Osaka University Medical School Research Articles

Pathophysiology and pathogenesis and visceral fat obesity

MATSUZAWA, YUJI, IICHIRO SHIMOMURA, TADASHI NAKAMURA, YOSHIAKI KENO, KASUAKI KOTANI, KATSUTO TOKUNAGA. Pathophysiology and pathogenesis of visceral fat obesity. Obes Res. 1995;3 (suppl2):187~-194s. Based on the analysis of fat distribution by computed tomography (CT) scans, the classification scheme for obesity should include visceral fat obesity in which fat accumulationis predominant in the intra-abdominalcavity. Obese subjectsivith visceral fat accumulation more frequently demonstrateimpairment of glucose andlipid metabolism than those withsubcutaneous fat accumulation. Wehaveshownthatvisceralfat obesity is present in almost90% ofobesepatientswithischemicheart disease. Even in non-obese subj ects, visceral fat accumulation is correlatedwith glucose intolerance, hyperlipidemia and hypertension. Forty percent of non-obese subjects with coronary artery disease (CAD) had increased visceral fat. In non-obese subjects, visceral fat area assessed by abdominal CT at the level of the umbilicus correlates with metabolic risk factors, whereas in obese subjects the visceralfat area to subcutaneous fat area ratio provides a more significant correlation. From clinical and basic investigations, aging, sex hormones, excess intake of sucrose and lackof physical exercise have been suggested to be determinants for visceral fat accumulation. Since intra-abdominal fat (mesenteric andomentum fat) has beenshown to havehigh activities of bothlipogenesis and lipolysis,its accumulation can induce high levels offree fatty acids, a product of lipolysis, in portal circulation which go into the liver. Excess free fatty acids may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis. From The Second D e p m c n t of Internal M d c m c , Osaka UNVCIX~~ Med~cal School. 2-2, Yamadaoka S u b , Osaka 565, Japan. Repnnt requests to Dr. Matsuzawa. The Second Department of Internal Medicine. Osaka University Medical School. 2-2. Yamadaoka Suita, Osaka 565. Japan. Copynght 01995 NAASO. Thus we propose a disease entity, visceral fat syndrome,whichmay increase susceptibility to atherosclerosis due to multiple risk factors induced by visceral fat accumulation.

Molecular characterization of a cloned human oxytocin receptor

We describe here the binding and functional properties of a cloned human oxytocin receptor (OTR). We established a transient OTR expression system on COS-1 cells, which do not express vasopressin receptors. With the transfected cells and [3H]oxytocin, the dissociation constant (Kd) of OTR to oxytocin was 6.0 +/- 1.1 nmol/l; the binding properties of several oxytocin-related peptides were also examined. The functional properties of OTR were determined by an electrophysiological method, using a Xenopus laevis oocyte injected with in vitro transcribed OTR mRNA. These two methods showed that [Phe2,Orn8]vasotocin, a vasopressin agonist, was an OTR antagonist. A combination of these methods using cloned OTR cDNA is a novel and effective method for the investigation of oxytocin-related ligands.

Involvement of autocrine mechanism of transforming growth factor-beta in the functional differentiation of pregnant mouse mammary gland.

We studied the presence and possible role of the autocrine mechanism of transforming growth factor-beta (TGF-beta) in pregnant mouse mammary gland. Northern blot analysis revealed the expression of the TGF-beta 1 gene transcript at 2.5 kb in mammary epithelial cells isolated from virgin and mid-pregnant mice. The TGF-beta activity was higher in the conditioned medium from mid-pregnant mouse mammary explants than that from virgin explants by a bioassay system using mink lung epithelial cells. A binding study using [125I]TGF-beta 1 as a ligand showed that pregnant mouse mammary epithelial cells possessed a single class of high-affinity TGF-beta 1 binding sites (Kd = 28.0 pmol/l, 1.2 x 10(4) sites per cell). These results suggested the presence of a TGF-beta autocrine mechanism in pregnant mouse mammary epithelial cells. Next, we examined the effect of TGF-beta 1 on the functional differentiation of pregnant mouse mammary gland. Transforming growth factor-beta 1 inhibited alpha-lactalbumin production in cultured mammary explants from mid-pregnant mice in a dose-dependent manner without inhibiting DNA synthesis. All these results suggest that TGF-beta may play a role in regulating the functional differentiation of mouse mammary glands during pregnancy.

Neuropathological changes in rat brain injected with Alzheimer tau. Paired helical filaments, and amyloid cores : T.Kudo 1, T.Tanaka 2, M.Takeda 1, T.Nishimura 1, I.Grundke-Iqbal 2, and K.Iqbal 2. 1Department of Neuropsychiatry, Osaka University Medical School, Suita, Osaka 565 Japan. 2New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 USA

Neuropathological changes in rat brain injected with Alzheimer tau. Paired helical filaments, and amyloid cores : T.Kudo 1, T.Tanaka 2, M.Takeda 1, T.Nishimura 1, I.Grundke-Iqbal 2, and K.Iqbal 2. 1Department of Neuropsychiatry, Osaka University Medical School, Suita, Osaka 565 Japan. 2New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 USA

Corneal Epithelial Wound Healing in the Denervated Eye

*Department of Ophthalmology, Osaka University Medical School, Osaka, Japan †Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Linkage analysis of early-onset Alzheimer's disease in the Japanese population : K. Kamino, K. Nagano, ∗K.I-i, T. Miki and T. Ogihara. Dept. Geriatric Medicine, Osaka University Medical School, Suita, Osaka 565, Japan, ∗Dept. 1st Pathology, Tokushima University Medical School, Tokushima 770, Japan

Linkage analysis of early-onset Alzheimer's disease in the Japanese population : K. Kamino, K. Nagano, ∗K.I-i, T. Miki and T. Ogihara. Dept. Geriatric Medicine, Osaka University Medical School, Suita, Osaka 565, Japan, ∗Dept. 1st Pathology, Tokushima University Medical School, Tokushima 770, Japan

Association study of apolipoprotein E and sporadic Alzheimer's disease in the Japanese population : A. Yoshiiwa 1, K. Kamino 1, T. Miki 1, K. Nagano 1, Y. Nonomura 2, H. Yoneda 2 T. Sakai 2 and T. Ogihara 1. 1.Dept. Geriatric Medicine, Osaka University Medical School. 2.Dept. Neuropsychiatry, Osaka Medical College, Osaka, Japan

Association study of apolipoprotein E and sporadic Alzheimer's disease in the Japanese population : A. Yoshiiwa 1, K. Kamino 1, T. Miki 1, K. Nagano 1, Y. Nonomura 2, H. Yoneda 2 T. Sakai 2 and T. Ogihara 1. 1.Dept. Geriatric Medicine, Osaka University Medical School. 2.Dept. Neuropsychiatry, Osaka Medical College, Osaka, Japan

Systemic nature of Alzheimer's disease: Special reference to the cutaneous tissue : T. Nishimura, M. Takeda, and Y. Ikura: Department of Neuropsychiatry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, JAPAN

Systemic nature of Alzheimer's disease: Special reference to the cutaneous tissue : T. Nishimura, M. Takeda, and Y. Ikura: Department of Neuropsychiatry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, JAPAN

The immunopositive structure in Alzheimer's disease brain demonstrated with monoclonal antibody against APP carboxy terminal sequence : M.Okochi, T.Takeda, T.Azuma, H.Hattori, H.Niigawa, T.Kudo, Y.Nakamura, and T.Nishimura. Department of Neuropsychiatry, Osaka University Medical School,Suita shi, Osaka, 56.5 JAPAN

The immunopositive structure in Alzheimer's disease brain demonstrated with monoclonal antibody against APP carboxy terminal sequence : M.Okochi, T.Takeda, T.Azuma, H.Hattori, H.Niigawa, T.Kudo, Y.Nakamura, and T.Nishimura. Department of Neuropsychiatry, Osaka University Medical School,Suita shi, Osaka, 56.5 JAPAN

High sensitivity to peripheral blood lymphocytes and low HLA-class I antigen expression of small cell lung cancer cell lines with diverse chemo-radiosensitivity : Tanio Y, Watanabe M, Osaki T, Tachibana I, Kawase I, Kuritani T et al. Department of Medicine III, Osaka University Medical School, 1-1-50, Fukushima, Fukushima-ku, Osaka 553. Jpn J Cancer Res 1992;83:736–745

High sensitivity to peripheral blood lymphocytes and low HLA-class I antigen expression of small cell lung cancer cell lines with diverse chemo-radiosensitivity : Tanio Y, Watanabe M, Osaki T, Tachibana I, Kawase I, Kuritani T et al. Department of Medicine III, Osaka University Medical School, 1-1-50, Fukushima, Fukushima-ku, Osaka 553. Jpn J Cancer Res 1992;83:736–745

Oxygen transport during incremental exercise load as a predictor of operative risk in lung cancer patients : Nakagawa K, Nakahara K, Miyoshi S, Kawashima Y. 1st Department of Surgery, Osaka University Medical School, Fukushima, Fukushima-ku, Osaka 553. Chest 1992;101:1369-75

Oxygen transport during incremental exercise load as a predictor of operative risk in lung cancer patients : Nakagawa K, Nakahara K, Miyoshi S, Kawashima Y. 1st Department of Surgery, Osaka University Medical School, Fukushima, Fukushima-ku, Osaka 553. Chest 1992;101:1369-75

A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer : Masuno T, Kishimoto S, Ogura T, Honma T, Niitani H, Fukuoka M et al. Department of Medicine III, Osaka University Medical School, 1-50 Fukushima, 1-chrome, Fukushima-ku, Osaka 553. Cancer 1991;68:1495–1500

A comparative trial of LC9018 plus doxorubicin and doxorubicin alone for the treatment of malignant pleural effusion secondary to lung cancer : Masuno T, Kishimoto S, Ogura T, Honma T, Niitani H, Fukuoka M et al. Department of Medicine III, Osaka University Medical School, 1-50 Fukushima, 1-chrome, Fukushima-ku, Osaka 553. Cancer 1991;68:1495–1500

Radical mastectomy with parasternal node dissection or radiation to the parasternal region for breast cancer of medial or central location.

In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n = 70): standard radical mastectomy alone; Group B (n = 34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n = 62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 percent and 79 percent in group A, 82 percent and 67 percent in group B, and 82 percent and 70 percent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found.

Inoculation study of buffy coat from Alzheimer patient with a mutation in amyloid beta-protein precursor: M. Takeda, S. Tanimukai, M. Okochi, T. Tanaka, Y. Nakamura, Y. Tatebayashi, T. Kudo, T. Nishimura. Dept. of Neuropsychiatry, Osaka University Medical School, Fukushima, Fukushima-ku, Osaka 553 JAPAN.

Inoculation study of buffy coat from Alzheimer patient with a mutation in amyloid beta-protein precursor: M. Takeda, S. Tanimukai, M. Okochi, T. Tanaka, Y. Nakamura, Y. Tatebayashi, T. Kudo, T. Nishimura. Dept. of Neuropsychiatry, Osaka University Medical School, Fukushima, Fukushima-ku, Osaka 553 JAPAN.

Characterization and purification of an immunosuppressive factor produced by a small cell lung cancer cell line : Ikeda T, Masuno T, Ogura T, Watanabe M, Shirasaka T, Hara H et al. Third Department of Internal Medicine, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553. Jpn J Cancer Res 1991;82:332–338

Characterization and purification of an immunosuppressive factor produced by a small cell lung cancer cell line : Ikeda T, Masuno T, Ogura T, Watanabe M, Shirasaka T, Hara H et al. Third Department of Internal Medicine, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553. Jpn J Cancer Res 1991;82:332–338

Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy : Tanio Y, Watanabe M, Inoue T et al. Third Department of Internal Medicine, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553. Jpn J Cancer Res Gann 1990;81:289–297

Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy : Tanio Y, Watanabe M, Inoue T et al. Third Department of Internal Medicine, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, Osaka 553. Jpn J Cancer Res Gann 1990;81:289–297

Introduction and implementation of problem-solving lectures for instruction in medical biochemistry at Osaka University Medical School in Japan

Introduction The scope of recent developments in the life sciences and particularly developments in the field of biochemistry is really remarkable, and the amount of scientific knowledge accumulated so far is enormous. The main problem lies in (a) the quantity and type of information which students should gain in the medical school in order to acquire the maximum necessary knowledge, and (b) how they should select from the information at their disposal. An international survey of the biochemistry curriculum was reported by Bryce. 1 However, it is now actually impossible to impart a thorough understanding of the field within limited period of time typical of a university course, and self-directed learning by the students is becoming increasingly important. Conventionally, medical school biochemistry has been taught almost entirely through one-sided lectures. Problem-solving lectures, in which the students engage in handling and solving problems of their own choice, are rare. The importance of this new type of lecture was pointed out by the GEPEP report. 2 In the present study, the new type of lecture was used for the first time at Osaka University Medical School, Japan and the results were evaluated.

Reflex Epilepsy Induced by “Soroban”, A Japanese Calculator

Three patients with reflex epilepsy and myoclonic jerks of the right arm and fingers precipitated by calculation using a Soroban are reported from the Department of Neuropsychiatry, Osaka University Medical School, Fukushima-ku, Osaka, Japan.

Intracellular free calcium dynamics and taurine prevention during the calcium paradox of cultured myocardial cells: K. Takahashi, K. Boku, Y. Ihara, H. Harada, A. Sawamura, J. Azuma. Third Department of Internal Medicine Osaka University Medical School, Osaka, Japan

Intracellular free calcium dynamics and taurine prevention during the calcium paradox of cultured myocardial cells: K. Takahashi, K. Boku, Y. Ihara, H. Harada, A. Sawamura, J. Azuma. Third Department of Internal Medicine Osaka University Medical School, Osaka, Japan

Real time visualization of cytosolic free calcium movement in anoxia-reoxygenaion using indo 1 loaded hearts: M. Nishimura, H. Matsuda, M.Kaneko, K.Kadoba, N.Sakagoshi, T.Kuratani, A.Amemiya, Y.Kawashima, K.Tagawa. First Department of Surgery and Department of Molecular and Physiological Chemistry, Osaka University Medical School, Osaka, Japan

Real time visualization of cytosolic free calcium movement in anoxia-reoxygenaion using indo 1 loaded hearts: M. Nishimura, H. Matsuda, M.Kaneko, K.Kadoba, N.Sakagoshi, T.Kuratani, A.Amemiya, Y.Kawashima, K.Tagawa. First Department of Surgery and Department of Molecular and Physiological Chemistry, Osaka University Medical School, Osaka, Japan