavopulmonary connection without prosthetic materials performed in a 3-year-old boy with tricuspid atresia, infundibular pulmonary stenosis, and normally positioned great arteries. The transected pulmonary trunk was bought down posterolaterally with respect to the right atrium and was anastomosed end-to-end with the inferior vena cava.