Molecular evidence that the genes for dioecism and monoecism in Spinacia oleracea L. are located at different loci in a chromosomal region.

Spinach (Spinacia oleracea L.) is widely known to be dioecious. However, monoecious plants can also occur in this species. Sex expression in dioecious spinach plants is controlled by a single gene pair termed X and Y. Our previous study showed that a single, incompletely dominant gene, which controls the monoecious condition in spinach line 03-336, should be allelic or linked to X/Y. Here, we developed 19 AFLP markers closely linked to the monoecious gene. The AFLP markers were mapped to a 38.2-cM chromosomal region that included the monoecious gene, which is bracketed between flanking markers with a distance of 7.1 cM. The four AFLP markers developed in our studies were converted into sequence-characterized amplified region (SCAR) markers, which are linked to both the monoecious gene and Y and are common to both populations segregating for the genes. Linkage analysis using the SCAR markers suggested that the monoecious gene (M) and Y are located in different intervals, between different marker pairs. Analysis of populations segregating for both M and Y also directly demonstrates linkage of the genes at a distance of ~12 cM. The data presented in this study may be useful for breeding dioecious and highly male monoecious lines utilized as the pollen parents for hybrid seed production, as well as for studies of the evolutionary history of sexual systems in this species, and can provide a molecular basis for positional cloning of the sex-determining genes.

Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis.

BACKGROUND: Molecules that are highly expressed in tumour endothelial cells (TECs) may be candidates for specifically targeting TECs. Using DNA microarray analysis, we found that the lysyl oxidase (LOX) gene was upregulated in TECs compared with its expression in normal endothelial cells (NECs). LOX is an enzyme that enhances invasion and metastasis of tumour cells. However, there are no reports on the function of LOX in isolated TECs. METHODS: TECs and NECs were isolated to investigate LOX function in TECs. LOX inhibition of in vivo tumour growth was also assessed using ß-aminopropionitrile (BAPN). RESULTS: LOX expression was higher in TECs than in NECs. LOX knockdown inhibited cell migration and tube formation by TECs, which was associated with decreased phosphorylation of focal adhesion kinase (Tyr 397). Immunostaining showed high LOX expression in human tumour vessels in vivo. Tumour angiogenesis and micrometastasis were inhibited by BAPN in an in vivo tumour model. CONCLUSION: LOX may be a TEC marker and a possible therapeutic target for novel antiangiogenic therapy.

Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells.

BACKGROUND: We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs. METHODS: The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients. RESULTS: Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers. CONCLUSION: These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

Induction of hypertrophic chondrocyte-like phenotypes by oxidized LDL in cultured bovine articular chondrocytes through increase in oxidative stress.

OBJECTIVE: It has been reported that the lectin-like oxidized low-density lipoprotein (Ox-LDL) receptor 1 (LOX-1) is expressed by chondrocytes in osteoarthritis (OA) cartilage and that Ox-LDL binding to LOX-1 increases intracellular oxidative stress in cultured bovine articular chondrocytes (BACs). It was recently demonstrated that reactive oxygen species (ROS) induce hypertrophic differentiation of chondrocytes in the growth plate. It has also been shown that activated chondrocytes in OA have hypertrophic chondrocyte-like phenotypes. The purpose of this study was to determine whether Ox-LDL induces hypertrophic chondrocyte-like phenotypes in BACs. DESIGN: Changes in type X collagen (COL10) and runt-related transcription factor 2 (Runx2) mRNA expression in BACs after Ox-LDL stimulation were investigated using real-time polymerase chain reaction (PCR). Western blotting and immunofluorescent cell staining were used to investigate changes in protein level. The antioxidant N-acetyl cysteine (NAC) was used to ascertain whether oxidative stress is involved in COL10 and Runx2 expression. We induced LOX-1 knockdown cells using small interfering RNA (siRNA) to examine the receptor specificity of Ox-LDL. RESULTS: COL10 expression was upregulated by Ox-LDL in a time- and dose-dependent manner. Immunofluorescent staining showed that Ox-LDL increased COL10 production in the extracellular matrix. Ox-LDL-induced upregulation of COL10 was suppressed by pretreatment with NAC and siRNA. Expression of Runx2 was upregulated by Ox-LDL and H(2)O(2), and these effects were suppressed by NAC pretreatment. CONCLUSION: Ox-LDL binding to LOX-1 induces a hypertrophic chondrocyte-like phenotype through oxidative stress, indicating that Ox-LDL plays a role in the degeneration of cartilage.

Thoracoscopic Esophagectomy for a Patient With Perforated Esophageal Epiphrenic Diverticulum After Kidney Transplantation: A Case Report.

A 58-year-old man who underwent cadaveric kidney transplantation twice presented to hospital with a perforated epiphrenic diverticulum. Computed tomography revealed epiphrenic diverticulitis and right pleural effusion. Upper gastrointestinal fibroscopy showed an epiphrenic diverticulum full of food residue. He was transferred to our hospital, where we performed percutaneous endoscopic gastrostomy under general anesthesia in the supine position before thoracoscopy. Thoracoscopic esophagectomy was performed in the semi-prone position under 6-10 mmHg artificial pneumothorax via the right thoracic cavity. We performed subtotal esophagectomy to remove sources of infection because the esophageal wall surrounding the diverticulum was too thick to close or to perform diverticulectomy. A cervical esophagostomy was constructed after the thoracic procedure. The patient was managed with continuous hemodiafiltration and administered immunosuppressants and steroids to preserve the transplanted kidney. Continuous hemodiafiltration was stopped on postoperative day (POD) 4. The patient was discharged from the intensive care unit on POD 10 and transferred to the original hospital on POD 24 for rehabilitation. The second operative stage was performed on POD 157 at our hospital. We performed gastric tube reconstruction via the ante-sternal route and anastomosed the tube to the cervical esophagus. The postoperative course was uneventful; the patient was transferred to the original hospital on POD 15 after the second operation. Minimally invasive surgery was sufficient to treat perforated epiphrenic diverticulum while preserving the transplanted kidney. We recommend completely removing the source of infection and reducing surgical invasiveness to preserve the transplanted kidney in cases of esophageal perforation following kidney transplantation.

IL-11 contribution to tumorigenesis in an NRF2 addiction cancer model.

The interaction between cancer cells and their microenvironment is an important determinant of the pathological nature of cancers, particularly their tumorigenic abilities. The KEAP1-NRF2 system, originally identified as a critical defense mechanism against oxidative stress, is often dysregulated in various human cancers forming solid tumors, resulting in the aberrant activation of NRF2. Increased accumulation of NRF2 in cancers is strongly associated with the poor prognoses of cancer patients, including those with lung and breast cancers. Multiple lines of evidence suggest that aberrantly activated NRF2 in cancer cells drives their malignant progression and that the cancer cells consequently develop 'NRF2 addiction.' Although the downstream effectors of NRF2 that are responsible for cancer malignancy have been extensively studied, mechanisms of how NRF2 activation contributes to the aggressive tumorigenesis remains to be elucidated. In this study, we found a significant correlation between NRF2 and IL-11 status in breast cancer patients. Based on a recent report demonstrating that IL-11 is induced downstream of NRF2, we examined the significance of IL-11 in NRF2-driven tumorigenesis with a newly established NRF2 addiction cancer model. Expression of Il11 was elevated during the tumorigenesis of the NRF2 addiction cancer model, but intriguingly, it was hardly detected when the cancer model cells were cultured in vitro. These results imply that a signal originating from the microenvironment cooperates with NRF2 to activate Il11. To the best of our knowledge, this is the first report showing the influence of the microenvironment on the NRF2 pathway in cancer cells and the contribution of NRF2 to the secretory phenotypes of cancers. Disruption of Il11 in the NRF2 addiction cancer model remarkably inhibited the tumorigenesis, suggesting an essential role of IL-11 in NRF2-driven tumorigenesis. Thus, this study suggests that IL-11 is a potential therapeutic target for NRF2-addicted breast cancers.

Management and algorithm for focal nodular hyperplasia of the liver in children.

PURPOSE: The aim of this study was to determine an appropriate management plan for childhood and adolescent FNH, in particular to establish an algorithm for preoperative diagnosis and treatment. PATIENTS AND METHODS: Between 1985 and 2003, 4 children with FNH were diagnosed. Of these 4 patients, 3 (Group A) underwent tumor resection, and 1 (Group B) was treated by conservative management. Clinical data, pathological findings and follow-up were evaluated retrospectively. RESULTS: The 3 patients in Group A were symptomatic, while the 1 patient in Group B was asymptomatic. In 3 of 4 patients, a homogeneous tumor with a central stellate area was noted on abdominal ultrasonography, CT scan and MR imaging. In case 2, SPIO-enhanced MR imaging was useful for differentiating FNH from hepatocellular carcinoma. Though percutaneous needle biopsy was performed in case 3, a pathologically definitive diagnosis was impossible. An open biopsy was performed in case 4 and FNH was diagnosed. In case 4 treated by conservative management, the tumor size did not change during the 7 years after the diagnosis of FNH. CONCLUSION: FNH is usually treated conservatively because of the good evolutionary outcome of the lesion. Surgery is indicated in cases of complications, compressed adjacent organs, lesion progression, or for symptomatic patients. We advocate the use of less invasive SPIO-enhanced MR imaging instead of open biopsy when the diagnosis of focal liver lesions is not clear after contrast-enhanced CT scan and non-enhanced MR imaging.

ZEB1 induces EPB41L5 in the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance.

Onset of the cancer mesenchymal program is closely associated with cancer malignancy and drug resistance. Among the different epithelial-mesenchymal transition (EMT)-associated transcriptional factors, ZEB1 has a key role in inducing the mesenchymal phenotypes and stem cell-like properties of different breast cancer cells. ARF6 and its effector AMAP1 are frequently overexpressed in breast cancer cells, and promote invasion, metastasis and drug resistance. EPB41L5 is induced during EMT, and mediates the disruption of E-cadherin-based cell-cell adhesion and the promotion of focal adhesion dynamics. Here we show that EPB41L5 is an integral component of the ARF6-based pathway, which is induced by ZEB1. We found that EPB41L5 is expressed at high levels in malignant breast cancer cells and binds to AMAP1. ZEB1 induced EPB41L5 both in cancer cells and normal cells. This relationship was recaptured with The Cancer Genome Atlas RNASeq data set, and correlated with the poor outcome of the patients. In contrast, diversified events, such as tumor growth factor ß1 stimulation, expression of SNAI1 and TP53 mutation, can each cause the induction of ZEB1 and EPB41L5, depending on the cellular context. Our results demonstrated that the ZEB1-EPB41L5 axis is at the core of the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance of significant populations of primary breast cancers, and is tightly correlated with the poor outcomes of patients.

The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition.

Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-ß-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT.

Difference in binding sites of autoantibodies against 230- and 170-kD bullous pemphigoid antigens on salt-split skin.

The purpose of this study is to clarify a relationship between bullous pemphigoid autoantibodies against two major BP antigens, 230 kilodalton (kD) (BPAG1) and 180 kD (BPAG2) and their binding sites, using immunoblot analysis and indirect immunofluorescence on salt-split skin. Of the 135 sera obtained from patients in whom bullous pemphigoid had previously been diagnosed by clinical and immunopathologic criteria, all 52 sera recognizing only BPAG1 stained only the epidermal side of split skin (epidermal pattern). Of 24 sera recognizing only BPAG2, 20 showed the epidermal pattern and four stained both the epidermal and dermal sides (combined pattern). Of 42 recognizing both BPAG1 and BPAG2, 35 showed the epidermal pattern and seven showed the combined pattern. Of 17 that reacted with neither antigen, nine showed the epidermal pattern, four showed the combined pattern, and four stained only the dermal side (dermal pattern). Two of the four cases that showed a dermal pattern were retrospectively identified as epidermolysis bullosa acquisita. Immunoelectron microscopy confirmed that a serum with combined pattern bound to both intracellular and extracellular sites of hemidesmosomes. Our results suggest that autoantibodies that react solely with BPAG1 bind exclusively to the epidermal side of salt-split skin and never show either a combined or a dermal pattern, and that most antibodies against BPAG2 bind to the epidermal side. The combined pattern suggests the presence of autoantibodies against the extracellular epitopes of BPAG2 that are separated from the epidermis during the salt-splitting process.

Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy.

The authors describe a patient with sporadic distal myopathy associated with reduced caveolin-3 in muscle fibers in which the muscle atrophy was restricted to the small muscles of the hands and feet. Gene analysis disclosed a heterozygous 80 G-->A substitution in the caveolin-3 gene that was identical to that of reported cases of elevated serum creatine kinase. This patient further demonstrated possible clinical heterogeneity of myopathies with mutations in the caveolin-3 gene.

Functional mapping of the human colour centre with echo-planar magnetic resonance imaging.

Clinical studies of cerebral achromatopsia have suggested a colour centre in the human fusiform gyrus. By using functional magnetic resonance imaging, we examined whether the fusiform gyrus shows activity correlated with the perception of colour. We tested three stimulus conditions in which the subject maintained fixation: (i) a circular array of six coloured circles; (ii) the same as (i) except that each circle is equiluminant grey with its colour counterpart; and (iii) the same as (i) plus a clockwise shift of circles to neighbouring positions every 1 s. After termination of the stimulus, the subject perceived an after-image of circles with complementary colours in (i), but not in (iii). In condition (i), we found a focal signal increase in the posterior part of the fusiform gyrus. In condition (ii), the activation in the same locus during the stimulation period was weaker than that in (i). In condition (iii), the signal intensity after termination of the stimulus was weaker than that in (i). The colour effect and after-effect on activation of the fusiform gyrus observed here suggest its critical role in human colour perception.

A conspicuous adaptability to antibiotics in the Escherichia coli mutator strain, dnaQ49.

By repeating the cycle of mutagenesis and selection, the Escherichia coli dnaQ49 mutator acquired high level resistance to ampicillin (30,000 micrograms ml-1), streptomycin (26,000 micrograms ml-1) and ofloxacin (3000 micrograms ml-1). Under the strong pressure of ofloxacin, dnaQ49 also followed the history of mutations in the gyrase and topoisomerase i.v. genes previously observed in clinical isolates of quinolone-resistant E. coli. The results of these in vitro experiments suggest that naturally existing mutators may participate in the rapid acquisition of resistance to various antibiotics in patients. A possible mechanism for the occurrence of this adaptability is discussed with special reference to the property of mutagenesis accompanying DNA replication.

A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan.

We have identified a novel two-base mutation in exon 1 of the Cu/Zn superoxide dismutase (SOD1) gene (TGC to TTT), which resulted in Cys6 to Phe substitution in a Japanese family with amyotrophic lateral sclerosis (ALS). This is the first case of familial ALS-associated two-base change of the SOD1 gene. Similar to several mutations in exon 1 of the SOD1 gene such as Ala4 to Val, Ala4 to Thr and Val14 to Met, affected members of the present family showed a rapid progression of motor dysfunction. Although Ala4, Cys6 and Val7 reside in the middle of the first beta-strand of the SOD1, a family with a mutation of Val7 to Glu associates with slow progression of the disease. These findings suggest that clinical courses are variable with each mutation, even in the same exon.

Intracranial vertebral artery dissection in Wallenberg syndrome.

PURPOSE: To assess the prevalence of vertebral artery dissection in Wallenberg syndrome. METHODS: Sixteen patients (12 men, 4 women; mean age at ictus, 51.6 years) with symptoms of Wallenberg syndrome and an infarction demonstrated in the lateral medulla on MR were reviewed retrospectively. The study items were as follows: (a) headache as clinical signs, in particular, occipitalgia and/or posterior neck pain at ictus; (b) MR findings, such as intramural hematoma on T1-weighted images, intimal flap on T2-weighted images, and double lumen on three-dimensional spoiled gradient-recalled acquisition in a steady state with gadopentetate dimeglumine; (c) direct angiographic findings of dissection, such as double lumen, intimal flap, and resolution of stenosis on follow-up angiography; and (d) indirect angiographic findings of dissection (such as string sign, pearl and string sign, tapered narrowing, etc). Patients were classified as definite dissection if they had reliable MR findings (ie, intramural hematoma, intimal flap, and enhancement of wall and septum) and/or direct angiographic findings; as probable dissection if they showed both headache and suspected findings (ie, double lumen on 3-D spoiled gradient-recalled acquisition in a steady state or indirect angiographic findings); and as suspected dissection in those with only headache or suspected findings. RESULTS: Seven of 16 patients were classified as definite dissection, 3 as probable dissection, and 3 as suspected dissection. Four patients were considered to have bilateral vertebral artery dissection on the basis of MR findings. CONCLUSIONS: Vertebral artery dissection is an important cause of Wallenberg syndrome.

High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan.

Autosomal dominant cerebeller ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders that differ in both the clinical manifestations and modes of inheritance. At present, eight different genes causing ADCAs have been found: spinocerebeller ataxia type 1 (SCA1), SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubropallidoluysian atrophy (DRPLA). The relative prevalence of each mutation varies according to race and native place. We studied 117 unrelated ADCA families that originated from the Tohoku District in the northernmost part of Honshu Island in Japan (mainly Miyagi Prefecture in the central part of Tohoku District). The SCA1 mutation was the most frequent among the known disorders (24.8% of all such families). The relative prevalence of SCA1 in the Tohoku District is very high compared with the values already reported from other regions in the world. Because the population of this area had seldom moved, the alleles with SCA1 mutations (including alleles with an intermediate CAG repeat number) are assumed to have been present in this area for a long time.

Clinical evaluation of the results of open or transurethral surgery for prostate hypertrophy.

We evaluated the outcome of surgery for prostate hypertrophy through measurement of the urine flow rate and the Boyarsky symptom score. The study covered 108 patients admitted to Showa University School of Medicine, Fujigaoka Hospital. Thirty-eight had been admitted for retropubic prostatectomy and the remaining 70 patients for transurethral resection of the prostate. Their ages ranged from 48 to 84 years, with an average age of 64.4 years. The urine flow rate was measured before and after prostatic operation using Dantec Urodyn 1000. The symptom scores were calculated according to the Boyarsky symptom score. The Student's t test was used for statistical analysis. Frequency (daytime, nighttime) was the most common preoperative symptom (97.2%, 96.3%), followed by impairment of stream (88.0%), and intermittency (78.7%). Frequently observed symptoms tended to raise the symptom scores. The period of admission, age and prostatic size did not correlate with the preoperative urine flow rate and symptom score. Significant improvements in the urine flow rate occurred after the operation. Frequency (daytime, nighttime) was the most common postoperative symptom (82.7%, 81.1%), followed by urgency (37.0%), then terminal dribbling (32.2%). Of 39 patients who were evaluated by symptom score and urine flow simultaneously, 6 patients (15.1%) failed to show improvement in 1 of the 2 evaluations, while 9 (23.1%) patients failed to show improvement in either. The irritative symptoms (frequency, urgency) tended not to show significant postoperative improvement.

[Some observations on prognosis in congenital hydrocephalus (first report)--with reference to the preoperative evaluation of the hydrocephalic infants (author's transl)].

Recently, the prognosis of congenital hydrocephalus has improved by shunting operation. There are some cases, however, showing poor prognosis even when this procedure has been performed. Thus, postoperative courses of hydrocephalus are variable, and do not always produce the same results. From the clinical viewpoint, we have studied preoperative signs and symptoms, and tried to find some factors which influence the prognosis. This report consists of 41 cases of congenital hydrocephalus and 7 cases of hydroencephalodysplasia over the past six years. For the purpose of observations before and after operation, we adopted some neurological symptoms, head circumference, thickness of cerebral mantle in pneumoventriculogram, intraventricular pressure and others. The average period of follow up of all the cases was two years and six months. Of the 41 patients of congenital hydrocephalus, 24 survived and 14 died. Of the 7 patients of hydroencephalodysplasia, 5 survived and 2 died. As to the age of the patients on admission, 57% of all the cases were infants from 2 months to 4 months old. The patients who had such neurological signs already on admission as motor disability, opisthotonic posture and severe optic nerve atrophy, had a tendency to show poor prognosis in general and to result in a higher mortality. The convulsion and so-called setting sun sign had no significant correlation to poor prognosis. From the morphological evaluation, we have examined increase of circumference and enlargement rate of the head. In the death group, abnormal increase of head circumference was recognized within the first three months of life. When the enlargement was higher than Nellhaus's standard rate within four months after birth, over half of the cases died. In the survival cases, the cerebral mantle thickness was found to be variable while a remarkable decrease was often noted in the death cases. If the mantle is less than 14 mm within three months after birth, prognosis of these cases was generally poor. In the evaluation of intraventricular pressure under endotracheal anesthesia, we found little difference between the survival cases and death cases. However, the death cases exhibited slightly higher average intraventricular pressure. In hydroencephalodysplasia, the cases with abnormal enlarged head marked dysplasia of cerebral hemisphere and thin cerebral cortex showed a tendency toward death, however, the cases with localized partial brain or a lobe dysplasia survived. In some cases by using the ventriculoscope, we could see directly the defect of the brain and obtain beneficial information on diagnosis. Due to the influence of various factors, it is impossible to predict or decide exactly the prognosis of congenital hydrocephalus before operation, but it is of critical necessity to anticipate the postoperative prognosis from preoperative synthetic information.

[Some observations on prognosis in congenital hydrocephalus (second report) -with reference to the physical handicap in survival cases (author's transl)].

The prognosis of surgically treated congenital hydrocephalus has lately proven to give a remarkably increased expectation of life for patient. However, numerous reports hve shown that the prognosis of congenital hydrocephalus have not always shown favourable turns from the viewpoints of physical and mental disability. This problem has been considered many times over the past years. But, an important problem has been left unsolved. The children of social and physical disability are most serious problem, so we attempt to obain a new interpretation about the influence factors upon the prognosis. Present report consists of follow-up studies of long surviving patients who have studied the fatty acid metabolism in the cerebrospinal fluid during postoperatively, the influeence on prognosis of complicated central nervous system malformation and discussed motor and mental disability in survival cases. Since lipids are essential factors in composing the brain tissues, quantitative composition of fatty acid inC.S.F. was determined by the method of gaschromatography using the arachidic acid as an indicator...