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Biomedical subjects

N Hanyu

Publications and source records attributed to N Hanyu.

At least 37 records · Page 2Linked to original sources

Leukoencephalopathy induced by chemotherapy with tegafur, a 5-fluorouracil derivative.

We report an autopsy case of a 64 year-old Japanese man diagnosed as having leukoencephalopathy caused by tegafur, a 5-fluorouracil derivative, and review seven previous cases, mostly reported in Japan. In the present case, tegafur had been orally administered for the shortest period of 3 weeks in pre- and postoperative cancer chemotherapy. He died 2 years later after having made a slight recovery from a prolonged akinetic mute state. Unlike similar cases previously reported, the degeneration of the white matter was most prominent in the temporal lobes. Histologically, the severely involved white matter showed nearly complete myelin and axonal loss with a proliferation of hypertrophic astrocytes. In the less severely involved areas, such as in the frontal white matter where myelin was relatively well preserved, numerous activated microglial cells and a small number of T lymphocytes were identified immunohistochemically. The cerebral cortex, cerebellum and brain stem were well preserved, which is consistent with the previous reports. Literature review revealed that the histopathological features of the lesions reported in human cases are quite different from those reported in animal experiments.

Antimetabolites, Antineoplastic↗

A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.

In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.

Adolescent↗

[Effects of L-threo-Dops on orthostatic hypotension in Parkinson's disease].

Effects of L-threo-Dops (Dops) administration on orthostatic hypotention were evaluated with changes in blood pressure by postural change (lying to standing position) and subjective symptoms in 15 patients of Parkinson's disease having symptoms of orthostatic hypotention. Orthostatic syncope had improved significantly (p < 0.01) after 2 and 4 weeks of administration with maintenance dose of 460 mg/day of Dops in average. In the standing-up (Schellong) test, decrease in blood pressure levels by a postural change, both with systolic and diastolic blood pressure, was significantly smaller at 3, 5 and 10 minutes after standing after 4 weeks of drug administration. Decrease in the blood pressure level immediately after standing-up improved by 10.2 +/- 4.0 for systolic and 6.5 +/- 1.8 for diastolic (mmHg, mean +/- SE) (p < 0.01). The group that showed improvement in orthostatic syncope had a significant improvement in decline in blood pressure by standing after administration of Dops, while the group without any change in severity of syncope did not show significant improvement in orthostatic hypotention.

Aged↗

[Steroid therapy and plasmapheresis in chronic inflammatory demyelinating polyradiculoneuropathy: a long-term follow-up study].

We report eight patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), paying special attention to the therapeutic effects of steroid and plasmapheresis. Each patient underwent 4 to 51 plasmapheresis sessions in addition to prednisolone therapy. Plasmapheresis was more effective in patients with motor neuropathy (6 patients) than in those with sensory neuropathy (2 patients). Concomitant steroid therapy enhanced the short-term efficacy of plasmapheresis. During a long-term follow-up, the patients who showed deteriorating clinical symptoms such as limb weakness, sensory disorder, decreased deep tendon reflexes and increased CSF proteins underwent plasmapheresis once or twice a month. This intermittent plasmapheresis could reduce the use of prednisolone or eventually discontinue the drug completely. We were not able to determine whether immunoadsorption plasmapheresis or double-filtration plasmapheresis was more effective for the patients with CIDP. CIDP is characterized by frequent recurrences of a chronic progressive course, and peripheral neuropathy and some patients with this disease are resistant to many therapeutic approaches. The present study strongly suggests that plasmapheresis with concomitant steroid therapy is very useful for both short- and long-term treatment of CIDP patients.

Administration, Oral↗

[Experiences with home enteral nutrition using PEG in patients with adult Crohn's disease].

In adult cases with Crohn's disease, treatment of both the disease and patients' social lives is required for therapeutic regimens. Therefore, we assessed the safety and effectiveness of home enteral nutrition using PEG in patients with adult Crohn's disease. Five patients who were diagnosed with Crohn's disease undergoing a domiciliary treatment with enteral nutrition using PEG in The Jikei University School of Medicine and related institutions from May, 1994, to July, 1998, were the subjects of this study. All patients were relieved of symptoms and returned to work, one of whom relapsed two years later to undergo reoperation. Improvements of nutritional status and almost complete disappearance of inflammatory response were found in all patients. As for PEG-related complications, there was one case complicated with wound infection at an early time, and late complications, included two cases with abnormal granulation and one case with pain in ambient PEG. However, neither major complications nor complications that hindered everyday living were observed. Results of a questionnaire relating to this regimen showed almost complete well-being, though there were complaints about limited of oral intake and the cumbersome procedure of enteral nutrition. In conclusion, home enteral nutrition using PEG is effective in maintaining relief of symptoms, both the time required for feeding and patient pain are less, patients can be readily socially rehabilitated, and complications related to PEG have been few. These suggest that it may become a beneficial measure for patients with adult Crohn's disease.

Adult↗

Efficient transfer of synthetic ribozymes into cells using hemagglutinating virus of Japan (HVJ)-cationic liposomes. Application for ribozymes that target human t-cell leukemia virus type I tax/rex mRNA.

We investigated the usefulness of ribozymes in inhibiting the expression of human T-cell leukemia virus type I (HTLV-I) gene. Two hammerhead ribozymes that were against HTLV-I rex (RR) and tax (TR) mRNA were synthesized. Both ribozymes were sequence-specific in the in vitro cleavage analysis of run-off transcripts from tax/rex cDNA. Intracellular activities of the ribozymes were studied in HTLV-I tax cDNA-transfected rat embryonic fibroblasts (Rat/Tax cells), which expressed the Tax but not Rex. Ribozymes were delivered into cells using anionic or cationic liposomes fused with hemagglutinating virus of Japan (HVJ). Cellular uptake of ribozymes complexed with HVJ-cationic liposomes was 15-20 times higher cellular uptake than naked ribozymes, and 4-5 times higher than that of ribozymes complexed with HVJ-anionic liposomes. HVJ-cationic liposomes promoted accumulation of ribozymes in cytoplasm and accelerated transport to the nucleus. Tax protein levels were decreased about 95% and were five times lower when the same amount of TR was introduced into the cells using HVJ-cationic, rather than HVJ-anionic liposomes. Inactive ribozyme and tax antisense oligodeoxynucleotides reduced Tax expression by about 20%, whereas RR and tax sense oligodeoxynucleotides had no effect. These results suggest that the ribozymes' effect against tax mRNA was sequence-specific, and HVJ-cationic liposomes can be useful for intracellular introduction of ribozymes.

Animals↗

Ribozyme-based gene cleavage approach to chronic arthritis associated with human T cell leukemia virus type I: induction of apoptosis in synoviocytes by ablation of HTLV-I tax protein.

OBJECTIVE: To develop gene therapy for patients with human T cell leukemia virus type I (HTLV-I)-associated arthropathy (HAAP), we investigated the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messenger RNA (mRNA) on synovial overgrowth. METHODS: We introduced 2 hammerhead ribozymes targeted against HTLV-I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV-I-negative rheumatoid arthritis (RA) and examined the ribozyme-mediated ablation of Tax expression. Using standard methods, we also determined the cells' ability to stop proliferating and to undergo apoptosis. RESULTS: The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synoviocytes. Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis. In contrast, synovial cells from RA patients were not affected. CONCLUSION: In vitro results suggest that ribozyme-mediated gene therapy can inhibit the growth of HTLV-I-infected synovial cells, which is maintained by Tax protein, in HTLV-I-related diseases including HAAP.

Apoptosis↗

Ictal muscle discharge pattern and SPECT in paroxysmal kinesigenic choreoathetosis.

We studied the pattern of muscle activity of the limbs during attacks and measured post-ictal regional cerebral blood flow (rCBF) in 3 patients with paroxysmal kinesigenic choreoathetosis (PKC). During attacks, a "Jacksonian march" pattern of tonic muscle activity in the limbs was observed. Two of 3 patients, who suffered from unilateral attacks, showed a noticeable increase in rCBF in the basal ganglia on the contralateral side of the attacks. Treatment with phenytoin improved symptoms and reduced the difference in rCBF between the right and left side. These observations suggest that abnormal hyperactivity of neurons in the basal ganglia may cause choreoathetotic movements in patients with PKC.

Adolescent↗

[Laparoscopic retrieval of a dislocated ventriculoperitoneal shunt catheter: report of three cases and a review of the literature].

Described are 3 cases of a disconnected ventriculoperitoneal shunting system that was successfully retrieved by using a laparoscopic procedure, with a review of the literature. All patients had symptoms of increased intracranial pressure. Roentgenograms showed disconnection of a ventriculoperitoneal shunt catheter at the connecting device and its migration into the peritoneal cavity. A laparoscope was introduced into the peritoneal cavity using the double puncture procedure and the catheter was extracted in less than 15 minutes. The use of a laparoscope enabled exploration of the entire space of the cavity without any large laparotomy incision. Furthermore, the laparoscopic procedure also easily enabled introduction of a replaceable ventriculoperitoneal shunt catheter into the appropriate portion in the cavity and confirmed the CSF flow into the cavity. Because catheters which have migrated into the cavity might cause an acute abdomen, it is important that they should be removed as soon as possible. It should be kept in mind, during the procedures of extracting catheters, that the inner absorptive surface of the peritoneal cavity must be preserved as much as possible. In this regard, laparoscopic retrieval of disconnected shunt catheters is a promising method.

Adult↗

[Home enteral nutrition of patients with terminal cancer].

Generally hospitalization is regarded as a prerequisite for patients with cancer who require terminal care. Recently, special attention has been directed to home care for these patients from the standpoints of patients quality of life (QOL) and health economics. In the case of home care for patients with terminal cancer, effective pain control, careful nutrition administration, psychological care for the patient and his/her family members and emergency care are indispensable. Due to the number and extent of these requirements, home care for terminal patients is not yet common. We have been promoting the adoption of home enteral nutrition as a method to meet the nutritional needs of patients with terminal cancer. In this report, we discuss home enteral nutrition focusing on its indication and methodology, as well as related problems and nutrition administration in the future.

Adult↗

Relationship between cognitive impairments, event-related potentials, and motor disability scores in patients with Parkinson's disease: 2-year follow-up study.

We studied event-related potentials and the cognitive state for 2 years in 29 patients with Parkinson's disease (PD). Of those patients, 11 were at stage II and 18 were at stage III at initial assessment, as measured on the Hoehn and Yahr scale. The peak latency of P300 in patients at stage III was significantly prolonged, as compared with that in age-matched normal controls or PD patients at stage II. There was no significant change in P300 latency among patients whose motor ability remained unchanged at stage II or stage III during follow-up period. The mean P300 latency prolonged significantly in patients whose motor ability worsened from stage III to stage IV. The cognitive state in the patients with PD was characterized by impairment in the categories of orientation, recall and constructional ability. The degree of impairment of these items increased as the motor disability increased. These results suggest that cognitive dysfunctions and abnormality of P300 latency increased as the motor disabilities progressed.

Aged↗

Enhanced E-cadherin expression and increased calcium-dependent cell-cell adhesion in human T-cell leukemia virus type I Tax-expressing PC12 cells.

Human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of host cellular genes, some of which are crucial in cell proliferation and differentiation. We examined the mechanisms by which HTLV-I Tax protein induces phenotypic changes in PC12 cells. We demonstrated that the HTLV-I Tax gene induces epithelioid changes and increases cell-cell contact in PC12 cells. No change in the expression of the neural cell adhesion molecule was observed between HTLV-I Tax-expressing PC12 cells and PC12 cells transfected with a control plasmid. However, HTLV-I Tax-expressing PC12 cells demonstrated a marked change in the abundance and distribution of E-cadherin, which was concentrated at regions of cellular contact and accompanied by changes in calcium-dependent cell adhesion. Although E-cadherin is expressed at low levels in PC12 and PC12 transfected with a control plasmid cells, the steady state level of E-cadherin in tax-expressing PC12 cells increases significantly, apparently as a result of regulation at the transcriptional level. Diminished expression of Tax protein in Tax-expressing PC12 cells exposed to antisense oligonucleotides for the Tax gene suppresses E-cadherin expression and decreases cell-cell adhesion. These findings imply that HTLV-I Tax protein enhanced E-cadherin expression modulates calcium-dependent cell-cell adhesion mechanisms.

Animals↗

Alpha-pattern coma in primary brainstem hemorrhage; clinical, electrophysiologic, and cerebral blood flow studies.

A patient with a brainstem hemorrhage and alpha-pattern coma is reported. Brainstem auditory and somatosensory evoked responses were severely abnormal, suggesting bilateral lesions of the pons, which was confirmed by magnetic resonance imaging. Regional cerebral blood flow, studied using IMP-SPECT, showed no remarkable regional radioactive accumulation or deficit in either the cerebral cortex or the subcortical regions. Based on these findings, we speculate that the alpha-pattern coma may be observed when the functions of brain structures rostral to the pontomesencephalic junction are preserved.

Alpha Rhythm↗

[Enteral alimentation at home: why PEG now?].

The history of percutaneous endoscopic gastrostomy (PEG) is relatively short. In 1980, a report entitled "Gastrostomy without laparotomy: A percutaneous endoscopic technique" by Ponsky and Gaudere was first published in the Journal of Pediatric Surgery. Thereafter, PEG soon saw widespread use in Western countries because of its clinical efficacy and economy. It has been performed in about 170,000 cases annually in the US. In contrast, its spread in Japan has been extremely slow: only about 10,000 cases have undergone this procedure annually, and this number accounted for less than 5% of patients receiving enteral alimentation. The reason why PEG has not spread may be the medical insurance system in Japan and the local distaste for operation scarring. However, in consideration of the unprecedented ageing of society that is surely coming in the near future, the role of PEG in Japan must be reexamined. In this report, we presented the methodology of enteral alimentation at home by means of PEG, giving special consideration to: (1) "What points are improved by using enteral alimentation at home by means of PEG in various diseases; (2) dysphagia due to cerebral angiopathy; (3) terminal cancer; (4) otolaryngological diseases; and (5) Crohn disease. We also discussed "Why PEG is important now?" in performing enteral alimentation at home.

Adult↗

[Clinical study of home hepatic arterial infusion chemotherapy for liver metastasis from colorectal cancer].

The clinical response and QOL were examined with 16 outpatients treated with home hepatic arterial infusion chemotherapy for liver metastasis from colorectal cancer. Fluorouracil 1,000 mg/body/week was administered by 5-hour intra-arterial infusion with a portable disposable pump. Six out of 8 who replied to a questionnaire survey led a their usual life during the treatment, and the average hospitalization period was only 7 days (including mortal cases). The clinical response was evaluated with 13 patients; 3 prophylactic treatment cases were excluded from the original 16 cases. The number of partial responses and no change were 3 and 7, respectively, and the overall response rate was 23.1%. These studies suggest that home hepatic arterial infusion chemotherapy is beneficial for patients with liver metastasis by improving their QOL.

Adult↗

An index to predict outcome of surgery for reflux esophagitis based on the AFP classification.

Fifteen patients with reflux esophagitis were treated surgically from July 1990 to April 1994. We evaluated these patients using the anatomic-functional-pathologic (AFP) classification both prior to and following the operation. An objective index for surgical outcome was devised. By using the grades Ai, Fj, and Pk, the i2 + j2 + k2 score was determined. The scores ranged from 3 to 22 (mean 9.1 +/- 5.4) prior to the operation. Postoperatively, 12 (80%) of 15 patients showed a complete recovery with a numerical score of 0, and their symptoms also disappeared. The scores of these 12 patients prior to the operation ranged between 3 and 11. However, the other 3 patients did not exhibit a complete recovery. Their scores prior to the operation ranged between 17 and 22, and the symptoms in 2 of these 3 patients persisted following the operation. These results suggest that surgical treatment for reflux esophagitis can be expected to be successful if the preoperative AFP score is less than 11.

Adult↗