ABNORMAL INTRACRANIAL VASCULAR NETWORKS ("MOYAMOYA" DISEASE), POSSIBLY DUE TO OCCLUSION OF BILATERAL INTERNAL CAROTID ARTERIES — A CASE REPORT WITH HISTOMETRICAL ANALYSIS —

An autopsy case of abnormal Intracranial vascular networks at the base of the brain corresponding to so-called rete mirabile, associated with occlusion of bilateral internal carotid arteries was reported. This patient was a 62 year-old female who died about two months after sudden onset of subarachnoid hemorrhage. At autopsy, abnormal vascular networks termed as rete mirabile were observed to be collateral blood supplies among the cerebral regions with flow of the anterior, middle, and posterior cerebral arteries, caused by long-stading obstruction of bilateral internal carotid arteries at the syphon level. Morphometrical analysis was done by measuring the length of internal elastic membrane of the internal carotid arteries in cross section, and comparing it with those of controlled persons of the same sex and age without any intracranial disorders and hypertensive histories. The result that no significant difference was observed between the former and the latter values suggested that the unusual cerebro-vascular disorder of this case developed not on the base of congenital anomaly including hypoplasia of internal carotid arteries or arteriovenous malformation but as an acquired lesion established for a long time.     

Mesp1-nonexpressing cells contribute to the ventricular cardiac conduction system.

Previous fate mapping analysis, using Cre recombinase driven by the Mesp1 locus, revealed that Mesp1 is expressed in almost all of the precursors of the cardiovascular system, including the endothelium, endocardium, myocardium, and epicardium. Mesp1-nonexpressing cells were found to be restricted to the outflow tract cushion and along the interventricular septum (IVS), which is a location that is suggestive of specialized cardiac conduction system (CCS). In our current study, we examined the identity of these IVS cells by using the pattern of beta-galactosidase activity in CCS-lacZ mice. In addition, by crossing Mesp1-Cre and floxed GFP reporter mice with CCS-lacZ mice, we have calculated that approximately 20% of the ventricular CCS within the IVS corresponds to Mesp1-nonexpressing cells. These data suggest that the ventricular CCS is of heterocellular origin. Furthermore, we indicate a possibility that a population of the cells that contribute to the ventricular CCS might be distinguished at an early stage of development.     

The proliferating cell nuclear antigen (PCNA) index correlates with the grade of cytologic atypia in well-differentiated early adenocarcinomas of the large intestine

Well-differentiated colorectal adenocarcinomas are subclassified into carcinoma with high-grade atypia (CAH) and carcinoma with low-grade atypia (CAL) based on their cellular atypia. It is proposed that CAH and CAL are different in histologic prognostic factors and that the former should be regarded as carcinoma with high-grade malignancy and the latter as low-grade malignancy. In this study, the differences in cell-proliferative activity between CAH and CAL were examined using a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The PCNA index and mitotic index of 27 early colorectal carcinomas (9 CAL, 5 CAH, and 13 carcinomas with mixed low- and highgrade atypia) was evaluated in relation to their depth of invasion. In intra-mucosal lesions, both indices were higher in CAH (78%, 0.89%) than in CAL (68%, 0.47%; P <0.01). In lesions invading into the submucosa, the PCNA and mitotic indices were also higher in CAH (7596, 0.65%) than in CAL (35%, 0.19%; P <0.01). A significant correlation was observed between the PCNA index and the mitotic index in the mucosal lesions (P<0.05). These results indicate that CAH has a higher proliferative activity than CAL, and support the current authors' proposal that CAH is a high-grade malignancy and CAL a low-grade malignancy.     

Myoglobinuria due to enzyme abnormalities in glycolytic pathway--especially lactate dehydrogenase M subunit deficiency]

Glycolysis is an important energy productive system. Enzyme abnormalities the in glycolytic pathway, which cause myoglobinuria, are deficiencies of phosphofructokinase, phosphoglycerate kinase, phosphoglycerate mutase, and lactate dehydrogenase (LDH). Common symptoms of these enzyme abnormalities are muscle cramp, muscle pain, and rhabdomyolysis after strenuous exercise. Acute renal failure owing to myoglobinuria is the most noteworthy symptom. In daily life, symptoms are rarely observed and prognosis is usually good. Correct and fast diagnosis of such latent symptomatic disorders is important to prevent a turn for the worse of these symptoms. LDH M subunit deficiency was first discovered by urinary discoloration and a discrepancy of laboratory data. Since then, only four cases have been reported in the Japanese population. The response to ischemic forearm work is characteristic (an increase of venous lactate concentration after ischemic work is not observed and a marked increase of venous pyruvate is found). The increase of pyruvate concentration is specific in LDH-M subunit deficiency, and is not observed in other abnormalities of the glycolytic pathway. Glycolysis was markedly retarded in the patient's muscle in the glyceraldehyde 3-phosphate dehydrogenase (GA3PD) step, possibly due to the impaired reoxidation of NADH produced by GA3PD activity. Then, the excess NADH is reoxidized by alpha-glycerophosphate dehydrogenase and triose phosphates are drained to alpha-glycerophosphate and glycerol. Therefore ATP production is significantly impaired and muscle tissue is damaged. A genetical study revealed a deletion of 20 base-pairs in exon 6 in LDH-M subunit deficiency. This mutation results in a frame-shift translation and premature termination.     

The Complete Nucleotide Sequence of the PanAsia Strain of Foot-and-Mouth Disease Virus Isolated in Japan

The complete nucleotide sequence of the foot-and-mouth disease virus (FMDV) O/JPN/2000 strain, the PanAsia strain, was determined by cycle sequencing and primer walking. The 5 end of the genome upstream from homopolymeric poly(C) tract (S-fragment) was 367 nucleotides in length, and the remainder of the genome (L-fragment), excepting the poly(A) tail, was 7808 nucleotides. The L-fragment contains a single open reading frame of 6996 nucleotides terminating at a UAA codon 96 bases from the 3 poly(A) sequence. Comparison of sequences shows that the length of the structural and non-structural protein coding regions are identical to those in the O1/Kaufbeuren strain, and no striking differences such as deletion or insertion were observed between them.     

Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and other antibodies.

AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.     

The electrogenic sodium pump in the hyperpolarizing and secretory effects of pancreozymin in the pancreatic acinar cell.

1. Transmembrane potential, effective membrane resistance, and amylase release were recorded simultaneously from acinar cells of isolated rat pancreas perfused with Krebs-Henseleit solution. 2. The hyperpolarizing effect of pancreozymin (Pz) was confirmed by perfusing with a solution containing 5 m-u. Pz/ml. 3. The hyperpolarizing effect of Pz disappeared in the following environments: (a) in low ambient temperature, (b) in K-free medium, (c) in low Na medium, and (d) in the presence of ouabain. In these environments, transient depolarization was frequently observed immediately after stimulation. It is suggested that there are two components in the effect of Pz on the membrane potential of the acinar cells: transient depolarization which coincides with an increase in Na permeability in the initial phase, and continuous hyperpolarization due to an electrogenic Na pump which conceals transient depolarizing phase when the pump is dominant. 4. The secretory effect of Pz was inhibited under conditions that suppressed the electrogenic Na pump. It is proposed that the Na pump activated by Pz maintains the passive Na-influx, increases [Ca2+]i, and, in consequence, uphold the amylase output during continuous stimulation. 5. A medium which was used to bathe the sectioned pancreas with Pz was found to contain a substance which depolarized the acinar cells.     

Masked excitatory action of noradrenaline on rat islet β-cells via activation of phospholipase C

The effect of noradrenaline (NE) on rat islet -cells was examined. NE reduced insulin secretion from rat islets exposed to extracellular solutions containing glucose at 5.5 or 16.6 mM. In islets treated with pertussis toxin (PTX), however, NE increased insulin secretion. The NE-induced augmentation of insulin secretion was inhibited by prazosin. In intact islets, NE increased phospholipase C (PLC) activity, an effect that was prevented by treatment of islets with U-73122. NE elevated intracellular [Ca²⁺] ([Ca²⁺]_i) in isolated -cells independently of PTX. Although this NE effect was inhibited by prazosin, phenylephrine did not mimic it. The [Ca²⁺]_i response to NE was also prevented by the treatment of cells with U-73122. NE produced depolarization of -cells followed by nifedipine-sensitive action potentials. NE reduced the whole-cell membrane currents through ATP-sensitive K⁺ channels (K_ATP), responsible for the depolarization. This NE effect was prevented by treatment of -cells with U-73122 or BAPTA/AM. Although at least some of our results imply the presence of ₁-adrenoceptors, -cells were not stained by a polyclonal IgG antibody recognizing all adrenergic ₁-receptor subtypes so far identified. These results suggest that an interaction of NE with an unknown type of receptor activates rat islet -cells via a PLC-dependent signal pathway. This effect is, however, masked by the inhibitory action via a PTX-sensitive pathway also activated by NE.     

Late-onset obesity in mice transgenic for the human renin gene

We previously generated a strain of transgenic mice carrying the human renin gene, hRN8-12, in the background of C57BL/6j. In this study, we discovered that hRN8-12 male mice, but not females, developed obesity starting at 15 weeks of age. The body weight of 60-week-old male transgenic mice was 2 times higher than that of age-matched wild-type mice. Interestingly, male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increase in weight in the adipose tissue, liver, heart, and kidneys. Histological analysis demonstrated that fatty hRN8-12 mice developed hypertrophy of pancreatic islets and fatty liver. These results suggested that hRN8-12 mice are associated with obesity dependent on the transgene dosage and should be a genetic model for late-onset obesity.