Clinicl Significance of Mesangial IgM Deposits in Minimal Change Nephrotic Syndrome

The clinicopathologic features and the response to corticosteroid therapy were compared in 9 patients with minimal change nephrotic syndrome (MCNS) and diffuse mesangial IgM deposits (Group I) and in 32 of those without IgM deposits (Group II). However, serum IgM levels in Group I in both relapse and remission were significantly higher than those of Group II and controls (p<0.001). In Group I mesangial IgM deposits were diffuse in 9 (100%), mesangial C_1q was present in 4, IgA and fibrinogen were each observed in 1, respectively. Electron dense deposits in the mesangium were also present in 2 to 5 patients in Group I. No significant differences were found between the two groups in age of onset, sex ratio, laboratory data except for serum IgM level, duration before biopsy, follow-up periods, outcome, and response to steroid therapy. Our data suggest that a more severe degree of either impairment of mesangial clearance of IgM or overproduction of IgM may be involved in patients with MCNS and mesangial IgM deposits but that these patients could not be considered a distinct group of patients.     

Macular nerve fibers temporal to fovea may have a greater potential to recover function in patients with Leber's hereditary optic neuropathy

PURPOSE: It is known that even after visual loss, younger patients with Leber's hereditary optic neuropathy (LHON) can recover vision. The purpose of this study was to determine the mean age at onset for LHON patients with and without visual recovery who carried the 11778 mutation, and to determine the pattern of central vision recovery. METHODS: Thirty-five LHON patients with the 11778 mutation of mitochondrial DNA who had visited the Keio University Hospital between 1980 and 1999 and were followed for 2 to 20 years, were the subjects of this retrospective study. The patients who had recovered vision were tested by Goldmann perimetry, Humphrey perimetry, and landmark-driven fundus microperimetry with a scanning laser ophthalmoscope (SLO). The fixation status was assessed by SLO microperimetry. RESULTS: Nine of the 35 patients (14 of 70 eyes) demonstrated a recovery of visual acuity to better than 0.3 in at least one eye. The mean age of disease onset was 15.9 +/- 4.6 years in patients with visual recovery and 25.5 +/- 8.9 years in patients without visual recovery. This difference in the mean age at onset was significant (P =.0001; Welch t-test). These 9 patients (14 eyes) showed fenestrated central scotomas in testing by Humphrey 10-2 threshold and SLO microperimetry. The nasal side of the central visual fields had a higher sensitivity than the temporal side in 7 of the 9 patients in Humphrey 10-2 threshold testing. Areas insensitive to 0 dB were detected on the nasal side of the central retina in these patients by SLO microperimetry, and fixation stability was related to the degree of clinical visual acuity. CONCLUSION: The LHON patients with the 11778 mutation and a younger age of onset were more likely to show visual recovery. The findings made by perimetry suggest that the nerve fiber bundles in the nasal field (retina temporal to the fovea) may have a greater potential to recover function in LHON patients.     

Dopamine receptors and calcium channels regulating striatal inhibitory synaptic transmission

A whole-cell patch-clamp study was performed to investigate the modulatory role of dopamine (DA), its ionic mechanisms and their developmental changes in the GABAergic synaptic transmission onto cholinergic interneurones in the rat striatal slices. Inhibitory postsynaptic currents (IPSCs) were evoked by focal stimulation. Bath application of DA inhibited the IPSCs in a concentration-dependent manner with an IC50 value of 10 microM. Pharmacological studies with DA receptor agonists and antagonists suggest the involvement of D2-like receptors. DA reduced the frequency of miniature inhibitory postsynaptic currents without affecting their amplitude distribution. Analyses using selective blockers for N-, or P/Q type Ca2+ channels could estimate the contribution of each Ca2+ channel subtype to the GABAergic transmission. DA had no longer affected the IPSCs after the effect of an N-type channel blocker, omega-conotoxin (omega-CgTX) had reached its steady state. The inhibitory effects of omega-CgTX and DA or a D2-like receptor agonist decreased in parallel during postnatal 12-60 days. DA's action was occluded by omega-CgTX throughout these developmental stages. These results suggest that activation of presynaptic D2-like receptors selectively blocks N-type Ca2+ channels, thereby inhibiting GABA release, and that contribution of N-type channels and D2-like receptor-mediated presynaptic inhibition decrease in parallel with development.     

Different effects of phencyclidine and methamphetamine on firing activity of medial prefrontal cortex neurons in freely moving rats

Immunohistochemistry detected calcium-binding proteins (CaBPs) in corpuscular and Merkel nerve endings of the rat vibrissa. CaBP-immunoreactive (ir) corpuscular endings were divided into two types: ramified and unramified endings. Ramified endings were subdivided into reticular and Ruffini endings. Unramified endings were identical to longitudinal lanceolate endings which have been described previously. Reticular and unramified endings as well as Merkel endings co-expressed neurocalcin (NC)- and parvalbumin (PV)-immunoreactivity (ir). However, such endings were devoid of peptide 19 (PEP19)-ir. PV-ir Ruffini endings were immunoreactive for PEP19 but not NC. The retrograde tracing method revealed that 34, 21 and 18% of trigeminal neurons which project to the infraorbital nerve exhibited NC-, PEP19- and PV-ir, respectively. In addition, 73 and 36% of the PV-ir neurons showed NC- and PEP19-ir, respectively. The content and co-expression of CaBPs in vibrissal low-threshold mechanoreceptors may depend on their terminal morphology.     

Prediction of relapse by plasma lipoprotein(a) concentration in children with steroid-sensitive nephrotic syndrome

AIM: To clarify whether plasma lipoproteins, including Lp(a), can predict relapse pattern in the first years after diagnosis of nephrotic syndrome (NS), we evaluated them in patients with steroid-sensitive NS. METHODS: We analyzed the medical records of 35 patients with steroid-sensitive NS who were seen by us from January 1992 to December 1999 followed for at least 1 year. These patients were divided into two groups. Group 1 consisted of 20 patients who infrequently relapse (IR: <2 in 6 months or <3 in a year), group 2 consisted of 15 patients who frequently relapse (FR: > or =2 in 6 months or > or =3 in a year). Clinical and laboratory findings such as age at onset, gender, urinalysis, serum level of total protein, albumin, and concentrations of serum lipid including lipoprotein(a) (Lp(a)) were investigated between group 1 and group 2. RESULTS: The concentration of plasma Lp(a) in group 2 was higher than that in group 1 (81.0 +/- 35.2 vs. 35.9 +/- 26.5 mg/dl, p < 0.01). On multivariate analysis using logistic regression model, the concentration of plasma Lp(a) was an independent risk factor for relapse of NS. CONCLUSIONS: Our findings suggest that of all the laboratory data examined, high values of Lp(a) can predict future relapse of NS and should be well documented.     

Non-blood contacting biventricular support for severe heart failure

BACKGROUND: Direct mechanical ventricular actuation (DMVA) is a non-blood contacting method of biventricular support. DMVA employs a vacuum attached, pneumatically regulated, flexible membrane to transfer both systolic and diastolic forces to the ventricular myocardium. The purpose of this study was to determine if DMVA effectively restores pump performance when applied to the severely failing heart. METHODS: Bovines (n = 10) underwent thoracotomy and were instrumented for continuous hemodynamic monitoring. Cardiac failure was induced by beta1-blockade to achieve a cardiac index of < 1.5 l/min/m2 for 1 hour. Heart rate was maintained at 100 bpm by atrioventricular sequential pacing. Synchronous DMVA support was then applied for 3 hours. RESULTS: Eight animals achieved significant reductions in cardiac index and mean arterial pressures (35%* and 43%* control, respectively; *p < 0.05). DMVA restored cardiac index to baseline and significantly increased arterial pressures (p < 0.05; DMVA versus cardiac failure). Pulmonary flow and mean pulmonary artery pressures were similar to baseline during DMVA (p = NS). Pathologic exam did not demonstrate evidence of significant device trauma. CONCLUSIONS: DMVA support can effectively restore pump performance of the acutely failing heart. Synchronization may be inherent to the stimulus of cardiac compression. These data further substantiate DMVA's potential as an adjunct to the field of circulatory support.     

Malignant fibrous histiocytoma of perirenal tissue: a case report

A 75-year-old woman was admitted to our hospital with an extremely large retroperitoneal tumor that had been detected with ultrasound on a routine health check. She had no complaint except lumbar pain. Computed tomography revealed a heterogenous tumor located outside the right kidney which was enhanced gradually. Doppler ultrasound showed mild vascularity in the tumor. We performed tumorectomy and right nephrectomy because the tumor was adherent to the right kidney. The tumor was 16 x 11 x 7 cm in size and weighed 621 g. The histopathological diagnosis was malignant fibrous histiocytoma. The tumor was considered to have arisen from perirenal tissue.     

Titania gel reduces thrombin generation

Titanium alloy (Ti) commonly is used for long-term blood pumps as a conventional blood contacting material. Thrombus formation in the pump, however, is still a critical problem. Once thrombin is generated on the Ti surface, it activates platelets and the coagulation cascade, leading to thrombus formation. It would be expected that an inhibition of thrombin generation on a blood-contacting surface would prevent thrombus formation. In this study, the titania gel (Ti-gel) on the surface of Ti was formed with chemical modification. The surface structure and its effects on the coagulation cascade were evaluated. Scanning electron microscopic study revealed numerous cracks on the dried surface of Ti-gel, indicating a water-enriched layer. Blood coagulation on the Ti-gel was less than that on the Ti. Generated thrombin on the Ti-gel was less than that on the Ti in both the extrinsic and intrinsic pathways. There was no statistical difference of thrombin degradation. These results suggest that coagulation cascade on the Ti surface was inhibited by the Ti-gel formation. The Ti-gel may have better antithrombogenic characteristics for blood pumps because of its antiblood-coagulation effects.     

In situ cancer vaccination with a replication-conditional HSV for the treatment of liver metastasis of colon cancer

In this study, we investigated the therapeutic efficacy of a replication-conditional mutant HSV, G207, for the treatment of liver metastasis of colon carcinoma. Three liver metastasis models in syngeneic BALB/c mice were developed: (i) splenic injection, (ii) splenic and subcutaneous (s.c.) injection, and (iii) orthotopic implantation of CT26 colon carcinoma. In the splenic injection model, G207 was injected into the established splenic tumor on day 7. In the splenic and s.c. injection model, G207 were injected into the established s.c. tumor on days 5 and 8. In the orthotopic implantation model, a piece of CT26 tumor tissue was transplanted onto the wall of the cecum and G207 was injected in the established cecum tumor on day 7. On day 21 or 28, animals were sacrificed and liver metastases were evaluated. In all three models in immunocompetent mice, liver metastases were significantly reduced by intratumoral inoculation with G207 compared to the control. In athymic mice, however, there was no significant therapeutic effect of intratumoral inoculation with G207 on liver metastases. Tumor-specific cytotoxic T-lymphocyte responses were induced in mice treated with G207 in the orthotopic implantation model. These results suggest that intratumoral inoculation of G207, as an in situ cancer vaccine, can be an effective approach against liver metastasis of colon cancer and the efficacy involves tumor-specific T-cell responses.