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Biomedical subjects

A Aoki

Publications and source records attributed to A Aoki.

At least 37 records · Page 2Linked to original sources

Response of bronchiolar Clara cells induced by a domestic insecticide. Analysis of CC10 kDa protein content.

Clara cells are the most reactive to xenobiotics among the mammalian respiratory tract cells. In this report, the response of Clara cells to acute or repetitive exposure to a commercial insecticide was studied, correlating the changes in the cell ultrastructure with the intracellular content of CC10 kDa protein as quantified by immunocytochemical morphometry. After a single exposure to insecticide, Clara cells reveal great expansion of their volume which is accompanied by a remarkable proliferation of smooth endoplasmic reticulum, swelling of the mitochondria, and changes in the nucleus. Morphometric analysis of CC10 bronchiolar content showed significant increases in both the number of Clara cells and the immunostained areas in individual cells. By western blot, CC10 immunoreactive bands strongly increased in lungs after insecticide treatment, but they were only slightly higher than the control when the vehicle of the insecticide was tested. By repetitive exposure to the insecticide, the rat bronchiolar epithelium undergoes extensive alterations, particularly on Clara cells, the number of which is considerably reduced. The remaining Clara cells shrink in size and the typical dome-like cytoplasm is lost. Secretory granule release is no longer seen and the changes of their shape and secretory content reflect a marked degradation and condensation process. Repetitive exposures to the insecticide produced a severe blockage of the proteinopoietic activity, particularly on the synthesis of CC10. Results reported here reveal that the acute inhalation of a commercial insecticide produces hypertrophy of Clara cells, a significant augmentation of CC10 synthesis, and probably differentiation de novo of Clara cells, and morphological changes compatible with a detoxification process. By contrast, exposure for 5 days provoked a general inhibitory effect on Clara cell activity with the loss of cell capability to synthesize and secrete CC10 kDa protein.

Animals↗

Cellular and functional interactions between gonadotrophs and lactotrophs in pituitary cell cultures.

Lactotroph secretory activity is regulated by hypothalamic stimulating and inhibiting factors as well as peripheral endocrine hormones. In addition to this important control domain, the pituitary gland displays an intrinsic regulatory ability through autocrine and paracrine signals. To evaluate the role of gonadotrophs in the regulation of prolactin (PRL) secretion, a comparative study was performed applying two regulatory agents that operate through different physiological mechanisms: gonadotropin-releasing hormone (GnRH), which releases regulatory factors co-localized in secretory granules of gonadotrophs, stimulating PRL secretion from lactotrophs; and angiotensin II (AII), with direct effects on lactotroph secretion through specific receptors. In these studies performed in regular and purified primary pituitary cell cultures from female rats, the lactotrophs comprised the largest population of cells (about 51%), whereas gonadotrophs represented only a small fraction (3%) of the total pituitary cell count. In regular cell cultures treatments with AII and GnRH showed a similar secretory behavior, increasing PRL output 73% and 63%, respectively. The stimulation with GnRH and AII of cell cultures with purified lactotrophs and gonadotrophs provided comparable results, but the response of lactotrophs was significantly higher (106% and 138%, respectively) than that recorded in regular cell cultures. Simultaneous AII treatment with an antipeptide antagonist to AII receptor (AII-antipep) completely blocked the PRL release induced by AII. The co-incubation of cells with GnRH and AII-antipep suppressed the peak of PRL release caused by GnRH, confirming that AII is a paracrine agent released by gonadotrophs stimulated with GnRH. The different secretory behavior of lactotrophs treated with AII and GnRH in both regular and purified cell cultures is indicative of the degree of functional interactions between different pituitary cell types. The present study supplies morphological and functional information on the cell-to-cell interactions, which plays an important role in the intrinsic regulatory control of PRL secretion.

Angiotensin II↗

In vitro evaluation of Er:YAG laser scaling of subgingival calculus in comparison with ultrasonic scaling.

The purpose of the present study was to evaluate the effectiveness of Er:YAG laser scaling and the morphological and histological changes of the laser-scaled root surface in comparison with the effectiveness and root surface changes produced by conventional ultrasonic scaling. Fifty-three periodontally involved human extracted teeth with a band of subgingival calculus were used. The teeth were divided randomly into 2 groups for laser scaling and ultrasonic scaling. Laser irradiation was performed at an energy output of 40 mJ/pulse and 10 pulses/s under water spray, with the probe tip contacted obliquely to the root surface. Ultrasonic scaling was performed at a clinically standard power setting. The time required for scaling, the scaled area and the temperature changes were determined using both methods of treatment. The features of the scaled surfaces were examined by histological and scanning electron microscope (s.e.m.) observations. The Er:YAG laser provided subgingival calculus removal on a level equivalent to that provided by the ultrasonic scaler, without major thermal elevation. Macroscopically, the laser-treated root surface was somewhat rougher than or similar to the ultrasonically scaled root. However, the efficiency of the laser scaling was lower than that of the ultrasonic scaling. In addition, histological examination revealed a thin deeply stained zone on the lased root surface, and s.e.m. analysis revealed a characteristic microroughness on the lased surface. The laser scaling provided a level of calculus removal that was similar to that provided by the ultrasonic scaling. However, the Er:YAG laser produced superficial, structural and thermal microchanges on the root cementum.

Dental Calculus↗

Somatotroph response to periodical IGF-I administration to male rats.

Insulin-like growth factor I (IGF-I) downregulates growth hormone (GH) expression in pituitary cell cultures. However, in vivo different results were found depending on the experimental protocol used. We determined the kinetics of changes of pituitary and serum GH concentrations after subcutaneous IGF-I administration (240 microg/100 g body weight) to rats every 12 h for various periods. These parameters were correlated with changes in the somatotroph cell population. A significant increase in serum GH was registered at 6 h after IGF-I injection. At this time, some somatotroph cells exhibited ultrastructurally signs of high secretory activity, whereas adjacent somatotroph cells showed a quiescent appearance with sizeable stores of secretory granules. In contrast, serum GH levels remained unchanged at 1, 2 and 12 h after each IGF-I injection. Pituitary GH concentrations were comparable to control levels during the first 48 h and declined significantly at 72 h and 96 h of IGF-I treatment. After these prolonged periods of time of treatment, the size and extension of organelles involved in protein synthesis decreased and mature secretory granules in the cytoplasm increased significantly in GH-secreting cells. The somatotroph cell density remained unchanged even at 96 h of treatment. In conclusion, our results suggest that periodical IGF-I administration to rats does not inhibit GH secretion. Interestingly, IGF-I injections induced early and significant increases in serum GH levels. This result may be a consequence of a temporary stimulatory action on somatotroph cells concurrent with increased secretory activity.

Animals↗

Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats.

Female F344 rats treated chronically with diethylstilbestrol (DES) develop prolactin (PRL)-producing pituitary tumors. These tumors are larger in female than in male rats. To investigate gender differences in DES-induced pituitary tumor formation, we employed female and male rats and neonatally androgenized females, which received 100 microg of testosterone propionate (TP) after birth. At 3 months of age, all rats were deprived of their gonads and divided into control and DES-treated groups. Forty days after beginning treatment, control pituitary weight and serum PRL were similar in gonadectomized males (GDX), ovariectomized females (OVX) and androgenized-ovariectomized females (OVX + TP), but weight of DES-induced tumors was 2.5-fold higher and serum PRL 5.6-fold higher in OVX + DES than in GDX + DES or OXV + TP + DES (p<0.001). At the pituitary level, nuclear estrogen receptors (NE(2)R) amounted to >100 fmol/mg DNA in all rats receiving DES. However, NE(2)R were lower in OVX + DES (101.3+/-9.0 fmol/mg DNA) than in GDX + DES (174.6 +/-16.8; p<0.05) and in OXV + DES + TP (150.3+/-27.7; p<0.05). A similar profile was found for cytosolic progestin receptors. Using electron microscopy (EM), hyperplasia/hypertrophy of lactotropes was found in all DES-stimulated pituitaries. However, tumors of OVX + DES rats were enriched in hyperstimulated typical lactotropes, i.e., cells with high rate of hormonal synthesis, processing and secretion. Instead, tumors from GDX + DES and OVX + TP + DES rats were a mixture of typical and atypical lactotropes, i.e. a cell subpopulation with refractory secretory response and a few gonadotropes. In agreement with these data, immunoreactive pituitary PRL was lower in OVX + DES than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity to DES, serum and tumor PRL, NE(2)R and progestin receptors between estrogenized female rats on one side and male and TP-androgenized females on the other, may by due in part to heterogeneity of cell populations. Our data further suggest that neonatal hypothalamic exposure to androgens, as in normal males or androgenized females with masculinization of hypothalamic centers, may condition the response to DES stimulation later in life.

Animals↗

Interhemispheric glioependymal cyst associated with agenesis of the corpus callosum--case report.

A male neonate was admitted because prenatal ultrasonography indicated central nervous system abnormalities. Neurological examination showed no abnormality except for electroencephalographic spike activities. Magnetic resonance imaging revealed a cystic lesion in the left interhemispheric fissure, agenesis of the corpus callosum, and microgyria in the left frontotemporal lobes. Cerebral blood flow (CBF) was diffusely reduced. The cyst wall was partially removed and a cyst-peritoneal shunt procedure was performed. The histological diagnosis was glioependymal cyst. The spike activity disappeared and CBF dramatically improved after the operation.

Agenesis of Corpus Callosum↗

[Hematological abnormalities of primary Sjogren's syndrome].

Sjogren's syndrome (SS) is an autoimmune disease characterized by a chronic inflammatory response mainly localized to the lacrimal and salivary glands. However, it sometimes involves extraglandular organs culminating in systemic disorders. Hematological abnormalities are not uncommon, although they rarely have clinical significance. In this study we examined 99 patients with primary SS who visited our hospital during 1989 to 1999. Patient's mean age was 54.1 years and 95 out of 99 were female. Lymphopenia and leukopenia was noted in 35 patients (35.3%) and 26 patients (26.2%) respectively, and 7 patients (7.1%) had thrombocytopenia. 43 patients (43.4%) had either of these hematological abnormalities. Patients with lymphopenia showed significantly low frequency of arthralgia and anti-SS-A/B antibody was more common in this group. Only one patient in this group required prednisolone therapy because of polyarthritis and general fatigue while others needed no specific therapy. Patients with thrombocytopenia were significantly younger and a male/female ratio was higher than those without this abnormality. They had higher tendency to accompany with skin eruption, positive anti-SS-B antibody, anti-nuclear antibody and rheumatoid factor. Three out of 8 patients with thrombocytopenia were treated with prednisolone according to the protocol for idiopathic thrombocytopenic purpura. All of 3 patients had positive PA-IgG and normocellular bone marrow. Autoimmune mechanism such as polyclonal B cell activation may play a role in the pathogenesis of thrombocytopenia.

Female↗

[Pulmonary hypertension in a patient with primary Sjogren's syndrome, Hashimoto's disease, and primary biliary cirrhosis].

A 53-year-old woman was admitted to our hospital in May 1999, because of progressive dyspnea and liver dysfunction. She had been receiving the replacement therapy of thyroid hormone for thirteen years and suffering from Raynaud's phenomenon for 9 years. She experienced exertional dyspnea and sicca symptom for 3 years, and had an episode of syncope 4 months before admission. An echocardiogram showed dilation of the right ventricle, tricuspid regurgitation and the estimated mean pressure of the pulmonary artery was higher than 120 mmHg. She was diagnosed as having severe pulmonary hypertension (PH) complicated with primary Sjogren's syndrome and primary biliary cirrhosis without portal hypertension She was treated with anticoagulant (warfarin) and oral prostagrandin I2 (prostacyclin). However, right heart failure and jaundice gradually progressed and she suddenly died in December 1999. At autopsy, the heart was enlarged with right ventricular hypertrophy. Small arteries and arterioles in the lung showed concentric intimal proliferation and severe plexogenic vascular disease. Deposition of immunoglobulin was not observed in the pulmonary arteries. Since the prognosis of PH is poor, it is important to analyze the etiology of the disease for the development of the treatment.

Fatal Outcome↗

[A case of Charcot-Marie-Tooth disease 1 B with Val 146Phe mutation of myelin protein zero showing a severe clinical phenotype].

A 15-year-old boy had complaints of progressive gait disturbance and foot deformity. He started to walk at the age of 18 months. Since two years of age, he had noticed unstable gait. He showed evident scoliosis and enlarged great auricular nerves. Moderate to slight degrees of muscular atrophy and weakness of distal upper, and proximal and distal lower limbs were observed. Pes equinovarus deformity of both feet was obvious. Muscle stretch reflexes were absent in both limbs except decreased triceps brachii reflex. Vibratory sensation was decreased severely in the toes and mildly in the fingers. In cerebrospinal fluid, protein was mildly elevated. Median nerve motor conduction velocity was 5.0 m/sec. On sural nerve biopsy, both demyelinated and remyelinated axons and onion-bulbs without hypomyelination were observed. Therefore, the diagnosis of Charcot-Marie-Tooth disease 1 was made. The direct sequencing of the genomic DNA encoding the Po gene revealed a mutant allele, a guanine to thymine substitution of nucleotide position 436, which caused a substitution of phenylalanine for valine at amino acid position 146. This type of Po mutation is different from any type of Po mutation reported in the literature.

Adolescent↗

[Assessment on intermittent intravenous cyclophosphamide pulse therapy in diffuse proliferative lupus nephritis].

OBJECTIVE: To determine whether intravenous cyclophosphamide pulse therapy (IVCY) is effective for treating patients with diffuse proliferative lupus nephritis (DPLN) who were 1) refractory to methylprednisolone pulse therapy (MP) or 2) could not be treated with MP because of severe diabetes or steroid induced psychosis. METHODS: Seven patients with biopsy proven DPLN were studied after informed consent. Five of them received IVCY after a failure to achieve renal remission with at least 2 cycles of MP therapy. Of the other 2 patients, one had severe diabetes and the other a history of steroid induced psychosis. Bolus therapy with cyclophosphamide (0.5 g/m2 body surface area) was given once a month for 6 consecutive months and then once every 3 months for a total treatment period of 1 year. All patients were given oral prednisone, 0.5 mg/kg per day. The prednisone dose was tapered to the minimal dose required for controlling the disease. After 1 year, the renal status of the patients were evaluated. RESULTS: At 1 year, 4 of the 7 patients achieved substantial improvement. Although the other 3 patients did not satisfy the definition of substantial improvement, none of them had progressive disease. Adverse events were mild and did not require any treatment, with 2 cases of leukocytopenia without fever or major infection. No cases of hemorrhagic cystitis or amenorrhea were observed. CONCLUSIONS: IVCY was 1) effective in the treatment of DPLN which was refractory to MP and 2) relatively safe with minimal side effects.

Adult↗

[Delayed sternal closure after open heart surgery in neonates and early infants].

Between November 1992 and February 1996, 84 patients (less than 3 months of age) underwent open heart surgery. Among 76 patients except 8 who required mechanical circulatory support, the sternum was left open. The indication of open sternotomy was hypoplastic left heart syndrome in 14 patients and unstable hemodynamics in 4 patients. Three patients died before delayed sternal closure. Delayed sternal closure was carried out in 15 patients with a mean of 4.7 days postoperatively. By the time of sternal closure, blood pressure, left atrial pressure and respiratory parameters improved and inotropics were reduced with the minus fluid balance. One patient died of sepsis 4 days after delayed sternal closure. Delayed sternal closure was effective modality to neonates or early infants after complex open heart surgery.

Cardiac Surgical Procedures↗

[A case of synchronous cervical lymph node metastases from testicular and thyroid cancers showing mixed response to chemotherapy].

We report a case of synchronous presentation of thyroid cancer and testicular seminoma with lymph node metastasis. A 37-year-old man presented with right scrotal swelling and multiple lymph node swelling. We performed right radical orchiectomy, and histological examination revealed a seminoma of the testis. After systemic work-up for staging, we diagnosed the patient with multiple lymph node metastasis of the seminoma, and administered three cycles of bleomycin, etoposide, and cisplatin (BEP) therapy. Although the chemotherapy was very effective for the retroperitoneal and left cervical lymph node metastases, the right cervical tumor did not change. Retroperitoneal lymphadenectomy combined with right cervical lymph node dissection and hemi-thyroidectomy were performed on September 8, 1998. Pathological examination of the thyroid revealed papillary thyroid cancer and its right cervical lymph node metastasis. There was no evidence of viable cancer cells from either of the primary cancers in the retroperitoneal lymph node. Unresponsiveness to chemotherapy for metastatic lesions from testicular cancer might be a useful clue to detect primary tumors of other origins.

Adult↗

[Prototype of light source for photodynamic therapy in Centre of Electron Microscopy].

The Photodynamic Therapy (PDT) is a cancer treatment based on specific accumulation of a photosensitizer in the malignant tissue and its subsequent irradiation at appropriate wave lengths induce the production of oxygen singlets responsible for peroxidation of cell organelles and cell death. A prototype of a 630 nm non coherent light source designed and constructed at the Centre of Electron Microscopy of The Cordoba National University allowed a successful application of PDT, in nonmelanoma skin tumors, for the first time in this Country. A topical treatment with 20% delta aminolevulinic acid (ALA) in aqueous solution was applied in 100 lesions of actinic keratosis of 27 patients. The results obtained in this study were the following: Complete Remission (RC) 84%, Partial Remission (RP) 10%, No Response (SR) 0% and No data (SD) 6%. In the latter group are included those patients who did not return for reevaluation. The high efficiency plus the excellent cosmetic response and low aggressiveness, make the PDT the method of choice treatment of this skin pathology. In addition to be no invasive and well tolerated, the prototype of light source used in this study, was remarkably effective.

Aged↗

[Two cases of acute lupus peritonitis].

We report two cases of systemic lupus erythematosus (SLE) diagnosed when acute peritonitis was appeared. Case 1 was a 20 year-old woman suffering from stomachache and right lower abdominal pain. Case 2 was a 40 year-old woman with diarrhea, epigastralgia, pollakisuria. In both cases, their peritoneal fluids were exudative with positive autoantibodies. After high dose steroid therapy, abdominal symptoms and ascites improved promptly. However, due to the complication of lupus nephritis, additional therapy was necessary. To characterize the feature of lupus peritonitis (LP), we examined the clinical and laboratory findings of LP from the literature. In patients with acute LP, abdominal pain, vomiting, diarrhea were significantly more common compared with chronic LP patients (P < 0.05), and fever, arthritis, central nervous system involvement and cystitis were more common. In patients with chronic LP, pleural effusion and pericardial effusion were more common compared with acute LP patients. Gastrointestinal manifestations such as abdominal pain, vomiting and diarrhea were more common in patients with acute LP compared with patients with chronic LP. Most patients with chronic LP were asymptomatic, ascites and serositis being the only clinical findings. The response to steroid therapy was better in acute LP.

Acute Disease↗