Expression of the TGF-β–ALK-1 Pathway in Dura and the Outer Membrane of Chronic Subdural Hematomas

Neovascularization of the outer membrane plays a critical role in the development and enlargement of chronic subdural hematomas (CSHs) and vascular endothelial growth factor (VEGF) may promote their progression. However, the precise mechanisms remain to be determined. We focused on the signaling pathway upstream of VEGF, transforming growth factor β (TGF-β), and activin receptor-like kinase 1 (ALK-1) to identify the mechanisms underlying the neovascularization of the outer membrane of CSH. Retrospective comparative study was conducted on 15 consecutive patients diagnosed as CSH with burr-hole drainage. Dura and the outer membrane were collected. We immunohistochemically examined the expression of VEGF, integrin-α, TGF-β, and ALK-1 on the outer membrane and dura of CSH and compared our findings with control samples and the signal intensity of hematomas on computed tomography (CT) scans. VEGF and integrin-α expression was markedly up-regulated in both the dura and outer membrane of CSH, the expression of TGF-β and ALK-1 in the dura was slightly increased in the dura and markedly up-regulated in the outer membrane. There was no significant correlation between their expression and CT density. Here we first report the expression of TGF-β and ALK-1 in the outer membrane and dura mater of CSH. We suggest that the TGF-β–ALK-1 pathway and VEGF affect neovascularization and the progression of CSH.     

Endoscopy and Crohn's Disease: Endoscopic Approach to the Pathogenesis of Crohn's Disease

Abstract: This review describes endoscopic and histopathological findings in Crohn's disease with reference to its pathogenesis. The number of patients with Crohn's disease has markedly and rapidly increased during the last 10 years in Japan. Minute lesions such as aphthoid ulcers as an early lesion in Crohn's disease were at first discussed endoscopically and histopathologically. Recent advances concerning the mechanism of how aphthoid ulcers may occur revealed that they are induced by mucosal ischemia due to vasculitis. Longitudinal ulcers and cobblestone appearance were observed only in advanced Crohn's disease. Finally, the etiology of Crohn's disease was reviewed from the viewpoint of infectious agents and immunological abnormalities which were clarified from the study of endoscopic biopsy specimens.     

Morphological Study of Pancreas Divisum in Niigata Using ERCP

Abstract: The morphological characteristics and incidence of pancreas divisum (PD) in Niigata were investigated by studying 16,646 cases diagnosed by ERCP. These cases had been patients in 16 hospitals located in Niigata prefecture. PD was found in 114 (63 cases confirmed, 51 cases unconfirmed) of these 16,646 cases (0.68%). An unconfirmed case was defined as being a patient in whom only the short ventral pancreatic duct was visible through the main papilla, and the confirmed cases were classified into the 3 types according to the ductal systems of the dorsal and ventral pancreas. The classification of these 3 types was as follows. Type 1: Nonfusion between the ventral (VPD) and dorsal pancreatic ducts (DPD), which was visualized through the main papilla (MP) and the accessory papilla (AP), separately. Type 2: Only DPD was visualized through the AP. In spite of the cannulation of the MP, the VPD was not demonstrated. Type 3: Miscellaneous cases. The frequency of Type 1, Type 2, and Type 3 was 58.7% (37 cases), 28.6% (18 cases), and 12.7% (8 cases), respectively. Type 3 consisted of two subtypes. One (7 cases) was regarded as being when the patient had a very fine communicating branch between VPD and DPD, whether an obvious communicating branch could be detected or not by ERCP. The other subtype (only one case) showed very strange findings in which through the AP a short pancreatic duct distributed to the head of the pancreas and to the uncinate process was visualized and in which through the MP a long pancreatic duct to the tail was demonstrated, separately.     

Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo

1. The metabolism of 50 μM [3-¹⁴C] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile.

2. [3-¹⁴C] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins.

3. For all 12 subjects, mean rates of [3-¹⁴C] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively.

4. Marked interindividual differences in [3-¹⁴C] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed.

5. Good correlations were observed between [3-¹⁴C] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes.

6. [3-¹⁴C] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.     

Merkel cells do not require trophic maintenance from the nerves in adult human skin

Summary A 34-year-old Japanese man with hereditary sensory neuropathy was examined to evaluate the distribution, density and inter-relationship between Merkel cells and peripheral nerves in the skin. An epidermal sheet of affected plantar skin showed numerous CAM 5.2-reactive Merkel cells, whereas PGP 9.5-reactive peripheral nerves were completely absent in the epidermis and dermis. These findings strongly suggest that Merkel cells do not require trophic maintenance from nerves in adult human skin.     

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.     

Duration of inter-facility neonatal transport and neonatal mortality: Systematic review and cohort study

BACKGROUND: Regionalization of perinatal health services has been actively discussed, although important determinants such as effect of duration of neonatal transport on neonatal outcomes have not been investigated well as yet. Therefore the purpose of the present paper was to investigate the association between duration of inter-facility transport and perinatal mortality. METHODS: For the systematic review, six major databases were searched. Any comparative studies investigating associations between duration of inter-facility neonatal transport and their outcomes, published in the English language were selected. The studies were screened and reviewed by two independent researchers. For the cohort study, study subjects included every neonate transported to neonatal wards in Osaka, Japan between 1980 and 2000 in an existing surveillance called Neonatal Mutual Cooperative System. They are followed up until 28 days of age, or discharge if earlier. Other variables were also considered as effect modifiers or confounders, including calendar year, birthweight (BW), gestational age (GA), sex, maternal/paternal age, Apgar scores at 1 and 5 min, place of birth and personnel accompanying the neonate during transport (transport personnel), body temperature before transport and on admission, severity of illness, and intraventricular hemorrhage (IVH) grade. Cox regression analyses were performed to obtain principal results, and sensitivity analysis to support them. RESULTS: Systematic review: only one cross-sectional study conducted in an urban area in India was identified. That study showed that neonates with a long duration of transport had 79% higher odds of death than those transported for a short duration after adjusting for the confounding effects. For the cohort study, among 16 429 subjects, full data were available for 4966 neonates. There was strong evidence that those transported for >90 min had more than twice the rate of neonatal death (rate ratio [RR] 2.26, 95% confidence interval [CI]: 1.26-4.04), and some evidence that those transported for between 60 and 89 min had an 80% higher rate of neonatal death (RR 1.81, 95%CI: 1.07-3.06), both compared with those transported for between 30 and 59 min, after adjusting for the confounding effects. A sensitivity analysis on missing values also supported the results. CONCLUSION: There is evidence of an association between duration of transport and increased neonatal mortality, which can be applied to organization of perinatal health services. A prospective cohort study is needed for further investigation.     

Pyodermatitis–pyostomatitis vegetans after subtotal colectomy for ulcerative colitis

A 51‐year‐old Japanese woman underwent subtotal colectomy for ulcerative colitis 5 years before her first visit to our hospital, and her symptoms stabilized. She presented with a 2‐month history of proliferative, pustular lesions on her face, scalp, and gingival and anal mucosae. Histological examination showed features similar to those of pemphigus vegetans. However, the results of immunofluorescence studies, immunoblot analysis and enzyme‐linked immunosorbent assay for pemphigus were negative, and colonoscopy revealed a relapse of ulcerative colitis in the remaining rectal mucosa, so a diagnosis of pyodermatitis–pyostomatitis vegetans was made. This is the first report of mucocutaneous lesions that developed with a relapse of ulcerative colitis in the remaining rectum after subtotal colectomy. Moreover, a close correlation was found between the condition of bowel inflammation and that of mucocutaneous lesions.     

Rapid detection of phenylketonuria mutations by non-radioactive single-strand conformation polymorphism analysis

A non-radioactive single-strand conformation polymorphism (SSCP) method was used to detect various phenylketonuria (PKU) mutations in Japanese and Chinese patients. Arginine⁴¹³-to-proline (R413P) mutation in exon 12 of the phenylalanine hydroxylase gene was identified in a Japanese patient by this method. The segregation of the R413P mutation in the proband's family was clearly demonstrated and the carrier status of each family member was determined. Analysis of DNA fragments containing exon 7 originated from Chinese patients revealed two mutations, arginine²⁴³-to-glutamine (R243Q) and arginine²⁶¹-to-glutamine (R261Q), and a polymorphism, valine²⁴⁵-to-valine (V245V). Although R261Q has been identified previously among Caucasian subjects, this report is the first to describe this mutation among Orientals. Since the non-radioactive SSCP method employs pre-cast acrylamide gels and pre-made gel buffer strips combined with semi-automated temperature-controlled electrophoresis, it can be performed without much expertise in molecular biological techniques. The ability of this method to detect various mutations as demonstrated in this study and its ease of use make it feasible to detect PKU mutations in a routine DNA diagnostic laboratory.