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Biomedical subjects

Y Furuta

Publications and source records attributed to Y Furuta.

At least 109 records · Page 6Linked to original sources

Latent herpes simplex virus type 1 in human geniculate ganglia.

Viral infection, especially by reactivation of herpes simplex virus (HSV) has been considered to be a possible explanation for the pathogenesis of idiopathic peripheral facial nerve palsy (Bell's palsy). We investigated whether the geniculate ganglia of man contain latent HSV type 1 (HSV-1), and compared the frequency of HSV-infected ganglia and that of latently infected neurons in human geniculate ganglia and in trigeminal ganglia. From autopsy specimens of eight adults 15 geniculate ganglia and 16 trigeminal ganglia were examined by means of in situ hybridization and immunohistochemical staining. The HSV-1 genome was detected in 11 of the 15 (71%) geniculate ganglia and in 13 of the 16 (81%) trigeminal ganglia. No HSV antigen was noted in any of the ganglia. The incidence of latently infected neurons was 0.9% in the trigeminal ganglia and 5.3% in the geniculate ganglia. The difference in percentages between the two types of ganglia was significant. Our results suggest that reactivation of latent HSV in the geniculate ganglia is a probable cause of some cases of herpetic stomatitis and of idiopathic peripheral facial nerve palsy.

DNA Probes↗

Detection of varicella-zoster virus DNA in human geniculate ganglia by polymerase chain reaction.

Latent varicella-zoster virus (VZV) has been demonstrated in the human trigeminal and thoracic ganglia by means of nucleic acid hybridization. However, the human geniculate ganglia in VZV latency have not been examined. Tissue DNA extracted from the trigeminal and geniculate ganglia of a newborn and 7 adults was examined by polymerase chain reaction with a pair of VZV-specific primers. None had symptoms of recent infection with VZV (chickenpox or shingles). VZV DNA was detected in 11 (79%) of 14 trigeminal ganglia and in 9 (69%) of 13 geniculate ganglia of the adults. VZV DNA was not detected in either type of ganglion from the newborn or from 1 adult who was seronegative for VZV antibodies. These findings indicate that VZV becomes latent in human geniculate ganglia after primary infection and suggest the possibility that reactivation of the virus from the geniculate ganglia may cause Ramsay Hunt syndrome.

Adult↗

Triple cancers in the urogenital area of a patient with aplastic anemia.

Three epithelial neoplastic lesions, perineal Bowenoid papulosis, uterine cervical carcinoma, and bladder transitional cell carcinoma, which occurred in a mildly immunosuppressed patient who had aplastic anemia were studied for human papillomavirus (HPV) infection. In the Bowenoid papulosis, HPV type 16 DNA was identified by polymerase chain reaction (PCR) and by in situ hybridization (ISH). In contrast, in the uterine cervical carcinoma, HPV 16 was not detected, although possibly another unidentified type of HPV in the lesion was suggested by the ISH findings. In the bladder transitional cell carcinoma, neither papillomavirus genus-specific (PGS) antigen nor HPV DNA was found.

Adult↗

Expression of the angiotensinogen gene and localization of its protein in the human heart.

BACKGROUND: There have been no reports on the presence of the tissue renin-angiotensin system in the human heart, although the presence of angiotensinogen has been described in the animal heart. METHODS AND RESULTS: To determine whether angiotensinogen is synthesized in the human heart, we examined angiotensinogen messenger RNA (mRNA) synthesis in autopsy hearts by using ribonuclease protection assay. As a result, angiotensinogen mRNA was detected in the atrial muscle, muscles of the conduction system, and the left ventricular wall. In the left ventricular wall, mRNA expression was more prominent in the subendocardial muscles than in the midcardial or epicardial muscles. Using a monoclonal antibody to human angiotensinogen in immunoblotting experiments, we detected two closely spaced bands at approximately 70 kd in the heart, which was quite consistent with the human angiotensinogen molecule. Immunohistochemical studies with this monoclonal antibody demonstrated intense immunoreactivity in the atrial muscles, the muscles of the conduction system, and those of the subendocardial layers. CONCLUSIONS: We conclude that angiotensinogen was synthesized in the human heart. It was evident that the localization of angiotensinogen was not ubiquitous in the cardiac muscles, showing its predilection for the atrial muscles, muscles of the conduction system, and subendocardial layer of the left ventricle.

Angiotensin II↗

Detection of latent herpes simplex virus DNA and RNA in human geniculate ganglia by the polymerase chain reaction.

By using the polymerase chain reaction (PCR) we detected latent herpes simplex virus type 1 (HSV-1) in human geniculate and trigeminal ganglia obtained from autopsy cases. A pair of primers which were specific for a part of the HSV-1 thymidine kinase domain were used for detection of HSV DNA. We also examined the latency-associated transcript (LAT), known as latency-specific RNA, by means of reverse transcription-PCR with a pair of LAT-specific primers. HSV-1 DNA was detected in 16 of 17 (94%) trigeminal ganglia and in 15 to 17 (88%) geniculate ganglia of adults. We also demonstrated HSV-1 RNA derived from the LAT in both types of ganglia. These findings suggest that HSV-1 latently infects the majority of geniculate and trigeminal ganglia of adults, and that PCR and reverse transcription-PCR are useful tools for analysis of HSV latency.

Adult↗

[Percutaneous transluminal coronary angioplasty and coronary bypass grafting for refractory angina in chronic dialysis patients].

Between June 1983 and July 1989, 25 consecutive chronic dialysis patients with medically refractory angina pectoris underwent revascularization, either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) (21 males and 4 females, mean age of 57 +/- 10 years, and mean duration of dialysis of 3.7 +/- 5.0 years). Patients with single-vessel disease and/or mildly calcified lesions received PTCA (n = 15), while those with multi-vessel disease and/or severely calcified lesions received CABG (n = 10). As controls for PTCA-treated dialysis patients, 208 non-dialysis patients who received initial PTCA in 1988 were used. The mean number of diseased vessels was 2.7 +/- 0.7 for CABG group, and 1.5 +/- 0.8 for PTCA group (p < 0.01). In both groups, 80% of patients were successfully revascularized. In CABG group, however, 7 of 10 patients had major complications including 2 hospital deaths, while no complications occurred in the PTCA group. During the follow-up period after CABG (35 +/- 30 months), recurrent angina developed in one patient, who was successfully treated with PTCA. In the PTCA group, angiographic success was initially obtained in 16 of 21 lesions (76%), which was significantly lower than that in the control group (92%, p < 0.05). Follow-up angiography revealed restenosis in 6 of 16 lesions with successful PTCA (38%), similar to that observed in the control group (32%, p = ns). A second PTCA was successful in 5 of 6 patients with restenosis, however, 4/5 patients developed recurrent angina. Three of 4 patients with a second episode of restenosis underwent a third PTCA, and angina recurred in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Contribution of proliferating cell nuclear antigen to prognostic evaluation of carcinomas of the maxillary sinus].

Proliferating cell nuclear antigen (PCNA) is a nuclear protein, synthesized in the late G1 and S phases of the cell cycle. Therefore, it is considered to be closely related to cell proliferation. The contribution of PCNA to prognostic evaluation of the disease was investigated in 42 squamous cell carcinomas of the maxillary sinuses, retrospectively. Histological sections were prepared by formalin-fixation, paraffin-embedding and staining with monoclonal antibody to PCNA (DAKO, PC10) using the Avidin-biotin peroxidase complex method. The percentage of tumor cells with positive staining for PCNA ranged from 26.3 to 92.3% (average; 61.7%). In order to evaluate PCNA in terms of prognosis, five-year survival rates in the following two groups were compared. One included cases with a PCNA positive rate above the mean level and the other, those below the mean level. Five year survival rate was 30.4% in the group with a higher positive rate, but 42.1% in the group with the lower rate. However, the difference in survival rate between the two groups was not statistically significant. In addition, no correlations either between the rate of PCNA positivity and T-classification of tumors or between the degree of tumor cell differentiation and metastasis to neck lymph nodes were obtained. Further study is necessary to evaluate PCNA as a prognostic marker in human malignancy.

Adult↗

Histological study of atelocollagen infused into the human vocal cords.

There have been only three case reports of histological study on injection of atelocollagen into the human vocal cords, and none of these have indicated foreign body reaction. We histologically examined the larynx of a 70-year-old man, which had to be excised 44 days after infusion of atelocollagen into the vocal cords. The atelocollagen infused was found to have been replaced with the collagen of host cells, but no foreign body reaction was observed. As in conventional reports, the histoaffinity of atelocollagen was confirmed.

Aged↗

Hepatocarcinogenesis in transgenic mice carrying albumin-promoted SV40 T antigen gene.

We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas at around 5 months and die of liver insufficiency by 7 months. Sequential morphological observation of hepatocarcinogenesis revealed 5 distinct stages: (I) newborn to 2 weeks of age, neither recognizable histological changes nor cellular replication in spite of T antigen expression; (II) between 3 and 7 weeks, diffuse cytomegalic change of hepatocytes with numerous abnormal mitoses, usually resulting in cell death; (III) from 7 weeks onwards, quasi-regenerative small hepatocyte foci with a decreased tendency for cytomegaly in spite of T antigen expression, rapidly replacing the hepatic tissue; (IV) 11 weeks of age and thereafter, neoplastic foci and nodules with enzymatic alteration; (V) 20 weeks of age and thereafter, gross hepatocellular carcinomas with occasional pulmonary metastases. Considerable variation existed both in morphological and enzymatic features and T antigen expression among neoplastic lesions, including carcinomas. Thus, these transgenic mice clearly show a multistep process in hepatocarcinogenesis with remarkable synchrony and provide a promising model for analyzing the essential events of carcinogenesis at different stages.

Animals↗

Pathological features of virus infections of the central nervous system (CNS) in the acquired immunodeficiency syndrome (AIDS).

Neurological disorders are a common cause of morbidity and mortality in the acquired immunodeficiency syndrome (AIDS). In this report we describe the neuropathological changes associated with both human immunodeficiency virus (HIV) infection and with the major opportunistic virus infections, cytomegalovirus (CMV), JC papovavirus (JCV) and herpes simplex virus (HSV) seen in AIDS. In addition "in situ" hybridization studies have been employed for the detection of virus genomic material in each case and the usefulness of this method in supporting the pathological diagnosis is demonstrated. Mechanisms whereby HIV infection results in leukoencephalopathy and the possible contributing roles of the three opportunistic virus infections are discussed.

Acquired Immunodeficiency Syndrome↗

Morphological and cytogenetic characterization and N-myc oncogene analysis of a newly established neuroblastoma cell line.

A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5-year-old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1, 10, 19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40- to 80-fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin-labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma.

Animals↗

Calcium supplementation in salt-dependent hypertension.

To clarify the mechanism of the antihypertensive effect of oral Ca loading, we studied the effect of Ca supplementation on salt-induced blood pressure elevations in patients with essential hypertension and DOCA-salt hypertensive rats. When the diet was changed from low to high salt (300 mEq/day), the percent increase in mean blood pressure was smaller (p less than 0.01) in the Ca-supplemented (2,160 mg/day) patients than in the Ca-restricted (250 mg/day) ones. Oral Ca loading resulted in a smaller weight gain, a greater urinary sodium excretion, and an increase in red cell Mg. In the experimental study, high Ca (4% CaCl2) intake attenuated the blood pressure elevation in DOCA-salt-treated rats, accompanied with an increase in urinary sodium excretion, with the resultant attenuation in intra- and extracellular sodium retention. The decrease in catecholamine contents of hearts was improved, and a higher survival rate was observed in Ca-supplemented DOCA-salt rats. The results suggest that Ca supplementation may prevent a rise in BP in salt-dependent hypertension by inducing natriuresis with the resultant attenuation in sodium retention. The altered intracellular Mg level in hypertensive patients and the normalization of enhanced sympathetic nervous activity in DOCA-salt rats may, in part, be involved in its mechanism.

Adult↗

Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses.

Nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma. To determine the etiological role of human papillomavirus in inverted papilloma, and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor, we retrospectively analyzed inverted papillomas from 26 patients, 7 of whom had squamous cell carcinoma. We used an immunohistochemical method and molecular pathologic techniques, or dot-blot hybridization of DNA extracted from paraffin-embedded tissues, in situ hybridization, and polymerase chain reaction. Human papillomavirus was detected in 5 of 26 patients (19%), 3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16. The latter 2 patients had inverted papillomas associated with squamous cell carcinoma. We speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas.

Adult↗

Multiple cerebral infarcts caused by emboli from carotid atheroma--a case confirmed by indium-111 platelet scintigraphy.

A 47-year-old male presented with frequent transient ischemic attacks (TIAs) of weakness of the left upper extremity. Computed tomography demonstrated multiple infarcts in the right cerebral hemisphere. Cerebral angiography showed marked atheromatous changes at the siphon of the right internal carotid artery, characterized by wall irregularities and heterogeneous filling. Indium-111-labeled platelet scintigraphy demonstrated abnormal tracer accumulation at the right carotid siphon. Following right carotid artery ligation, this abnormal platelet deposition was resolved and no further TIA was experienced. This suggests that the release of microthrombi from thrombogenic carotid atheroma contributes to embolic stroke.

Arteriosclerosis↗

Bilateral oculomotor nerve palsies due to posterior cerebral arterial compression relieved by microvascular decompression--case report.

A 59-year-old male developed peripheral oculomotor nerve paresis due to compression by the left posterior cerebral artery (PCA), which was successfully treated by microvascular decompression. Two months later, a similar oculomotor nerve paralysis due to the same mechanism occurred contralaterally and was also treated by microvascular decompression. The previous condition was probably caused by arteriosclerotic changes in the PCA, and the following condition by postsurgical adhesion of the arachnoid membrane. The possibility of vascular compression should be considered when oculomotor nerve palsy rapidly develops, although not proven by angiography.

Cerebral Angiography↗

[Treatment of malignant gliomas by selective intraarterial infusion chemotherapy with high-dose ACNU and autologous bone marrow transplantation--preliminary report].

Six patients with malignant gliomas were treated by selective intracarotid infusion of ACNU at 15 mg/kg (about 600 mg per m2) or 10 mg/kg with or without radiotherapy and rescue of autologous bone marrow transplantation after surgery. These high doses of ACNU were well tolerated if bone marrow rescue was performed and granulocyte colony stimulating factor was used. With the development of microcatheters for use in selective intraarterial infusion, it has become possible to cannulate the major artery and infuse drugs at high dose into the artery feeding the tumor. The complication of ocular toxicity can be avoided by using the Tracker-18 or Balt (Magic) angiographic catheter. On the other hand, drug dosage and infusion rate must be chosen carefully, because of the increased likelihood of local arteritis and local necrosis caused by high dosage of ACNU. In the present study, local arteritis or cerebral infarction in the area of the middle cerebral artery was considered to have been prevented by extending the infusion time to 80 minutes. When combined with radiotherapy, 10 mg/kg of ACNU and 80 min. of infusion time were found to be optimal in relation to brain tolerance.

Adolescent↗

Multistep hepatocarcinogenesis in transgenic mice harboring SV40 T-antigen gene.

We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T-antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas (HCCs) at around 5 months and die of liver insufficiency by 7 months in remarkable synchrony. The liver tissue appears normal in the initial 3 weeks, and thereafter rapid cytomegalic degeneration of original hepatocytes, proliferation of quasi-regenerative hepatocytes, neoplastic cell foci, nodules and finally HCCs develop in sequence. Considerable variation existed both in morphological and enzymatic features and in T-antigen expression among neoplastic lesions, including carcinomas. Oligonucleotide hybridization studies revealed activating point mutations of the c-H-ras oncogene in 40% (10/25) of tumors obtained at around 6 months. The positive signals were, however, considerably weaker in half of them suggesting that such tumors comprised cells both with and without ras mutation. Sequential observation of culture cell lines established from tumors also revealed the appearance of activated c-H-ras with time, which was associated with biological progression. Thus, in this model system, ras activation may be an event occurring in a relatively late phase of carcinogenesis associated with progression of tumors. Karyotype analysis of cell lines revealed remarkable chromosomal instability. In studies of sister chromatid exchange in hepatocytes, twice as frequent occurrence was demonstrated in transgenic mice as in their counterpart hepatocytes. Thus T-antigen may be contributing as a mutagen to the hepatocarcinogenesis, in addition to its cytotoxic and growth modifying activities.

Animals↗

[Long-term prognosis in patients with echocardiographic left ventricular dysfunction masquerading as dilated cardiomyopathy].

The long-term prognosis and prognostic factors were assessed in patients with left ventricular dilatation with impaired function secondary to idiopathic dilated cardiomyopathy (DCM) or to heart diseases of various pathogeneses masquerading as DCM (DCM-like). The echocardiographic criteria for DCM-like disease were 1) left ventricular end-diastolic dimension exceeding 60 mm and 2) fractional shortening less than 15%. Those who showed improvement in either of these 2 parameters within 3 months were excluded from this study. One hundred and fifty-eight of 35,250 serially examined patients fulfilled the definitions. The pathogeneses of diseases were valvular heart disease (VHD) in 30 patients, ischemic heart disease (IHD) in 37, alcoholic cardiomyopathy (AC) in 12, hypertensive heart disease (HHD) in 31 and DCM in 48. All of the survivors were followed for more than 24 months; an average of 40 months. During this period, there were a total of 75 deaths, 18 (27%) of whom were judged as sudden death. Five-year survival rates calculated using the Kaplan-Meier method in AC and HHD were 86% and 77%, respectively, which were significantly higher than those in DCM (48%; p < 0.05); whereas, patients with VHD and IHD had lower values (60% and 46%, respectively) which were nearly equal to those in DCM. Factors that contributed to the increase in total cardiac mortality were advanced age, higher NYHA functional class, larger cardiac size on chest radiograph and history of heavy alcohol intake. Each of these factors were closely related to the specific pathogeneses as follows: age to IHD, cardiac size to VHD, and NYHA functional class to DCM. Long-term prognosis of DCM-like heart diseases, especially those of IHD and VHD, seemed to be as bad as those of DCM.

Adult↗