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Biomedical subjects

S Nonaka

Publications and source records attributed to S Nonaka.

At least 19 recordsLinked to original sources
PubMed2005

Incidence of xeroderma pigmentosum in Larkana, Pakistan: a 7-year study.

Xeroderma pigmentosum (XP) is a rare autosomal recessive inherited disorder caused by a defect in the normal repair of DNA of various cutaneous cell types damaged by exposure to ultraviolet radiation. We present our 7-year experience with 36 XP patients who either visited the Department of Dermatology or were seen in the medical camps arranged in remote areas for patients' welfare, from 1995 to 2001. For ease of discussion we classified all cases into the following subgroups on clinical grounds only: mild, those with light brown freckles on the face alone; moderate, those with dark brown freckles with burning on the face, neck, ears, chest, hands and photophobia but without other associated obvious cutaneous and ocular changes; severe, those with extensive dark brown freckles with burning on the exposed parts as well as on the unexposed parts of the body, i.e. the chest, back, abdomen and arms including other associated cutaneous and ocular changes such as ulcers and malignancy. Of 36 patients, three (8.3%) were classified as mild, nine (25%) moderate and 24 (66.7%) severe; there were 18 males and 18 females, age range 2-30 years (mean 8.9 years). Seventeen patients had cutaneous changes: actinic keratosis, keratoacanthoma, fissures and ulcerative nodules on the exposed parts of the body. Four patients had wide ulcers, along with mass formation and severe pigmentation on the face, neck and head. Twenty-nine patients developed ocular symptoms: photophobia, conjunctivitis, corneal keratitis and lid ulcer. One patient had complete loss of vision. Histopathological findings revealed that six patients had squamous cell carcinoma (SCC) on the face, head, ear or lip. More than one sibling (two to four) was affected in four families. The majority of cases (20/36, 55.6%) were from the Brohi tribe (skin type III), while the remaining cases (16/36, 44.4%) were from the Sindhi population (skin type IV). The large number of XP patients seen in those with skin type III (Brohi tribe) compared with skin type IV (Sindhi population) indicates that the skin type and the race has a considerable value in the pathogenesis of XP. Furthermore, 24 of 36 patients were in the severe group and six of these had SCC. Moreover, no neurological abnormalities were observed in our patients. All patients were treated according to disease severity by prescribing oral antibiotics, local steroids, sunscreens and/or chemotherapy followed by irradiation in malignant cases. Two patients died because of extensive SCC.

Adolescent↗
PubMed2005

Elevated macrophage migration inhibitory factor (MIF) levels in the urine of patients with focal glomerular sclerosis.

The pathogenesis of focal glomerular sclerosis (FGS) is poorly understood. Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine released from T cells and macrophages, and is a key molecule in inflammation. To examine further the possible role of MIF in FGS, we measured MIF levels in the urine. The purpose of the present study was to evaluate the involvement of MIF in FGS. Urine samples were obtained from 20 FGS patients. The disease controls included 40 patients with minimal-change nephrotic syndrome (MCNS) and membranous nephropathy (MN). A group of healthy subjects also served as controls. Biopsies were performed in all patients prior to entry to the study. The samples were assayed for MIF protein by a sandwich enzyme-linked immunosorbent assay (ELISA). The levels of MIF in the urine of FGS patients were significantly higher than those of the normal controls and patients with MCNS and MN. In contrast, the levels of urinary MIF (uMIF) in patients with MCNS and MN did not differ significantly from normal values. In the present study, attention also focused on the relationship between uMIF levels and pathological features. Among the patients with FGS, uMIF levels were significantly correlated with the grade of mesangial matrix increase and that of interstitial fibrosis. There was also a significant correlation between uMIF levels and the number of both intraglomerular and interstitial macrophages. Although the underlying mechanisms remain to be determined, our study presents evidence that urinary excretion of MIF is increased in FGS patients with active renal lesions.

Adult↗
PubMed2005

Bovine posterior pituitary extract stimulates prolactin release from the anterior pituitary gland in vitro and in vivo in cattle.

It has been reported that the posterior pituitary (PP) gland contains a potent, unknown prolactin (PRL)-releasing factor (PRF) in rats. PRFs are assumed to be produced in neurones located within the hypothalamus, and to be peptidergic in nature. However, little is known about PRFs in domestic animals. To characterize the PRF in the PP of domestic animals, the present study examined the PRL-releasing activity of an acidic extract from bovine PP (bPP) in vitro and in vivo in cattle. First, the PRL-releasing effect of bPP extract was compared with that of PRL-releasing peptide (PrRP), and thyrotropin-releasing hormone (TRH) from cultured bovine anterior pituitary cells. The extract significantly increased PRL concentrations in the culture medium, at doses of 0.002 and 0.02 eq./ml (one eq. is the PP extract from one animal), compared with the control (p < 0.05). PrRP failed to stimulate the release of PRL. TRH significantly increased PRL concentrations in the culture medium, at doses from 10(-9) to 10(-7) M, compared with the control (p < 0.05). The rate of increase in the PRL concentration, by 0.02 eq./ml bPP extract, was significantly greater than that in TRH (p < 0.05). Secondly, plasma PRL responses to the intravenous (i.v.) injection of bPP extract (0.5 eq./head), PrRP [3.59 mug/kg body weight (BW)], TRH (1 mug/kg BW), and a dopamine receptor antagonist (sulpiride, 0.1 mg/kg BW), were examined in calves. PrRP failed to stimulate PRL release; however, plasma PRL increased immediately following the injection of bPP extract, TRH and sulpiride. The PRL-releasing effect of i.v. injections of TRH and sulpiride was more potent than that of bPP extract. Finally, plasma PRL responses to the intra-hypothalamic injection of bPP extract were examined in calves. The intra-hypothalamic infusion (arcuate nucleus) of 0.0625 eq./head of bPP extract strongly stimulated PRL release in calves (p < 0.05). The present results show that PP contains a physiologically potent PRF in cattle.

Animals↗
PubMed2004

Sequence variation of the cytochrome b gene of various human infecting members of the genus Leishmania and their phylogeny.

The Cytochrome b (Cyt b) gene has proved to be useful for identification and classification of many mammals and plants. In order to evaluate the utility of this gene for discrimination of Leishmania parasites as well as for exploring their phylogenetic relationships, we determined the nucleotide sequences of the Cyt b gene from 13 human-infecting Leishmania species (14 strains) from the New and Old Worlds. The Cyt b genes, approximately 1080 base pairs, were found to be A/T rich, and their 5' terminal-editing regions were highly conserved. The nucleotide sequence variation among them was enough to discriminate parasite species; 245 nucleotide positions were polymorphic and 190 positions were parsimony informative. The phylogenetic relationships based on this gene, showed good agreement with the classification of Lainson & Shaw (1987) except for the inclusion of L. (L.) major in the L. (L.) tropica complex and the placement of L. tarentolae in another genus. These data show that the Cyt b gene is useful for phylogenetic study of Leishmania parasites.

Amino Acid Sequence↗
PubMed2003

Effects of Ghrelin on growth hormone secretion from cultured adenohypophysial cells in pigs.

To clarify the direct effects of Ghrelin on growth hormone (GH) release from anterior pituitary (AP) cells in pigs, GH-releasing effects of human Ghrelin (hGhrelin) and rat Ghrelin (rGhrelin) on porcine AP cells were compared with GHRH in vitro. The AP cells were obtained from 6-month-old pigs and the cells (2 x 10(5) cells per well) were incubated for 2 h with the peptides after incubating in DMEM for 3 days. hGhrelin and rGhrelin significantly stimulated GH release from the cultured cells at doses of 10(-8) and 10(-7)M (P < 0.05). The rates of increase in GH at 10(-8) and 10(-7)M of hGhrelin were 82.7 and 131.9%, while those with rGhrelin were 43.9 and 79.5%, respectively. GHRH significantly stimulated GH release from the cells at a dose as low as 10(-11)M (P < 0.05), and the response to GHRH was greater than that induced by Ghrelins. In time-course experiments, GHRH continued to increase GH concentrations in media until 120 min after incubation; however, those in media treated with hGhrelin reached a plateau 60 min after incubation, and the maximal value was approximately one third that obtained with GHRH. When hGhrelin (10(-8)M) and GHRH (10(-8)M) were added together, additive effects of both peptides on the release of GH were observed (P < 0.05). Somatostatin (SS, 10(-7)M) significantly blunted GH release induced by hGhrelin (10(-8)M) and GHRH (10(-8)M) (P < 0.05). In the presence of SS, additive effects of hGhrelin and GHRH on the release of GH were observed (P < 0.05). These results show that Ghrelin directly stimulates GH release from anterior pituitary cells in pigs; however, the GH-releasing effect is weaker than that of GHRH in vitro. The present results also show that Ghrelin interacts with GHRH and SS to in the release of GH from porcine adenohypophysial cells.

Animals↗
PubMed2002

Usefulness of sampling with cotton swab for PCR-diagnosis of cutaneous leishmaniasis in the New World.

In this study, we tested the polymerase chain reaction (PCR)-method to diagnose cutaneous leishmaniasis (CL) by taking exudate materials from lesions with cotton swabs, using our previously tested (PCR) panel comprised of Leishmania (Viannia) panamensis, L. (V.) braziliensis, L. (V.) guyanensis, L. (Leishmania) mexicana and L. (L.) amazonensis. The objectives of the present study were to improve the sampling method convenient for the patients and to test the usefulness of samples taken with cotton swabs. Sixteen patients were clinically diagnosed to have CL including one case of diffuse cutaneous leishmaniasis (DCL) in Ecuador and the causative Leishmania parasites were identified by PCR. All the 12 samples from CL patients of La Mana, positive for Leishmania DNA, were identified as L. (V.) panamensis, while two from CL of Huigra and one from DCL of San Ignacio were L. (L.) mexicana. In the field condition, taking biopsy material is not only painful but sometimes causes iatrogenic bacterial infections. Considering the sensitivity of the test, and convenient sampling procedure, it may be suggested that collection of exudates using cotton swabs may be a better alternative to biopsy sample for PCR-diagnosis of CL.

Adult↗
PubMed2002

Dermatitis herpetiformis in Japan: an update.

BACKGROUND: Although dermatitis herpetiformis (DH) is a relatively common disease in Caucasian populations, it is rare in Asian populations including the Japanese. We encountered a Japanese case of DH which showed granular IgA and C3 deposits in the papillary dermis and which was associated with gluten-sensitive enteropathy but no HLA-B8/DR3/DQ2. OBJECTIVE: The purpose of this study is to describe the characteristics of Japanese DH cases, since most of them have been reported in Japanese language and dermatologists outside Japan are not familiar with the characteristics of Japanese DH. METHODS: We have reviewed all 34 Japanese DH cases reported previously. RESULTS: We found several features of Japanese DH compared with Caucasian DH, such as a high frequency of the fibrillar pattern, rarity of gluten-sensitive enteropathy and an absence of the HLA-B8/DR3/DQ2 haplotype. CONCLUSION: There might be significant differences in pathophysiology between Caucasian and Japanese DH cases.

Biopsy, Needle↗
PubMed2001

Treatment outcome of maxillary sinus squamous cell carcinoma.

BACKGROUND: Optimal treatment policies of maxillary sinus carcinoma remain to be defined. METHODS: Seventy-four patients with squamous cell carcinoma of maxillary sinus were treated at Department of Otolaryngology, Asahikawa Medical College between 1983 and 1997. The T classification according to the 1997 International Union Against Cancer was as follows: 9 with T2, 35 with T3, and 30 with T4. Eight patients had lymph node metastasis with N1 at diagnosis. Of 62 patients who started multimodality therapy that comprised preoperative radiochemotherapy including local irradiation with total dose of 50 grays along with concomitant intramaxillary arterial infusion of 5-fluorouracil with total dose of 5000 mg followed by total or partial maxillectomy, 59 received the complete therapy. Eleven patients had to be treated with radiotherapy alone, and 1 patient received postoperative radiotherapy. The median follow-up time for surviving patients was 117 months. RESULTS: The 5-year overall survival, disease free survival, and local control (LC) rates for all patients were 58.5%, 63.7%, and 73.6%, respectively. The patients who underwent multimodality therapy showed significantly better 5-year overall survival, disease free survival, and LC rates as compared with those who underwent radiotherapy alone (68.5% vs. 9.1%; 73.2% vs. 18.2%; 84.0% vs. 18.2%; P < 0.0001 each). Multivariate analysis revealed that T classification and treatment modality are independent predictors for disease free survival. CONCLUSIONS: The authors' treatment method, which did not include any complicated techniques, produced higher survival and LC rates because of high effectiveness of multimodality therapy. They concluded that their multimodality therapy could offer a better chance for cure from maxillary sinus carcinoma at many institutions.

Carcinoma, Squamous Cell↗
PubMed2001

EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing differentiation or apoptosis.

Differentiation and apoptosis are precisely regulated events in early embryogenesis. Retinoic acid-induced differentiation in the embryonal carcinoma (EC) cell line NCR-G3 triggers concurrent induction of apoptosis. Using this system, which serves as a model of early embryogenesis, the expression of various bcl-2-related genes was analyzed as these genes display either positive or negative regulatory effects on apoptosis. EAT/mcl-1, an antiapoptotic bcl-2-related gene and immediate early gene, was dramatically expressed at an early stage of NCR-G3 differentiation. Bcl-xL, another antiapoptotic gene, was induced at a middle stage of differentiation and then gradually decreased to basal level. Expression of Bax, a proapoptotic molecule, was detected at a high level and remained relatively constant. Meanwhile, Bcl-2 and Bcl-xS were below detectable levels throughout the various stages of differentiation. As the balance of bcl-2 genes is a crucial regulatory step in apoptosis, the results suggest that EAT and Bax likely regulate apoptosis in the early stages of differentiation. In later stages of differentiation, down-regulation of EAT was found to coincide with a gradual increase in apoptosis of NCR-G3 cells. Furthermore, use of the monoclonal antibody (3A2) specific to EAT revealed that EAT is localized to the outer mitochondrial membrane in human EC cells. In addition, EAT immunoreactivity was not detected in apoptotic NCR-G3 cells while it was observed in nearly all viable cells. The findings suggest that rapid induction of EAT may prevent NCR-G3 cells from undergoing apoptosis, thereby supporting viability at the early stage of differentiation.

Antineoplastic Agents↗
PubMed2001

Presence of neuronal nitric oxide synthase in autonomic and sensory ganglion neurons innervating the lacrimal glands of the cat: an immunofluorescent and retrograde tracer double-labeling study.

It is generally considered that parasympathetic postganglionic nerve fibers innervating the lacrimal gland (LG) arise from the pterygopalatine ganglion (PPG), while sympathetic and sensory innervations arise from the superior cervical ganglion (SCG) and trigeminal ganglion (TG), respectively. Recently, we reported for the first time that the parasympathetic innervation of the cat LG was also provided by the otic ganglion (OG) and ciliary ganglion (CG), and that the sensory innervation was also provided by the superior vagal ganglion (SVG) and superior glossopharyngeal ganglion (SGG). To determine if nitric oxide (NO) is a neurotransmitter of the autonomic and sensory neurons innervating the LG, we injected the cholera toxin B subunit (CTB) as a retrograde tracer into the cat LG, and used double-labeling fluorescent immunohistochemistry for CTB and nitric oxide synthase (NOS). We found that NOS-/CTB-immunofluorescent double-labeled perikarya were localized in the PPG, OG, TG, SVG and SGG, but not in the CG and SCG. The highest numbers of NOS-/CTB-immunofluorescent double-labeled neurons were found in the PPG and TG. In addition, we examined the presence of nitrergic nerve fibers in the LG using NADPH-d histochemistry and found that a large amount of NADPH-d-stained nerve fibers were distributed around the glandular acini and in the walls of glandular ducts and blood vessels. This study provides the first direct evidence showing that NO may act as a neurotransmitter or modulator involved in the parasympathetic and sensory regulation of lacrimal secretion and blood circulation, but may not be implicated in the sympathetic control of LG activities, and that nitrergic nerve fibers in the LG arise mainly from parasympathetic postganglionic neurons in the PPG and sensory neurons in the TG. The present results suggest that NO plays an important role in the regulation of LG activities.

Animals↗
PubMed2001

Pre-exposure with low-dose UVA suppresses lesion development and enhances Th1 response in BALB/c mice infected with Leishmania (Leishmania) amazonensis.

This study was conducted to determine whether exposing mice to ultraviolet (UV) radiation would alter the pathogenesis of infection with Leishmania (Leishmania) amazonensis (L. amazonensis) which causes progressive cutaneous disease in susceptible mouse strains. BALB/c mice were irradiated with 10 and 30 J/cm(2) UVA on shaved skin of the back from Dermaray (M-DMR-100) for 4 consecutive days before infection with Leishmania promastigotes. The course of disease was recorded by measuring the size of lesions at various times after infection. Mice groups irradiated with UVA 10 and 30 J/cm(2) showed significantly suppressed lesion development compared with the non-irradiated mice. Light and electron microscopy revealed a few parasites at the site of inoculation in UVA-irradiated subjects. Sandwich enzyme-linked-immunosorbent-assay (ELISA) examination of sera showed dose dependently upregulated interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12, and downregulated interleukin (IL)-4 and interleukin (IL)-10 levels in UVA-irradiated as compared with the non-irradiated mice. Positive signals for IFN-gamma mRNA in irradiated mice were obtained by RT-PCR, while non-irradiated mice showed negative results. None of the examined samples showed signal for IL-4 mRNA. The present study disclosed that exposure of mice to different low-doses of UVA irradiation prior to infection may interfere with immunity to L. amazonensis in the murine model. This indicates that the cell-mediated response switch from Th2 to Th1 pattern suppressed the cutaneous lesions of L. amazonensis.

Animals↗
PubMed2001

Decreased expression of MAP-2 and GAD in the brain of cats infected with feline immunodeficiency virus.

HIV-1 infection is often complicated by the dysfunction of central nervous system (CNS). Degenerative neuronal changes as well as neuronal loss have been documented in individuals with acquired immunodeficiency syndrome. Feline immunodeficiency virus (FIV) causes similar CNS manifestation and FIV infected cats provide an animal model for human immunodeficiency virus infection in humans. In this study, we examined the brain of FIV-infected cats and controls with immunohistochemical techniques using antibodies to microtubule-associated protein 2 (MAP-2) and glutamic acid decarboxylase (GAD). We found a significant decrease in expression of MAP-2 and GAD in neurons of infected animals compared to controls. In contrast, the expression of neurofilaments and glial fibrillary acidic protein was rather increased. The changes observed in the brain were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases like Alzheimer's disease and other dementing disorders. These changes in the feline brain give insight into the deleterious effects of FIV on the CNS.

Animals↗
PubMed2001

[Efficacy of tonsillectomy on psoriasis and tonsil histology].

Treatment outcomes of tonsillectomy were studied in 7 Japanese patients with psoriasis--3 males and 4 females aged 9 to 46 years (median: 23 years)--followed up 2 to 9 years after tonsillectomy. All skin lesions disappeared in 3 patients, 80% of those in 2, and no change in the remaining 2 during follow-up. Of 5 in whom skin lesions improved, 4 were females and had a history of tonsillitis making skin lesions worse. In quantitative immunohistologic analysis on tonsillar tissues by CD20 and anti-ssDNA antibodies, areas of T cell-nodules were significantly expanded, but those of the B-lymphoid follicles were smaller, and the number of apoptotic cells increased in tonsils from patients with psoriasis and PPP compared to those with recurrent tonsillitis. The area of T cell-nodules and the number of apoptosis cells were significantly larger in tonsils from 4 patients with complete recovery after tonsillectomy compared to the remaining 9 without complete recovery. This suggests that histologic evaluation may be helpful in estimating the effectiveness of tonsillectomy.

Adolescent↗
PubMed2001

[Left adrenocortical cancer with inferior vena cava tumor thrombus--a case report].

An 62-year-old male was admitted to our hospital for an evaluation of high grade fever, body weight loss and lumbago. He was diagnosed as having a left adrenal tumor with intracaval extension and underwent a radical surgery, including resection of the tumor, left kidney, spleen and IVC tumor thrombus. Histopathological diagnosis was adrenocortical carcinoma with tumor thrombus. To our knowledge, our case seems to be the 8th case report of left adrenocortical cancer with tumor thrombus extension into IVC. Average survival of reported cases was about 15 months. At 4 months after surgery, the patient died due to lung metastasis.

Adrenal Cortex Neoplasms↗
PubMed2000

Simultaneous production of granulocyte colony-stimulating factor and parathyroid hormone-related protein in bladder cancer.

A case of bladder cancer with simultaneous production of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) is reported. An 81-year-old male patient was admitted to the Saitama Medical School for treatment of gross hematuria, leukocytosis and hypercalcemia and diagnosed as having advanced bladder cancer. Immediately after a cystectomy was carried out, his white cell count and serum calcium levels returned to normal. However, the tumors recurred locally and the recurrence was accompanied by an increase in the serum G-CSF and PTHrP levels with a recurrent elevation of white cell count and the serum calcium level. The production of G-CSF and PTHrP in the tumor cells was confirmed by immunohistochemistry.

Aged↗
PubMed2000

Hypercalcemia in a patient with renal cell carcinoma producing parathyroid hormone-related protein and interleukin-6.

A patient with renal cell carcinoma who developed humoral hypercalcemia of malignancy is reported. A 52-year-old male patient was diagnosed with renal cell carcinoma and multiple lung metastases. A cell line isolated from the surgical specimen exhibited continuous production of parathyroid hormone-related protein (PTHrP) in vitro. The production of PTHrP from the cancer cells was confirmed by RT-PCR and immunoradiometric assay. The serum calcium level was not enhanced, whereas the lung lesion was developing and producing interleukin-6, a possible modulator of osteoclastic resorption. Hypercalcemia was induced when the PTHrP concentration increased up to 3.3 pmol/L.

Carcinoma, Renal Cell↗
PubMed2000

The extracellular domain of BPAG2 has a loop structure in the carboxy terminal flexible tail in vivo.

The 180 kDa bullous pemphigoid antigen is a hemidesmosome-associated transmembranous protein with a molecule length estimated to be 190-230 nm, which is much longer than the transverse length of the lamina lucida and lamina densa. The purpose of this study was to clarify the precise in vivo structure of the 180 kDa bullous pemphigoid antigen in normal human skin. We used three monoclonal antibodies directed to (i) the intracellular globular head of the 180 kDa bullous pemphigoid antigen, (ii) the mid-portion of the flexible tail of the antigen, corresponding approximately to amino acids 1000-1320, and (iii) the carboxyl terminal end, corresponding approximately to amino acids 1320-1500 of the antigen. Using low temperature postembedding immunoelectron microscopy, we quantitated the distribution of immunogold labeling of these monoclonal antibodies in normal human skin. The results showed that the monoclonal antibodies (i) bound to the intracellular portion of the hemidesmosome at a mean distance of 20 nm from the plasma membrane, (ii) bound to the lamina densa beneath the hemidesmosome at a mean distance of 65 nm from the plasma membrane, and (iii) bound to the lamina densa-lamina lucida interface at a mean distance of 39 nm from the plasma membrane. Considering the reported size of the 180 kDa bullous pemphigoid antigen, our results indicate that the extracellular domain of the antigen has at least one loop structure in the lamina densa in vivo. This unique structure of the antigen is thought to contribute to dermo- epidermal adhesion by intertwining with other basement membrane components.

Amino Acid Sequence↗