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Biomedical subjects

T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 487 records · Page 27Linked to original sources

Comparison of muscle force, muscle endurance, and electromyogram activity during an expedition at high altitude.

Handgrip force (HF), maximal pinch force (MF), muscle endurance (ME), and the median power frequency (MdPF) of the activity shown in the electromyogram (EMG) were studied at various altitudes in eight normal healthy subjects. MF and ME were measured between the index finger and thumb, and all measurements were obtained at altitudes ranging from 610 to 4860 m during an expedition in the Qinghai Plateau in China. With the change in altitude HF, ME, and MF showed no significant change. Compared to the MdPF at 2260 m on ascent, the MdPF at other altitudes showed a significant decrease (P < 0.01). Thus, we conclude that muscle performance (HF, MF, and ME) was not affected by the environment at high altitude. However, MdPF was affected and the mean MdPF at 610 m after the expedition did not recover to initial values of MdPF. We suggest these results may have been affected by fatigue and chronic exposure to the hypobaric hypoxic environment, since the members of the expedition party expressed feelings of sluggishness and fatigue after the expedition.

Acclimatization↗

The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers.

We previously reported that introduction of the wild-type p53 gene into human cancer cells with deleted p53 enhanced apoptosis induced by chemotherapy [Fujiwara et al. (1994) Cancer Res 54:2287]. This suggests that p53 status could be a potent determinant of the therapeutic efficacy of DNA-damaging cancer therapy. We analyzed 24 patients with gastric or colorectal cancer for p53 mutations and apoptotic changes in surgical specimens. Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining. The preoperative DNA-damaging therapies increased the number of apoptotic cells in wild-type-p53-expressing tumors; tumors with mutant p53, however, significantly showed fewer apoptotic cells compared with those expressing wild-type p53. The p53-inducible WAF1/CIP1 protein was immunohistochemically observed in wild-type-p53-containing tumors, whereas mutant-p53-expressing tumors expressed no detectable WAF1/CIP1. Taken together, we conclude that p53 mutations are associated with the poor response of chemotherapy and radiotherapy.

Adult↗

Appendiceal mucocele with concomitant colonic cancer. Report of two cases.

PURPOSE: Mucocele of the appendix is an uncommon disorder, usually found incidentally during ultrasonography or radiographic studies. We report two cases of combined appendiceal mucocele and colonic cancer. METHODS: The two cases were analyzed for the clinicopathologic characteristics such as history, presentation, laboratory data, radiologic and endoscopic studies, pathology, and p53 immunoreactivity. RESULTS: Two patients were diagnosed with an appendiceal mucocele by ultrasound of the abdomen, together with computed tomography. Colonoscopic examination subsequently revealed synchronous colonic adenocarcinoma in both patients. Ileocecal resection following endoscopic polypectomy and a right hemicolectomy was performed for each patient. An appendiceal mucocele was histologically diagnosed as a mucinous cystadenoma. Immunohistochemical detection of abnormally high level of p53 protein was observed in colonic adenocarcinomas of both patients, whereas both appendiceal cystadenomas were negative for p53. CONCLUSIONS: To be remembered is the high frequency of concomitant gastrointestinal tumors in patients with appendiceal mucocele, especially caused by mucinous neoplasms. A total colonoscopic surveillance will afford earlier diagnosis of synchronous colonic cancers in these patients.

Adenocarcinoma↗

Tumour necrosis factor is expressed in cardiac tissues of patients with heart failure.

Tumour necrosis factor (TNF), a cytokine produced mainly by macrophages, has also been found in vascular smooth muscle cells. Elevated serum levels of TNF have been reported in various cardiac diseases, especially congestive heart failure (CHF). Although the myocardium produces several cytokines, the expression of TNF in human cardiac tissue has not yet been demonstrated. We examined TNF expression in right atrial (RA) specimens obtained from 15 patients during cardiac surgery with immunohistochemistry using an anti-human TNF monoclonal antibody, enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). TNF immunoreactivity was found only in cardiac myocytes and some vascular smooth muscle cells of small vessels of specimens from patients with severe CHF (3/5), and not in those from patients without severe CHF (0/10). ELISA of four RA specimens revealed that RA tissues from two patients with severe CHF contained more TNF than did those from two patients without severe CHF (3.1 and 4.7 pg/mg vs. 0.1 and 0.3 pg/mg). RT-PCR revealed TNF mRNA in all seven cases we examined. It was concluded that TNF mRNA is expressed by atrial tissue. The production of immunoreactive TNF-like peptides by myocytes and vascular smooth muscle cells is augmented in patients with severe CHF.

Aged↗

Non-penetrating traumatic tricuspid regurgitation after mitral valve replacement.

A case of traumatic rupture of the tricuspid chordae tendineae with severe regurgitation in a patient who previously had mitral valve replacement is presented. In this case, it is strongly suggested that a firm pericardial adhesion of the anterior right ventricular wall became a factor of the disruption of the tricuspid valve under a slight precordial blow.

Adult↗

Measurement of ventricular volumes by cine magnetic resonance imaging in complex congenital heart disease with morphologically abnormal ventricles.

This study assessed the validity of cine magnetic resonance imaging (MRI) for measuring right and left ventricular volumes by using Simpson's rule in children with complex congenital heart disease. Forty-five patients with complex congenital heart disease (average age 2.6 years) and 10 controls (average age 2.3 years) were evaluated. The whole heart was encompassed by contiguous transverse sections. Ventricular volumes were calculated by adding luminal areas determined in each section at end diastole and end systole. End-diastolic and end-systolic volumes by MRI in both groups correlated well with those by ventriculography (r>0.89). Comparison of the ejection fraction in both ventricles in both groups yielded a good correlation between MRI and ventriculography (r>0.67). MRI technique in both groups had low intraobserver and interobserver variation (<6%). Cine MRI provides a suitable noninvasive means of quantifying ventricular volume in children with complex congenital heart disease.

Child↗

Heterotopic splenic autotransplantation in a neonate with splenic rupture, leading to normal splenic function.

Loss of the spleen in infants and young children frequently results in overwhelming infection. To preserve splenic function, heterotopic splenic autotransplantation after splenectomy was performed on a newborn in whom the spleen was traumatized beyond repair because of birth trauma. Postoperatively, the percentage of pitted red blood cells that accurately reflects splenic reticuloendothelial function was normal. Splenic scintigrams obtained 3 weeks after the operation showed uptake by the reimplanted tissue. The otherwise mandatory long-term antibiotic prophylaxis could be reduced to 3 weeks in the newborn. At 7 years of age, the patient has not shown any increased susceptibility to infections.

Antibiotic Prophylaxis↗

Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis.

The pathogenesis of infantile hypertrophic pyloric stenosis (IHPS) is not well understood. Recent studies have shown that the protonocogene c-kit is essential for the development or maintenance of autonomic gut motility, and also show that the c-kit gene protein product (C-KIT) positive cells in the mammalian gut are responsible for intestinal pacemaker activity. This study examines cells in the pyloric muscles of 23 patients (16 with IHPS, 7 controls) for the presence of the C-KIT (C-KIT+), using immunohistochemical techniques with antihuman C-KIT sera. In the controls, many C-KIT immunoreactive (IR+) cells were observed in the muscle layers. The myenteric plexuses were demarcated by a moderate number of C-KIT-IR+ cells. However, in the IHPS patients, C-KIT-IR were either absent or significantly reduced. No C-KIT-IR+ cells were found around the myenteric plexuses. These findings suggest that a lack of c-kit expression (as an indicator of intestinal pacemaker activity) in the hypertrophic pyloric smooth muscles may be an important factor in the pathogenesis of IHPS.

Biological Clocks↗

Localization of intestinal pacemaker cells and synapses in the muscle layers of a patient with colonic hypoganglionosis.

Bowel dysmotility in association with hypoganglionosis remains unexplained. The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor, and the c-kit protein-product (C-KIT) positive cells in the mammalian gut are responsible for intestinal pacemaker activity. The authors examined the localization of intestinal pacemaker cells in the muscle layers of a patient with colonic hypoganglionosis, using an antihuman C-KIT serum. In the normoganglionic ileum, many C-KIT immunoreactivity positive (C-KIT-IR+) cells were present in the muscle layers. In contrast, there were no C-KIT-IR+ cells in the muscle layers of the hypoganglionic colon. These findings suggest that a lack of c-kit expression may be responsible for the autonomic gut dysmotility in hypoganglionic bowels.

Colon↗

Hepaticoenterostomy after excision of choledochal cyst in children: a 30-year experience with 180 cases.

In the long-term follow-up of patients with choledochal cyst, postoperative ascending cholangitis and/or stone formation in the intrahepatic bile ducts (IHBD) owing to anastomotic stricture present serious problems. To prevent the formation of anastomotic strictures, some surgeons recently have performed hepaticoenterostomy at the hepatic hilum, with a wide stoma, in all patients with choledochal cyst. The authors of the present study review the surgical procedures performed on a total of 180 children with choledochal cyst and discuss the treatment of choice, with special reference to the types of hepaticoenterostomy. The medical records and radiographs of all patients treated for choledochal cyst between January 1964 and December 1993 at the authors' institutions were reviewed. A total of 180 patients (mean age at time of surgery, 4.3 years) had follow-up for a mean of 11.1 years; 174 of them had cyst excision and hepaticoenterostomy, and six had cystoenterostomy. Of the 174 patients who underwent cyst excision, 171 had a conventional hepaticoenterostomy; two had an intrahepatic cystoenterostomy, and one had a hepaticoenterostomy at the hepatic hilum. IHBD stones with or without cholangitis developed postoperatively in four (2.3%) of the 171 patients who had conventional hepaticoenterostomy. The age at time hepaticoenterostomy of these four patients was 12, 7, 16, and 6 years. Postoperative IHBD stone formation and cholangitis were not found in 121 patients under 5 years of age. The authors recommend conventional hepaticoenterostomy as the treatment of choice for children with choledochal cyst. Hepaticoenterostomy at the hepatic hilum is indicated in only selected cases.

Adolescent↗

Brain 6-[18F]fluorodopa metabolism in early and late onset of Parkinson's disease studied by positron emission tomography.

We measured 6-[18F]fluorodopa (FDOPA) uptake in the caudate nucleus and the putamen of 20 patients with early and late onset of Parkinson's disease (EOPD and LOPD) and 20 normal control subjects using positron emission tomography. The mean influx rate constant values (Ki) were significantly reduced in the caudate nucleus and the putamen of the patients with EOPD and LOPD compared with age-matched control groups (p < 0.01), respectively. There were significant negative correlations between Ki values in the caudate nucleus (r = -0.67, p = 0.0024) and the putamen (r = -0.67, p = 0.0014), and duration of disease in the LOPD group compared with the EOPD group. Similar negative relationships between Ki values and clinical stages by Hoehn and Yahr and degrees of main clinical symptoms (bradykinesia, tremor and rigidity) were more markedly seen in the LOPD group than in the EOPD group. The present results suggest that the function of presynaptic dopaminergic terminals correlates well with clinical disease severity and degrees of main symptoms in the LOPD group, but not in the EOPD group. We speculate that compensatory up-regulatory function in the postsynaptic dopaminergic receptors may modify disease severity and the degrees of main clinical symptoms of EOPD.

Adult↗

Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog.

The role of cortisol in directing the metabolic response to a combined infusion of glucagon, epinephrine, norepinephrine, and cortisol (stress hormones) was investigated. Chronically catheterized, conscious fasted dogs were studied before hormone infusion and after a 70-hour stress hormone infusion containing glucagon, epinephrine, norepinephrine, and cortisol (n = 11) or containing all these hormones except cortisol (n = 5). Combined stress hormone infusion increased arterial plasma glucagon, cortisol, epinephrine, and norepinephrine approximately sixfold. Whole-body glucose production (Ra), glycogenolysis, and gluconeogenesis were assessed using tracer and arteriovenous-difference techniques. The absence of an increase in cortisol during stress hormone infusion attenuated the increase in arterial plasma glucose concentration and Ra (delta 81 +/- 16 v 24 +/- 3 mg/dL and 1.7 +/- 0.3 v 0.8 +/- 0.4 mg/ kg/min, respectively). However, it did not alter the increase in net hepatic glucose output (delta 0.7 +/- 0.3 v 0.8 +/- 0.4 mg/kg/min). When the increase in cortisol was absent, the increase in net hepatic gluconeogenic precursor uptake was attenuated (delta 0.7 +/- 0.3 v 0.1 +/- 0.3 mg glucose/kg/min) due to a decrease in gluconeogenic precursor levels. The efficiency of gluconeogenesis increased to a greater extent (delta 0.19 +/- 0.07 v 0.31 +/- 0.11) when cortisol was not infused. The absence of an increase in cortisol also led to marked glycogen depletion in the liver (10 +/- 4 v 55 +/- 10 mg/g liver). Cortisol thus plays a pivotal role in the metabolic response to stress hormone infusion by sustaining gluconeogenesis through a stimulatory effect on hepatic gluconeogenic precursor supply and by maintaining hepatic glycogen availability.

Animals↗

Metastasizing uterine leiomyoma. A case with cardiac and pulmonary metastasis.

A case of histologically benign cardiac and pulmonary metastases from a uterine leiomyoma in a 45-year-old woman is reported. The solitary cardiac tumor consisted of five lobules with a stalk attached to the anterior papillary muscle of the right ventricle, which occupied the right ventricular cavity and almost completely obstructed the pulmonary main trunk in the systolic cycle. Multiple small nodules were found throughout both lungs. The cardiac tumor was resected at open heart surgery and open lung biopsy of the pulmonary lesion was simultaneously performed. Both of them were histologically identical to the apparently histologically benign uterine leiomyoma which had been resected five years previously. Based on the clinical and laboratory findings, it is postulated that antegrade metastases via the venous system resulted in the cardiac metastasis from the uterine leiomyoma and the secondary pulmonary metastasis from the cardiac tumor. In contrast to the light microscopic findings, ultrastructural examination suggested the possibility of malignancy associated with the presence of immature smooth muscle cells. This is the first reported case of a so-called benign metastasizing leiomyoma occurring in the heart.

Female↗

PET imaging of primary mediastinal tumours.

Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours.

Adolescent↗

Gene Replacement Strategies for Lung Cancer.

Advances in our understanding of the molecular genetics of cancer present an opportunity to develop prevention and treatment strategies based on the reversal of specific genetic lesions. This strategy is analogous to the classic concept of gene therapy for replacement of defective or nonfunctioning genes. The gene families implicated in carcinogenesis include dominant oncogenes and tumor suppressor genes. Regional administration of viral vectors expressing wildtype p53 and antisense K-ras prevents tumor growth for tumors with the specific genetic lesions in orthotopic tumor models and mediates regression of large established tumors. These studies provide a rationale for a new clinical protocol recently approved by the National Institutes of Health Recombinant DNA Advisory Committee and Food and Drug Administration to replace a defective p53 gene with intratumor injection of recombinant retrovirus expressing wild-type p53 or elimination of activated K-ras by expression of antisense K-ras messenger RNA. If these agents are efficacious, their lack of toxicity may provide a sufficiently high therapeutic index such that they could be used as an adjuvant to surgery to treat patients with earlier stages of cancer or as prevention for second primary cancers for individuals with genetic abnormalities in premalignant lesions. Although much research needs to be done, the possibility of specific gene targeting with a high therapeutic index makes this a promising area of investigation.

Journal Article↗

Transvenous embolization of traumatic carotid cavernous fistula with mechanical detachable coils.

An attempt at transarterial balloon embolization of a traumatic carotid cavernous fistula was made but the carotid artery rent was too small for this approach. The patient was then treated by antegrade embolization through a superior ophthalmic vein using mechanical detachable coils. Successful obliteration of the fistula was achieved with preservation of the carotid artery. Transvenous embolization is an alternative technique to treat patients with traumatic carotid cavernous fistulas, especially when a transarterial approach has failed.

Adult↗

Pancreaticobiliary maljunction associated with nondilatation or minimal dilatation of the common bile duct in children: diagnosis and treatment.

It is known that the etiology of congenital biliary dilatation (CBD) is closely associated with pancreaticobiliary maljunction (PBMJ). Treatment of CBD today is primary excision of the cyst followed by hepaticoenterostomy. However, PBMJ without dilatation of the biliary tract has recently been reported and its treatment is still controversial. In adults, simple cholecystectomy without biliary reconstruction is often performed, because it usually presents as an anomaly of the gallbladder. Over 30 years, we have encountered 8 patients with PBMJ without dilatation of the common bile duct in 180 pediatric cases of CBD. The presenting symptoms of these patients were those of pancreatitis i.e. abdominal pain associated with elevation of serum amylase levels. Five cases presented with jaundice or a history of pale colored stools. Endoscopic retrograde cholangiopancreatography was performed to confirm the diagnosis. Five (62.5%) of these 8 patients were found to have dilatation of the common channel, which was seen in 50 (29%) of the 172 other cases with biliary tract dilatation. Three cases (37.5%) had proven protein plugs or debris at the level of the common channel, and this was observed in 28 (16%) of the 172 other cases. It is strongly suggested that the manifestation of clinical symptoms in these patients results from stasis or obstruction at the level of the common channel. In children who present with recurrent pancreatitis, PBMJ must be suspected even if the common bile duct appears to be normal. It is difficult to resolve these anomalies without operative repair. The authors consider that radical treatment of PBMJ is required in these children to prevent serious long-term complications.

Abdominal Pain↗