Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.     

Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma

The histogenesis of malignant fibrous hlstlocytoma (MFH) was studled using clsplatln (CDDP)-resistant MT-R8 and MT-R9 cells derlved from cloned undlfferentiated MT-8 and flbrohlstlocytic MT-9 cells, resoecthfely, which had been established from transplantable rat MFH. CDDP concentrations requlred for 50% suppression of prollferation of MT-R8 and MT-R9 cells were 5.4– and 3.3-fold greater than those of parental MT-8 and MT-9, respectively. MT-R8 and MT-Rg showed the higher positive rates to histimytic lysosomal/ antigenic (ED1 and ED2) markers. The number of a-smoath muscle actin (SMA)-positive cells significantly Increased in MT-RB; SMA-positlve cells were also obsenred in MT-R9, but no difference was seen between MT-9 and MT-R9. MT-R8 and MT-R9 expressed both histiwytic and myofibroblastic phenotypes. However, the histology of subcutaneous tumors induced in syngeneic rats by MT-R8 and MR-R9 did not always reflect their in vitro nature. MT-R8 developed undiffer-entlated sarcomas similar to parental MT-8 tumors. In contrast, MT-R9 induced tumors with polytypic histologies such as the storiform growth pattern, neoplastlc growth of granular cells and myofibroblasts, osteosarcoma-like areas, collagen-rich areas containing well-developed fibroblasts and areas involvlng many lipoblasts. These In vivo observatfons suggest the multidlrectional differentiation of MT-R9 cells. Phenotypic modulation of rat MFH cells seemed to be easily induced by CDDP. A possible histogenesis of MFH was discussed based on the data collected.     

Effects of adrenoceptor antagonists on the cutaneous blood flow increase response to sympathetic nerve stimulation in rats with persistent inflammation

There is some evidence that the sympathetic nervous system plays a role in the development and/or maintenance of painful states, and that sympathetic nervous function is altered in these conditions. Our previous experiments showed that electrical stimulation of the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally induces a decrease in blood flow (BF) of plantar skin, induced its BF increase in about 50% of adjuvant-inflamed rats. To investigate the mechanism of this BF-increase response, we examined whether noradrenaline (NA) plays any role in this changed response to SS, and which receptor subtype is involved. We measured paw cutaneous BF response with a laser Doppler flowmeter in rats chronically inflamed with complete Freund's adjuvant. SS induced the BF-increase response in 50-67% of measured sites. Close-arterially injected NA induced the BF-increase response at dosages between 10-100 ng/kg only at the sites with the BF-increase response to SS. The BF-increase and -decrease responses to NA was significantly reduced after the close-arterial injection of either alpha1- or alpha2-adrenoceptor antagonists (p lt; 0.05, respectively). In contrast, although the BF-decrease responses to SS were significantly reduced by administration of alpha1- and alpha2-adrenoceptor antagonist, BF-increase response was reduced only by alpha1-adrenoceptor antagonist, and that only at a higher dose. In addition, the beta-adrenoceptor antagonist had no effects on both responses. These results suggest that the BF-increase response to SS involves, additionally to NA, a non-adrenergic mechanism.     

Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in Thai,Sri Lankan and Paraguayan populations

The genetic polymorphism of orosomucoid (ORM) and alpha-2-HS-glycoprotein (AHSG) were studied in Thai, Sri Lankan and Paraguayan populations using isoelectric focusing. Gene frequencies in these populations were compared with those in other populations. Four new ORM variants were detected:ORM1 ^* 15 in Thai,ORM1 ^* 16 in Paraguayan,ORM2 ^* 21 andORM2 ^* 22 in Sri Lankan.     

HEPATITIS-ASSOCIATED APLASTIC ANEMIA WITH SYSTEMIC PLASMACYTOSIS

An autopsy case of hepatitis associated aplastic anemia was presented. A 58-year-old Japanese female with non-A, non-B hepatitis was admitted on August 2, 1983. Moderate grade of fever and hemorrhagic diathesis appeared on September 16, when hepatitis was evaluated as being under resolving. The peripheral blood and bone marrow findings were consistent with aplastic anemia. Since infection was suggested by increased levels of serum gamma-globulin and CRP, treatment with antibiotics as well as prednisolone and blood transfusion was initiated. Since September 21, gradual tenderness and edema on the right lower abdominal wall appeared. She died on October 3.
On postmortem examination, systemic plasmacytosis with lymphadenopathy and septic monilial infection was revealed. Numerous plasma cells were atypical, but were immunohistochemically proved to be polyclonal. The bone marrow showed a massive and diffuse plasma cell proliferation with extremely scarce myeloid cells and megakaryocytes. There was a large granulomatous lesion with monilial infection in the wall of the ileocecum. By these findings, systemic plasmacytosis was suspected to be due to chronic monilial infection.
The pathogenesis of systemic plasmacytosis in aplastic anemias and in other diseases were discussed with relation to the present case.     

Dna ploidy of pheochromocytoma on cytology specimen by image analysis

Pheochromocytoma usually shows prominent nuclear atypia, but the presence of such atypical cells is known to be an unreliable predictor of malignancy. DNA ploidy of pheochromocytomas has been analyzed by flow cytometry or photospectrometry on paraffinem-bedded tissue, but the results were controversial. We performed DNA analysis on cytology specimens of 11 pheochromocytomas using an image analysis system. All tumors had a mixed pattern of a large population of diploid cells and a small population of polyploid cells. DNA content correlated with nuclear size, and larger cells had more DNA content. Such larger tumor cells had polyploid nuclei, such as 4 C, 8 C, 16 C, and 32 C, in both malignant and benign pheochromocytomas. The larger polyploid nuclei may result from difficulty of duplication at the mitotic phase of the cell cycle.     

An Epstein-Barr virus-producer line Akata: Establishment of the cell line and analysis of viral DNA

An Epstein-Barr virus (EBV)-producer line, designated Akata, was established from a Japanese patient with Burkitt's lymphoma. The Akata line possessed the Burkitt's-type chromosome translocation, t(8q-; 14q+), and was derived from the tumor cell. Akata cells produced a large quantity of transforming virus upon treatment of cells with anti-immunoglobulin antibodies (Takada, 1984). Southern blot analysis of viral DNA indicated that the Akata EBV is nondefective and more representative of wild-type viruses. Akata cells should be useful as a source of EBV.     

Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse

In humans, maternal fibrinogen (Fg) is required to support pregnancies by maintaining hemostatic balance and stabilizing uteroplacental attachment at the fibrinoid layer found at the fetal-maternal junction. To examine relationships between low Fg levels and early fetal loss, a genetic model of afibrinogenemia was developed. Pregnant mice homozygous for a deletion of the Fg-gamma chain, which results in a total Fg deficiency state (FG(-/-)), aborted the fetuses at the equivalent gestational stage seen in humans. Results obtained from timed matings of FG(-/-) mice showed that vaginal bleeding was initiated as early as embryonic day (E)6 to 7, a critical stage for maternal-fetal vascular development. The condition of afibrinogenemia retarded embryo-placental development, and consistently led to abortion and maternal death at E9.75. Lack of Fg did not alter the extent or distribution pattern of other putative factors of embryo-placental attachment, including laminin, fibronectin, and Factor XIII, indicating that the presence of fibrin(ogen) is required to confer sufficient stability at the placental-decidual interface. The results of these studies demonstrate that maternal Fg plays a critical role in maintenance of pregnancy in mice, both by supporting proper development of fetal-maternal vascular communication and stabilization of embryo implantation.     

A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep]

In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).     

Short half-lives of ataxia-associated aprataxin proteins in neuronal cells

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1) is caused by mutations in the gene encoding aprataxin (APTX). Although several in vitro findings proposed that impaired enzymatic activities of APTX are responsible for EAOH/AOA1, potential instability of mutant proteins has also been suggested as the pathogenesis based on in vivo finding that mutant proteins are almost undetectable in EAOH/AOA1 tissues or cells. The present study aimed to experimentally prove instability of mutant proteins in neuronal cells, the cell type preferentially affected by this disease. Results of pulse-chase experiments demonstrated that all of the disease-associated mutants had extremely shorter half-lives than the WT. We further found that mutants were targeted for rapid proteasome-mediated degradation. These results help establish pathogenic and physiological protein characteristics of APTX in neuronal cells.