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Biomedical subjects

Y Nishiyama

Publications and source records attributed to Y Nishiyama.

At least 19 recordsLinked to original sources

[A case with delayed-onset radiation pneumonitis suspected to be induced by oral etoposide].

Radiation pneumonitis usually occurs within 1-3 months after the completion of radiation therapy. A 63-year-old male with primary lung cancer treated by radiation therapy developed radiation pneumonitis 5 months after the completion of radiation therapy. He received 60 Gy to the lung tumor in a conventional fractionation schedule, and then two courses of intravenous chemotherapy using cis-diamine-dichloroplatinum (II) (110-140 mg) and etoposide (140-175 mg). Oral etoposide was initiated for bone metastases on the 104th day after the completion of radiation therapy at a daily dose of 20 mg, to a total dose of 1075 mg. He complained of fever and exertional dyspnea 5 months after the completion of radiation therapy. Chest radiography showed homogeneous infiltrates in the irradiated lung. These clinical signs and symptoms were refractory to antibiotic therapy, but steroid therapy resulted in marked improvement. The development of radiation pneumonitis was suspected to be induced by oral etoposide, which was given before the onset of radiation pneumonitis. These data suggest that etoposide induces a recall phenomenon, as has been demonstrated with such drugs as adriamycin and actinomycin-D.

Administration, Oral

[Temperature distribution and geometry of the electrodes in RF interstitial hyperthermia using circular and interstitial electrodes].

To evaluate the feasibility of clinical application of a newly developed interstitial hyperthermia system, which consists of an 8 MHz radiofrequency generator, interstitial needle electrodes, and a superficial circular electrode, we conducted preclinical experiments using an agar phantom and VX-2 carcinoma in the rabbit. In the experiment with an agar phantom, four 4 cm needle electrodes were placed in a square array at intervals of 1.0, 1.5, and 2.0 cm. Thermography demonstrated homogeneous temperature distribution at electrode intervals of 1.0 and 1.5 cm, but hot spots around the electrodes at an interval of 2.0 cm. When electrode deviation was less than 8 degrees from the parallel plane, no temperature deviation was observed. Using two 2 cm electrodes and two 4 cm electrodes in square array, thermography demonstrated a homogeneous temperature distribution in the area surrounded by the electrodes. Even if the electrodes were located at the periphery of the agar phantom, a homogeneous temperature distribution was obtained in the area surrounded by the electrodes. Using four 4 cm electrodes at intervals of 1.5 cm in VX-2 carcinoma in the rabbit, ideal heating was obtained: 42 degrees C at the periphery of the tumor and 43 degrees C at the center. These data suggest that the newly developed interstitial hyperthermia apparatus provides homogeneous heat distribution at electrode intervals of 1.5 cm or less and can be used in a Phase I study for deep-seated or superficial tumors.

Animals

[Results of radiation therapy for squamous cell carcinoma of the uterine cervix using high dose-rate intracavitary irradiation].

We retrospectively analyzed 216 previously untreated patients with cervical cancer treated by high dose-rate intracavitary irradiation between 1978 and 1986. Cumulative 5-year survivals in stage Ib, IIa, IIb, IIIa, IIIb and IVa were 72.3%, 88.9%, 68.9%, 75.0%, 64.0% and 16.7%, respectively. Cause-specific 5-year survivals in stage Ib, IIa, IIb, IIIa, IIIb and IVa were 93.3%, 88.9%, 74.7%, 75.0%, 68.9%, and 18.8%, respectively. Recurrences outside the pelvis in stage IIb and IIIb (14.9% and 24.0%) were more common than loco-regional recurrences (10.3% and 12.0%). However, loco-regional recurrences (50%) were most frequent in stage IVa. Thirteen patients (6.0%) required surgical management for intestinal complications (severe). Six patients (2.7%) died due to intestinal complications (fatal). These fatal and severe complications were closely correlated with the dose of external radiation. These data suggest that intracavitary irradiation using a high dose-rate system is useful for the treatment of uterine cancer; however, further efforts to reduce intestinal complications by lowering the dose of external radiation will be necessary. It is also suggested that a combined modality, such as chemotherapy, is necessary for controlling metastases outside the pelvis in stage IIb and IIIb, and for local control in stage IVa.

Adult

Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals.

We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.

Allopurinol

Construction of a US3 lacZ insertion mutant of herpes simplex virus type 2 and characterization of its phenotype in vitro and in vivo.

We have constructed and characterized a mutant of herpes simplex virus type 2 (HSV-2) which was inserted a modified lacZ gene, placed under the control of HSV-1 beta 8 promotor, into the US3 protein kinase gene. The mutant, L1BR1, could not induce the virus-encoded protein kinase activity, but could replicate in Vero cells as efficiently as the parental virus. When the biological properties of L1BR1 were examined in mice by using four routes (footpad, intraperitoneal, corneal, and intracerebral) of infection, the mutant displayed the route-dependent reduction of virulence; after inoculation by footpad and intraperitoneal routes, the mutant was more than 10,000-fold less virulent than the parental virus, but it exhibited only about a 10-fold decrease in virulence following the corneal and intracerebral infection. In the intraperitoneal inoculation into adult mice, the replication of L1BR1 in the liver and spleen was severely restricted, but in newborn mice the mutant could grow as well as the parental virus in these organs. The adoptive transfer of peritoneal macrophages from adult mice resulted in a marked inhibition in the replication of L1BR1 in the liver and spleen of newborn mice, while the transfer exhibited little or no effect on the production of the wild-type virus in these organs. We also found that the mutant, unlike the parental virus, could not replicate in precultured peritoneal macrophages from adult mice. Taking these observations together, it seems likely that L1BR1 lost the ability to overcome the mononuclear-phagocytic defense system and thereby lost its pathogenicity by intraperitoneal and footpad routes. Furthermore, the mutant was shown to be rescued by a 4.8-kb HindIII/Xbal fragment containing the entire US3 open reading frame. However, we could not rule out the possibility that some of the phenotypes of L1BR1 are due to mutations in the US3-neighboring genes, US2 and US4.

Aging

On the association of human beta 2 microglobulin with cell culture-grown human cytomegalovirus (HCMV).

We studied the production of human beta 2 microglobulin (beta 2m) in mock-infected or human cytomegalovirus (HCMV) infected human embryonic lung fibroblasts (HEL) and the association of human beta 2m with HCMV virions. Titration of beta 2m by two-step sandwich enzyme immunoassay revealed that HEL released considerable amounts of human beta 2m into the culture medium and that the production of beta 2m was significantly enhanced by HCMV infection. The concentration of human beta 2m in the culture medium of HCMV-infected HEL reached 500 to 600 ng/ml, which corresponded to 7- to 12-fold of levels found in healthy adult urine. Immunoprecipitation assays showed that HEL-grown HCMV bound a significant amount of endogenous beta 2m, but the viruses were efficiently neutralized by either human hyperimmune anti-HCMV globulin or anti-HCMV monoclonal antibody even when treated with a large amount of human beta 2m or with dialysed urine. Thus it seems unlikely that the binding of beta 2m by HCMV is involved in masking the viral antigenic site necessary for neutralization.

Cells, Cultured

Results of the combination of external-beam and high-dose-rate intracavitary irradiation for patients with cervical carcinoma.

We retrospectively analyzed 220 patients with squamous cell carcinoma of the uterine cervix treated by the combination of external-beam and high-dose-rate intracavitary brachytherapy between 1978 and 1986. Five-year survivals for Stage Ib (n = 15), IIa (n = 18), IIb (n = 107), IIIb (n = 50), and IVa (n = 18) were 72.3, 88.9, 68.9, 64.0, and 16.7%, respectively. The incidences of recurrence outside the pelvis in Stage IIb and IIIb patients (15.0 and 24.0%) were higher than those of local recurrences (10.3 and 12.0%). Eighteen patients (8.2% of the total) had serious intestinal complications. These serious complications were closely correlated with the external-beam dosages. External-beam therapy was performed at 1.8-2.0 Gy/day, and high-dose-rate brachytherapy using a remotely controlled afterloading system (RALS) was performed once a week with 6.0-7.5 Gy at points A/fraction. Treatment dosages to the whole pelvis (WP), with central shieldings (CS), and with RALS according to FIGO stage were as follows: Stages Ib, IIa, 30-40 Gy (WP) plus 24-30 Gy (RALS); Stages IIb, IIIb, 40 Gy (WP) plus 10-20 Gy (CS) plus 24-30 Gy (RALS); Stage IVa, 40-50 Gy (WP) plus 10-20 Gy (CS) plus 20-30 Gy (RALS). From these data, the combination of external-beam and high-dose-rate intracavitary irradiation is an effective therapy for cervical cancer. It is also suggested that an additional combined chemotherapy is necessary to control metastic lesions outside the pelvis for Stages IIb and IIIb.

Adult

Patterns of failure and survival in locally advanced carcinoma of the uterine cervix treated with high dose-rate intracavitary irradiation system.

We retrospectively analyzed 71 patients with locally advanced carcinoma of the uterine cervix treated by irradiation using high dose-rate intracavitary brachytherapy between 1978 and 1985. Seven patients were Stage IIIa, 46 Stage IIIb, and 18 Stage IVa. Five-year survivals for Stage IIIa, IIIb, and IVa were 71.4, 60.9, and 16.7%, respectively. An analysis of patterns of failure demonstrated that loco-regional recurrences were observed in 1 (14.3%) for Stage IIIa, 6 (13.0%) for Stage IIIb, and 9 (50.0%) for Stage IVa. The incidence of recurrence outside the pelvis observed in Stage IIIb patients (7 para-aortic nodes, 5 distant metastases) was much higher than that of local recurrence. Five patients (7.0% of the total: 1 with Stage IIIa, 3 with Stage IIIb, 1 with Stage IVa) required surgery to manage the complications. These data suggest that a high dose-rate intracavitary irradiation system is an effective tool for the treatment of cervical cancer. Further efforts to control metastatic lesions outside the pelvis are required for patients with Stage IIIb. To increase a loco-regional control rate for patients with Stage IVa disease, it is important to give additional treatment such as chemotherapy in conjunction with radiation therapy.

Adult

Morphological changes associated with growth inhibition of Trichophyton mentagrophytes by amorolfine.

Amorolfine inhibited the in-vitro growth of Trichophyton mentagrophytes to some extent at a low drug concentration of 0.8 ng/ml. Corresponding to the growth inhibition, SEM studies revealed a slight modification of hyphal morphology, i.e. a waving of the hyphal surface. These morphological alterations were more extensive with increases in drug concentration and treatment period: collapsed and distorted hyphae and exfoliation of the surface of T. mentagrophytes occurred at 8 ng/ml and marked deformation and disruption of the hyphal structure at 80 ng/ml of amorolfine. TEM revealed thickening of the cell walls and the accumulation of electron-dense granular structures in both the wall and cytoplasm in thin-sectioned cells pretreated with 8 ng/ml or more of amorolfine, although the nuclear and mitochondrial architecture was not noticeably influenced. Cytoplasmic membranes and other membranous structures of organelles such as nuclei and mitochondria were disrupted or fused, thereby losing their essential physiological activity in hyphal cells pretreated with 80 ng/ml of amorolfine. The ultrastructural study thus supports the observation that morphological changes of T. mentagrophytes caused by amorolfine were associated with its growth-inhibitory and killing activity, which depended on the drug concentration and treatment time.

Antifungal Agents

Characterization of transmural and subendocardial infarction by typing and grading of ischemic lesions in autopsied human hearts.

Two types of myocardial infarction, transmural and subendocardial, were macroscopically examined, and the gross and microscopic findings were correlated. The transmural type usually consisted of yellowish-brown coagulation necrosis in the center of an infarcted focus and coagulative myocytolysis at the marginal zone. The subendocardial type was characterized by coagulative myocytolysis throughout the entire focus. Wavy fiber and colliquative myocytolysis of non-specific ischemic lesions were seen only microscopically in both peripheral and subendocardial areas of infarcted foci. Coagulation necrosis was associated with obstructive thrombus formation in 79% of cases as a result of absolute ischemia in the transmural type. Coagulative myocytolysis was associated with obstruction by plaque hemorrhage in 27% of cases, and multivessel disease was frequently encountered in the subendocardial type due to insufficient blood supply. Based on histochemical and immunohistochemical examinations, the ischemic lesions were graded in descending order of coagulation necrosis, coagulative myocytolysis, wavy fiber, and colliquative myocytolysis. The close relation between coagulation necrosis and the transmural type as well as that of coagulative myocytolysis with the subendocardial type suggests two different pathogenetic mechanisms of transmural and subendocardial infarction.

Adult

Preparation and antitumor activity of 2''-O-, 3''-O- and 2'',3''-di-O-substituted derivatives of etoposide.

The 2''-O-, 3''-O- and 2'',3''-di-O-substituted derivatives (4a--p) of etoposide were prepared by nucleophilic substitution of 4'-O-benzyloxycarbonyletoposide (2) followed by deprotection. Controlled reaction (a limited amount of reagents and low temperature) was required for preparing the mono-O-substituted derivatives. In terms of ED125 values, doses which show 125% of T/C against P388 leukemia in mice, both the 2''-O-acetate (4a, ED125 = 0.18 mg/kg) and 3''-O-acetate (4b, 0.23 mg/kg) were nearly as active as etoposide (1, 0.19 mg/kg), while the 2'',3''-di-O-acetate (4c, 1.9 mg/kg) was somewhat less potent. In the replacement with other substituents, antitumor activity of the 2''-O-substituted derivatives was affected much more by the difference of the substituents as compared with that of the corresponding 3''-O-substituted derivatives. In the 2'',3''-di-O-substituted derivatives, the activity was decreased additively on the substituents.

Animals

Amino acids and peptides. XXXV. Synthesis of mouse metallothionein I. (2). Synthesis of a nonacosapeptide corresponding to N-terminal sequence 1-29 (beta-fragment) of mouse metallothionein I and related peptides and examination of their heavy metal-binding properties.

A nonacosapeptide corresponding to the N-terminal sequence 1-29 (beta-fragment) of mouse metallothionein I and related peptides were synthesized by the conventional solution method and their heavy metals (Cu2+, Cu+ and Cd2+)-binding properties were examined. The Cu(2+)- or Cu(+)-binding activities of various peptides were not greatly dependent on the peptide structure, so far as examined, as in the cases of N. crassa MT and A. bisporus MTs. On the contrary, the Cd(2+)-binding activities of these peptides were fairly structure-dependent.

Amino Acid Sequence

[Immunohistological investigation of type IV collagen in the basement membrane surrounding the cancer nest (cancer nest membrane) of head and neck squamous cell carcinoma--its relation to frequency of cervical lymph node metastasis].

Lymphoducts and blood vessels exist in the stroma, while none can be detected in the cancer nest itself within cancerous tissue. This explains why metastasis of carcinoma cannot occur without the escape of tumor cells through the basement membrane surrounding the cancer nest into the stroma. Accordingly, observation of the continuity of the basement membrane, what we call the cancer nest membrane, is essential for elucidating the first step of metastasis. Since type IV collagen is the most important structure composing the basement membrane, investigation of the immunohistological localization and continuity of type IV collagen is of value in predicting the metastatic aggressiveness of squamous cell carcinoma. We therefore studied biopsy tissues from the advancing lesion of head and neck squamous cell carcinoma in 95 untreated patients. The tissues were fixed in 85% ethanol and embedded in paraffin, and 5-um thin sections prepared were then immunohistochemically stained for type IV collagen by the ABC method for observation of the continuity status of the cancer nest membrane in relation to metastasis. The basement membranes of normal mucosal epithelium and normal interstitial capillaries were utilized as positive controls, and negative controls were obtained by using PBS in place of the primary antibodies for the immunohistochemical reaction. Membrane discontinuity (breaks or absence) correlated significantly with cervical lymph node metastasis, while intact membrane was associated with a low frequency of cervical lymph node metastasis. There was no obvious relation between the clinical T category and the continuity of the membrane; pN (+) carcinomas with membrane discontinuity included even T1 supraglottic and hypopharyngeal carcinomas, as well as T2 or higher oral mucosal carcinomas and T3 or higher glottic carcinomas, suggesting variation with tumor site. Hypopharyngeal and supraglottic carcinoma was associated with membrane discontinuity and a high incidence of cervical lymph node metastasis. On the other hand, glottic and oral carcinoma more often presented with intact membranes and had a lower incidence of metastasis, although carcinomas in these sites that did present with discontinuity of the membrane were associated with a high incidence of cervical metastasis. Therefore, observation of the continuity of the cancer nest membrane by the expression of type IV collagen may be useful in selecting better specific therapies and determining the necessity of prophylactic neck dissection. A correlation between the degree of tumor differentiation and the continuity of the membrane was also found; well-differentiated tumors with discontinuity of the membrane were frequently associated with cervical lymph node metastasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

[Adenoid cystic carcinoma of the head and neck: a clinical review of 29 cases].

Pathological data and the outcomes of 29 patients with adenoid cystic carcinoma of the head and neck treated between 1975 and 1990 were reviewed. Patients consisted of 21 females and 8 males, with a median age of 59 years. The overall 5-year and 10-year survival rates determined by Kaplan-Meier analysis were 84.2% and 52.9%, respectively. Patients in whom pathological data indicated a frequent solid pattern of carcinoma had high incidences of metastasis and poor prognoses. The effectiveness of local control was found to have no relation to the pathological data of the tumor, but rather depended upon whether anatomical limitations restricted complete resection of the tumor. All 7 patients who had cervical lymph node metastasis underwent neck dissection, which was useful in controlling metastatic spread. Distant metastases were present in 6 patients, and the lung was the most frequent site of metastasis.

Adult

[Immunohistological investigation of epithelial components of adenolymphoma of the parotid gland].

In order to develop a more objective method of evaluating the origin of adenolymphoma, we immunohistochemically investigated the expression of cytokeratins, vimentin, S-100 protein, and alpha-smooth-muscle actin using the avidin-biotin-peroxidase (ABC) method in ethanol-fixed paraffin-embedded specimens from 8 adenolymphomas. Several kinds of monoclonal antibodies which react monospecifically with each subclass of cytokeratins were used. Results were compared with specimens of 8 normal parotid glands by radical neck dissection in patients with other diseases who had not undergone radiotherapy. In the adenolymphoma specimens, basal cells were strongly positive for CK-6, but reactivity of columnar cells was apparently reduced. In contrast, columnar cells were strongly positive for CK-7, but reactivity of basal cells was reduced. In normal parotid gland specimens, CK-7 was also detected in all columnar cells in the ductal system, although some duct cells around the columnar cells, which showed strong CK-6 expression, showed poor CK-7 expression. alpha-smooth-muscle actin was present in myoepithelial cells in normal parotid gland specimens, but not in basal cells of adenolymphoma or of the normal ductal system, which were CK-6-positive. As these characteristic findings were consistently observed in all specimens, the demonstration of CK-6, CK-7, and alpha-smooth-muscle actin may be useful in the recognition and classification of columnar and basal cells. CK-8 was present in both columnar and basal cells of adenolymphoma and of the normal duct, but in the normal parotid gland, acinus cells were also strongly positive for CK-8.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins

Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus. Production, isolation, structure and biological activity.

Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and potent in vivo antitumor activity against P388 and L1210 leukemias, and B16 melanoma. Sultriecin is composed of several unique structural units; a conjugated triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality.

Animals