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Biomedical subjects

H Kondo

Publications and source records attributed to H Kondo.

At least 469 records · Page 26Linked to original sources

Dopamine D2 receptor plays a critical role in cell proliferation and proopiomelanocortin expression in the pituitary.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the inhibitory control of secretion of pituitary hormones and in the regulation of motor function in the striatum. To elucidate the specific role of the dopamine D2 receptor (D2R) in the pituitary and brain, we generated D2R deficient (D2R mutant) mice using the gene targeting method. RESULTS: Electrophysiological studies as well as ligand binding assays show no functional D2R in mutant mice. The D2R mutant mice display a hypoactivity and a slow, creeping movement. The expression of enkephalin mRNA in the striatum is increased in the mutant mice, but not that of dynorphin and substance P. D2R mutant mice have significantly darker coat colour than their wild-type littermates and show an elevation of plasma alpha-melanocyte stimulating hormone (alpha-MSH) levels. We found corresponding hyperplastic changes of intermediate lobe of the pituitary and the increased expression of pro opiomelanocortin (POMC) in the pituitary in D2R mutant mice. CONCLUSIONS: D2R plays a critical role in the inhibitory regulation of endocrine cell proliferation and the transcription of POMC mRNA, and consequently in the regulation of alpha-MSH in plasma. D2R might be involved in the regulation of enkephalin expression in the striatum, and hence might affect the movement and the behaviour.

Animals↗

Soft-X-ray damage to biological samples.

X-ray damage to biological samples was investigated in the wavelength region of 2.7-5 nm, which overlaps the so-called 'water-window', the wavelength range of 2.4-4.3 nm usually used in X-ray microscopy. Yeast cells and myofibrils were chosen as representatives of whole cell samples and motile protein systems, respectively. The samples were exposed to X-rays using an apparatus composed mainly of a laser-plasma X-ray source, a Wolter mirror condenser, and a sample cell. The yeast cells lost their dye exclusion ability when the X-ray flux was higher than 1 x 10(6) photons micron-2, while the myofibrils lost contractility when the X-ray flux was higher than 4 x 10(5) photons micron-2. These X-ray fluxes are lower than the flux required for the X-ray microscope observation of biological samples at a resolution higher than that of light microscopes.

Animals↗

An early phase II study of etoposide (VP-16) in advanced gastric cancer.

An early phase II study was conducted to evaluate the anti-tumor effects and toxicity of etoposide in patients with unresectable or relapsed advanced gastric cancer. From April 1991 to December 1992, 13 patients were enrolled into this study; one was subsequently considered ineligible. Before enrollment, all the patients had been treated with chemotherapy which did not include etoposide. Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120 min for five consecutive days and was repeated every four weeks. Seven patients received one course of this therapy and the remaining five received two. No patient showed a complete or a partial response. No change and progressive disease were observed in three and nine patients, respectively. The clinical toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in 50, 42, and 42% of the patients, respectively. We conclude that this dose of etoposide administered according to the present schedule is ineffective in previously treated patients with advanced gastric cancer.

Adenocarcinoma↗

AFP-producing squamous cell carcinoma of the lung in an adolescent.

We report a case of primary lung cancer in a 16-year-old boy. A histologic diagnosis of squamous cell carcinoma was made by bronchoscopic biopsy before surgery. The serum alphafetoprotein (AFP) level was markedly elevated at 193 ng/dl. Preoperative and postoperative evaluation revealed no evidence of scrotal mass. We performed right pneumonectomy with combined resection of the invaded portion of the left atrium under extracorporeal circulation. Despite the rapid improvement in the patient's general condition after surgery, the AFP level continued to increase without a transient decrease and reached 3160 ng/ml on the 23rd postoperative day. When the patient was readmitted because of dyspnea and headache on the 36th postoperative day, hypercalcemia of 13.9 mg/dl was noted, and this was resistant to subsequent treatment. The patient died on the 46th postoperative day.

Adolescent↗

Altered mitochondrial gene expression in a maternal distorted leaf mutant of Arabidopsis induced by chloroplast mutator.

Chloroplast mutator (chm) of Arabidopsis is a recessive nuclear mutation that causes green and white variegation in leaves and is inherited in a non-Mendelian fashion. In this study, we have identified and characterized a mutant observed in F1 and backcrossed BC1 populations from a cross between chm1-3 and ecotype Columbia. This mutant, maternal distorted leaf (MDL), grows very poorly and is distinguished by distorted rough leaves and aborted flowering organs. Electron microscopic observation showed that in MDL plants, a significant portion of mitochondria are abnormal and appear to be nonfunctional. DNA gel blot and sequence analysis of the MDL mitochondrial DNA (mtDNA) revealed rearrangements in two mtDNA fragments associated with rps3-rpl16 genes (encoding ribosomal proteins S3 and L16, respectively). One rearrangement resulted in the insertion of the rps3-rpl16 operon downstream of atp9. An independent deletion in this region had eliminated the majority of rps3. In contrast, another rearrangement deleted part of rpl16, whereas rps3 remained intact. RNA gel blot analysis indicated that expression of these genes is also altered as a consequence of the mtDNA rearrangements. Thus, a mutation at the CHM locus affects mitochondrial gene expression, and impaired mitochondrial function may result in the distorted phenotype.

Amino Acid Sequence↗

Epidemiological analysis of prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc). Scleroderma Research Committee Japan.

For the first time, we performed an epidemiological study of SSc in Japan to study the factors influencing prognosis, survival rate and cause of death of Japanese SSc patients and to compare our data with those from foreign countries. Prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc) was analyzed based on clinical data described in case cards provided by the members of the Scleroderma Research Committee of the Japanese Ministry of Health and Welfare. The essential observation period was from 5 to 20 years, at ending in 1994. Ninety patients died (males 11, females 79). The age of onset of the deceased patients was significantly higher than that of surviving patients (deceased, 45.6 yrs, surviving 41.3 yrs). Statistically significant factors for a poor prognosis were as follows: Barnett type III > type II > type I, positive for anti-Scl-70 antibody, negative for anti-centromere antibody. The survival rate at 5 years after the onset of the disease was 0.937, followed by 0.82 at 10 years, 0.567 at 20 years and 0.40 at 30 years after the onset. Sex was not a predictor for prognosis, although male patients died at an earlier stage of the disease. The most common causes of death were heart failure, pulmonary insufficiency, lung fibrosis, and renal failure. Twenty-four patients had cancer of which 13 were lung cancers. The current status of the survival rate and prognostic factors of 496 Japanese SSc patients is summarized. In future, more well-controlled studies using the same criteria should be performed for the better understanding and management of SSc.

Adult↗

Construction of a dimeric DNA-binding peptide model by peptide-anthraquinone conjugation.

A peptide-anthraquinone conjugate was designed and synthesized containing linked peptide chains composed of Asp-Pro-Ala-Ala-Leu-Lys-Arg-Ala-Arg-Asn-Thr-Glu-Ala- Ala-Arg-Arg-Ser-Arg-Ala-Arg-Lys-Leu-Gln-Arg-Met, representing the basic region of GCN4. The two peptides were joined with anthraquinone at its 1- and 8-positions in a two-fold symmetric fashion, mimicking dimeric DNA-binding proteins. Experimental data indicated both an interaction of the anthraquinone moiety with the DNA double strand and an increase in the alpha-helicity of the peptide moieties of the ligand when it binds to DNA.

Amino Acid Sequence↗

Higher cerebral dysfunction in a case with atypical multiple sclerosis with concentric lesions.

A patient with atypical multiple sclerosis (MS) with clear concentric structure was studied using high field magnetic resonance imaging (MRI). This case was considered to be Baló's concentric sclerosis. Magnetic resonance imaging showed diffuse multiple concentric demyelinating lesions in the bilateral centrum semiovales, which finally regressed with the necrotic lesions remaining when the patient was discharged. During his clinical course, he showed some higher cerebral dysfunctions, such as memory disturbance, constructual apraxia and acalculia. He was treated with glycerin, prednisone and rehabilitation; all of which were effective in his recovery. Over a 4 month period, the patient recovered clinically, but some intellectual impairment remained.

Adult↗

Nuclear p53 accumulation by small-sized adenocarcinomas of the lung.

In order to evaluate the alterations of nuclear p53 accumulation in early stage adenocarcinomas of the lung, nuclear p53 accumulation by small-sized peripheral adenocarcinomas of the lung was examined immunohistochemically. Peripheral adenocarcinomas of the lung, 2 cm or less in diameter, have been classified into two groups; one showing replacing growth of the pulmonary alveolar structure and the other showing non-replacing growth. The former group has been subdivided into three microscopic subtypes: type A, localized bronchioloalveolar carcinoma (LBAC); B, LBAC with foci of pulmonary alveolar structural collapse; and C, LBAC with foci of active fibroblastic proliferation. Type C is thought to be advanced carcinoma, which develops progressively from types A and B. Two of 32 (6%) types A and B carcinomas, 37 of 133 (28%) type C carcinomas and 14 of 35 (40%) non-replacement-type adenocarcinomas showed positive nuclear staining for p53. The positive staining frequency was significantly higher for type C than for types A and B (P < 0.05). These results suggest that nuclear p53 accumulation occurs in the transition from the early to advanced stages of replacement-type adenocarcinoma development and it may be a clinically useful indicator of the degree of tumor malignancy.

Adenocarcinoma↗

[A SLE case with toxic shock syndrome after delivery].

We experienced a SLE patient with TSS after delivery. A 32-year-old SLE patient was transferred to our division due to fever, diarrhea, erosive rash, pericardial effusion, myalgia, low blood pressure, thrombocytopenia and hypoproteinemia which appeared two days after transvaginal delivery. At the time of admission, we considered these symptoms as the exacerbation of SLE, and treatment with high doses of steroid was started. It was when TSST-1-producing-MRSA was cultured from the vagina and uterus that TSS was suspected. 2 g/day of vancomycin was administered and her symptoms improved. As observed in this case, it is important to consider TSS as one of the complications seen with SLE patients after delivery.

Adult↗

Coronary back flow pressure is elevated in association with increased left ventricular end-diastolic pressure in humans.

To clarify the effect of left ventricular (LV) diastolic pressure on the coronary pressure-flow relation in humans, the instantaneous diastolic coronary pressure-Doppler flow velocity relation was analyzed at rest and during papaverine-induced maximal vasodilation in 15 patients with angiographically normal coronary arteries. The values for slope (alpha PF) and zero-flow pressure intercept (Pzf index) of the instantaneous diastolic coronary pressure-flow velocity relation were obtained by a linear regression analysis. Although alpha PF did not correlate with LV end-diastolic pressure (EDP), the Pzf index correlated positively with LVEDP both at rest and during maximal vasodilation (r = 0.64, P < 0.05 and r = 0.58, P < 0.05, respectively). Thus, the back pressure to coronary inflow, as indicated by the Pzf index, may be elevated in patients with increased LVEDP, resulting in the rightward shift of the maximally dilated coronary pressure-flow relation and decreased maximal coronary flow and reserve at any given perfusion pressure.

Adult↗

Gastric attaching and effacing Escherichia coli lesions in a puppy with naturally occurring enteric colibacillosis and concurrent canine distemper virus infection.

A puppy suffering from chronic diarrhea was humanely killed at 90 days of age. Numerous Gram-negative bacilli were found adhering to the surface of as well as within epithelial cells from the stomach to the colon. Canine distemper virus inclusions were in the epithelial cytoplasm of the esophageal, gastric, and intestinal mucosa. Typical attaching and effacing ultrastructural lesions were in the stomach, and some bacilli were in the cytoplasm of the epithelial cells. Escherichia coli, isolated from the contents of the small intestine, belonged to serotype 0118: NM and were negative for plasmid-encoded EPEC adherence factor (EAF) and positive for the E. coli attaching effacing (eae) gene. Immunohistologically, bacilli attached to the epithelium from the stomach to the colon were positive for antisera against E. coli 0118. E. coli 0118: NM inoculated into human tissue culture cells (HEp-2 cells) were attached to the surface of the cells and within the cytoplasm. This is the first report of attaching and effacing E. coli (AEEC) infection in the stomach of the dog.

Animals↗

Immunological evidence for the expression of the Fas antigen in the infant and adult human ovary during follicular regression and atresia.

Immunohistochemical localization of the Fas antigen in the infant and adult human ovary during follicular growth, regression, and atresia was examined by the avidin/biotin immunoperoxidase method with a monoclonal antibody to the Fas antigen. Western blotting was used to confirm the presence of the Fas antigen protein. In primordial and primary follicles within the normal adult ovary, only the oocyte showed moderate immunostaining for the Fas antigen. In secondary and antral follicles, only the oocyte showed weak staining for the Fas antigen, while in preovulatory follicles, neither the oocyte nor the granulosa and theca cells were immunostained for the Fas antigen. In corpora lutea, the Fas antigen staining became apparent in the granulosa lutein cells during the early luteal phase and intensified during the mid luteal phase, while the theca lutein cells became positive for the Fas antigen staining during the mid luteal phase. During the late luteal phase, the staining intensity of the Fas antigen in the regressing corpora lutea further increased. As the regressing corpora lutea were converted into corpora albicans, the staining intensity decreased, and the corpora albicans and stromal cells were negative for the Fas antigen. In atretic primordial and primary follicles, only the degenerating oocyte showed the Fas antigen staining. By contrast, in atretic antral follicles, the Fas antigen staining was profound in the degenerating granulosa cells at the early stage of atresia, and at the mid stage of atresia it was intensified in the cell surface of the scattered granulosa cells and became apparent in the theca cells. At the late stage of atresia the Fas antigen remained only in the hypertrophied theca cells. In the infant ovary, only the oocyte in primordial and primary follicles exhibited intense staining for the Fas antigen. In the postmenopausal ovary, the Fas antigen staining was entirely negative. Western blot analysis revealed the presence of the Fas antigen protein with a molecular mass of 45 kDa in luteal tissues. On the basis of the recent evidence, that the Fas antigen mediates an apoptotic signal in a variety of cells, the abundant expression of the Fas antigen in the regressing corpora lutea and atretic follicles suggests that the Fas antigen participates in luteal regression and follicular atresia through the apoptotic process. Furthermore, notable expression of the Fas antigen in the oocyte of primordial and primary follicles within the infant and adult human ovary followed by the decrease in the Fas antigen expression in the oocyte with the advance of follicular maturation suggests that the Fas antigen expression in the oocyte may play a role in follicular selection.

Adult↗

Necrotizing myopathy with pipestem capillaries and minimal cellular infiltration: a case associated with cutaneous signs of dermatomyositis.

In 1991, Emslie-Smith and Engel described a distinct form of idiopathic inflammatory myopathy they called "necrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC) and minimal cellular infiltration." We describe a patient with exercise-dependent painful myopathy related to a necrotizing myopathy with pipestem capillaries in whom mild cutaneous signs of dermatomyositis were detected 7 years after onset and who subsequently developed multiple cerebral infarcts.

Capillaries↗

Characterization of cyclophilin 40: highly conserved protein that directly associates with Hsp90.

Cyclophilin 40 (CyP4O) is a recently identified member of the cyclophilin family that may be a component of unactivated steroid receptor complexes. It consists of an N-half portion that is highly homologous to cyclophilin A and has peptidyl prolyl isomerase (PPIase) activity, and a C-half portion that resembles the C-terminal portion of FKBP52 (FK506 binding protein 52), another component of unactivated steroid receptor complexes. To better understand the structure and functional characteristics of this new class of cyclophilin, we have raised monoclonal antibodies against the C-half portion of human CyP4O. Immunostaining with the antibodies showed its preferential localization in cytoplasm. One antibody cross-reacted with a 45 kDa protein in yeast, suggesting high conservation throughout evolution. A CyP4O-associated protein was isolated from rabbit reticulocyte lysate by means of an affinity resin, and was identified as hsp90. The C-half portion of CyP4O was necessary and sufficient for the interaction.

Amino Acid Isomerases↗

NAD-specific 6-phosphogluconate dehydrogenase in lactic acid bacteria.

6-Phosphogluconate dehydrogenase was screened in for cell-free extracts from seventeen strains of lactic acid bacteria. Three types of the enzyme could be classified according to the coenzyme specificity: NAD-specific, NADP-specific, and non-specific types. The two strains that had a heterofermentative pathways had an NAD-specific 6-phosphogluconate dehydrogenase. This type had higher enzyme activity per proteins in the cell-free extracts, and more specificity to NAD compared to the other types of the enzyme in the lactic acid bacteria studied.

Cell-Free System↗

Peripheral neuropathy of dietary riboflavin deficiency in racing pigeons.

An occurrence of peripheral neuropathy in nine 14- to 55-day-old racing pigeons was documented. The predominant clinical signs were diarrhea, and leg and wing paralysis. Grossly, there was discoloration and swelling of all the peripheral nerve trunks. Microscopic lesions comprising swelling, fragmentation and demyelination of myelin sheaths, and proliferation of Schwann cells, were seen in the peripheral nerves of all birds examined. These changes were associated with moderate to severe swelling, fragmentation, atrophy and loss of axons. The peripheral nerve lesions in these cases were similar to those of dietary riboflavin deficiency in chickens. An analysis of the diet given to the pigeons indicated that the riboflavin concentration was only 0.9 mg/kg feed.

Animal Feed↗

Alveolar hydatidosis in a gorilla and a ring-tailed lemur in Japan.

Alveolar hydatidosis by Echinococcus multilocularis (Em) infection occurred on a 22-year-old (approx.) male gorilla (Gorilla gorilla) and a 4-year-old female ring-tailed lemur (Lemur catta) in a zoo, in Hokkaido, Japan. Case 1: The gorilla presented neurologic signs in course of nine months and died. Pathologically, alveolar hydatid lesions were found in the liver, the liver-associated lymph nodes, the cerebrum, and the lungs. A protoscolex was found only in one hepatic cyst. Case 2: In the lemur, large masses of hydatide cysts were found on the liver and at the lung-associated lymph nodes. Cysts contained numerous calcareous corpuscles and protoscolices. The lemur appears a favorable intermediate-host for Em. The identification of Em in both cases were confirmed by PCR.

Animals↗