Intra-uterine physical growth in schizophrenia: evidence confirming excess of premature birth

BACKGROUND: Many studies have suggested a possible aetiological role for obstetric complications in the development of schizophrenia. We focused on prenatal physical growth in schizophrenia, a contentious issue in the literature. METHODS: We compared gestational age at birth, birth weight (BW) and birth head circumference (BHC) between 312 schizophrenics and 517 controls, and between 187 schizophrenics and their matched healthy siblings. Information on obstetric histories was obtained from the Maternal and Child Health Handbooks (i.e. contemporaneous records). RESULTS: Gestational age at birth was significantly earlier in the schizophrenics than in the controls (P = 0.017). Pre-term birth (gestational age of 36 weeks or less) was more common in schizophrenics than in controls (8.0% v. 3.4%, P = 0.005, odds ratio 2.5). Low BW (2500 g or less) was more frequent in schizophrenics than in controls (9.6% v. 4.6%, P = 0.005, odds ratio 2.2). The schizophrenics had significantly lighter BW (P = 0.0003) and tended to have smaller BHC (P = 0.081) compared with controls. However, multiple regression analysis showed that there was no significant difference in BW or BHC between the schizophrenics and controls when gestational age and maternal weight were controlled. There was no significant difference in BW or BHC between schizophrenics and their siblings, although the schizophrenics tended to be born at earlier gestational age than their siblings. CONCLUSIONS: Our results suggest that prematurity at birth is associated with a risk of developing schizophrenia in adulthood. When gestational age and maternal body weight were allowed for, there was no evidence that schizophrenics tend to have lower mean BW or smaller BHC.     

Astroblastoma: clinicopathologic features and chromosomal abnormalities defined by comparative genomic hybridization

Astroblastomas are uncommon brain tumors whose classification and histogenesis have been debated. Precise criteria for diagnosis have been described only recently, but have not found wide acceptance. We report the clinical, radiographic, and histopathologic features of 20 astroblastomas, and the chromosomal alterations in seven cases as detected by comparative genomic hybridization (CGH). The tumors occurred both in children and young adults (average age, 14 years), most often as well circumscribed, peripheral, cerebral hemispheric masses. Radiographically, the lesions were contrast-enhancing and solid, often with a cystic component. All were characterized histologically by astroblastic pseudorosettes, and most displayed prominent perivascular hyalinization, regional hyaline changes, and pushing borders in regard to adjacent brain. Tumor cells were strongly immunoreactive for S-100 protein, GFAP, and vimentin. Staining for EMA was focal. Ten of 20 astroblastomas were classified as "well differentiated" and 10 were classified as "malignant," largely on the basis of hypercellular zones with increased mitotic indices, vascular proliferation, and necrosis with pseudopalisading. All 10 well differentiated lesions and 8 of 10 malignant lesions were completely resected. None of the well differentiated astroblastomas recurred within the limited follow-up period. Three malignant astroblastomas recurred, including two incompletely resected tumors, and one that had been totally resected. One patient died of disease following recurrence. The most frequent chromosomal alterations detected by CGH were gains of chromosome arm 20q (4/7 tumors) and chromosome 19 (3/7). The combination of these gains occurred in three, including two well differentiated and one malignant astroblastoma. Other alterations noted in two tumors each were losses on 9q, 10, and X. These chromosomal alterations are not typical of ependymoma or infiltrating astrocytic neoplasms, and suggest that astroblastomas may have a characteristic cytogenetic profile in addition to their distinctive clinical, radiographic, and histopathologic features.     

Anterior segment evaluation of infants with retinopathy of prematurity

To understand the mechanisms of glaucoma in retinopathy of prematurity (ROP), anterior segment evaluation is essential. The authors prospectively examined the anterior segment of 27 eyes of 17 premature infants with stages IV and V ROP. Twenty-six eyes received no previous surgery or treatment. Schi?tz and applanation tonometry were performed. Structural evaluation of each anterior segment was conducted by biomicroscopy and Koeppe gonioscopy. In the 26 eyes, angle closure of greater than 180 degrees was noted in 3 (12%). The authors noted prominent Schwalbe's line in 4 eyes (15%), high iris convexity in 15 (58%), hypopigmentation of the iris root in 19 (73%), translucent matrix in the angles ("Barkan's-type" membrane) in 18 (69%), posterior synechiae in 16 (62%), visible iris or angle vessels in 12 (46%), and pigment clumping in the angle recess in 12 (46%). This study identified structural abnormalities in the anterior segment of ROP infants, including pathologic changes and anatomic features that could have a developmental origin.     

Inhibition by 8-hydroxy-2-(di-n-propylamino) tetralin and SM-3997, a novel anxiolytic drug,of the hippocampal rhythmical slow activity mediated by 5-hydroxytryptamine1A receptors

Summary Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxytryptamine_1A (5-HT_1A) agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 3 , 4 , 7 , 7 -hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-IH-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT_1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT_1A antagonistic activity. Direct microinjection of these 5-HTIA selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HTIA receptors. Send offprint requests to A. Hirose at the above address     

Nondomain biopolymers: Flexible molecular strategies to acquire biological functions

A long-standing assumption in molecular biology posits that the conservation of protein and nucleic acid sequences emphasizes the functional significance of biomolecules. These conserved sequences fold into distinct secondary and tertiary structures, enable highly specific molecular interactions, and regulate complex yet organized molecular processes within living cells. However, recent evidence suggests that biomolecules can also function through primary sequence regions that lack conservation across species or gene families. These regions typically do not form rigid structures, and their inherent flexibility is critical for their functional roles. This review examines the emerging roles and molecular mechanisms of “nondomain biomolecules,” whose functions are not easily predicted due to the absence of conserved functional domains. We propose the hypothesis that both domain- and nondomain-type molecules work together to enable flexible and efficient molecular processes within the highly crowded intracellular environment.     

A 13-week subchronic toxicity study of chitin in F344 rats

A subchronic toxicity study of chitin, a natural structural component of crustacean shells, was performed in F344 rats by feeding of the powdered diet containing 5%, 1.7%, 0.6%, 0.2%, and 0% concentrations of the substance. Each group consisted of 10 males and 10 females. All animals survived until the end of the experiment. There were no changes indicating obvious toxicity of chitin in the clinical signs, body weight, food intake, hematology, serum biochemistry, or histopathological findings, except a slight decrease in body weight gain in the 5% chitin-treated males. Although the mechanism is unclear, the suppression of body weight gain may be due to the slight decrease in caloric content of the food in the 5% chitin-treated animals, a change unrelated to toxicity. Thus, there was no obvious toxicity of chitin in F344 rats at concentrations up to 5% in the diet for 13 weeks.     

The efficiency of intermittent antegrade warm blood cardioplegia

We studied the effects of modified Calafiore technique that is intermittent antegrade warm blood cardioplegia including potassium solution and oxygenated with normothermic cardiopulmonary bypass. From January 1996 to March 1997, 45 patients who had undergone elective coronary artery bypass grafting were assigned retrospectively to two groups. Warm group: 25 patients received intermittent antegrade warm blood cardioplegia with normothermic cardiopulmonary bypass. Cold group: 20 patients received intermittent antegrade cold blood cardioplegia with slight hypothermic cardiopulmonary bypass. Preoperative variables were similar in both groups. The rate of sinus rebeating after aorta declamping with DC was lower in warm group than in cold group [warm group 2/25 (8%) versus cold group 8/20 (40%); P < 0.05]. The levels of CK and CK-MB were significantly lower in warm group than in cold group on postoperative day 0. On postoperative day 0 and day 1, the dosage of cathecholamines were significantly less for the warm group than in the cold group. Perioperative events of IABP, PMI and neurological dysfunction were not statistically different. These results show that intermittent antegrade warm blood cardioplegia is a safe and effective method for myocardial protection. But it requires further assessment.     

A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy

OBJECTIVE: To identify the mutation responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a nonwhite family. BACKGROUND: ADNFLE is newly recognized as an entity of idiopathic partial epilepsy. Recently, two different mutations of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) gene were identified in a white family as a cause of ADNFLE. METHODS: Four affected and three unaffected individuals in three generations of a Japanese family with ADNFLE, and 100 unrelated healthy Japanese volunteers were studied. Clinical features and EEG findings in affected individuals were consistent with those of ADNFLE reported in white families with ADNFLE. Mutations within the CHRNA4 gene were screened for using single-strand conformation polymorphism analysis (SSCA) and were determined by direct sequencing. The mutation identified was sought in volunteers by the amplification refractory mutation system. RESULTS: A C-to-T exchange (C755T) was found in exon 5 of the CHRNA4 gene on one allele of affected individuals. C755T segregated in affected individuals and was not found in 200 alleles obtained from the volunteers. C755T replaced serine 252 (Ser252) in the second membrane-spanning domain (M2) of CHRNA4 with a leucine. Ser252 is conserved characteristically in the alpha-subunit of acetylcholine receptor and is considered to play an important role in channel function. CONCLUSION: C755T is a novel missense mutation of the CHRNA4 gene causing autosomal dominant nocturnal frontal lobe epilepsy in this Japanese family.