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Biomedical subjects

M Mochizuki

Publications and source records attributed to M Mochizuki.

At least 253 records · Page 14Linked to original sources

Human T lymphotropic virus type 1 uveitis.

The human retroviruses, HTLV-I and HIV, are playing clinically important roles in a variety of ocular disorders, particularly in uveitis. Both viruses are integrated in the genome of infected T cells. HIV-I infection causes the death of the infected T cells, thereby affecting the host defence system and causing AIDS. Subsequent opportunistic infections of ocular tissues, such as CMV retinitis, are a serious problem in clinical ophthalmology all over the world. Another human retrovirus, HTLV-I, has been known as the causative agent of T cell malignancies (ATL and T cell lymphoma) and chronic myelopathy (HAM/TSP), and is now recognised as a causative agent for a specific type of intraocular inflammation characterised by vitreous opacities with mild iritis and mild retinal vasculitis (HTLV-I uveitis). The mechanism by which HTLV-I causes uveitis is still unknown, but our recent data suggest that it is most probably an immune mediated mechanism by activated CD4 T cells infected with the virus. HTLV-I uveitis, therefore, may implicate a significant role of retroviruses in autoimmune diseases and further the pathogenesis of diseases with infection/autoimmune overlap.

HIV Infections↗

Human T lymphotropic virus type 1 uveitis after Graves' disease.

A distinct clinical entity of uveitis associated with human T lymphotropic virus type 1 (HTLV-I) has been reported previously. During the period between January 1989 and April 1992, 93 patients were observed with HTLV-I uveitis and a significant correlation was found between Graves' disease and HTLV-I uveitis. Sixteen of the 93 patients with HTLV-I uveitis (17.2%) had a previous history of Graves' disease. Fifteen patients were female (15/60, 25.0%) and one was male (1/33, 3.0%). Interestingly, uveitis occurred after the onset of Graves' disease in all cases. On the other hand, none of 222 patients with idiopathic uveitis who were seronegative to HTLV-I had a history of Graves' disease. Although the mechanisms by which HTLV-I causes the correlation between uveitis and Graves' disease are unknown, the present data suggest that immune mediated or autoimmune mechanisms are involved in HTLV-I uveitis.

Adult↗

Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng, ginsenoside-Rb2.

We studied the effect of ginsenoside-Rb2 extracted from Panax ginseng on angiogenesis and metastasis produced by B16-BL6 melanoma cells in syngeneic mice. Intravenous administration of ginsenoside-Rb2 on day 1, 3 or 7 after tumor inoculation achieved a remarkable reduction in the number of vessels oriented toward the tumor mass, but did not cause a significant inhibition of tumor growth. The anti-angiogenic effect was dose-dependent ranging from 10 to 500 micrograms/mouse. In contrast, intra-tumoral or oral administration of ginsenoside-Rb2 caused a marked inhibition of both neovascularization and tumor growth. Ginsenoside-Rb2 did not affect the growth of rat lung endothelial (RLE) cells, B16-BL6 melanoma cells or various types of murine normal cells in vitro. The invasion of RLE cells into the reconstituted basement membrane (Matrigel), which is considered to be an essential event in tumor neovascularization, was inhibited by ginsenoside-Rb2 in a concentration-dependent fashion, while ginsenoside-Rb2 did not inhibit the haptotactic migration of endothelial cells to fibronectin-substrate. Multiple administrations of ginsenoside-Rb2 after the intravenous inoculation of B16-BL6 melanoma cells resulted in a significant inhibition of lung metastasis as compared with the untreated control. These results suggest that the inhibition of tumor-associated angiogenesis by ginsenoside-Rb2 may partly contribute to the inhibition of lung tumor metastasis.

Animals↗

Studies on dissolution tests for soft gelatin capsules. IV. Dissolution test of nifedipine soft gelatin capsule containing water soluble vehicles by the rotating dialysis cell method.

The dissolution of oval soft gelatin capsules containing 5 mg of nifedipine dissolved in a water soluble vehicle was evaluated by the rotating dialysis cell (RDC) method and the paddle (PD) method as described in the Japanese Pharmacopoiea (JP) XI. The dissolution pattern of nifedipine obtained by the PD method was linear, and almost 100% of the content was dissolved within 7 to 10 min. The dissolution pattern obtained by the RDC method corresponded to the absorption pattern vs. time curve obtained by th oral administration test in humans. When the RDC method was performed with the cell containing a buffered solution coupled with n-octanol as the dissolution medium, the in vitro dissolution pattern best simulated the in vivo absorption pattern.

Biological Availability↗

Histopathological findings of the digits in dairy cows in Japan.

Two hundred and thirty-nine digits of 45 Holstein dairy cows, which were raised in typical Japanese dairy farms and received poor hoof management, were randomly obtained in the slaughterhouses and examined histopathologically. The findings were classified into 5 grades on the basis of the severity of circulatory disturbances and of keratogenesis. The lesions from Grade 1 to 5 were considered as manifestations of serial lesions indicating that subclinical laminitis advanced to other hoof lesions. The incidence of Grade 2, regarded as subclinical laminitis, reached approximately 50% of digits examined. The lesions classified as Grades 3 (23.9%) and 4 (5.4%) were mainly characterized by circulatory disturbances, which were similar to those of chronic laminitis in the previous reports. The incidence of Grade 5, characterized by sole ulcer, was 5.4%. It is suggested that a considerable number of daily cows in Japan suffered from subclinical laminitis, which may be the cause of recent high incidence of hoof diseases in dairy cows.

Animals↗

Expression of transforming growth factor-alpha in the human ovary during follicular growth, regression and atresia.

The cytologic localization and cellular levels of TGF alpha in the human ovary during follicular growth and regression were examined by avidin/biotin immunoperoxidase techniques with a monoclonal antibody to TGF alpha. In primordial follicles, only the oocyte showed intense immunostaining for TGF alpha, whereas the flattened pregranulosa cells were negative for the immunostaining. The earliest stage of follicular growth at which immunostaining for TGF alpha in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of follicles, the intensity of TGF alpha immunostaining in the oocyte decreased, whereas the staining intensity of the granulosa and theca cells increased. The immunostaining for TGF alpha in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral theca lutein cells adjacent to the central scar tissue. The corpus albicans was negative for the immunostaining. Stromal cells exhibited weak staining for TGF alpha. In atretic follicles, the theca interna cells exhibited intense staining for TGF alpha without appreciable staining in the scattered granulosa cells. This is the first report to demonstrate that TGF alpha expression in the oocyte is maximal in primordial follicles, whereas TGF alpha expression in granulosa and theca cells increases with the progress of follicles and reaches its maximum in the lutein cells during the mid luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stage-limited expression of myc oncoprotein in the human ovary during follicular growth, regression and atresia.

The cytologic localization and cellular levels of myc oncoprotein in the human ovary during follicular growth, regression and atresia were examined by the avidin/biotin immunoperoxidase method with a specific antibody to myc oncoprotein. In primordial follicles, only the oocyte showed intense immunostaining for myc protein, whereas the granulosa cells were negative for the staining. In preantral follicles, both the oocyte and granulosa cells were moderately immunostained for myc protein. In antral and preovulatory follicles, there was no appreciable staining for myc protein in the granulosa or theca cells, while myc protein staining in the oocyte persisted with less intensity. It is of interest that myc protein expression in granulosa cells was apparent only during the preantral follicle stage. Corpora lutea during the early and mid luteal phase were negative for myc protein staining, whereas in regressing corpora lutea during the late luteal phase, peripheral theca lutein cells adjacent to the central core of scar tissue were immunostained for myc protein. Corpora albicans showed no staining for myc protein. In atretic follicles, granulosa cells and theca interna cells demonstrated positive staining for myc protein. Ovarian stromal cells were negative for the immunostaining throughout the menstrual cycle. This demonstrates that myc protein is expressed in a stage-limited manner in the human ovary during follicular growth and regression. The abundant expression of myc protein in the oocyte at the primordial and preantral follicle stages and in the granulosa cells at the preantral follicle stage suggests a role for myc expression in the initial growth of the oocyte as well as in the autonomous growth of granulosa cells during the preantral stage seemingly independent of gonadotropic stimulation. Furthermore, notable expression of myc protein in the granulosa cells and theca interna cells of atretic follicles and in the peripheral theca lutein cells of regressing corpora lutea implies the possible participation of myc expression in remodelling the ovarian local tissue following atresia and luteolysis in the human ovary.

Adult↗

Stage-specific expression of c-myc messenger ribonucleic acid in porcine granulosa cells early in follicular growth.

In the present study, the expression of c-myc mRNA in porcine granulosa cells harvested from varying follicle stages was analyzed using northern blot hybridization with a c-myc probe, and compared during follicular growth. Northern blot analysis revealed that porcine granulosa cell RNA obtained from small (1-2 mm) follicles contained an abundance of c-myc transcript of 2.4 kb, the size of which was identical to the c-myc transcript obtained with human early placental RNA used as the control. In contrast to small-follicle granulosa cell RNA, total RNA preparations from either medium (3-5 mm)-follicle granulosa cells or large (6-11 mm)-follicle granulosa cells exhibited no detectable transcripts with the c-myc probe. These results suggest that expression of c-myc mRNA in porcine granulosa cells is limited only at the early stage of follicular growth. The stage-specific expression of c-myc mRNA in granulosa cells early in follicular growth may play a physiological role in the autonomous growth of immature granulosa cells in early folliculogenesis, seemingly independent of pituitary gonadotropic stimulation.

Animals↗

[Tenascin expression in idiopathic interstitial pneumonia].

The expression of tenascin, a of extracellular matrix glycoprotein, was studied immunohistochemically in the lungs of 22 autopsy cases, including chronic idiopathic interstitial pneumonia (chronic IIP) associated with lung cancer (5 cases), chronic IIP without lung cancer (6 cases), acute idiopathic interstitial pneumonia (acute IIP; 6 cases) and alveolar pneumonia (AP; 5 cases). In the honeycomb lesion of chronic IIP, tenascin expression was observed in the basement membrane of metaplastic epithelia and in the subepithelial stroma of thickened septa with fibrosis. In the non-honeycomb area of chronic IIP, tenascin was expressed in mildly thickened alveolar walls with fibrosis. The distribution of tenascin expression in chronic IIP associated with lung cancer resembled that in chronic IIP without lung cancer. In acute IIP, tenascin expression was observed in mildly thickened alveolar walls with fibrosis, in organizing hyaline membranes. In AP, tenascin was expressed in organizing exudate of alveoli and was scarcely observed in the alveolar wall. It is very possible that tenascin is associated with the fibrosing process and remodelling in IIP, and has a promoting effect in carcinogenesis in IIP lung.

Aged↗

[Early cytomegalovirus retinitis].

We report the clinical course of cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS) from the initial onset. The patient was a 40-year-old human immunodeficiency virus antibody-positive male with hemophilia A. He was diagnosed as having AIDS on the basis of pneumocystis carinii pneumonia. Ophthalmoscopic examination disclosed a small white punctate lesion at the macular area in his right eye. Because the lesion enlarged gradually with hemorrhages, it was suspected to be CMV retinitis. However, further examination was impossible due to his severe general condition. He died five months later and the autopsy disclosed disseminated CMV infection. Ocular histopathological examination revealed CMV retinitis. The earliest sign of CMV retinitis is supposed to be a white punctate retinal lesion, which becomes a small white patchy lesion resembling a cotton-wool spot. It may gradually progress to diffuse retinal involvement, frequently associated with hemorrhages.

Acquired Immunodeficiency Syndrome↗

[A case of carcinomatous meningitis from transitional cell carcinoma of the urinary bladder].

We report a case of carcinomatous meningitis from transitional cell carcinoma of the urinary bladder. A 70-year-old man with invasive bladder cancer and multiple pulmonary metastases received 3 courses of systemic M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy, after which the primary tumor and pulmonary metastases diminished in size and number. During the 4th course of chemotherapy, he complained of nausea, headache, diplopia, and neck stiffness. Computer tomographic (CT) scan of the brain showed no evidence of parenchymal metastases, cerebral hemorrhage, or infarction. Cerebrospinal fluid examination revealed an increase in cells along with elevated protein and depressed glucose concentrations, but no malignant cells were identified. He died two weeks after the onset of neurological symptoms. Autopsy revealed numerous tiny metastatic lesions in the leptomeninx, so called carcinomatous meningitis, without parenchymal metastases in the brain. Although metastases to the central nervous system from transitional cell carcinoma of the bladder, especially carcinomatous meningitis rarely have been reported, this unusual complication will be seen more frequently with the development of more effective systemic chemotherapy such as M-VAC.

Aged↗

Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection.

We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.

Adult↗

A nationwide survey on the occurrence of Vogt-Koyanagi-Harada disease in Japan.

A nationwide survey was carried out to estimate the frequency and distribution of Vogt-Koyanagi-Harada disease in Japan. A questionnaire was mailed to the Departments of Ophthalmology in hospitals with 200 or more beds. Responses were received from 489 out of 1,077 institutions, or 45.5%. The annual prevalence was estimated to be 15.5 per million and the incidence was 6.5 per million, based on the number of reported cases and the response rate per prefecture. It was estimated that 1,800 patients were treated for this disease annually and that there were about 800 new cases each year. Geographical distribution showed no special characteristics such as those seen with Behçet's disease. The results of the analysis of 1,833 reported cases showed that females were slightly more often affected than males. For both male and female patients, the age distribution on the first visit showed a peak in the fifth decade and a median age of 42.3 years.

Adolescent↗

[A multicenter clinico-epidemiological study of HTLV-I associated uveitis].

To elucidate the clinical and epidemiologic features of HTLV-I associated uveitis (HAU), a multicenter case-control study was performed by collaboration of university hospitals throughout Kyushu and Okinawa and two university hospitals in the central metropolitan area. A total of 426 cases of endogenous uveitis were collected and studied between September 1992 and January 1993; about half of the cases were definable for etiology or clinical entity, and the remaining cases were unknown. Assessment of the serum antibodies to HTLV-I revealed that the group of entity-undefined uveitis had a significantly high prevalence of HTLV-I as compared with the age- and sex-matched control subjects, giving supportive evidence for HAU. The titer of serum HTLV-I antibodies was significantly higher in entity-undefined uveitis than in HTLV-carriers. Assuming that a collection of 50 cases of HTLV-I seropositive, etiology-undefined uveitis represents HAU, its clinical features consisted were: (1) middle-aged, otherwise healthy adults developed acute inflammatory uveal disease and presented with visual haze and/or floaters; (2) the disease showed granulomatous or nongranulomatous anterior uveal reactions accompanied by vitreous opacities and retinal vasculitis; (3) the lesions resolved in response to topical or systemic corticosteroids; (4) the visual outcome was usually favorable; (5) nearly half of the cases had recurrent disease; (6) the cases remained systemically unremarkable, except for two cases of HTLV-I associated myelopathy and eight cases of hyper thyroid disease.

Adolescent↗

[Foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome].

A 41-year-old man with acquired immunodeficiency syndrome (AIDS) developed cytomegalovirus (CMV) retinitis. Intravenous administration of ganciclovir arrested progression of the retinitis, but it was discontinued due to side effects of severe anemia, neutropenia, and thrombocytopenia. Reactivation of CMV retinitis occurred two weeks after stopping ganciclovir, and then forscarnet was given intravenously. The response was prompt with resolution of the retinitis. There was no progression of retinitis during the treatment. The patient experienced renal dysfunction as a side effect of foscarnet, but it was reversible. As with ganciclovir, foscarnet appeared to be an effective drug for CMV retinitis associated with AIDS. Both drugs have severe adverse events: foscarnet causes renal dysfunction and ganciclovir causes myelosuppression, that necessitated discontinuation of the therapy. We suggest that alternating ganciclovir and foscarnet administration, switching to other treatment on the basis of the clinical response and side effects of the drugs, is an efficacious regimen for the treatment of CMV retinitis associated with AIDS.

AIDS-Related Opportunistic Infections↗

[Insulin-like growth factor-I (IGF-I) as a local regulator of proliferation and differentiation of villous trophoblasts in early pregnancy].

In order to elucidate the role of insulin-like growth factor-I (IGF-I) in human placental growth and function, the effects of IGF-I on the proliferation and differentiation of villous trophoblasts were investigated in vitro using an organ culture system of human early placental tissues. Explants of trophoblastic tissues obtained from 4-5 week and 6-12 week placentas were cultured with or without IGF-I (1 ng/ml, 100 ng/ml), in the presence or absence of 10(-8) M triiodo-L-thyronine (T3) respectively, in a serum-free condition. The possible effect IGF-I on the proliferative activity of the cells was examined by immunocytochemical techniques with a monoclonal antibody to proliferating cell nuclear antigen (PCNA), while the possible effect of IGF-I on the differentiated function was assessed by determining the ability to secrete hCG and hPL. In the 4-5 week placentas, IGF-I and IGF-I receptor were almost exclusively localized in cytotrophoblasts and IGF-I augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL. By contrast, in the 6-12 week placentas, IGF-I and IGF-I receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF-I stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of cytotrophoblasts. In column chromatography of the serum-free medium obtained following a 5-day culture of trophoblasts, an elution peak of immunoreactive IGF-I was found in the fractions similar to the elution of 125I-IGF-I. The eluted amount of immunoreactive IGF-I was increased by the addition of 10(-8) MT3 to the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗

Human T-lymphotropic virus type I uveitis.

In addition to adult T-cell leukemia (ATL) and chronic myelopathy (HAM/TSP), our current study indicates that human T lymphotropic virus type I (HTLV-I) is a causative agent for a specific type of uveitis with unknown etiology (idiopathic uveitis). The present paper describes the seroepidemiological, clinical, and molecular biological evidences that indicate uveitis seen in HTLV-I asymptomatic carriers (HTLV-I uveitis) is a distinct clinical entity. In an HTLV-I endemic area in Japan, the seroprevalence of HTLV-I in idiopathic uveitis was 38%, while those in uveitis with defined etiology and in non-uveitic ocular diseases were 10% and 19%, respectively. Strikingly, the HTLV-I seroprevalence in younger aged patients (20-49 years) with idiopathic uveitis was 49%, while only 8% in the control group (P < 0.001). A very similar observation was recorded even in HTLV-I less endemic area, suggesting that HTLV-I infection plays a role as a risk factor for idiopathic uveitis. Clinical analysis revealed that an intermediate uveitis characterized by moderate opacities in the vitreous body and retinal vasculitis was seen in the majority the patients. The proviral DNA of HTLV-I was detected from inflammatory cells in the eye of all tested patients using PCR technique. These data thus indicate that HTLV-I is closely related to a certain type of uveitis and the uveitis (HTLV-I uveitis) is a distinct clinical entity.

Adolescent↗

[Juvenile muscular atrophy of the bilateral upper limbs associated with peculiar transformation of the dural tube induced by neck flexion].

We described an 18-year-old man with slowly progressive muscular atrophy in upper limbs on both sides. Regarding muscular atrophy, sensory disturbances in both palms were disproportionally very mild. Electrophysiological study suggested involvement of anterior horn restricted to the cervical cord, which resembled juvenile muscular atrophy of unilateral upper limb (Hirayama's disease). This patient, however, was unique in that the atrophy was bilateral and wider distribution of a lesion from C5 to T1 segments unlike Hirayama's disease. Neuroradiological findings in neutral position of the neck showed no abnormalities, but in flexion there was a characteristic change of the cervical cord and the posterior wall of dural canal. On myelography in flexion, anterior-posterior diameter of the middle and lower cervical dural canal decreased presumably due to an anterior shift of the dorsal part of dura mater. CT-myelography in neck flexion showed characteristic folding of the dorsal part of dura mater whose median portion seemed to intrude anteriorly and consequently concave the spinal cord. Anterior shift of the dorsal part of dura mater is known to occur in Hirayama's disease, but the folding is a peculiar finding in this patient. After laminectomy and laminoplasty of vertebrae from C3 to C7, his symptoms improved a little. On palpating the dorsal surface of dural canal, its median portion was harder than the lateral portion. A small fraction of the dura mater which was removed from hard median portion was thick, but showed no histological abnormalities. In normal functioning anatomy the dural canal is lengthened more posteriorly than anteriorly with neck flexion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗