Extensive post-traumatic ossification of the patellar tendon. A report of two cases

Two men, aged 21 and 50 years, were seen with ossification of the patellar tendon after injury to the knee in adolescence. They complained of pain and had patella alta. Large bony masses were excised from below the affected patellae. The patellar tendon was then reconstructed using a Leeds-Keio ligament. The results at six and ten years, respectively, were good, with neither patient having pain or an extension lag.     

17 Beta-estradiol increases VEGF receptor-2 and promotes DNA synthesis in retinal microvascular endothelial cells.

PURPOSE: Estrogen is known to promote angiogenesis in gonads. The presence of estrogen receptors in the vascular endothelium of organs other than gonads has been reported. The goal of this study was to determine whether estrogen promotes the proliferation of retinal microvascular endothelial cells and to explore the mechanism of it. METHODS: DNA was quantitated using primary cultures of bovine retinal endothelial cells that were incubated with different doses of 17 beta-estradiol (E2), VEGF, or both. The changes in expression level of VEGF and VEGF receptor-2 (VEGFR2) were measured using northern blot analysis after treatment with E2. The presence of estrogen receptors in the endothelial cells was studied by immunohistochemistry and western blot analysis. RESULTS: 17 Beta-estradiol (E2) increased the DNA level in bovine retinal capillary endothelial cells (BRECs) by 177% at 1 nM (P < 0.05) and 150% at 10 nM (P < 0.05) by comparison with unstimulated BREC. One hundred nanomole tamoxifen completely blocked the E2-induced DNA synthesis in BRECs. Ten nanomole E2 augmented vascular endothelial growth factor (VEGF)-induced DNA synthesis in BRECs significantly (160%, P < 0.01). Ten nanomole E2 also increased VEGF mRNA expression, which peaked after 24 hours (6.7 times, P < 0.05), and VEGF receptor-2 (VEGFR2) mRNA expression, which peaked after 9 hours (2.4 times, P < 0.05). The mRNA expression level of VEGFR2 peaked with 10 nM E2 (P < 0.05) and that of VEGF reached maximum with 1 nM E2 (15 times, P < 0.001). VEGFR2 and VEGF proteins increased in parallel with their mRNA levels. Immunocytochemistry showed estrogen receptor expression in BRECs, and western blot analysis indicated the presence of a 67-kDa protein that was compatible with the estrogen receptor. CONCLUSIONS: These findings suggest that E2 may stimulate BREC growth by the receptor-mediated pathway and that E2 may augment the VEGF-dependent angiogenesis partly through the upregulation of VEGFR2.     

N-Benzoyl derivatives of amino acids and amino acid analogs as growth inhibitors in microbial antitumor screen.

Twenty-seven N-benzoyl derivatives of amino acids and amino acid analogs were prepared and tested for growth-inhibitory activity in a microbial antitumor screen. Of these, 19 showed some inhibitory capacity, from a modest 13% to a potent 96% at 1 mg/ml. The activities of the "modest" inhibitors were comparable to those of most inhibitory chloracetyl and trifluoroacetyl derivatives reported earlier. The intermediate inhibitors were as active as N-chloroacetyl-beta-hydroxy-D-norleucine isomer B, the most active acyl derivative noted previously. The most active compounds in this study were N-benzoyl-p-chloro-DL-phenylalanine and N-benzoyl-m-fluoro-DL-phenylalanine, which inhibited the test organism almost completely under the assay conditions.     

Suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the high-affinity antibody response in C57BL/6 mice.

In the humoral immune response to an invasion of foreign antigens, B cells differentiate into low-affinity antibody-forming cells (AFCs) that mainly secrete IgM or, through germinal center (GC) formation, into high-affinity AFCs that secrete IgG-class antibodies with a higher affinity for the antigen. Previous studies have established the suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on low-affinity antibody responses to antigens. However, whether and how TCDD affects the high-affinity antibody response to antigens has not yet been clarified. In this paper we investigate the effects of TCDD on GC formation, high-affinity AFC generation, and high-affinity antibody production in the primary humoral immune response. C57BL/6 mice were orally administered 0 or 20 microg/kg of TCDD and subsequently immunized with alum-precipitated ovalbumin (OVA) on day 0. Then the GC formation in the spleen and OVA-specific antibodies in the plasma, was evaluated until day 14 postimmunization. TCDD exposure reduced the production of OVA-specific IgG1 on days 10 and 14. GC formation in the spleen was also suppressed by TCDD exposure, and the suppression persisted from day 7 until day 14. In TCDD-administered mice, on day 7, cellular proliferation in the GCs was significantly suppressed, although apoptosis was not markedly affected. In order to measure high-affinity antibody and high-affinity AFCs, the mice were administered TCDD followed by immunization with alum-precipitated (4-hydroxy-3-nitrophenyl) acetyl linked to chicken gamma-globulin (NP-CG). The frequency of high-affinity NP-specific AFCs that bind to low-haptenated antigen was clearly shown to be reduced in the spleen on days 10 and 14. Furthermore, the high-affinity anti-NP IgG1 levels on days 10 and 14 postimmunization were significantly reduced by TCDD exposure. Taken together, the results of this paper demonstrate that TCDD exposure inhibits the generation of high-affinity AFCs and high-affinity antibody production during the primary humoral immune response and suggest that these alterations were caused by the suppression of antigen-responding B-cell proliferation induced by TCDD during GC formation.     

Membranous glomerulonephritis with nephrotic syndrome associated with chronic lymphocytic leukemia

A 66-year-old woman was admitted to our hospital for evaluation of edema of the extremities. Laboratory findings suggested that she had nephrotic syndrome and chronic lymphocytic leukemia (CLL). Renal biopsy (with PAM staining) showed a spike formation in the capillary wall. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG) and the third component of complement in the glomerular basement membrane. Electron microscopy showed fibrillary deposits in the subepithelium. These findings indicated membranous glomerulonephritis (MGN). In addition, focal segmental sclerosis and interstitial lymphocytic infiltration were observed in the renal biopsy specimen. In CLL patients nephrotic syndrome occurs rarely. Even if the complication occurs, MGN is not frequent. Both diseases are suspected to occur in association with each other, and immunologic abnormality contributes to their coexistence. Although administration of prednisolone and endoxan improved leukocytosis, proteinuria was not sufficiently improved with combination therapy.     

The role of the sentinel lymph node in gastrointestinal cancer

Evaluation of the clinical significance of the sentinel node concept in GI cancer has just begun. The authors' preliminary data, using intraoperative radiation techniques and the gamma probe, suggest that it is worthwhile to continue the evaluation of this procedure to determine its role in an accurate staging and a minimally invasive approach to GI cancers.     

Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan

BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis affect the incidence of diabetic vascular complications is unknown. That both type 1 and type 2 diabetes occur in the young Japanese population prompted us to investigate whether the type of diabetes and the year of diagnosis are related to the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578 (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620 (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy was analyzed in the patients according to postpubertal duration and year of diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%, 95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic patients has declined during the past two decades, whereas it has not among type 2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.     

Expression of the long form of leptin receptor (Ob-Rb) mRNA in the brain of mouse embryos and newborn mice

The long form of the leptin receptor (Ob-Rb) has a cytoplasmic domain which activates the JAK-STAT signal transduction pathway. It is related to appetite and energy expenditure and is expressed in various parts of the brain in adults. In embryos, however, the detailed distribution of Ob-Rb expression sites and the function of the leptin-Ob-Rb system remain unclear, although leptin is detected in human cord plasma and leptin mRNA is detected in mouse embryos. In this study, we investigated the Ob-Rb mRNA expression pattern in the brains of mouse embryos and newborn mice by RT-PCR and in situ hybridization. At embryonic day 10.5 (E10.5), Ob-Rb mRNA was already detected in the brain by RT-PCR. By in situ hybridization, Ob-Rb mRNA was observed in the ventricular zone of the rhombencephalon at E11.5. At E12.5, it was also expressed in the ventricular zone of the telencephalon, mesencephalon and cerebellar primordium. From E14. 5 it was expressed in the cortical plate of the telencephalon and the ventricular zone of the thalamus. At E16.5, it was expressed in the premamillary hypothalamic nucleus, superficial gray matter of the superior colliculus, external germinal and Purkinje cell layers of the cerebellum, and facial nucleus. At E18.5, it was expressed in the arcuate nucleus and ventromedial hypothalamic nucleus. These results suggest that the leptin-Ob-Rb system is related to brain development.