The lethal effect of an Escherichia coli pgsA null mutation, which causes a complete lack of the major acidic phospholipids, phosphatidylglycerol and cardiolipin, is alleviated by a lack of the major outer membrane lipoprotein encoded by the lpp gene, but an lpp pgsA strain shows a thermosensitive growth defect. Using transposon mutagenesis, we found that this thermosensitivity was suppressed by disruption of the rcsC, rcsF, and yojN genes, which code for a sensor kinase, accessory positive factor, and phosphotransmitter, respectively, of the Rcs phosphorelay signal transduction system initially identified as regulating the capsular polysaccharide synthesis (cps) genes. Disruption of the rcsB gene coding for the response regulator of the system also suppressed the thermosensitivity, whereas disruption of cpsE did not. By monitoring the expression of a cpsB-lac fusion, we showed that the Rcs system is activated in the pgsA mutant and is reverted to a wild-type level by the rcs mutations. These results indicate that envelope stress due to an acidic phospholipid deficiency activates the Rcs phosphorelay system and thereby causes the thermosensitive growth defect independent of the activation of capsule synthesis.

We identified a novel human long fatty acyl CoA synthetase 2 gene, ACS2, as a new ETV6 fusion partner gene in a recurrent t(5;12)(q31;p13) translocation in a patient with refractory anemia with excess blasts (RAEB) with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). ACS2 is expressed in the brain and bone marrow and is highly conserved in man and rats. The resulting ETV6/ACS2 fusion transcripts showed an out‐frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL case, an out‐frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the AML case, and a short in‐frame fusion of ETV6 exon 1 to the 3′ untranslated region of ACS2 in the RAEB case. Reciprocal ACS2/ETV6 transcripts were identified in two of the cases. Fluorescence in situ hybridization (FISH) analysis with ETV6 cosmids on 12p13, and BACs and P1s on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5′ portion of the ACS2 gene, and that the 5q31, breakpoint of the RAEB case involved the 3′ portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the RAEB case led to a fusion protein. Disruption of the second ETV6 allele by t(12;19) was detected in the AML case by FISH analysis. These observations suggest that the disruption of ETV6 and/or ACS2 may lead to the pathogenesis of hematologic malignancies with t(5;12)(q31;p13). Genes Chromosomes Cancer 26:192–202, 1999. © 1999 Wiley‐Liss, Inc.

Studies on the Adsorption of Vitamin. B12 to Intestinal Mucosa Homogenate of Adult and Unweaned Rats. Tohoku J. exp. Med., 1971, 104 (3), [215][216][217][218][219][220][221][222][223] For the purpose of elucidat ing the physiological significance of intrinsic factor (IF) in vitamin B12 absorption, comparative studies on the adsorption of vitamin B12 to intestinal mucosa homogenate of unweaned (aged 48 hours old) and adult rats were carried out. Any material having IF activity on the intestine of the adult rat and the unweaned rat was not secreted from the stomach of the unweaned rat. This result was confirmed by the histologic findings that the chief cells of the unweaned rat, when examined on the fundus portion of the stomach, were still undeveloped. The adsorption of vitamin 13.2 to the intestinal mucosa homogenate of the unweaned rat seemed to be independent on the IF and the presence of Ca++ ion. The amount of vitamin B12 adsorbed to intestinal mucosa homogenate of the unweaned rat, as expressed by jig vitamin B,,/kg body weight, was from 4 to 10 times larger than that of the adult rat. The high capacity of the intestinal mucosa homogenate of the unweaned rat to adsorb vitamin B12, regarded as the first step of vitamin B,2 absorption, may be related to the fact that unweaned rat can absorb a large amount of vitamin B12. The small intestine of the unweaned rat appears to take indiscriminately fairly large molecules. The results of the experiments which investigated the effects of bivalent cations on the adsorption of vitamin B12 to intestinal mucosa homogenate suggested that the so-called sequential uptake might have occurred.B12 absorption; intrinsic factor; unweaned rat It has been known that the absorption of vitamin B12 requires the aid of intrinsic factor (IF) in adult animals of many species. On the other hand, it was found by the experiments on intestinal segments that the small intestine of the unweaned rat can take vitamin B12 without IF, and that any material having IF activity on the intestine of the adult rat is not secreted front the stomach of the unweaned rat (Boass and Wilson 1963). Recently Williams and Spray (1968) reported similar results from the experiments in vivo. They also found that rat's milk given with vitamin B12 did not affect the absorption.We have attempted to know whether the stomach of the unweaned rat secretes any material which has IF activity specifically on the intestine of the unweaned rat.Comparative studies were also made on the IF dependent vitamin B12 absorption in the adult rat and IF independent vitamin B12 absorption in the unweaned rat in

67of the 30 cases had seizures at the time of divorce and nine (30%) had neuropsychiatric complications. Seven cases (two men and five women) had divorced because of having epilepsy or epileptic seizures. Six (86%) of the seven cases had not informed their spouses that they had epilepsy.Conclusions: In this study, we determined that epileptic seizures and neuropsychiatric complications have negative effects on social status. We emphasize that both seizures and neuropsychiatric complications should be carefully managed to improve the QOL in adult patients with epilepsy. A more aggressive therapy, such as treatment with new antiepileptic drugs and surgical treatment, should be considered when poor social prognosis is anticipated. ).Purpose: Angelman syndrome is now diagnosed appropriately because of the development of the fluorescence in situ hybridization (FISH) method. We encountered two cases of this syndrome, and the follow-up studies until adulthood produced some interesting clinical findings.Case Reports: Case 1 was a 23-year-old man. Albinism, delayed speech development, hyperactivity, avoidance of eye contact, and hypersalivation were noticed. Cerebral palsy -was suspected. He could walk independently by age 2 years but could not speak a single word. At age 3 years, epileptic seizures developed and were observed frequently until age 10 years. At that time, his condition was consistent with epilepsia partialis continua because of tremors of the left hand and a continuation of the electroencephalographic (EEG) findings of spikes on the midtemporal and right central regions. The epileptic attacks were controlled with clonazepam (CZP). A constant happy demeanor has been noticed but outbursts of laughter have not been observed. Diffuse high-amplitude slow-wave activity with intermittent spike-wave discharges, which are the characteristic EEG features of Angelman syndrome, disappeared and spike-wave-like discharges over the frontal area were observed thereafter. The present clinical features are severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, oculocutaneous albinism, and semiopened large mouth with protruding tongue and salivation. A chromosomal analysis disclosed 46XYde1(15)(qI l.lql2), and the FISH method detected the deletion of the signal SNRNP.Case 2 was a 20-year-old man. Intellectual disability and hyperactivity had been noticed since infancy. Cerebral palsy was suspected. He could walk independently by 3 years and 6 months but could not speak a single word. The initial epileptic seizure occurred at age 2 years and 7 months. However, no seizures were observed after age 9 years. He has had a constant happy demeanor but no outbursts of laughter. At the present, he shows severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, hypopigmented skin color, and semiopened large mouth with protruding tongue and salivation. EEG examination during childhood revealed the characteristic EEG activities of Angelman syndrome, diffuse high-amplitude...