Biomedical subjects

M Honjo

Publications and source records attributed to M Honjo.

At least 55 records · Page 3Linked to original sources

PubMed1998

Phacoemulsification, intraocular lens implantation, and trabeculotomy to treat pseudoexfoliation syndrome.

PURPOSES: To determine the long-term risk/benefit ratio of phacoemulsification and intraocular lens (IOL) implantation combined with trabeculotomy to manage eyes with pseudoexfoliation syndrome and co-existing cataract. SETTING: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine; Kurihara Eye Clinic; Departments of Ophthalmology, Tenri Hospital, Kumamoto University, and Matsue Red Hospital; Nagata Eye Clinic, Japan. METHODS: This multicenter retrospective study comprised 49 eyes of 36 patients with pseudoexfoliation syndrome and co-existing cataract who had the combined procedure for uncontrolled intraocular pressure (IOP) (> 21 mm Hg) even on antiglaucoma medication. RESULTS: After a mean follow-up of 20.0 months +/- 13.2 (SD), IOP in all 49 eyes was well controlled (< or = 21 mm Hg). Mean IOP at the final examination was 14.6 +/- 2.6 mm Hg on a mean of 0.9 +/- 0.8 glaucoma medications. Complications included an IOP spike in 11 eyes and fibrin exudation in 1 eye. CONCLUSION: Phacoemulsification and IOL implantation combined with trabeculotomy was an effective treatment for patients with pseudoexfoliation syndrome and cataract.

Aged↗

PubMed1998

The 20-kilodalton (kDa) human growth hormone (hGH) differs from the 22-kDa hGH in the complex formation with cell surface hGH receptor and hGH-binding protein circulating in human plasma.

In spite of recent advance in understanding of the stoichiometry of 22-kDa human GH (22K-hGH) with cell surface hGH receptor (hGHR) and hGH-binding protein (hGH-BP) circulating in human plasma, that of 20-kDa hGH (20K-hGH) is poorly understood. To clarify this, mouse pro-B Ba/F3 cells stably expressing the full-length hGHR (Ba/F3-hGHR) and both recombinant and native hGH-BP were used in this study. Cell proliferation assay revealed that the two hGH isoforms increased Ba/F3-hGHR cells to the same extent in a dose-dependent manner at 0.1 pM-10 nM. However, the self-inhibition observed in 20K-hGH at 5 microM was significantly less than that in 22K-hGH. Furthermore, addition of 1 and 10 nM recombinant hGH-BP caused a slight inhibition in 20K-hGH, but a drastic inhibition in 22K-hGH. Gel filtration chromatography of mixtures of 20K-hGH with recombinant hGH-BP clearly demonstrated that 20K-hGH formed a 1:2 (hGH:hGH-BP) complex efficiently but no detectable 1:1 complex in any conditions. Supporting data were also obtained with native hGH-BP. Computer-aided homology modeling of 20K-hGH has provided speculative data that the conformational change caused by deletion of 15 residues may occur only in the loop between helix 1 and helix 2, resulting in the reduction of its site 1 affinity. In conclusion, 20K-hGH possesses a unique property for forming a 1:2 complex to the same extent as 22K-hGH but has difficulty in forming a 1:1 complex, which might be attributed to the conformational change restricted to its site 1 region.

Animals↗

PubMed1998

Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase activation and gene expression.

GH binding to its receptor, which belongs to the cytokine receptor superfamily, activates Janus kinase (JAK) 2 tyrosine kinase, thereby activating a number of intracellular key proteins such as STAT (signal transducers and activators of transcription) proteins and mitogen-activated protein (MAP) kinases, which finally lead to GH's biological actions including gene expression. In contrast to receptor tyrosine kinases, the signalling pathways leading to MAP kinase activation by GH are poorly understood but appear to involve Grb2 and Shc. We now show that GH stimulated tyrosine phosphorylation of epidermal growth factor receptor (EGFR) and its association with Grb2, and concomitantly stimulated MAP kinase activity in liver, a major target tissue. Expression of EGFR and its mutants into CHO-GH receptor (GHR) cells revealed that GH-induced full activation of MAP kinase and c-fos expression required tyrosine phosphorylation sites of EGFR but not its intrinsic tyrosine kinase activity. Moreover, by also using dominant negative JAK2 and in vitro kinase assay, we demonstrated that tyrosine 1068 of EGFR was evidently one of the major phosphorylation and Grb2 binding sites stimulated by GH via JAK2. These data suggest that the role of EGFR in GH signalling is to be phosphorylated by JAK2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression. This novel cross talk pathway may provide the first example of the hormone and cytokine receptor superfamily transducing signals via associated nonreceptor tyrosine kinase by phosphorylating growth factor receptor and utilizing it as a docking protein independent of its receptor tyrosine kinase activity.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Surgical results of pars plana vitrectomy combined with phacoemulsification and intraocular lens implantation for complications of proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To evaluate the effectiveness and safety of combining phacoemulsification (PEA), pars plana vitrectomy (PPV), and intraocular lens (IOL) implantation. PATIENTS AND METHODS: Combined operations of PEA and PPV were performed in 76 eyes of 54 patients with cataract complicated by proliferative diabetic retinopathy (PDR). The mean follow-up period was 24.4 months. Gas tamponade was employed in 15 eyes. IOLs were implanted during surgery. RESULTS: Visual acuity improved by 2 lines or more in 59 eyes (78%). Forty-seven eyes (77%) without tamponade and 12 eyes (80%) with tamponade had improved visual acuity. Postoperative complications included fibrin reaction in 8 eyes (10%), posterior synechia of the iris in 11 eyes (14%), and recurrence of retinal detachment in 8 eyes (10%). The incidence of these complications and of additional operations was higher in eyes that required tamponade, which corresponded with the severity of each case and the complexity of the surgical procedures. CONCLUSIONS: Although further studies are indicated, this study suggests that the combined operation of PPV, PEA, and IOL implantation is safe and effective for patients with PDR. The choice of IOL may be correlated with postoperative complications.

Adult↗

PubMed1997

Tyrosine phosphorylation of the EGF receptor by the kinase Jak2 is induced by growth hormone.

When growth hormone binds to its receptor, which belongs to the cytokine receptor superfamily, it activates the Janus kinase Jak2 which has tyrosine-kinase activity and initiates an activation of several key intracellular proteins (for example, mitogen-activated protein (MAP) kinases) that eventually execute the biological actions induced by growth hormone, including the expression of particular genes. In contrast to receptors that themselves have tyrosine kinase activity, the signalling pathways leading to MAP kinase activation that are triggered by growth hormone are poorly understood, but appear to be mediated by the proteins Grb2 and Shc. We now show that growth hormone stimulates tyrosine phosphorylation of the receptor for epidermal growth factor (EGFR) and its association with Grb2 and at the same time stimulates MAP kinase activity in liver, an important target tissue of growth hormone. Expression of EGFR and its mutants revealed that growth-hormone-induced activation of MAP kinase and expression of the transcription factor c-fos requires phosphorylation of tyrosines on EGFR, but not its own intrinsic tyrosine-kinase activity. Moreover, tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR. This may represent a novel cross-talk pathway between the cytokine receptor superfamily and growth factor receptor.

Adaptor Proteins, Signal Transducing↗

PubMed1997

The full agonistic effect of recombinant 20 kDa human growth hormone (hGH) on CHO cells stably transfected with hGH receptor cDNA.

The agonistic effect of the recombinant 20 kilodalton human GH (20K-hGH) with authentic primary structure was studied using Chinese hamster ovary (CHO) cells stably transfected with hGH receptor (hGHR) cDNA and was compared with that of 22K-hGH. The binding affinities (dissociation constants) of 20K- and 22K-hGH were identical (0.41 +/- 0.11 nM and 0.41 +/- 0.04 nM, respectively). In addition, the two hGHs possessed the same potencies in activating the rat serine protease inhibitor (Spi) 2.1 gene promoter. 20K-hGH was similarly internalized as 22K-hGH but its internalization rate was a little slower than that of 22K-hGH. We also found that proliferation of CHO-hGHR cells stimulated by serum was remarkably inhibited by both hGHs to the same degree. In conclusion, both hGH isoforms exhibited the same binding affinities for hGHR and were potent enough to induce some hGHR-mediated cellular events. These suggest that 20K-hGH exerts a full agonistic activity for hGHR.

Animals↗

PubMed1997

Secretion of authentic 20-kDa human growth hormone (20K hGH) in Escherichia coli and properties of the purified product.

Using Bacillus amyloliquefaciens neutral protease gene (npr), we have constructed a secretion system of 20-kDA human growth hormone (20K hGH) in E. coli. The secretion-signal region from npr was modified inserting a fragment coding a 2Lys-5Leu cluster. In this system we found that co-expression of glutathione reductase remarkably increased accumulation level of 20K hGH in periplasm and confirmed that secreted 20K hGH was correctly processed. The recombinant 20K hGH was highly purified and subjected to analyses of physicochemical properties and biological activities which are still unclear and controversial due to difficulty in preparing the sample with authentic structure. The secreted recombinant product had authentic disulfide linkages and showed molecular weight of 20,270.5 +/- 3.7 (theoretical value, 20,269.9). The results suggest that the recombinant 20K hGH is a full agonist on rat growth promotion and lipolysis stimulation in isolated rat adipose tissues. In particular, the lipolysis-stimulating activity of 20K hGH was distinct as compared with that of 22K hGH under physiological concentration. Cell proliferation activity via prolactin-receptor in Nb-2 lymphoma was obviously low as compared with that of 22K hGH.

Amino Acid Sequence↗

PubMed1997

Semi-micro-scale frontal gel chromatography of interacting systems of a protein and small molecules: binding of warfarin, tryptophan, or FMN to albumin, and of o-nitrophenol to catechol 2,3-dioxygenase.

Frontal gel chromatography is a convenient and accurate method to obtain the free ligand concentration of a protein-ligand mixture. Because a large amount of sample (more than 6 ml) is required for the method, it has been rarely used for binding experiments. We have developed a system to carry out frontal gel chromatography on a semi-micro scale using short gel filtration columns (4.6 mm x 50-100 mm); frontal chromatograms could be obtained with small amounts of samples (1-2.5 ml) within 20 min. We used this technique to examine the binding of warfarin, L-tryptophan, or FMN to human serum albumin, the binding of warfarin to bovine serum albumin, and the interaction of catechol 2,3-dioxygenase with o-nitrophenol. The data fitted to a binding model in which a protein has one or several independent binding sites. Both human and bovine serum albumin showed the high-affinity bindings of two warfarin molecules. The binding number for L-tryptophan on human serum albumin was confirmed to be one, whereas maximal binding of FMN was 0.6 molecule per albumin molecule. o-Nitrophenol showed high-affinity binding only to holocatechol 2,3-dioxygenase. The absorption spectrum of the bound o-nitrophenol resembled that of anionic o-nitrophenol. These results demonstrated that frontal gel chromatography on a semi-micro scale is useful for the study of binding systems; the method is rapid and would be easy to automate fully.

Animals↗

PubMed1997

Angle closure caused by multiple, bilateral iridociliary cysts.

A case of high, broad, peripheral anterior synechiae caused by multiple, bilateral iridociliary cysts is reported. The peripheral anterior synechia in our case extended to the corneal endothelium beyond Schwalbe's line, and iris atrophy in the region of the cysts was found. Ultrasound biomicroscopic imaging showed that multiple, bilateral iridociliary cysts causes elevation of the iris structure.

Adult↗

PubMed1997

Trabeculotomy combined with phacoemulsification and implantation of an intraocular lens for the treatment of primary open-angle glaucoma and coexisting cataract.

BACKGROUND AND OBJECTIVE: The authors previously reported the usefulness of trabeculotomy ab externo for the treatment of primary open-angle glaucoma in adult patients. In an attempt to elucidate the long-term risk-to-benefit ratio of this surgical modality in combination with cataract surgery, the authors conducted a retrospective study of the surgical effects and complications of a triple procedure: phacoemulsification, implantation (of an intraocular lens), and trabeculotomy (PIT). PATIENTS AND METHODS: The authors conducted a retrospective study of patients treated with PIT at multiple hospitals. Intraocular pressure (IOP) and visual function data were obtained from patients after PIT as an initial surgical treatment in cases where antiglaucoma medications failed to resolve uncontrolled IOP (higher than 21 mm Hg). Included in this study were 96 eyes of 64 patients with primary open-angle glaucoma and coexisting cataract. The mean follow-up period was 22.6 +/- 14.7 months (range 3-56 months). RESULTS: In 94 (98%) of the 96 eyes, the IOP was well controlled, having achieved a level of 21 mm Hg or lower at the final examinations. The mean preoperative IOP of the 33 eyes that underwent the triple procedure using a single flap method (PIT-I) was 24.3 +/- 3.9 mm Hg, with an average of 2.1 +/- 1.1 medications. At the final examinations, the mean IOP had dropped to 16.0 +/- 1.2 mm Hg, with an average of 1.2 +/- 1.2 medications. The mean preoperative IOP of the 63 eyes that underwent the triple procedure using a double flap method (PIT-II) was 26.2 +/- 6.2 mm Hg, with an average of 1.9 +/- 1.2 medications. At the final examination, the mean IOP for this group was 15.6 +/- 2.9 mm Hg, with an average of 1.0 +/- 0.9 medications. CONCLUSION: The long-term results from this multicenter study showed that the triple procedure, PIT, can be useful and effective as an initial surgical treatment for open-angle glaucoma in glaucoma patients with coexisting cataract.

Adult↗

PubMed1996

Trabeculotomy ab externo, cataract extraction, and intraocular lens implantation: preliminary report.

PURPOSE: To compare the results of a triple procedure using either extracapsular cataract extraction (ECCE) or one of two phacoemulsification techniques combined with trabeculotomy ab externo and intraocular lens (IOL) implantation. SETTING: Kyoto University Hospital, Kyoto, Japan, and Nagata Eye Hospital, Nara, Japan. METHODS: In this comparative study, 25 eyes with primary open-angle glaucoma had ECCE combined with trabeculotomy ab externo and IOL implantation and 22 had the same procedure using phacoemulsification instead of ECCE. Of the eyes that had phacoemulsification, 10 had a single-flap and 12 had a double-flap procedure. RESULTS: All 22 eyes that had phacoemulsification had a postoperative IOP of 21 mm Hg or less, as did all ECCE eyes except 2. Although the self-sealing incision might have caused the higher incidence of IOP spikes in the immediate postoperative period, IOPs in the phacoemulsification groups were lower after 3 months. Results were similar in the single-flap and double-flap phacoemulsification groups. There were no significant complications. CONCLUSION: Cataract extraction by phacoemulsification or ECCE combined with IOL implantation and trabeculotomy ab externo is a safe, effective treatment for patients with coexisting glaucoma and cataract.

Aged↗

PubMed1992

Secretion of correctly processed and folded pancreatic secretory trypsin inhibitor by Bacillus subtilis.

We constructed a plasmid, designated pNPP126, containing a DNA sequence encoding a fusion protein composed of Bacillus amyloliquefaciens neutral protease prepeptide (signal peptide) and human pancreatic secretory trypsin inhibitor (hPSTI), where the mature hPSTI is accurately fused to the 3'-terminal of the prepeptide coding region. It was observed that the strain Bacillus subtilis MT600 harboring pNPP126 could secrete a trypsin inhibitory activity into the culture medium. The N-terminal amino acid sequence, the amino acid composition and the stoichiometry of the purified hPSTI produced by B. subtilis were the same as those of natural hPSTI, indicating that the transformant B. subtilis MT600 (pNPP126) could efficiently secrete the correctly processed and folded hPSTI into the culture medium.

Bacillus subtilis↗

PubMed1992

Processing of the prepropeptide portions of the Bacillus amyloliquefaciens neutral protease fused to Bacillus subtilis alpha-amylase and human growth hormone during secretion in Bacillus subtilis.

A set of nested 3'-terminal deletions of the prepropeptide of the Bacillus amyloliquefaciens neutral protease gene was constructed. Alpha-amylase and human growth hormone were secreted using these truncated genes in Bacillus subtilis. The level of the secreted alpha-amylase varied with the region for the truncated prepropeptide contained in the fusion gene but was independent of its length. Even though length of the prepropeptide varied, the mobilities of secreted alpha-amylases were the same as that of the control alpha-amylase derived from the alpha-amylase clone, pTUB4 (Yamazaki et al., 1983). Analyses of the secreted N-terminal amino acid sequences confirmed that they were all identical to that of the authentic one. Precursor proteins of the alpha-amylase were found in the cell-associated fraction, suggesting that the prepropeptide portion was processed during secretion. On the other hand, the N-terminus of hGH secreted using one of these prepropeptide portions varied by 1 to 4 additional N-terminal amino acid residues derived from the junction sequence between the sequence for propeptide portion and mature hGH or from C-terminal region of the propeptide portion. These results suggest that the prepropeptide portion can be generally processed even in the heterogeneous fusion. A probable mechanism of processing and maturation of the fusion gene products is also discussed.

Amino Acid Sequence↗

PubMed1991

A case of cutaneous metastases of gastric carcinoma showing peculiar clinical features.

A 52-year-old male patient presented with multiple cutaneous nodules on the face, trunk, and upper extremities. Examination of a skin biopsy specimen disclosed numerous signet ring cells throughout the dermis. Histopathologic examination of the stomach, along with gastroscopy, revealed that the cutaneous metastases were of gastric origin. The metastatic skin lesion on the shoulder and the back of the patient grew relatively rapidly, showing an erysipelas-like lesion followed by prominently large tumor masses. The clinical appearance seen in our case is thought to be rare. Radiotherapy and chemotherapy appeared to be effective in reducing some tumors and the swelling on the anterior of the neck, and in prolonging life.

Adenocarcinoma↗

PubMed1991

[An evaluation of the attitudes and productivity of public health nurses in mental health service programs for the elderly].

The relationship between productivity of public health nurses (PHN) employed in mental health programs including home visit service for elderly people with dementia, and their attitudes toward mental health services was studied by surveying PHN at 31 health centers (HC) in Osaka Prefecture. A review of the services provided for 382 clients with dementia visited during a one-year period showed that PHN had provided the following services: home health care education: family education to promote understanding of the disease; management of interpersonal relations in the family; intervention to reduce the burden placed on the family members; medical facility referral; social service resource referral. For each of these PHN-provided services, the service had been provided to more than 60% of the clients. The percentage of clients who had been visited by a PHN accompanying a psychiatrist or a social worker was significantly higher at the 13 HC where PHN attach importance to counseling programs for the elderly, the 8 HC which provide group work services, and the 13 HC which hold case conferences more than six times a year than at other HC. In addition, the service provision rates for many PHN-provided services were significantly higher for these HC than for other HC. Analysis on the basis of whether PHN did or did not attach importance to the counseling program, showed that in either group, clients who had been visited by a PHN accompanying a psychiatrist or a social worker were more likely to have received PHN-provided services than other clients. Furthermore, at HC where PHN actively participated in mental health programs, PHN attitudes toward mental health care were more enthusiastic than at other HC. These results indicate that increased productivity of PHN employed in mental health programs and promotion of a multidisciplinary approach in client services are correlated with each other, and that both factors contribute to improving the quality of home visit services provided by PHN.

Aged↗

PubMed1990

Thymus-independent generation of Thy-1+ epidermal cells from a pool of Thy-1- bone marrow precursors.

Thy-1+ dendritic epidermal cells (Thy-1+ DEC) and immature thymocytes share several phenotypic features: CD45+, Thy-1+, asialo-GM1+, CD3+, CD4-, and CD8-. In view of this similarity, it has been suggested that the epidermis may be a site of either post-thymic or extra-thymic T-cell development. In order to address this issue, we used C3H/He/Han (Thy-1.2)----AKR/Ola (Thy-1.1) radiation bone marrow chimeras. Animals were first either thymectomized or sham-thymectomized, then lethally irradiated (750R) and, finally, reconstituted with allogeneic bone marrow cells previously depleted of Thy-1-bearing cells. Six weeks after bone marrow transplantation, spleens and lymph nodes of sham-treated animals, but not of thymectomized animals, contained large numbers of CD3+ donor-type Thy-1+ cells. The epidermis of both thymectomized and sham-treated animals contained not only many recipient-type CD3+, Thy-1+ DEC, but also small numbers of CD3-, donor-type Thy-1+ cells. After 4 months, the frequency of donor cells had greatly increased, but they still lacked CD3 antigens. Most of the donor cells had a rounded shape, but some exhibited a dendritic configuration. These results demonstrate that Thy-1- bone marrow-derived precursors of Thy-1+ DEC can migrate to the epidermis without thymic influence and yet acquire Thy-1 antigens during their journey. Although donor-type Thy-1+ epidermal cells failed to mature into CD3+ dendritic epidermal cells, the experimental model used in this study may be a versatile tool for studying the influence of thymic and extrathymic epithelia on T-cell maturation.

Animals↗

PubMed1990

A novel Bacillus subtilis gene involved in negative control of sporulation and degradative-enzyme production.

We have cloned a 2.5-kilobase fragment of the Bacillus subtilis genomic DNA which caused the reduction of extracellular and cell-associated protease levels when present in high copy number. This fragment, in multicopy, was also responsible for reduced levels of alpha-amylase, levansucrase, alkaline phosphatase, and sporulation inhibition. The gene relevant to this pleiotropic phenotype is referred to as pai. By DNA sequencing, two open reading frames--ORF1 and ORF2, encoding polypeptides of 172 and 207 amino acid residues, respectively--were found. These open reading frames seemed to form an operon. Deletion analysis revealed that an entire region for ORF1 and ORF2 was necessary for the pai phenotype. In addition, it was observed that the presence of the pai gene, in multicopy, caused overproduction of two proteins (molecular masses, 21 and 24 kilodaltons [kDa]). Analyses of the N-terminal amino acid sequences of these two proteins suggested that they were products of ORF1 and ORF2. Disruption of the pai gene at ORF1 in the genomic DNA resulted in the release of repression on protease synthesis and sporulation in glucose-enriched (2%) medium. The mutant carrying insertional disruption at ORF2 could not be constructed, suggesting that the ORF2 product, the 24-kDa protein, is essential for growth. The 21-kDa protein contains a helix-turn-helix domain observed in other DNA-binding proteins. Chromosomal mapping of pai indicated that this gene is located close to thr-5. These results suggest that the pai gene is a novel transcriptional-regulation gene involved in glucose repression.

Alkaline Phosphatase↗

PubMed1990

Synthesis and antiviral activities of carbocyclic oxetanocin analogues.

9-Cyclobutyladenine (4a), cis- and trans-9-[3- (hydroxymethyl)cyclobutyl]adenine (4b) and 9-[3,3-bis(hydroxymethyl)cyclobutyl]adenine(4d) were prepared from the corresponding cyclobutylamine derivatives (1a, 1b and 1d). Guanine congeners (9a, cis- and trans-9b and 9d) and carbocyclic oxetanocin G (1',2'-trans-9f) were also prepared. Carbocyclic oxetanocin A(1',2'-trans-4f), the preparation of which we have already published, and G were found to be active against herpes simplex virus (type 1 and 2) in vitro, while cis-4b and cis-9b showed an in vitro antiretroviral activity against human immunodeficiency virus (type 1).

Adenine↗