Biomedical subjects

R Imai

Publications and source records attributed to R Imai.

At least 37 records · Page 2Linked to original sources

PubMed1996

Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older.

Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N1 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates wer 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36% respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expect a realistic probability of long-term survival with definitive radiation therapy.

Actuarial Analysis↗

PubMed1996

[Determination of 5-FU tissue concentrations after oral UFT administration in tumors of the head and neck].

We determined the 5-FU concentrations in the tumor tissue, normal tissue surrounding the tumor, metastatic lymph nodes, normal lymph nodes, and serum after oral UFT administration to 26 patients with primary squamous cell carcinoma in the head and neck. The 5-FU concentration was mean 0.20 +/- 0.13 micrograms/g in the tumor tissue and mean 0.14 +/- 0.08 micrograms/g in the metastatic lymph nodes. The 5-FU concentrations in the tumor tissue and metastatic lymph nodes were significantly higher than in the corresponding normal tissue surrounding the tumor and normal lymph nodes. In addition, the 5-FU concentration was significantly higher in the tumor tissue than in the metastatic lymph nodes. No significant differences were observed in the 5-FU concentration according to the sites of the primary tumor. However, the difference in the 5-FU concentration between the tumor and normal tissues was smaller in tongue cancer than in pharyngeal cancer.

Administration, Oral↗

PubMed1995

Hepatocyte growth factor/scatter factor expressed in follicular papilla cells stimulates human hair growth in vitro.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide which acts as mitogen, motogen, or morphogen. In this study, we examined the effect of HGF/SF on human hair growth using organ and cell culture systems. HGF/SF was found to stimulate hair length and DNA synthesis in hair follicles at increasing concentrations up to 10 ng/ml (P < 0.05 and P < 0.01, respectively). HGF/SF stimulated [3H]thymidine incorporation by hair bulb-derived keratinocytes with the strongest response at 30 ng/ml of HGF/SF (P < 0.05). Cultured follicular papilla cells secreted HGF/SF, measured by an enzyme-linked immunoassay, in response to interleukin 1-alpha (IL1-alpha, 10 ng/ml), tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml), or tetradecanoylphorbolacetate (100 nM) at levels ranging from 0.2 to 0.3 ng/mg protein/48 h. HGF/SF mRNA expressions, measured by the reverse transcription-polymerase chain reaction, were detected in follicular papilla cells, and were also stimulated by the three reagents. Transforming growth factor-beta (10 ng/ml) suppressed both protein and mRNA levels. These results suggest that hair follicle elongation induced by HGF/SF in organ culture occurs partly due to the mitogenic activity of HGF/SF expressed in follicular papilla cells on hair bulb-derived keratinocytes.

Base Sequence↗

PubMed1995

The effect of hepatocyte growth factor/scatter factor on human hair follicle growth.

The effect of hepatocyte growth factor/scatter factor (HGF/SF) on human hair follicle growth was examined using a serum-free organ culture system. The DNA synthesis in human hair follicles and elongation of the hair shaft were measured subsequent to the follicle isolation and culture at 31 degrees C in 95% O2-5% CO2 for 72 h. Results showed that HGF/SF significantly increased 3H-thymidine (P < 0.001) incorporation and hair follicle length (P < 0.05). The effect of HGF/SF was dose-dependent with a maximal stimulation at 10 ng/ml.

Adolescent↗

PubMed1994

The effect of various cytokines on hair growth of mouse vibrissae in organ culture.

Hepatocyte growth factor/scatter factor (HGF) is a multifunctional polypeptide which acts as a mitogen, motogen or morphogen depending on the biological context. In this study, we examined the effect of HGF on hair growth using a serum-free organ culture system. Vibrissal hair follicles isolated from newborn mice were cultured at 31 degrees C in 95% O2-5%CO2 for 72 h in the presence of various cytokines or growth factors. DNA, protein synthesis and elongation of the hair shaft in the hair follicles were measured. Among the agents tested, only HGF significantly increased hair follicle length (P < 0.001) and 3H-thymidine (P < 0.001) incorporation. The effect of HGF was dose-dependent, with maximal stimulation obtained at 10 ng/ml. The increase in hair follicle length and thymidine incorporation were specifically inhibited by a neutralizing antibody against HGF. These results indicate that HGF is able to promote hair growth and may have clinical utility in this regard.

Animals↗

PubMed1994

Dermal papilla cells express hepatocyte growth factor.

In the induction, development and maintenance of hair follicles, it is thought that an epithelial-mesenchymal interaction is important and that the dermal papilla plays some important roles. Hepatocyte growth factor is a multifunctional polypeptide which acts as mitogen, motogen or morphogen depending on the biological context. Recently, we found that HGF stimulates hair follicle growth in a mouse organ culture system, and therefore proceeded to investigate the expression of HGF on cultured human dermal papilla cells (DPC) and the effect of HGF on cultured human keratinocytes derived from hair bulb. Using an enzyme immuno assay, HGF immunoreactivities were not detected in conditioned media of DPC that were either non-treated or treated with TGF-beta, but were detected in conditioned media of DPC treated with IL1-alpha, TNF-alpha and TPA. Using the reverse transcription-polymerase chain reaction (RT-PCR) method, HGF mRNA was also detected in DPC. This expression was enhanced by IL1-alpha, TNF-alpha and TPA, but suppressed by TGF-beta. Furthermore, HGF stimulated the DNA synthesis in keratinocytes derived from human hair bulb in a dose-dependent manner. These results indicate that DPC express HGF in vitro and that HGF stimulates the growth of human keratinocytes derived from hair bulb in vitro.

Animals↗

PubMed1994

Early effects of beta,beta'-iminodipropionitrile on tubulin solubility and neurofilament phosphorylation in the axon.

To elucidate the role of neurofilaments in microtubule stabilization in the axon, we studied the effects of beta,beta'-iminodipropionitrile (IDPN) on the solubility and transport of tubulin as well as neurofilament phosphorylation in the motor fibers of the rat sciatic nerve. IDPN is known to impair the axonal transport of neurofilaments, causing accumulation of neurofilaments in the proximal axon and segregation of neurofilaments to the peripheral axoplasm throughout the nerve. Administration of IDPN at various intervals after radioactive labeling of the spinal cord with L-[35S]methionine revealed that transport inhibition occurred all along the nerve within 1-2 days. Transport of cold-insoluble tubulin, which accounts for 50% of axonal tubulin, was also affected. A significant increase in the proportion of cold-soluble tubulin was observed, reaching a maximum at 3 days after IDPN treatment and returning to the control level in the following weeks. Preceding this change in tubulin solubility, a transient decrease in the phosphorylation level of the 200-kDa neurofilament protein was detected in the ventral root using phosphorylation-dependent antibodies. These early changes agreed in timing with the onset of segregation and transport inhibition, suggesting that interaction between neurofilaments and microtubules possibly regulated by phosphorylation plays a significant role in microtubule stabilization.

Actin Cytoskeleton↗

PubMed1994

Hepatocyte growth factor/scatter factor stimulates hair growth of mouse vibrissae in organ culture.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide that acts as a mitogen, motogen, or morphogen, depending on the biologic context. In this study, we examined the effect of HGF/SF on hair growth using a serum-free organ culture system. Vibrissal hair follicles isolated from newborn mice were cultured at 31 degrees C in 95% O2/5% CO2 for 72 h in the presence of various cytokines or growth factors, and elongation of hair shaft, DNA, and protein synthesis in hair follicles were measured. Among the agents tested, only HGF/SF significantly increased hair follicle length (p < 0.001), 3H-thymidine (p < 0.001), and 35S-cysteine (p < 0.05) incorporation. The effect of HGF/SF was dose dependent, with maximal stimulation obtained at 10 ng/ml. The increase in hair follicle length and thymidine incorporation were specifically inhibited by a neutralizing antibody against HGF/SF. These results indicate that HGF/SF can promote hair growth and may have clinical utility in this regard.

Animals↗

PubMed1994

Changes in populations of HLA-DR+CD3+ cells and CD57-CD16+ cells in alopecia areata after corticosteroid therapy.

We investigated the populations of activated T (HLA-DR+CD3+) cells and natural killer (CD57-CD16+) cells in the peripheral blood of patients with various types of alopecia areata (AA) and noted any changes that occurred in the said populations after administration of local and systemic corticosteroid therapy. In type 2 (severe multiple AA and alopecia totalis) and type 3 (alopecia universalis), the mean percentages of HLA-DR+CD3+ cells and CD57-CD16+ cells were significantly higher when compared with those of the normal controls. The percentages of both subsets in type 1 (mild AA) and the normal controls were consistent. Twenty-four patients in types 2 and 3 had received corticosteroid treatment, and all patients experienced new hair growth. With the changes in disease activity, the populations of HLA-DR+CD3+ cells in these patients after corticosteroid therapy significantly decreased when compared with those recorded prior to treatment. Subsequent to treatment, the mean percentages of CD57-CD16+ cells decreased to levels that were not significant relative to that of the normal controls. These findings indicate that HLA-DR+CD3+ and CD57-CD16+ cells in the peripheral blood of patients with AA may be correlated with the disease activity of AA.

Adult↗

PubMed1993

Organ culture of human hair follicles in serum-free medium.

Human hair follicles were cultured in serum-free media at 31 degrees C in an atmosphere containing 95% O2 and 5% CO2. Results showed that the length of the cultured hair increased time dependently for 96 h. Histological findings revealed that the hair germinative cells maintained their normal morphology throughout the 96 h culture period. DNA synthesis in the hair bulb also increased time dependently for 96 h. Autoradiographs of 3H-thymidine-labelled follicles indicated that they were localized in the germinative cells below Auber's critical line. The effects of minoxidil sulphate on DNA synthesis in this culture system were concentration dependent. Minoxidil sulphate at concentrations of 10(-10), 10(-9) and 10(-8) M significantly increased DNA synthesis compared with DNA synthesis in the control medium. Autoradiographs of the follicles cultured in 10(-10) M minoxidil sulphate showed that 3H-thymidine localized primarily in the germinative cells below Auber's critical line. These results suggest that this organ culture system may be useful for studying DNA synthesis by hair germinative cells in serum-free media.

Culture Media, Serum-Free↗

PubMed1993

Effects of cytokines, anti-cancer agents and cocarcinogen on DNA synthesis in hair bulb cells.

We analysed the effects of cytokines, anti-cancer agents and cocarcinogen on DNA synthesis in human hair germinative cells cultured in serum-free media. Epidermal growth factor and gamma interferon were found to inhibit DNA synthesis slightly, while strong inhibition was demonstrated by doxorubicin, cytosine arabinoside and tetradecanoyl-phorbolacetate. Basic fibroblast growth factor had very little influence on DNA synthesis. This organ culture model in serum-free media is a useful method by which to examine the effects of various cytokines and drugs on DNA synthesis in hair germinative cells and/or to study the pathogenesis of various alopecia diseases.

Antineoplastic Agents↗

PubMed1993

Organ culture of mouse vibrissal hair follicles in serum-free medium.

We developed a method for organ culture of mouse vibrissal hair follicles in a serum-free medium. Cultures conducted at 31 degrees C in 95% O2-5% CO2 were found to be suitable for the follicles, with several findings of considerable interest pertaining to hair growth. During the 96 h culture period, the length of the isolated follicles significantly increased; the hair bulb cells maintained their normal morphology; and DNA and protein synthesis within the bulb increased time-dependently. Furthermore, autoradiography showed that 3H-thymidine-labeling was localized in the matrix cells below Auber's critical line in the hair bulb; 3H-leucine-labeling was found in the epithelial region; and 35S-cysteine-labeling was detected in the cortex of hair, particularly in the keratogenous zone. These results indicate that the culture system using mouse vibrissal hair would be potentially useful as an effective model for examination of hair growth.

Animals↗

PubMed1993

Isolation and characterization of Tn5-induced mutants of Pseudomonas paucimobilis UT26 defective in gamma-hexachlorocyclohexane dehydrochlorinase (LinA).

Pseudomonas paucimobilis UT26 grows on gamma-hexachlorocyclohexane (gamma-HCH) as a sole source of carbon and energy. Tn5 mutation was introduced into UT26, and two kinds of mutants defective in gamma-HCH degradation were phenotypically isolated; one (UT64) completely lacked the activity to degrade gamma-HCH, while the other (UT61) retained a very low level of activity. Tagging and sequencing analysis showed that both mutants had a Tn5 insertion at the same site of the linA (gamma-HCH dehydrochlorinase encoding) gene. However, UT61 had an additional rearrangement, which could be the cause of its retaining a low level of activity. An in vitro complementation test with a crude extract from UT64 plus partially purified LinA protein showed that LinA was essential not only for the first-step reaction (gamma-HCH to gamma-pentachloro-cyclohexene; gamma-PCCH), but also for the second-step reaction (gamma-PCCH to compound B) of gamma-HCH degradation in UT26.

Amino Acid Sequence↗

PubMed1993

Visual dysfunction in aged Fischer 344 rats.

To investigate age-related changes in visual function in rats, male and female Fischer 344 (F344) rats at 30 months of age were examined electrophysiologically and histopathologically. The selection rate for the dark area in a T-shaped test box was 80% in aged rats, and the ability of light-dark discrimination was definitely depressed. Electroretinogram (ERG) was non-recordable in 25 out of the 28 eye balls examined, and amplitudes of the ERG a- and b-waves were markedly depressed in the remaining three eye balls. Histopathologic examination of the retina revealed marked atrophy of photoreceptor cells on the outer nuclear and photoreceptor layers; the change was less extensive in the retina of eye balls in which ERG was recordable. Immunohistochemically, increased reactivity to anti-glial fibrillary acid protein serum was observed in the retina of the aged animals. These results evidenced that the number of photoreceptor cells is decreased in age F344 rats, resulting in the reduced reactivity to light and the depressed light-dark discrimination.

Aging↗

PubMed1992

Organ culture conditions of human hair follicles.

Experimental results revealed that although [3H]thymidine uptake in the hair bulb increased time dependently for 12 days under normal culture conditions (95% air-5% CO2 at 37 degrees C), striking morphological changes occurred in the hair bulb cells as demonstrated by histological findings. As such, organ culture conditions applicable to human hair follicles were studied utilizing observations from both histology and DNA synthesis. We found that culture conditions of 95% O2-5% CO2 at 31 degrees C were superior when compared to normal culture conditions for cultures of human hair follicles when attempting to maintain the normal morphology of hair germinative cells. The hair bulb and the germinative cells successfully maintained their normal morphology throughout the 96 and 48 h culture period, respectively. Autoradiographs of [3H]thymidine-labeled follicles showed localization in the germinative cells below Auber's critical line. Hair bulb DNA synthesis increased time dependently for 96 h after culture initiation. Under conditions of 95% O2-5% CO2 at 31 degrees C, the synthesis of DNA in hair germinative cells was observed. Such an organ culture method may prove useful for studies on the human hair growth mechanism.

Autoradiography↗

PubMed1991

Induction of reinitiation of meiosis in amphibian Bufo and Xenopus oocytes by injection of M-phase extracts of ciliate Tetrahymena needs the recipient protein synthesis.

We show here that germinal vesicle breakdown of amphibian Bufo and Xenopus oocytes can be induced if ciliate Tetrahymena extracts are injected into them. The activity of meiosis-reinitiation-inducing factor (MRIF) appeared only a M-phase of a synchronously dividing culture, indicating that this MRIF has an important function for induction of M-phase in the mitotic cell cycle. MRIF of Tetrahymena differed from MPF (M-phase-promoting factor), because its action on the induction of GVBD was inhibited by cycloheximide and it could not induce GVBD in starfish oocytes by microinjection. MPF activity was not detected in extracts of vegetatively growing Tetrahymena. Preliminary experiments showed that MRIF was a heat-labile, Ca2(+)-sensitive, and trypsin-sensitive soluble protein.

Animals↗

PubMed1991

Increased HLA-DR+ T-lymphocyte population in peripheral blood of alopecia areata.

The populations of activated T-cell subsets [HLA-DR(+)-Leu 4+ cells, interleukin 2 receptor positive (IL-2R+)-Leu 4+ cells] in the peripheral blood of patients with alopecia areata (AA) were investigated using double direct immunofluorescence staining. Fifty-eight patients with AA were classified into one of three types: those with inactive single AA (type 1) lesions, active multiple alopecia areata (MAA) lesions and active alopecia totalis (AT) (type 2) and chronic alopecia universalis (AU) (type 3). Compared to normal controls, high percentages of HLA-DR(+)-Leu4+ cells were detected in types 2 and 3 AA patients, but not in type 1 AA patients. These findings suggest that T cells are activated in the peripheral blood of active MAA, AT and chronic AU.

Adult↗

PubMed1991

Molecular cloning of a Pseudomonas paucimobilis gene encoding a 17-kilodalton polypeptide that eliminates HCl molecules from gamma-hexachlorocyclohexane.

Pseudomonas paucimobilis UT26 is capable of growing on gamma-hexachlorocyclohexane (gamma-HCH). A genomic library of P. paucimobilis UT26 was constructed in Pseudomonas putida by using the broad-host-range cosmid vector pKS13. After 2,300 clones were screened by gas chromatography, 3 clones showing gamma-HCH degradation were detected. A 5-kb fragment from one of the cosmid clones was subcloned into pUC118, and subsequent deletion and gas chromatography-mass spectrometry analyses revealed that a fragment of ca. 500 bp was responsible for the conversion of gamma-HCH to 1,2,4-trichlorobenzene via gamma-pentachlorocyclohexene. Nucleotide sequence analysis revealed an open reading frame (linA) of 465 bp within the fragment. The nucleotide sequence of the linA gene and the deduced amino acid sequence showed no similarity to any known sequences. The product of the linA gene was 16.5 kDa according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Amino Acid Sequence↗