The role of ficolins in innate immunity

Ficolins are a group of proteins containing both a collagen-like domain and a fibrinogen-like domain and are found in varying tissues. Ficolins present in sera have a lectin activity toward N-acetylglucosamine through their fibrinogen-like domains. The domain organizations between ficolins and mannose-binding lectin (MBL) are very similar in that both consist of a collagen-like domain and a carbohydrate-binding domain, although their carbohydrate-binding moieties are different. MBL acts as an opsonin and activates complement in association with MBL-associated serine proteases (MASPs) and sMAP, a truncated protein of MASP-2, via the lectin pathway. Like MBL, two types of human serum ficolins, L-ficolin/P35 and H-ficolin, are associated with MASPs and sMAP, and activate the lectin pathway. In addition, L-ficolin/P35 acts as an opsonin. These findings indicate that serum ficolins play an important a role in innate immunity in a similar manner to MBL.     

Transposition of the oculomotor nerve for resection of a midbrain cavernoma. Technical note

The authors discuss the utility of anterior transposition of the oculomotor nerve from the lateral wall of the cavernous sinus to widen the corridor posterior to the cisternal segment of the oculomotor nerve; this allows exposure of the anterolateral surface of the midbrain. This additional exposure was successfully used for the resection of a large calcified cavernoma in the upper brainstem of a 67-year-old woman who had presented with sudden onset of left hemiparesis and oculomotor palsy. The patient's postoperative course was uneventful and she displayed symptomatic improvement.     

A case of immunotactoid glomerulopathy with IgA2, kappa deposition ameliorated by steroid therapy

We report a case of idiopathic immunotactoid glomerulopathy with IgA2, kappa light chain deposition, ameliorated by steroid therapy. A 28-year-old male patient was admitted to our hospital due to exacerbation of nephrotic syndrome. The onset of his renal disease was at 24 years of age and the renal biopsy revealed membranoproliferative glomerulonephritis with moderate-degree deposition of IgA, IgG, IgM, C3 and C1q. Prednisolone therapy was started at the dose of 50 mg/day and effective for nephrotic syndrome and renal dysfunction. Two years later, the proteinuria and microscopic hematuria gradually exacerbated during reduction of prednisolone. The second renal biopsy showed mesangioproliferative glomerulonephritis with predominant deposition of IgA and C3. The glomerular proliferative changes were successfully suppressed by steroid treatment. On electron microscopy, a microtubular deposit with an average width of 40 nm and double-tracked appearance was observed in the mesangial and subendothelial areas. Immunohistochemical examination revealed that the deposit was predominantly composed of IgA2 subclass and kappa light chain. Selective deposition of IgA2 subclass and kappa light chain indicated that the glomerular lesion should be induced by monoclonal immunoglobulin, although it could not be detected in the serum and urine clinically. Immunoglobulin subclass staining of renal biopsy specimens provides an important clue for understanding the pathogenesis of immunotactoid glomerulopathy or fibrillary glomerulonephritis.     

Serious renal infection: report of three cases

In renal infections, lack of peculiar symptoms and consequent delay of diagnosis can sometimes lead to a critical condition of the patient. We report three cases of life-threatening renal infections in female patients, two of which were subsequently fata. One patient died of left emphysematous pyelonephritis with bilateral pleuritis. The patient was correctly diagnosed 13 days after the onset of symptoms and expired 2 months later despite nephrectomy on the day of diagnosis. The second patient died of septic shock 3 days following the onset of symptoms. Autopsy revealed multiple perinephric abscess of the left kidney. The non-fatal case was a perinephric abscess spread to the iliopsoas muscle. The patient was diagnosed with perinephric abscess 11 days after the onset of symptoms and eventually underwent nephrectomy 9 days later. Two of the patients were diabetics and the third was a probable diabetic, who died too suddenly to confirm the diagnosis. Herein, we review the literature of, and discuss the diagnosis and management of serious renal infection.     

Detection of the four sequence variations of MDR1 gene using TaqMan MGB probe based real-time PCR and haplotype analysis in healthy Japanese subjects

OBJECTIVES: P-glycoprotein (P-gp) is significant from the viewpoint of pharmacokinetics/pharmacodynamics (PK/PD). MDR1 gene encodes P-gp and has a wide variety of SNPs. As the SNPs may be one of the factors that induce pharmacogenetic individual difference, haplotype analysis is necessary to evaluate the PK/PD. DESIGN AND METHODS: The SNPs of the detected MDR1 were -129T>C, 325G>A, 2677G>T/A, and 3435C>T. For the analysis of linkage disequilibrium (LD) and haplotype analysis, and for the reconstruction of the haplotype pair, ARLEQUIN and PHASE were employed. RESULTS: The result of the chi(2) test detected significant LD between -129 and 2677, -129 and 3435, and 2677 and 3435. There were 9 haplotypes: T-G-C, T-T-C, C-T-C, T-A-C, C-A-C, T-G-T, T-T-T, C-G-T, and C-T-T. CONCLUSIONS: LD was found among the positions -129, 2677 and 3435. As a result, 9 haplotypes exists in the Japanese population. These results suggest that it would be necessary to give consideration to haplotype for the purpose of evaluating the PK/PD of the drugs transported by P-gp.     

Respiratory control during postural changes in anesthetized cats

The effect of postural changes on respiration was investigated in ten anesthetized cats by applying body tilting during the inspiration phase while recording respiratory patterns, as given by the diaphragmatic EMG, together with either the lung volume or the air flow temperature. The results show that the head-up tilting during inspiration reduced the period of the inspiratory phase and increased the end-inspiratory lung volume. On the other hand, the head-down tilting during inspiration had opposite effects. These effects disappeared after transection of the vagus nerve. However, labyrinthectomy did not diminish the effects, probably because of functional suppression of the vestibular system due to the anesthetic. When correlating the activity of 15 vagal afferents presumably originating from the slowly adapting lung stretch receptors with lung volume changes during tilting, their maximum firing rate (87 +/- 15.7 Hz) was increased with an increase in the lung inflation volume and was attained earlier on head-up tilting and it was reduced with a decrease of the lung volume on head-down tilting (63 +/- 16.6 Hz) as compared with the value in the horizontal position (74 +/- 14.2 Hz). These results suggest that respiratory modulation during head-up or head-down tilting is consistent with the Hering-Breuer reflexes and minimizes the externally induced lung volume changes during postural changes.     

Structure and expression of the glycine cleavage system in rat central nervous system

This study investigated the expression of corticotropin releasing hormone (CRH) and its receptor CRHR-1, and arginine vasopressin (AVP) mRNAs during the stress hyporesponsive periods of late pregnancy and lactation (day-3) and in virgin stress-responsive females. In situ hybridization histochemistry showed that basal CRH mRNA in the paraventricular nucleus (PVN) decreased in pregnant and increased in lactating rats (compared with virgin controls), whereas it increased after restraint stress only in virgin rats. Basal PVN CRHR-1 mRNA increased markedly in all groups but reached lower levels in pregnant rats. Basal AVP mRNA in the parvocellular PVN was higher in lactating rats, and in contrast to CRH mRNA, it increased after stress in all groups. In medial preoptic area (MPOA) CRH mRNA levels were higher in lactating females compared with virgin and pregnant rats, and unexpectedly they decreased markedly after stress only in virgin rats. CRH mRNA levels in the central and medial nuclei of the amygdala were higher in lactating rats than in virgin or pregnant ones, and stress had no effect in either group. These data suggest that these stress hyporesponsive periods: (1) do not depend on basal CRH mRNA expression in the PVN; (2) appear to have intact stress-activated afferent pathways to the PVN, as shown by preservation of CRHR-1 and AVP responses to stress, but the information may be differently processed; (3) are associated with an alteration in a CRH mediated pathway from the MPOA.     

Increased urinary excretion of collagen metabolites in cadmium-metallothionein nephropathy

In order to investigate the effect of cadmium-metallothionein (Cd-MT) on renal reabsorption of collagen metabolites, urinary excretion of hydroxylysine (Hyl), glucosyl-galactosyl-Hyl (Glc-Gal-Hyl), galactosyl-Hyl (Gal-Hyl), and hydroxyproline (Hyp), which are unique collagen metabolites, was determined in rats. Administration of Cd-MT resulted in acute renal failure in the form of proteinuria, aminoaciduria and glycosuria. Protein content in urine was greatly increased 1 day after injection of Cd-MT and decreased from 5 days, while the maximum levels of excretion of amino acids and glucose were observed at 6 days post-injection. The urinary excretion of total Hyp and Hyl, including Glc-Gal-Hyl, Gal-Hyl and free Hyl, were significantly increased at 3, 6 and 8 days after injection of Cd-MT with the maximum level at 6 days. Moreover, the molar ratio of Glc-Gal-Hyl/Gal-Hyl of urine in the Cd-MT-treated group was almost the same as that in the controls. These results suggest that a portion of Hyp, Hyl and its glycosides is normally reabsorbed from the renal tubule in the controls, and Cd-MT exposure caused an increase in urinary excretions of Hyp and Hyl, including its glycosides, through a renal tubular defect in reabsorption of Hyl in the same manner as with common amino acids.This work was presented in part at the Annual Meeting of the Pharmaceutical Society of Japan, Chiba, Japan, April 5, 1986     

Rectal administration of nifedipine: haemodynamic effects and pharmacokinetics in hypertensives

The haemodynamic effects and pharmacokinetics of nifedipine suppositories, used mainly for hypertensive emergencies, were studied in 10 severely hypertensive patients. Following rectal administration, significant hypotensive effects occurred after 0.5 h and lasted until 7 h after administration. The mean (+/- SE) maximum decreases in systolic and diastolic blood pressures 1.5 h after administration were: systolic, 61.8 +/- 7.9 mmHg (P less than 0.001); and diastolic, 30.8 +/- 4.0 mmHg (P less than 0.001). No serious side-effects were reported and heart rate did not change significantly. Mean nifedipine concentration in the blood peaked at 52.4 ng/ml, 1 h after administration and, after 7 h, was still 14.3 ng/ml which is higher than the minimum plasma concentration required for hypotensive effects to occur. There was a close correlation between nifedipine concentration in the blood and hypotensive effects. These results indicate that rectal administration of nifedipine should be regarded as a useful alternative treatment in hypertensive emergencies.