The Drosophila Ral GTPase regulates developmental cell shape changes through the Jun NH(2)-terminal kinase pathway.

The Ral GTPase is activated by RalGDS, which is one of the effector proteins for Ras. Previous studies have suggested that Ral might function to regulate the cytoskeleton; however, its in vivo function is unknown. We have identified a Drosophila homologue of Ral that is widely expressed during embryogenesis and imaginal disc development. Two mutant Drosophila Ral (DRal) proteins, DRal(G20V) and DRal(S25N), were generated and analyzed for nucleotide binding and GTPase activity. The biochemical analyses demonstrated that DRal(G20V) and DRal(S25N) act as constitutively active and dominant negative mutants, respectively. Overexpression of the wild-type DRal did not cause any visible phenotype, whereas DRal(G20V) and DRal(S25N) mutants caused defects in the development of various tissues including the cuticular surface, which is covered by parallel arrays of polarized structures such as hairs and sensory bristles. The dominant negative DRal protein caused defects in the development of hairs and bristles. These phenotypes were genetically suppressed by loss of function mutations of hemipterous and basket, encoding Drosophila Jun NH(2)-terminal kinase kinase (JNKK) and Jun NH(2)-terminal kinase (JNK), respectively. Expression of the constitutively active DRal protein caused defects in the process of dorsal closure during embryogenesis and inhibited the phosphorylation of JNK in cultured S2 cells. These results indicate that DRal regulates developmental cell shape changes through the JNK pathway.

Musashi and seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development.

We have examined the roles played by the Drosophila neural RNA-binding protein Musashi (MSI) in eye development. MSI expression was observed in the nuclei of all photoreceptor cells (R1-R8). Although a msi loss-of-function mutation resulted in only weak abnormalities in photoreceptor differentiation, we found that the msi eye phenotype was significantly enhanced in a seven in absentia (sina) background. sina is known to be involved in the degradation of the Tramtrack (TTK) protein, leading to the specification of the R7 fate. We demonstrated that MSI also functions to regulate TTK expression. The sina msi mutants showed significantly high ectopic expression of TTK69 and failure in the determination of the R1, R6, and R7 fates. Other photoreceptor cells also failed to differentiate with abnormalities occurring late in the differentiation process. These results suggest that MSI and SINA function redundantly to downregulate TTK in developing photoreceptor cells.

Herpes simplex encephalitis with transient global amnesia as an early sign.

Cerebral ischemia has been proposed as the etiology of transient global amnesia. Recently, however, migranous and epileptic etiologies have attracted attention. A 56-year-old man had transient global amnesia and the next day began to display symptoms of meningoencephalitis. Herpes simplex encephalitis was diagnosed based on the titer of herpes simplex virus antibodies. The transient global amnesia appears to have occurred as an early sign of herpes simplex encephalitis and may have been provoked by an epileptic mechanism.

Changes in granulocyte-macrophage colony formation in relation to chemotherapy and clinical progress in acute myeloblastic leukaemia patients.

To investigate the correlation between granulocyte-macrophage colony formation and the prognosis of acute myelocytic leukaemia, an in vitro colony formation assay using a practical method was performed at diagnosis in 50 patients newly diagnosed with acute myelocytic leukaemia. Granulocyte-macrophage colony counts were significantly lower in acute myelocytic leukaemia patients than in the control group (n = 5). The diminished colony formation was restored to within the normal range in 15 patients after complete remission was achieved. In eight patients, serial evaluation of granulocyte-macrophage colony formation was performed, and suppression of colony formation was observed at relapse. The comparison of granulocyte-macrophage colony counts at diagnosis between a group of patients with complete remission (n = 26) and a group of treatment failure cases (n = 24) revealed a significant difference suggesting that high counts of granulocyte-macrophage colony formation are predictive of a favourable prognosis for acute myelocytic leukaemia.

[Anesthetic management of two patients with polymyositis].

We report anesthetic experience of two patients suffering from polymyositis. The first case is a 56 year old woman who underwent tympanoplasty for cholesteatoma of the middle ear. Anesthesia was induced with thiopental and deepened with oxygen-nitrous oxide and sevoflurane. No muscle relaxant was used for endotracheal intubation and for maintaining anesthesia. Another is a 61 year old man who underwent open reduction and internal fixation for condyle fracture of the tibia. Epidural catheter was inserted at L 3-L 4. Epidural blockade was established with 2% mepivacaine, and sedation was achieved by intravenous midazolam. Concerning the anesthetic management of a patient with polymyositis, there are some informations on the appropriate use of muscle relaxants. It is generally believed that the patient is sensitive to nondepolarizing muscle relaxants and the use of antagonist drug (reversal) may cause muscle weakness, severe dysrhythmia, et al. Therefore we think it is appropriate to manage such a patient without muscle relaxants.

[A case of suspected pulmonary air embolism in endoscopic neurosurgery].

Sudden reduction in end-tidal PCO2 and SpO2 occurred during the endoscopic third ventriculostomy in a patient with hydrocephalus under general anesthesia. We suspect that it was caused by pulmonary air embolism. A 63-year-old female was scheduled for endoscopic third ventriculostomy under general anesthesia. Endoscopic manipulation caused hemorrhage from chorioid plexus 21 minutes after the procedure was begun, and intraventricular irrigation was performed to achieve hemostasis. In the subsequent 3 minutes, end-tidal PCO2 declined from 26 mmHg to 15 mmHg (PaCO2 39.6 mmHg), and SpO2 declined from 98% to 92% (PaO2 69.2 mmHg). Nitrous oxide was discontinued immediately because pulmonary air embolism was suspected and the oxygen concentration was increased to 100%. At the same time the surgical procedure was discontinued. After 15 minutes, end-tidal PCO2 recovered to 25 mmHg, and SpO2 recovered to 98% (PaO2 136.5 mmHg), and surgery was resumed. The patient recovered from anesthesia. The chest X-p at the end of operation, and pulmonary scintigraphy on the following day revealed no abnormal findings, but brain CT demonstrated a large quantity of air in both lateral ventricles.

[Sitting position in the neurosurgery: the results of a questionnaire sent to neurosurgeons of medical colleges].

We analyzed questionnaire on the sitting position among neurosurgeons. We sent questionnaire to 80 medical colleges in Japan and obtained response from 61 universities (76.3%). The sitting position surgery was performed in 7 institutions (11.5%) and was not in other 54 (88.5%). The first reason for not adopting the sitting position was "other position was good enough to perform the surgery" (44 institutions, 81%). This reason exceeded "objection from the anesthesiologist" (17 institutions, 31%). Twenty institutions (33%) adopted or wished to perform the surgery in sitting position, indicating that neurosurgeons still are interest in performing the sitting position surgery. But 6 institutions adopting the sitting position predicted that the sitting position would diminish in the future, and the sitting position surgery would decrease in number in Japan.

Leukoaraiosis in relation to prognosis for patients with lacunar infarction.

BACKGROUND AND PURPOSE: Close relations between leukoaraiosis detected by computed tomography or magnetic resonance imaging and stroke, particularly lacunar infarction, have been reported. We studied whether leukoaraiosis is related to long-term prognosis for patients with lacunar infarction. METHODS: We examined monthly 215 patients with lacunar infarction after their first stroke. They comprised 95 patients with leukoaraiosis disclosed by computed tomography on admission (58 men and 37 women; mean age, 71.3 +/- 9.0 years) and 120 patients without leukoaraiosis (81 men and 39 women; mean age, 65.5 +/- 8.9 years). These patients had no previous history of either stroke or obvious dementia before their index stroke. We compared the prognosis with and without leukoaraiosis based on analysis of recurrent stroke, survival, and the prevalence of dementia and rate of dependence in activities of daily living. RESULTS: Life table analysis revealed that the recurrent stroke rate was significantly higher in the patients with leukoaraiosis than in those without it (p = 0.004). The prevalence of dementia and rate of dependence in activities of daily living both 1 month after the index stroke and at the end of the follow-up period were significantly higher in the patients with leukoaraiosis (all parameters, P less than 0.001). Their survival rate was significantly lower than in those not suffering from leukoaraiosis (p = 0.012). Significant differences in these comparisons were also observed after matching for age and sex. CONCLUSIONS: The presence of leukoaraiosis as identified by computed tomography indicates a poor prognosis for patients with lacunar infarction.

Precipitating antibody against protease of Corynebacterium pyogenes in pigs.

Antibody in sera from pigs carrying an abscess associated with Corynebacterium pyogenes and healthy pigs was examined by the agar gel diffusion test. In the test, the concentrated culture fluid containing the protease of C. pyogenes was used as antigen. As a result, precipitating antibody was demonstrated in sera from 25 of 30 abscessed pigs and a few of the healthy pigs. When the relationship between precipitating antibody and protease was examined by the immunoelectrophoresis and gel filtration of the concentrated culture fluid, the antibody was shown in the same position as the protease. From the result, it was clear that the precipitating antibody was against the protease of C. pyogenes. All the proteases produced by 27 strains of C. pyogenes of porcine and bovine origin were serologically identical with one another. They were, however, serologically different from those of Staphylococcus aureus, Bacillus cereus, and B. subtilis. In the inhibition test, the proteolytic activity of C. pyogenes was inhibited by the serum of the abscessed pig. It was also inhibited by healthy pig serum. From the results, it seems that the determination of precipitating antibody may be useful for the diagnosis of C. pyogenes infection.

The manifestation of genotypes responsible for blood pressure and blood sugar level.

It has been known for a long time that hypertension and diabetes mellitus are often complicated by each other. The aim of this paper was to disclose possible causes of such complications by investigating 1) whether or not hypertension and diabetes mellitus are entirely two independent diseases, 2) whether or not they occur together only by chance, 3) whether or not there are some causal factors which are shared by these two diseases and 4) whether or not these two diseases occur together with some probability. The genetic analyses of these two diseases were carried out on the basis of the genetic analyses on blood pressures (BP) and blood sugar levels (BS) in the present studies. It was proved that the genotypic correlation coefficients of BP and BS ranged from 0.075 to 0.573 with a mean value of 0.337 and their environmental correlation coefficients were from -0.029 to -0.337 with a mean value of -0.164. These results suggest that 1) the respective polygenic systems responsible for BP (hypertension) and BS (diabetes mellitus) have multiple effects and 2) the environmental factors responsible for BP and BS have inverse effects. The negative values of the environmental correlation coefficients between BP and BS indicate that the environmental factors which lower BP may elevate BS, and vice versa. An induction of an abnormal glucose tolerance as one of the side effects of thiazides, the most widely used anti-hypertensive diuretics, coincides with the inverse environmental correlation between BP and BS. This finding may be of great importance in the field of clinical genetics.