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Biomedical subjects

K Kawai

Publications and source records attributed to K Kawai.

At least 109 records · Page 6Linked to original sources

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer.

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.

Adult↗

Involvement of keratinocyte activation phase in cutaneous graft healing: comparison of full-thickness and split-thickness skin grafts.

BACKGROUND: Little is known about keratinocytic activation in the graft take and healing process. OBJECTIVE: To investigate the clinical and molecular differences between pure epidermal sheet graft (PESG), split-thickness skin graft (STSG), and full-thickness skin graft (FTSG). METHODS: Three different thickness skin grafts (PESG, STSG, and FTSG) were performed onto three kinds of porcine wounds: shallow, deep, and full. Graft take, contraction, and Ki-67 and beta1 integrin expression in epidermis were studied. RESULTS: All grafts took well. As expected, full wounds covered by PESG and STSG contracted more than those covered by FTSG, whereas shallow wounds covered by FTSG contracted more than those covered by STSG. No difference in contracture was observed among deep wounds covered by PESG, STSG, and FTSG. Up-regulation of Ki-67 and beta1 integrin expression was greater in PESG and STSG, compared with little expression in FTSG. CONCLUSION: The keratinocytic activation phase may occur both in the STSG and PESG healing process, as well as serum imbibition, inosculatory, and revascularization phases.

Animals↗

Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge.

In the oriental population including the Japanese, donor-site hypertrophy is more pronounced than in Caucasians. To solve the problem of donor-site morbidity and to ensure graft 'take', we started the second-stage procedure of a thin split thickness skin graft (STSG) onto acellular 'bilayer artificial skin', or 'artificial dermis'. Since reporting the original version of the material (OV), a revised version (RV) and the present version (PV, Pelnac) have been developed in stages to eliminate inconveniences associated with its use and to reduce the primary cost of manufacture. We have now used our materials, consisting of OV, RV and PV, on 52 skin defects in 41 patients. STSG took almost perfectly in all patients. The long-term results of these three materials were investigated in 20 patients who had been followed up for more than 2 years, excluding three patients whose donor sites had been directly closed. The longest and the mean follow-up periods of these patients were 12 years 5 months and 6 years 10 months, respectively. At the grafted sites, wrinkles caused by shrinkage, partial depigmentation and hypertrophy were observed in five (25%), one (5%) and one (5%) of the 20 patients, respectively. At the donor sites, slight unsightliness was observed in five (25%) of the 20 patients. Excellent or good results were obtained in 18 (90%) of the 20 patients in comprehensive evaluation. There were no significant differences in the long-term follow-up evaluations among these materials. In conclusion, the long-term postoperative appearance of the STSG site was good though a very thin (approximately 0.2mm) STSG is used; scarring of the donor site was minimal and it was possible to take repeated skin grafts from the same donor site.

Adolescent↗

Clinicopathological studies of esophageal carcinosarcoma: analyses of its morphological characteristics using endoscopic, histological, and immunohistochemical procedures.

BACKGROUND AND STUDY AIMS: Carcinosarcoma of the esophagus is a rare malignant neoplasm consisting of both carcinomatous and sarcomatous components, which characteristically forms polypoid tumors. PATIENTS AND METHODS: Seven carcinosarcomas were analyzed using endoscopic, histological, and immunohistochemical procedures. Endoscopically, six of the seven lesions were found to be of the protruding type, while the other one was an ulcerating tumor. RESULTS: In all seven cases, the carcinomatous component consisted of differentiated squamous cell carcinoma, and the sarcomatous component was spindle cell carcinoma. Histological analyses demonstrated that the majority of the protruding tumors consisted of the sarcomatous component, while the ulcerating tumor mainly consisted of squamous cell carcinoma. The Ki-67 (MIB-1) labeling index (LI) of the carcinomatous component (28.2%) did not differ significantly from that of the sarcomatous component (25.5%). The sarcomatous component showed abundant expression of type IV collagen and laminin. CONCLUSIONS: It is conceivable that the carcinomatous and sarcomatous components grow separately from the early stage of the tumors, and that the sarcomatous component forms a protruding tumor mass because it has abundant stroma positive for type IV collagen and laminin.

Aged↗

Intestinal absorption and excretion of troglitazone sulphate, a major biliary metabolite of troglitazone.

1. Deconjugation by sulphate transfer and intestinal absorption of troglitazone sulphate (M1), the major metabolite of a thiazolidinedione antidiabetic drug, troglitazone, were studied in the male F344 rat using 14C-troglitazone, 4C-M1 and 35S-M1. 2. Some part of M1, produced in the liver and excreted mostly in the bile, was deconjugated in the intestine to the parent compound, troglitazone, by arylsulphate sulphotransferase originated from intestinal flora. However, deconjugation of M1 was not catalyzed by arylsulphatases. Caecal injection of M1 led to the appearance of troglitazone and M1 in plasma. 3. Biliary excretion mostly as M1, and, following absorption, as M1 and troglitazone after deconjugation, were indicated as the basis for the enterohepatic circulation of troglitazone. 4. Enterohepatic circulation may prolong the pharmacological effects of troglitazone.

Animals↗

Ex vivo gene therapy using granulocyte-macrophage colony-stimulating factor-transduced tumor vaccines.

There is no standard effective therapy for metastatic renal-cell carcinoma (RCC) or prostate cancer. Both of these cancers may be immunogenic, so therapy targeted to a tumor-associated antigen may be effective. Transduction of the gene encoding granulocyte-macrophage colony-stimulating factor has shown promise in preclinical studies, and clinical trials are in their early stages. Both autologous cancer cells and partially HLA-matched allogenic cells are being studied. No dose-limiting side effects have been observed, and a few patients have had transient objective tumor regressions. Further trials with more frequent and, probably, longer immunization schedules are needed to define efficacy.

Animals↗

A new radiopharmaceutical for the cerebral dopaminergic presynaptic function: 6-radioiodinated L-meta-tyrosine.

Geometric isomers of radioiodinated L-meta-tyrosine, 6-[I-125]iodo-and 4-[1-125]iodo-L-meta-tyrosine (6-I-L-mTyr, 4-I-L-mTyr) were separated by high-performance liquid chromatography . Both 6-I- and 4-I-L-mTyr had high energy-dependent brain accumulation. 6-I- and 4-I-L-mTyr were also metabolically stable and were rapidly excreted through the urine. 6-I-L-mTyr had a predilection for the cerebral aromatic L-amino acid decarboxylase (DOPA decarboxylase), the final enzyme of dopamine biosynthesis. 6-Radioiodinated L-mTyr is a new radiopharmaceutical that can be both useful in assessing cerebral amino acid transport mechanism and quantifying metabolically active DOPA decarboxylase.

Animals↗

A new approach to three-dimensional reconstructed imaging of hormone-secreting cells and their microvessel environments in rat pituitary glands by confocal laser scanning microscopy.

There has been considerable interest in the relationship between hormone- secreting endocrine cells and their microvessels in human pituitary gland. However, microcirculatory networks have rarely been studied in three dimensions (3D). This study was designed to visualize and to reveal the relationship between hormone-secreting endocrine cells and their microvessel environment in 3D, using rat pituitary glands under various (hyper/hypo) experimental conditions by confocal laser scanning microscopy (CLSM). Female adult Wistar rats were used after bilateral adrenalectomy or ACTH administration for 2 weeks. Clear 3D reconstructed images of ACTH cells, the microvessel network and counterstained nuclei were obtained at a maximal focus depth of 1 mm by CLSM without any background noise. In the hyperfunctional state, slender cytoplasmic processes of hypertrophic stellate ACTH cells frequently extended to the microvessels. In the hypofunctional state, ACTH cells appeared atrophic and round with scanty cytoplasm, and cytoplasmic adhesions to microvessel network patterns were inconspicuous. Therefore, 3D reconstructed imaging by CLSM is a useful technique with which to investigate the microvessel environment of hormone-secreting cells and has the potential to reveal dynamic hormone-secreting pathways.

Adrenalectomy↗

Antioxidant properties of a new type of polyene, falconensone A and its derivatives.

Falconensones A and B are new type of yellow compound extracted from ascomycetous fungi, Emericella falconensis. Falconensone A p-bromophenylhydrazone and falconensone A dioxime are derivatives of falconensone A which have also been synthesized recently. The structural similarity of the falconensones to alpha-tocopherol (vitamin E) led us to investigate whether falconensones exhibit antioxidant activity. These studies found that falconensone A p-bromophenylhydrazone and falconensone A dioxime scavenge alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical in a 1 : 1 ratio in contrast to vitamin E, where a 1 : 2 ratio relative to DPPH radicals was observed. In addition, linoleic acid peroxidation initiated by hydroxyl radicals was diminished by falconensone A p-bromophenylhydrazone to a greater extent than by vitamin E, and lipid peroxidation in rat liver microsome was reduced by falconensone A dioxime and falconensone A p-bromophenylhydrazone. In contrast, falconensone A and falconensone B, the 4'-nor-methyl derivative of falconensone A, showed much lower activity or were inactive in scavenging radicals. These results suggest that falconensone A p-bromophenylhydrazone and falconensone A dioxime, may be useful new antioxidant agents, wherein the bromophenyl and hydroxy residues of falconensone A may be important for antioxidant activity. Based on these results, derivatives of falconensone A appear to be effective antioxidants that may have clinical utility for diseases treated with vitamin E.

Animals↗

A new pentanorlanostane derivative, cladosporide A, as a characteristic antifungal agent against Aspergillus fumigatus, isolated from Cladosporium sp.

In the course of searching for new antifungal agents, a new pentanorlanostane derivative, cladosporide A (1), was isolated along with ergosterol, ergosterol peroxide and 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) from Cladosporium sp. as a characteristic antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established as 3beta,22-dihydroxy-23,24,25,26,27-pentanorlanostane-29-al by spectroscopic and chemical investigation and X-ray crystallographic analysis. Inhibitory activity against A. fumigatus (IC80 0.5-4.0 microg/ml) was observed for cladosporide A (1), but no activity was observed against pathogenic yeasts, Candida albicans and Cryptococcus neoformans, and other pathogenic filamentous fungi, Aspergillus niger and A. flavus. The 4beta-aldehyde residue in 1 might be essential for the antifungal activity, since 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) showed no inhibition against the above four fungi.

Antifungal Agents↗

Characterization of protease-activated receptors in rat peritoneal mast cells.

Activation of protease-activated receptor (PAR)-1 or PAR-2 elicits inflammation most probably via mast cell degranulation in vivo. The present study aimed at characterizing PARs in rat peritoneal mast cells (PMC). Messenger RNA for PAR-1, but not for PAR-2, was detected in PMC. Thrombin, the PAR-1 agonist SFLLR-NH2 or the PAR-2 agonist SLIGRL-NH2 failed to induce histamine release from PMC. Surprisingly, the PAR-2-inactive control peptide LSIGRL-NH2 triggered histamine release from PMC. Thus, PAR-1, but not PAR-2, are expressed in PMC, whereas neither PAR-1 nor PAR-2 are considered to be involved in degranulation of PMC. LSIGRL-NH2 does not appear to be appropriate as a control peptide for PAR-2 in inflammation studies.

Animals↗

An anatomical study of the retroaortic left renal vein.

Retroaortic left renal vein was found in a 55-year-old male cadaver during a student course anatomical dissection. This anomaly coursed dorsal to the abdominal aorta and opened into the inferior vena cava at the upper level of the 3rd lumbar vertebra. This retroaortic left renal vein connected directly to the azygos vein system and the 3rd lumbar vein. It also received the posterior suprarenal and posterior inferior phrenic veins.

Aorta, Abdominal↗

Use of a Technovit 7200 VLC to facilitate integrated determination of aluminum by light and electron microscopy.

Technovit 7200 VLC is an excellent embedding medium for both inorganic histochemistry by light microscopy and X-ray microanalysis by scanning and transmission electron microscopy. Liver samples from rats after intraperitoneal treatment with aluminum chloride were fixed in glutaraldehyde and embedded in the resin. Thick sections were easily cut on an ultramicrotome and stained with aluminon for aluminum (Al). An intense positive reaction with aluminon was observed in the Kupffer cells by light microscopy. The surface structures of the same resin block cut for light microscopy were observed under a scanning electron microscope fitted with an energy dispersive X-ray spectrometer. The Kupffer cells appeared white in the backscattered mode. Localization of Al in the Kupffer cells was confirmed by an X-ray distribution map in the scanning electron microscope. Subcellular localization of Al in the Kupffer cells was performed on the same semithin sections using a transmission electron microscope equipped with an energy dispersive X-ray spectrometer. Most Al was found in lysosomes of the Kupffer cells. The resin was stable in the electron beam and chlorine-free.

Acrylic Resins↗

[Early management of acute myocardial infarction in the elderly].

UNLABELLED: The efficacy of reperfusion treatment has been established in patients with acute myocardial infarction (AMI), however, its role is still controversial in the elderly patients. Data from Kochi Acute Myocardial Infarction Registry, consisting of 1,248 cases, showed that, compared to younger patients, elderly patients had greater ratio of women, painless infarction, delayed presentation, worse Killip classes, lower reperfusion procedure and higher mortality. To clarify the early management of AMI in the elderly, we analyzed the clinical data of 1,160 cases, according to age subgroup (317 advanced elderly, aged 75-84; 438 elderly, aged 65-74; 405 middle-aged, aged 45-64) and according to the period (term I, 1990-92; term II, 1993-95; term III, 1996-98). RESULTS: 1) The advanced elderly received less reperfusion treatment (37% vs. 65%) and showed higher mortality (21% vs. 8%), compared to middle-aged patients. 2) In advanced elderly patients, mortality was reduced (term I, 27%; term II, 20%; term III, 19%), according to increasing application of reperfusion treatment (term I, 22%; term II, 45%; term III, 40%). 3) Inoadvanced elderly patients with reperfusion treatment, thrombolysis resulted in a higher mortality (17% vs. 7%) compared to direct angioplasty, probably due to increased incidence of cardiac rupture and pump failure in this age group. CONCLUSIONS: Reperfusion treatment improves mortality of AMI even in elderly patients. To minimize complications, direct angioplasty may be better for elderly patients.

Age Factors↗

[Usefulness of nitrendipine and its effects on quality of life and brain blood flow in elderly hypertensive patients].

There are many reports on the efficacy of Ca-antagonists for treatment of elderly essential hypertension. In particular, many studies have noted the beneficial effects of antihypertensive therapy on the quality of life (QOL). Nevertheless, there are no reports on antihypertensive therapy regarding the relationship between brain blood flow (BBF) and QOL. Therefore, we examined the efficacy of nitrendipine, a Ca-antagonist, on the brain blood flow and QOL, and its side effects in elderly essential hypertensive patients. The subjects were 17 (males: 4, females: 13) patients with untreated hypertension of WHO stage I or II, aged 70 years or older. The mean dose of nitrendipine was 9.4 +/- 0.4 mg daily. Before and 6 months after treatment, we examined blood pressure (BP), heart rate (HR), echocardiography (left ventricular mass index [LVMI], % fractional shortening [% FS]), plasma noradrenaline (Nad), plasma renin activity (PRA), BBF using the IMP-ARG method with BBF scintigraphy, and QOL was examined with a questionnaire. Two patients were excluded from this study because 1 had no decrease in BP, and another was moved to a different hospital. BP significantly decreased from 178/93 to 137/77 mmHg, but HR was not changed after treatment. BBF significantly increased from 37.0 +/- 4.9 to 41.0 +/- 4.9 ml/dl/min, but % FS, Nad, and PRA did not significantly change. The degree of QOL was improved by 4.2 +/- 1.2 points and there was a significant positive correlation between the changes of BBF and of QOL (r = 0.66, p = 0.04). However, moderate pharmacotherapy for BP seems to be necessary because there were 2 patients whose BBF decreased accompanied by excessive drop in BP after treatment. In conclusion, it is possible to safely use nitrendipine for elderly essential hypertensive patients. Nitrendipine has beneficial effects on BBF, and it was suggested that the increase of BBF is one of the most important factors in improvement of QOL.

Aged↗

[Intrascrotal tumors: a clinicopathologic study of 15 cases].

PURPOSE: We reviewed cases of intrascrotal tumors treated at our institution except for germ cell testicular tumors. PATIENTS AND METHODS: From 1977 to 1998 (22 years), 120 cases of intrascrotal tumors treated at the University of Tsukuba. Of these, 15 cases (12.5%) were not germ cell testicular tumors. The patients' ages varied between 2 and 77 years with a mean of 49.6. RESULTS: The most common complaint regarding symptoms was painless testicular enlargement. Tumor weight ranged from 2 to 200 g, with an average of 104.6 g. The histological diagnoses of 15 patients were 8 malignant lymphomas, 2 paratesticular rhabdomyosarcomas, 2 metastatic tumors (origin; stomach and prostate), 1 epidermoid cyst, 1 cyst of tunica testis, and 1 adenomatoid tumor. As for the cases with malignant lymphoma, all of them were non-Hodgkin's lymphoma whose clinical stages were stage I in 2 cases and stage IV in 6 cases. Five 8 patients died in spite of systemic chemotherapy after an orchiectomy, whereas 2 cases with metastatic tumors died of primary cancer, and two cases with paratesticular rhabdomyosarcoma are still alive and have had no evidence of disease. CONCLUSIONS: Intrascrotal tumors except for germ cell testicular tumors are not common, and consist of various diseases. In particular, some kinds of malignant lymphoma mimic anaplastic seminoma histopathologically. Therefore, accurate diagnosis and precise treatment is important in the patient with intrascrotal tumors.

Adolescent↗

Three-dimensional imaging of tumor angiogenesis.

OBJECTIVE: To three-dimensionally visualize the microvessel environment of tumor angiogenesis by confocal laser scanning microscopy (CLSM). STUDY DESIGN: To reveal underlying mechanisms of tumor angiogenesis, a 7, 12-dimethylbenz(a) anthracene-induced rat cancer model was used. For demonstrating tumor vasculature, fluorescence injection method (FITC-conjugated gelatin solution) was employed. FITC gelatin was injected into the left ventricle of the rat heart. After complete perfusion, the mammary glands were resected, fixed under ice cold conditions and subjected to immunohistochemistry (IHC) for tumor cells. The LSM-410 (Carl Zeiss, Jena, Germany) was employed on thick sections (300-2,000 microns) to elucidate detailed microvessel networks (MVN) and tumor cells. RESULTS: Tumor vasculature on thick sections was clearly detected by CLSM at the maximum focus depth of 2,000 microns. Three-dimensional (3-D), reconstructed images of normal mammary glands showed regular and linear MVN. In DMBA-induced mammary cancer, vascular density of MVN was markedly increased and showed an anastomosing, irregular MVN pattern. Furthermore, focal segmentation and tortuous, branching patterns of microvessels were also seen. CONCLUSION: Application of the fluorescence injection method and IHC using CLSM was very useful for studying the 3-D relationship between tumor angiogenesis and neoplastic epithelial changes. These results suggest that application of this technique is ideal for studying 3-D imaging of tumor angiogenesis.

9,10-Dimethyl-1,2-benzanthracene↗