Centripetal Propagation of Vasoconstriction at the Time of Headache Resolution in Patients with Reversible Cerebral Vasoconstriction Syndrome.

BACKGROUND AND PURPOSE: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and diffuse segmental vasoconstriction that resolves spontaneously within 3 months. Previous reports have proposed that vasoconstriction first involves small distal arteries and then progresses toward major vessels at the time of thunderclap headache remission. The purpose of this study was to confirm centripetal propagation of vasoconstriction on MRA at the time of thunderclap headache remission compared with MRA at the time of reversible cerebral vasoconstriction syndrome onset. MATERIALS AND METHODS: Of the 39 patients diagnosed with reversible cerebral vasoconstriction syndrome at our hospital during the study period, participants comprised the 16 patients who underwent MR imaging, including MRA, within 72 hours of reversible cerebral vasoconstriction syndrome onset (initial MRA) and within 48 hours of thunderclap headache remission. RESULTS: In 14 of the 16 patients (87.5%), centripetal propagation of vasoconstriction occurred from the initial MRA to remission of thunderclap headache, with typical segmental vasoconstriction of major vessels. These mainly involved the M1 portion of the MCA (10 cases), P1 portion of the posterior cerebral artery (10 cases), and A1 portion of the anterior cerebral artery (5 cases). CONCLUSIONS: This study found evidence of centripetal propagation of vasoconstriction on MRA obtained at the time of thunderclap headache remission, compared with MRA obtained at the time of reversible cerebral vasoconstriction syndrome onset. If clinicians remain unsure of the diagnosis during early-stage reversible cerebral vasoconstriction syndrome, this time point represents the best opportunity to diagnose reversible cerebral vasoconstriction syndrome with confidence.

Neuroradiologic Diagnosis of Minor Leak prior to Major SAH: Diagnosis by T1-FLAIR Mismatch.

BACKGROUND AND PURPOSE: In major SAH, the only method to diagnose a preceding minor leak is to ascertain the presence of a warning headache by interview; however, poor clinical condition and recall bias can cause inaccuracy. We devised a neuroradiologic method to diagnose previous minor leak in patients with SAH and attempted to determine whether warning (sentinel) headaches were associated with minor leaks before major SAH. MATERIALS AND METHODS: We retrospectively evaluated 127 patients who were admitted with SAH within 48 hours of ictus. Previous minor leak before major SAH was defined as T1WI-detected clearly bright hyperintense subarachnoid blood accompanied by SAH blood on FLAIR images that was distributed over a larger area than bright hyperintense subarachnoid blood on T1WI (T1-FLAIR mismatch). RESULTS: The incidence of warning headache before SAH was 11.0% (14 of 127 patients, determined by interview). The incidence of T1-FLAIR mismatch (neuroradiologic diagnosis of minor leak before major SAH) was 33.9% (43 of 127 patients). Of the 14 patients with warning headache, 13 had a minor leak diagnosed by T1-FLAIR mismatch at the time of admission. Variables identified by multivariate analysis as significantly associated with minor leak diagnosed by T1-FLAIR mismatch included 80 years of age or older, rebleeding after admission, intracerebral hemorrhage on CT, and mRS scores of 3-6. CONCLUSIONS: We conclude that warning headaches diagnosed by interview are not a product of recall bias but are the result of actual leaks from aneurysms.

Pathogenic GLUT9 mutations causing renal hypouricemia type 2 (RHUC2).

Renal hypouricemia (MIM 220150) is an inherited disorder characterized by low serum uric acid levels and has severe complications such as exercise-induced acute renal failure and urolithiasis. We have previously reported that URAT1/SLC22A12 encodes a renal urate-anion exchanger and that its mutations cause renal hypouricemia type 1 (RHUC1). With the large health-examination database of the Japan Maritime Self-Defense Force, we found two missense mutations (R198C and R380W) of GLUT9/SLC2A9 in hypouricemia patients. R198C and R380W occur in highly conserved amino acid motifs in the "sugar transport proteins signatures" that are observed in GLUT family transporters. The corresponding mutations in GLUT1 (R153C and R333W) are known to cause GLUT1 deficiency syndrome because arginine residues in this motif are reportedly important as the determinants of the membrane topology of human GLUT1. Therefore, on the basis of membrane topology, the same may be true of GLUT9. GLUT9 mutants showed markedly reduced urate transport in oocyte expression studies, which would be the result of the loss of positive charges in those conserved amino acid motifs. Together with previous reports on GLUT9 localization, our findings suggest that these GLUT9 mutations cause renal hypouricemia type 2 (RHUC2) by their decreased urate reabsorption on both sides of the renal proximal tubule cells. However, a previously reported GLUT9 mutation, P412R, was unlikely to be pathogenic. These findings also enable us to propose a physiological model of the renal urate reabsorption via GLUT9 and URAT1 and can lead to a promising therapeutic target for gout and related cardiovascular diseases.

cDNA cloning and promoter analysis of rat caspase-9.

Caspase-9 is the apex caspase of the mitochondrial pathway of apoptosis, which plays a critical role in apoptotic initiation and progression. However, gene regulation of caspase-9 is largely unknown. This is in part due to the lack of information on the gene promoter. Here we have cloned the full-length cDNA of rat caspase-9 and have isolated promoter regions of this gene. The rat caspase-9 cDNA of 2058 bp predicts a protein of 454 amino acids, which contains a caspase-recruitment domain ('CARD') at the N-terminus and enzymic domains at the C-terminus. The enzyme's active site, with a characteristic motif of QACGG, was also identified. Overall, rat and human caspase-9 have 71% identity. With the cDNA sequence, we subsequently isolated the proximal 5'-flanking regions of rat caspase-9 by the procedure of genomic walking. The 2270 bp genomic segment is 'TATA-less', but contains several GC boxes. Elements binding known transcription factors such as Sp-1, Pit-1, CCAAT-enhancer-binding protein (C/EBP), glucocorticoid receptor and hypoxia-inducible factor 1 (HIF-1) were also identified. When cloned into reporter gene vectors, the genomic segment showed significant promoter activity, indicating that the 5'-flanking regions isolated by genomic walking contain the gene promoter of rat caspase-9. Of significance is that the cloned promoter segments were activated by severe hypoxia, conditions inducing caspase-9 transcription. Thus, the genomic sequences reported here contain not only the basal promoter of rat caspase-9 but also regulatory elements responsive to pathophysiological stimuli including hypoxia.

Up-regulation of apoptosis inhibitory protein IAP-2 by hypoxia. Hif-1-independent mechanisms.

Hypoxia is a key determinant of tissue pathology during tumor development and organ ischemia. However, little is known regarding hypoxic regulation of genes that are directly involved in cell death or death resistance. Here we report the striking induction by severe hypoxia of the anti-apoptotic protein IAP-2. Hypoxic cells with IAP-2 up-regulation became resistant to apoptosis. IAP-2 was induced by hypoxia per se rather than by the secondary effects of hypoxia, including ATP depletion and cell injury. The inductive response did not relate to alterations of cellular redox status or arrest of mitochondrial respiration. On the other hand, IAP-2 induction was attenuated by actinomycin D, suggesting a role for gene transcription. In vitro nuclear run-on assays demonstrated specific increases in IAP-2 transcriptional activity after hypoxia exposure. HIF-1, the primary transcription factor that is responsible for multiple gene activation under hypoxia, does not have a role in IAP-2 expression. HIF-1 and IAP-2 were induced by different degrees of hypoxia; severe hypoxia or anoxia was required for IAP-2 induction. Moreover, cobalt chloride and desferrioxamine activated HIF-1 but not IAP-2. Finally, IAP-2 was induced by severe hypoxia in mouse embryonic stem cells that were deficient of HIF-1. Thus, this study not only provides the first demonstration of hypoxic regulation of an anti-apoptotic gene but also suggests the participation of novel hypoxia-responsive transcription mechanisms.

Modification of guide wire for 22-gauge safe guide.

Safe guide is a central venous catheterization kit that serves as both pilot needle and introducer. With a single puncture, a guide wire can be introduced by inserting it through the side port of the 22-gauge needle. The advantage is that this needle can be placed within a blood vessel using no more force than is required to insert a pilot needle. However, the 0.018-inch guide wire is vulnerable to kinks and locking. Because the tip has been shaped into a sharp J-shaped angle, it can kink at the puncture site, and locking sometimes occurs when the guide wire is passed through the side port of the needle, or when the dilator is introduced. In order to resolve these issues, we modified the device by making an experimental guide wire with a gentler angle. In addition, we fortified the body of the wire without altering its thickness. We then investigated the effectiveness of our modifications. The subjects of the study were 120 patients, who required central venous catheterization. They were divided into 2 groups. The original J-type guide wire was used in one group (Group A: n = 60) and the modified guide wire in the other group (Group B: n = 60). Catheters were introduced by right internal jugular vein puncture. We observed the following: 1) incidence of back-flow appearing at withdrawal of the needle without back-flow during advancement, 2) incidence of kinking or locking of the guide wire when it was passed through the side port, 3) incidence of kinking of the guide wire at the puncture site when introducing the dilator, and 4) complications. The results were as follows: 1) back-flow appeared upon withdrawal in 3.4% of both groups; 2) kinking and locking occurred when passing the guide wire through the side port of the Safe guide needle in 16.7% of Group A and 1.7% of Group B; 3) kinking of the guide wire occurred when introducing the dilator in 5 % of Group A in contrast to 0% in Group B; 4) the only complication caused by the passing of the guide wire was accidental puncture of the common carotid artery, which occurred in 1.7% of both groups. No problems with the guide wire were noted in either group. The use of our modified guide wire decreased the incidence of kinking and locking of the guide wire when passing it through the side port. In addition, no guide wire kinking at the puncture site occurred when introducing the dilator. Issues associated with the original J-type guide wire were resolved by 1) changing the guide wire tip to a gentler angle, and 2) fortifying the guide wire by altering its composition.

Valsalva maneuver prevents guide wire trouble associated with 22-gauge safe guide.

UNLABELLED: The Safe guide is a central venous puncture needle that serves as both a pilot needle and as an introducer. A guide wire can be inserted into a vein through the side port at the hub of the 22-gauge Safe guides needle initially inserted as a pilot needle. However, guide wire insertion may fail due to kinking or locking at the side port. Increasing airway pressure to 20 cm H2O by squeezing a respiratory bag during insertion of the guide wire together with venous puncture was attempted to determine if would decrease guide wire trouble. SUBJECTS AND METHODS: A total of 120 patients scheduled for central venous catheterization by right internal jugular puncture were divided into two groups. Patients in group-A (n = 60) were catheterized by the conventional method and those in group-B (n = 60) were catheterized by applying the Valsalva maneuver. Three observations were made: 1) Frequency of cases in which blood back-flow occurred during withdrawal only and not upon advancement of the puncture needle. 2) Frequency of cases in which kinking and/or locking of the guide wire occurred at the hub during its insertion. And 3) the occurrence of complications. RESULTS: 1) The patency of the vein was preserved and blood back-flow was obtained during advancement of the puncture needle in all cases in which the Valsalva maneuver was applied. 2) The incidence of kinking and/or locking during insertion of the guide wire decreased from 16.7% to 3.4% by applying positive airway pressure during the Valsalva maneuver. And 3) complications were negligible. Additionally, the application of the Valsalva maneuver allowed successful guide wire insertion in 6 out of 9 cases (67%) in group-A, in which the initial attempt using the conventional method had failed. CONCLUSION: The application of positive airway pressure using the Valsalva maneuver may prevent the guide wire trouble associated with the 22-gauge Safe guide.

Up-regulation of galectin-3 in acute renal failure of the rat.

Galectin-3, a multifunctional beta-galactoside-binding lectin, is known to participate in development, oncogenesis, cell-to-cell attachment, and inflammation. We studied to determine whether galectin-3 is associated with cell injury and regeneration in two types of acute renal failure (ARF), namely ischemic and toxic ARF. In ischemia/reperfusion renal injury in rats (bilateral renal pedicles clamped for 40 minutes), galectin-3 mRNA began to increase at 2 hours and extended by 6.2-fold at 48 hours (P: < 0.01 versus normal control rats), and then decreased by 28 days after injury. In addition, a significant negative correlation between galectin-3 mRNA expression and serum reciprocal creatinine was shown at 48 hours after injury (n = 13, r = -0.94, P: < 0.0001). In folic acid-induced ARF, galectin-3 mRNA was found to be up-regulated at 2 hours after injury and increased levels continued until at least 7 days post-injury. In immunohistochemistry, at 2 hours following reperfusion, galectin-3 began to develop in proximal convoluted tubules. From 6 hours up to 48 hours, galectin-3 was also found in proximal straight tubules, distal tubules, thick ascending limbs, and collecting ducts. In later stages of regeneration, galectin-3 expressions were found in macrophages. In conclusion, we demonstrated that galectin-3 expressions were markedly up-regulated in both ischemic and toxic types of ARF. Galectin-3 may play an important role in acute tubular injury and the following regeneration stage.

Developmentally and regionally regulated expression of growth hormone secretagogue receptor mRNA in rat brain and pituitary gland.

Distribution and development of growth hormone secretagogue receptor (GHS-R) mRNA expression in rat brain and pituitary gland were examined using ribonuclease protection assay. In adult male rats, GHS-R mRNA levels were highest in the pituitary gland, whereas those in the hypothalamus and hippocampus were 57 and 30% of those in the pituitary gland, respectively. Less abundant but detectable levels of GHS-R mRNA were found in the midbrain, pons, and medulla oblongata, but expression was barely detectable in the cerebellum and cerebral cortex. The expression of GHS-R mRNA was detected at late gestation (embryonic day 19) in the pituitary gland, hypothalamus, and brainstem. The mRNA levels increased with age in the pituitary gland, and decreased postnatally in the brainstem, while they remained constant in the hypothalamus during development. In contrast, GHS-R mRNA was not detectable in the hippocampus during the fetal period, but was first detected on postnatal day 7. Expression of GHS-R mRNA was also examined in the spontaneous dwarf rat (SDR), a model for isolated GH deficiency, to examine alterations in GHS-R mRNA expression in a GH-deficient state. GHS-R mRNA levels in the pituitary gland of SDRs were higher than those of control rats, suggesting negative regulation of GHS-R mRNA by GH in this region. GHS-R mRNA levels increased in the hypothalamus of female, but not in male SDRs. In contrast, GHS-R mRNA levels were not affected by GH in the brainstem and hippocampus. These results indicate that region-specific, developmentally regulated expression of GHS-R mRNA may reflect divergent physiological roles of GHS/GHS-R in distinct regions of the central nervous system and the pituitary gland.

[PGE1 and dopamine administration in a pediatric patient during hepatectomy].

A 2-year-old male underwent medial inferior hepatectomy for the treatment of metastatic tumors. Due to congenital hepatoblastoma, at 6-months of age, right lobectomy of his liver had been performed. To protect liver functions, PGE1 and dopamine were administered during the surgery. Although half of his circulating blood volume was lost, his perioperative hemodynamics was stable, with no development of postoperative liver dysfunction. PGE1 and dopamine may thus be beneficial in pediatric hepatectomy.

Juxtaglomerular cell tumor with retroperitoneal fibrosis and secondary immune-complex glomerulonephritis: a possible contribution of the renin angiotensin system to renal fibrosis.

We present a case of a 25-year-old woman with a renin-secreting juxtaglomerular cell tumor, retroperitoneal fibrosis associated with glomerular hypertrophy, glomerulonephritis, and marked tubulointerstitial alterations. Myofibroblasts, as shown by positive immunostaining for alpha-smooth muscle actin, were found along with transforming growth factor-beta (TGF-beta) in the interstitium of the tumor-free kidney. Regarding the pathogenesis of renal fibrosis and glomerular hypertrophy, this case may provide evidence not only experimentally but also clinically that the renin-angiotensin system plays an important role because angiotensin II is known to induce renal fibrosis associated with increased TGF-beta and the appearance of myofibroblasts.

[Optimal length of nasopharyngeal airway and its correlation with height and body weight].

We studied 26 patients (11 males and 15 females) undergoing elective surgery under general anesthesia. The purpose of this study was to decide how long the length of nasopharyngeal airway should be by measuring distance A (permitting airway obstruction to be released), distance B (giving the most effective ventilation), and distance C (between nostril and arytenoid). The values of distance A in male group and female group were 12.73 +/- 0.85 cm and 11.70 +/- 0.75 cm, respectively. The values of distance B were 14.55 +/- 0.96 cm in male group and 13.93 +/- 1.12 cm in female group. The values of distance C were 18.84 +/- 0.90 cm in male group and 17.40 +/- 0.97 cm in female group. This showed that it is necessary to advance the nasopharyngeal airway about 2 cm from the distance A to give the most effective ventilation to the patients with airway obstruction. Therefore, most of standard nasopharyngeal airways commercially available are too short. In addition, the distance B has no correlation with height and body weight and it is difficult to predict the optimal length of the airway.

Reactivity of soybean lipoxygenase-1 to linoleic acid entrapped in phosphatidylcholine vesicles.

The linoleic acids embedded in the SUVs of soy-PC, DMPC, and DPPC served as substrate for soybean lipoxygenase-1 (L-1). The initial velocity of the catalytic reaction and the concentration of the substrate showed a hyperbolic relation. The Km values of L-1 for the linoleic acids in soy-PC, DMPC, and DPPC vesicles were 0.07, 0.09, and 0.11 mM, respectively, being comparable with that for Tween-20 micellar linoleic acid. Soy-PC and DMPC competitively inhibited the enzyme with Ki values of 0.20 and 0.13 mM, respectively, whereas DPPC had no effect. DSC analysis revealed the phase separation of linoleic acid and DPPC in vesicles in the temperature range in which the enzyme reaction was carried out. This may account for the lack of inhibitory effect of DPPC on the enzyme. From the temperature dependence of the specific activity of the enzyme, the Ea values of the catalytic reaction were estimated to be 26.7 and 35.3 kJ.mol-1 for soy-PC and DPPC vesicles, respectively. For linoleic acid-DMPC vesicles, a two-phase temperature dependence of the activity across the transition temperature of the mixed vesicles was suggested.

Experimental acute glomerulonephritis induced in the rabbit with a specific streptococcal antigen.

FITC-labelled IgG obtained from patients convalescing from acute poststreptococcal glomerulonephritis (APSGN) stains glomeruli of patients with early APSGN. We previously reported a streptococcal antigen (preabsorbing antigen (PA-Ag)) that preabsorbed the stain out of sera from the convalescent patients and thus prevented glomerular staining. To confirm the nephritogenicity of PA-Ag, we administered up to 40 mg of this antigen to rabbits for 8 days and observed them for up to 9 weeks. Immunohistological analysis showed diffuse and global glomerular staining for C3 without notable staining for gamma-globulin. Light microscopic examinations revealed slight to moderate proliferative glomerulonephritis with exudative change. Control rabbits, which received similar doses of bovine serum albumin, did not show significant staining for C3. A transient and significant decrease in CH50 was observed from weeks 3 to 7 (9.7 +/- 0.3 U/ml at week 3; normal range 12.9 +/- 0.6 U/ml). This experimental model showed a resemblance to immunological and immunohistological features of APSGN in humans. Although the precise mechanisms are yet to be determined, complement activation by PA-Ag seems to hold a key position in this model and in the human disease.

Glomerular proliferating cell kinetics in acute post-streptococcal glomerulonephritis (APSGN).

To investigate the time sequence of glomerular cell proliferation in acute human glomerulonephritis, renal biopsy tissues were examined from 15 acute post-streptococcal glomerulonephritis (APSGN) patients (who were biopsied 1-31 days after onset), using an immunoperoxidase technique with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and various cell surface markers. Few, if any, PCNA+ cells were observed in normal glomeruli, but many cells were positive for PCNA in the acute phase of APSGN. Glomerular PCNA+ cells were observed either within glomerular tufts, or lining Bowman's capsule (parietal epithelial cells); the number of positive cells tended to decrease exponentially as the disease duration increased (r = -0.91, P < 0.0001). PCNA+ cells within glomerular tufts were further identified by double immunostaining. PCNA was not found in PMN or T cells, but a small proportion of macrophages were PCNA+. Most of the remaining PCNA+ cells were resident glomerular cells; the proportion of PCNA+ endothelial cells (CD31+) was over 80 per cent in the early phase, but as the disease continued the proportion of mesangial cells (alpha-smooth muscle actin+) increased to about half of the total PCNA+ cells within the tuft. These data indicate that the hypercellular glomeruli in APSGN are due not only to immune cell infiltration, but also to resident glomerular cell proliferation, probably induced by locally produced growth factors.

[Evaluation of the bite block wedged between the maxillary and mandibular molars].

The purpose of this study was to compare our original bite block (T-X Block) wedged between the maxillary and mandibular molars, with the standard gum bite block, in 200 patients whose tracheas were intubated. During emergence from isoflurane anesthesia, no trouble occurred in T-X Block group (n = 100). On the other hand, lip damage and ejection of the bite block were found in 11 and 10 cases, respectively, in gum bite block group (n = 100). As another study, an opening between the maxillary and mandibular incisor edges was measured with T-X Block placed in twenty patients under general anesthesia. The inter-incisal distances in one way of using it as a smaller wedge and in the other way as a bigger one were 21.6 +/- 2.4 and 25.2 +/- 2.6 mm, respectively. Those values were significantly larger than thickness of the gum bite block. T-X Block is very useful because its use causes no complications and makes it easier to insert a naso-gastric tube as well as to clean the oral cavity with suction by giving a larger opening of the mouth.

Treatment of hypervascular small hepatocellular carcinoma with ultrasound-guided percutaneous acetic acid injection: comparison with segmental transcatheter arterial embolization.

OBJECTIVE: To compare the efficacy of ultrasound-guided percutaneous acetic acid injection and segmental transcatheter arterial embolization for hypervascular small hepatocellular carcinoma. METHODS: The prognosis of 40 patients with one to three angiographically hypervascular hepatocellular carcinoma smaller than 3 cm in diameter treated with either percutaneous acetic acid injection (25 patients) or transcatheter arterial embolization (15 patients) during the past 4.5 yr were analyzed retrospectively. RESULTS: After initial therapy, none of 25 patients treated with percutaneous acetic acid injection developed ascites, whereas 5 of 15 (33%) patients treated with transcatheter arterial embolization developed it (p < 0.01). All tumors became smaller once after each therapy. However, local recurrence (reenlargement of the original tumor) occurred in 1 of 29 (3%) tumors treated with percutaneous acetic acid injection and 11 of 22 (50%) tumors treated with transcatheter arterial embolization (p < 0.005). During the follow-up, 4 of 25 (16%) patients treated with percutaneous acetic acid injection and 10 of 15 (67%) patients treated with transcatheter arterial embolization died. The 1-, 2-, and 3-yr survival rate was 100, 94, and 83%, respectively, in patients treated with percutaneous acetic acid injection and 72, 65, and 39% in patients treated with transcatheter arterial embolization (p < 0.005). The cancer-free survival rate was also significantly better in the former than in the latter group (p < 0.005). CONCLUSIONS: Percutaneous acetic acid injection is superior to segmental transcatheter arterial embolization in the treatment of hypervascular small hepatocellular carcinoma.