To study the normal gait development in childhood, we performed a systematic gait analysis on 37 normal children (20 boys and 17 girls) aged between two and six years. The gait cycle, single support phase, ratio of stride length to body height, plantiflexor angles of the feet and propelling force increased with age, whereas the ratio of gait width to stride length and dorsiflexor angles of the feet decreased. The knee-flexion waves, heel-strikes were found in all subjects. From two to six years of age, balance-holding ability and feet plantiflexor forces developed, resulting in more efficient locomotion. The pattern of the lower limb movements on gait is considered to mature during the first three years of life.

Child↗

PubMed2001

[Investigation to sequelae of acute encephalopathy].

We investigated 22 children with sequelae of acute encephalopathy. The patients were divided into 4 groups; group I with almost complete recovery (2 cases), group II with mild mental deterioration (4 cases), group III with severe mental deterioration (8 cases) and group IV with severe mental deterioration and severe physical disabilities (8 cases). There was no difference between 4 groups with regard to the past history, and status at the onset. The period of rehabilitation in hospital was different, being 0.4 month in group I, 2.6 months in group II, 3.0 months in group III and 3.6 months in group IV. The rehabilitation approach consisted mainly of medical therapy and range of motion exercise in the early stage followed trainings for walking and cognition. Family support was essential during the entire course. Evaluation with the functional independence measure was very useful for the rehabilitation.

Activities of Daily Living↗

PubMed2001

[Protein S deficiency in three patients with thrombosis].

Protein S (PS) deficiency, which is caused by various factors including congenital and acquired disorders, is a risk factor for thrombophilia. We described 3 patients with different backgrounds, who all exhibited PS deficiency. The first patient was a 47-year-old woman who suffered from frequent cerebral infarctions, deep-vein thrombosis (DVT) of her lower extremities, and pulmonary thromboembolism. Her son suffered from skin necrosis due to PS deficiency and both had the same mutant allele of the PS gene. The second patient was a 50-year-old woman who experienced a cold sensation in her fingers. Her relatives had a history of cerebrovascular disease. No mutation was detected in her PS gene. The third patient was a 27-year-old man with antiphospholipid antibody. He suffered from thrombocytopenia, skin necrosis, DVT of his lower extremities, and pulmonary thromboembolism. A mutation was identified in the steroid hormone-binding globulin-like (SHBG) domain of his PS gene. Neither his parents nor siblings had a history of thrombosis. The mutations found in the first and third patients were both missense mutations in the SHBG domain that have not been reported previously. The third patient had a mutation in the site that is involved in binding to C4b-binding protein, which modifies the immune response. These three cases provide key insights into the pathophysiology of PS deficiency.

Adult↗

PubMed2001

[An electrophysiological study of ropivacaine on excised cervical vagus nerves of rabbit].

Ropivacaine, a new long acting local anaesthetic of amide type is structurally related to mepivacaine and bupivacaine. This study was designed to compare the in vitro potency and neurotoxicity of ropivacaine with those of other commercially available local anaesthetics using an isolated rabbit vagus nerve model. Ropivacaine dose-dependently suppressed the evoked compound action potentials of A beta nerve and C nerve components. Minimum concentration of ropivacaine for producing complete suppression of the compound action potentials of all components was 0.008%. Electron microscopic observation showed that ropivacaine did not destroy any peripheral nervous structures in concentrations up to 0.75%. When the neurotoxic effect of ropivacaine was compared, in terms of risk ratio (clinically used concentration/concentrations producing 2 hr irreversible block), with that of commercially available local anesthetics, the rank oder was dibucaine, tetracaine, lidocaine, bupivacaine and ropivacaine.

Action Potentials↗

PubMed2001

Subgingival microflora and antibody responses against periodontal bacteria of young Japanese patients with type 1 diabetes mellitus.

Periodontal disease is a complication of patients with type 1 diabetes mellitus (T1DM), although the mechanisms responsible for this relationship remain unclear. The aim of this study was to examine oral manifestations and the prevalence of periodontal pathogens from subgingival plaque samples and serum IgG antibody levels against them in young Japanese type 1 diabetic subjects. One hundred and seventeen Japanese T1DM subjects (53 male, 64 female, mean age +/- SD, 16 +/- 6.5 years) participated in this study. Thirty-nine periodontally healthy, age-matched nondiabetics served as controls. T1DM subjects were clinically assigned into three groups: 12 periodontitis, 32 gingivitis and 73 periodontally healthy. Microbiological tests for four periodontal pathogens, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia and Capnocytophaga ochracea were performed using 16S ribosomal RNA-based polymerase chain reaction methods. Serum IgG antibody levels against 12 periodontal bacteria including the four species assessed by polymerase chain reaction were measured by enzyme-linked immunosorbent assay. In the T1DM subjects, the Periodontitis group had a significantly longer mean duration of diabetes and a higher percentages of subjects harbouring P. gingivalis and P. intermedia than the Periodontally Healthy group. Serum IgG antibody levels against P. gingivalis were significantly elevated in the Periodontitis group compared with Gingivitis and Periodontally Healthy groups. These results indicate that Japanese T1DM subjects are a high-risk group for periodontal disease and both P. gingivalis infection and duration of T1DM are risk factors for the progression of periodontitis in patients with T1DM.

Adolescent↗

PubMed2000

Synthesis, biological evaluation, and conformational analysis of A-ring diastereomers of 2-methyl-1,25-dihydroxyvitamin D(3) and their 20-epimers: unique activity profiles depending on the stereochemistry of the A-ring and at C-20.

All eight possible A-ring diastereomers of 2-methyl-1, 25-dihydroxyvitamin D(3) (2) and 2-methyl-20-epi-1, 25-dihydroxyvitamin D(3) (3) were convergently synthesized. The A-ring enyne synthons 19 were synthesized starting with methyl (S)-(+)- or (R)-(-)-3-hydroxy-2-methylpropionate (8). This was converted to the alcohol 14 as a 1:1 epimeric mixture in several steps. After having been separated by column chromatography, each isomer led to the requisite A-ring enyne synthons 19 again as 1:1 mixtures at C-1. Coupling of the resulting A-ring enynes 20a-h with the CD-ring portions 5a,b in the presence of a Pd catalyst afforded the 2-methyl analogues 2a-h and 3a-h in good yield. In this way, all possible A-ring diastereomers were synthesized. The synthesized analogues were biologically evaluated both in vitro and in vivo. The potency was highly dependent on the stereochemistry of each isomer. In particular, the alpha alpha beta-isomer 2g exhibited 4-fold higher potency than 1 alpha,25-dihydroxyvitamin D(3) (1) both in bovine thymus VDR binding and in elevation of rat serum calcium concentration and was twice as potent as the parent compound in HL-60 cell differentiation. Furthermore, its 20-epimer, that is, 20-epi-alpha alpha beta 3g, exhibited exceptionally high activities: 12-fold higher in VDR binding affinity, 7-fold higher in calcium mobilization, and 590-fold higher in HL-60 cell differentiation, as compared to 1 alpha,25-dihydroxyvitamin D(3) (1). Accordingly, the double modification of 2-methyl substitution and 20-epimerization resulted in unique activity profiles. Conformational analysis of the A-ring by (1)H NMR and an X-ray crystallographic analysis of the alpha alpha beta-isomer 2g are also described.

Animals↗

PubMed2000

A concise and efficient route to 2alpha-(omega-hydroxyalkoxy)-1alpha,25-dihydroxyvi tam in D3: remarkably high affinity to vitamin D receptor.

[reaction: see text]A convenient and potentially valuable synthetic approach to the novel 2alpha-functionalized 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] derivatives (1a-c), which are the C2-epimer of ED-71 and its analogues, has been developed. The C2alpha-modified ring A precursors (1,7-enynes 16, n = 0, 1, and 2) were constructed stereoselectively starting from D-glucose in high yield. In the synthesized 2alpha-(omega-hydroxyalkoxy)-1alpha,25(OH)2D3 derivatives, 1a and 1b showed a greater binding affinity to vitamin D receptor (VDR), up to 1.8 times that of the native hormone.

Animals↗

PubMed2000

Trans-4-hydroxy-2-nonenal, an aldehydic lipid peroxidation product, lacks genotoxicity in lacI transgenic mice.

In order to cast light on the significance of lipid peroxidation products for carcinogenesis, the lacI mutant frequency (MF), micronucleus induction and cell proliferation were analyzed in lacI transgenic mice treated with trans-4-hydroxy-2-nonenal (HNE), a typical example. Male mice were ip injected with HNE at doses of 0, 5 or 50 mg/kg bw and 48 h thereafter, peripheral blood was collected for analyzing micronucleus induction. After 14 days, the mice were sacrificed to allow tissue sampling for examination of lacI MF and cell proliferative activity. Sixty percent of the mice given 50 mg/kg HNE died within 5 days after the treatment, but no other mortalities were observed. Histopathologically, marked pulmonary hemorrhage was found in the 50 mg/kg HNE group mice that survived until day 14. Immunohistochemically, HNE-modified proteins were detected in their alveolar macrophages. The HNE treatment did not increase lacI MF in the liver, kidney and lung and no significant increase in micronucleus induction or cell proliferation in major organs was found in either treatment. Moreover, no tumors developed in the 5 mg/kg HNE-treated mice which survived until week 78. Our results thus indicate that HNE lacks in vivo genotoxicity in lacI transgenic mice even when lethal doses are applied.

Aldehydes↗

PubMed2000

A case of rapidly growing ovarian squamous cell carcinoma successfully controlled by weekly paclitaxel-carboplatin administration.

BACKGROUND: Primary squamous cell carcinoma of the ovary is uncommon and has a poor prognosis. Because of its rarity, the effective postoperative treatment is unknown. We describe a remarkable response of this tumor to weekly paclitaxel-carboplatin administration. CASE: A 53-year-old woman had rapidly growing primary squamous cell carcinoma of the ovary that metastasized to the abdominal wall and transverse colon after maximum cytoreductive surgery. The tumor was resistant to primary chemotherapy with cisplatin, vincristine, mitomycin C, and bleomycin. A combination of paclitaxel and carboplatin was used for second-line chemotherapy and was repeated every week. The patient tolerated the chemotherapy well and demonstrated a pathological complete response in the abdominal metastases following the five courses of chemotherapy. CONCLUSION: Weekly paclitaxel-carboplatin administration may be a safe and effective treatment for advanced and rapidly growing ovarian squamous cell carcinoma with primary resistance to chemotherapy.

Abdominal Neoplasms↗

PubMed2000

Coexistence of gland mucous cell-type mucin and lysozyme in gastric gland mucous cells.

Class III mucin, identified by paradoxical concanavalin A staining, is confined to gastric gland mucous cells and is an essential component of the gastric surface mucous gel layer. The pretreatment required has hampered the application of this method to electron microscopic studies. Antibody HIK1083 reacts selectively with class III mucins. The present study was undertaken to explore, electron microscopically, the immunoreactivity of the human stomach to HIK1083. We examined normal mucosa from resected human stomachs (five cases; formalin-fixed, paraffin-embedded) and gastric biopsy specimens from patients with early gastric cancer [nine cases; glutaraldehyde- and osmium-fixed, epoxy-embedded (seven cases) and half-strength Karnovsky's solution-fixed, Lowicryl K4M-embedded (two cases)]. Immunostaining with HIK1083 and anti-lysozyme antibody was examined under light and electron microscopes. Gland mucous cells were labeled with HIK1083, and lysozyme was detected in some gland mucous cells and surface mucous cells. Electron microscopically, the secretory granules of gland mucous cells contained a single electron-dense core. HIK1083-positive mucins and lysozyme coexisted in the secretory granules of gastric gland mucous cells. HIK1083-reactive mucins and lysozyme were distributed in the matrix and in the dense core of these secretory granules, respectively. HIK1083 can be used for electron immunohistochemistry.

Antibodies↗

PubMed2000

Skull metastasis of hepatocellular carcinoma associated with acute epidural hematoma: a case report.

BACKGROUND: Although epidural hematoma is well documented in trauma patients, its association with other etiologies, such as neoplasms, is not widely known. Here the authors report a case of acute epidural hematoma that originated from a metastatic hepatocellular carcinoma (HCC) in the skull. CASE DESCRIPTION: A 70-year-old male was admitted to our hospital with left-sided hemiparesis. Preoperative computed tomography (CT) revealed a lenticular high-density area adjacent to the right parietal bone, consistent with an acute epidural hematoma. A subsequent magnetic resonance image (MRI) showed a skull tumor adjacent to the epidural hematoma. Removal of the tumor and evacuation of the hematoma were performed and the pathological diagnosis was metastatic HCC. Postoperatively, the patient gradually recovered but he died of pneumonia 2 months later. CONCLUSION: This report represents an additional example of a rare case of metastatic skull tumor associated with acute epidural hematoma. The authors suggest that metastatic skull tumors may be one of the important differential diagnoses in patients with acute epidural hematoma.

Acute Disease↗

PubMed2000

Adult mesoblastic nephroma with ciliated epithelium. A case report.

A case of renal pelvic tumors occurring in a 44-year-old man is reported. There were two polypoid renal pelvic tumors which consisted of glandular and stromal components. Some glands in the tumors had ciliated epithelium and were quite similar to the epididymal tubules. Other glands in the tumors resembled the collecting duct or the mesonephric remnant seen in female genitalia. Immunohistochemistry and electron microscopy revealed smooth muscle differentiation of the stromal cells of these tumors. Some psammoma bodies were seen in the glands of the tumors. We diagnosed these tumors as adult mesoblastic nephroma (MN). The patient has been followed up for 14 months, showing no evidence of recurrence. Differentiation of the tumors from angiomyolipoma, leiomyoma, and nephrogenic adenofibroma is discussed. Adult renal tumors that consist of epithelial and stromal components have been reported under various names. They constitute clinicopathologically different entities originating from pediatric MN. We suggest that these tumors should be termed "adult MN".

Adult↗

PubMed2000

Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities.

To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.

Adenocarcinoma↗