Initiating factors of gallstones, especially cholesterol stones. II.
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Biomedical subjects
Publications and source records attributed to M Hirano.
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We have examined glial cell lineages during rat spinal cord development by using a variety of antibodies that react with immature and mature glia. Radial glia in embryonic cord bound 1) A2B5, an antibody that reacts with a glial precursor cell population in optic nerve; 2) AbR24, which is directed against GD3 ganglioside and binds to immature neuroectodermal cells and to developing oligodendrocytes in forebrain and cerebellum; and 3) an antibody to the intermediate filament, vimentin. With time, two different populations emerged, both of which seemed to be derivatives of radial cells. One cell type expressed the astrocyte intermediate filament, GFAP, in addition to vimentin. GFAP-containing cells eventually took on the forms of astrocytes in gray and white matter. The other type expressed carbonic anhydrase, an enzyme characteristic of oligodendrocytes and enriched in myelin. Carbonic anhydrase-positive cells eventually developed into small cells with oligodendrocyte morphology. Our observations suggest a common lineage for astrocytes and oligodendrocytes from radial cells during spinal cord gliogenesis.
PURPOSE: To evaluate the efficacy of embolization of portal-systemic shunts in cirrhotic patients with chronic recurrent hepatic encephalopathy (CRHE). METHODS: Seven cirrhotic patients with CRHE refractory to medical treatment (3 men and 4 women, mean age 66 years) were studied. Five patients had splenorenal shunts, 1 had a gastrorenal shunt, and 1 had an intrahepatic portal vein-hepatic vein shunt. Shunt embolization was performed using stainless steel coils, with a percutaneous transhepatic portal vein approach in 4 patients and a transrenal vein approach in 3 patients. RESULTS: After embolization, the shunt disappeared in 4 patients on either ultrasound pulsed Doppler monitoring or portography. Complications observed in the 7 patients were fever, transient pleural effusion, ascites, and mild esophageal varices. For 3-6 months after embolization, the 4 patients whose shunts disappeared showed minimal or no reappearance of a shunt, and had no recurrence of encephalopathy. The serum ammonia levels decreased and electroencephalograms also improved. One of the 4 patients, who developed mild esophageal varices, required no treatment. Treatment was effective in 3 of the 4 patients (75%) who underwent embolization via a transhepatic portal vein. CONCLUSION: Transvascular embolization of shunts improved the outcome in 4 of 7 patients. The most effective embolization was achieved via the percutaneous transhepatic portal vein approach.
The effect of systemically administrated cholecystokinin analog, caerulein, on monoaminergic neurons was examined in discrete regions of rat brain. A single injection of caerulein (400 micrograms/kg, i.p.) significantly elevated 5-hydroxyindoleacetic acid (5HIAA) levels in the prefrontal cortex lateral field, nucleus accumbens, tuberculum olfactorium and striatum after 2 hours, together with a significant increase in striatal serotonin (5HT). Moreover, the time-course study showed that the caerulein-induced increase in both 5HIAA and 5HT levels lasted even for 24 hours, and their levels tended to recover to the control values gradually. This time-dependent change was not found in the other monoamines and their metabolites. These results suggest a long-lasting action of caerulein on 5HT neurons in specific regions of rat brain.
We designed a post-induction therapy including intensive sequential therapy with non-cross-resistant drugs in an effort to prolong disease-free survival (DFS) for adults with acute myelogenous leukemia. Forty-five patients entered this study and 33 of 35 patients entering complete remission received the post-induction therapy. With a median follow-up for survivors of 3.5 years from complete remission, the actuarial 5-year DFS was 46% +/- 19% (95% confidence interval). The five-year DFS for patients over 45 years of age was comparable to that for patients under 45 years of age (50% +/- 26% vs 47% +/- 28%). Furthermore, the actuarial 5-year DFS for patients who required two courses of induction therapy was comparable to that for patients who required only one course of induction therapy (45% +/- 29% vs 50% +/- 25%). The toxicity of post-induction therapy was tolerable and no patients died during complete remission.
Acute and chronic effects of gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide (DN-1417) were investigated on motor activity, dopamine (DA) metabolites and DA receptors in various brain regions of rats. The motor activity, as measured with Automex recorder, was enhanced after a single injection with DN-1417 (20 mg/kg, IP), and the motor stimulating action persisted during 21 daily injections. Acute DN-1417 elevated both homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in 7 brain regions, prefrontal cortex polar, medial and lateral fields, nucleus accumbens, olfactory tubercles, amygdala and striatum. After chronic treatment for 7 days, the acute effect of DN-1417 on DA metabolites disappeared in all regions except for the striatum in which DN-1417 still increased HVA and DOPAC. The response of striatal DA metabolites was also observed after chronic treatment for 21 days. Chronic DN-1417 produced no significant change in 3H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal 3H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment. These results indicate that DN-1417 interacts with mesocortical, mesolimbic and nigrostriatal DA systems in the different modes of action. The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons. The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested.
During 1992 and 1993 an epidemic of optic and peripheral neuropathy affected over 50,000 Cubans. This occurred in the unique setting of a communist country which had a widespread health care network and wherein sudden changes in the economy affected most of the population. Although nutritional factors appeared to play a key role in the pathogenesis of the epidemic neuropathy, viral, toxic, and genetic factors were investigated by Cuban and North American scientists. The authors, representing different disciplines and different groups that visited Cuba during the epidemic, review and reflect on the clinical and laboratory findings which became available through their own experience and through reviewing the literature. The recent Cuban epidemic is compared to similar outbreaks of optic and peripheral neuropathy which have occurred in the past.
Calcium phosphate cement consisting of alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate dibasic (DCPD) and tetracalcium phosphate monoxide (TeCP) was implanted into surgically created full-thickness defects in the cranial bone (bone defect experiment) and directly onto the cranial bone under the periosteum (augmentation experiment). Three months after the implantation, the implants were retrieved with the surrounding tissues and studied histologically and micrographically to evaluate if the cement can be used as a cranioplasty and skeletal augmentation material. In the bone defect experiment, successful reconstruction of the defect was seen in 8 out of 12 specimens. Four specimens, where bleeding control was difficult at the time of implantation, showed partial loss of the cement. Histological and microradiographic studies of the successfully implanted cement revealed that new bone surrounded the implant nearly completely and united directly with the cement surface. In the augmentation experiment, the augmented area maintained the hemispherical shape and was connected tightly with the host bone. Histology and microradiography demonstrated that new bone formation was seen in the gap between the cement and the host bone, and on the outer surface (periosteum side) of the cement at the edge of the implant. From this preliminary short-term study, it could be concluded that the cement is a promising material for cranioplasty and skeletal augmentation with indications that it has good osteoconductivity.
The survival was determined of hamster-heart grafts subcutaneously placed in rat ears. Thirteen out of the 14 grafts tested in rats without immunosuppression were rejected by day 7 post-transplantation, and the one graft was rejected by day 9. Cyclosporine A fully protected the grafts for 2 weeks, the entire experimental period. By contrast, leflunomide seemed only to delay the graft rejection. The formation of antidonor antibodies was fully suppressed by both drugs. These results reveal a pivotal role of T-cells in this model. The results with leflunomide suggest that this drug preferentially affected humoral responses in our study.
PURPOSE: This study was performed to 1) evaluate the proliferative activity in premalignancies of the larynx by immunostaining for proliferating cell nuclear antigen (PCNA), 2) to examine the relationship between PCNA expression and histological diagnosis and 3) to evaluate clinical values of PCNA immunostaining. MATERIALS AND METHODS: The percentage of PCNA-positive nuclei (PCNA index) and their highest location (PCNA grade) were evaluated in 44 specimens of premalignant lesions, 7 premalignant lesions near carcinomas, 9 normal epithelium, and 12 early invasive carcinomas of the larynx. Follow-up was conducted. RESULTS: The mean of PCNA indices in premalignancies was significantly higher than in normal epithelium but lower than in early invasive carcinomas. PCNA index had no apparent correlation with the histological diagnosis, but in the same case, the higher degree of dysplasia showed higher PCNA index. PCNA grade showed significant correlation with the histological diagnosis. Cases with higher PCNA expression showed higher percentages of recurrence and cancerization. Premalignant lesions near carcinomas presented significantly high PCNA expression. CONCLUSIONS: The proliferative activity in premalignancies of the larynx is higher than in normal epithelium and lower than in carcinomas. It differs from case to case, but in the same case the higher degree of dysplasia possesses higher proliferative activity. Dysplasia is associated with abnormal proliferation pattern. Special attention should be paid to those with abnormal proliferation patterns as well as high proliferative activity. PCNA immunostaining is of some referential value in predicting clinical outcome and guiding to make an early diagnosis of malignancy.
In 1992-1994, a disorder known as the epidemic neuropathy afflicted more than 50,000 Cubans. Three different forms of the illness were identified: epidemic optic neuropathy, peripheral neuropathy and mixed optic and peripheral neuropathy. The causes are still unknown. Skeletal muscle biopsy samples were analyzed by standard histological techniques and by biochemical assays. Elevated activities of citrate synthase, a non-respiratory-chain mitochondrial matrix enzyme, suggested possible mitochondrial proliferation in 7 of the 8 patients. Nicotinamide adenine dinucleotide phosphate (NADP(+)) levels were higher in the patients than in the controls (p = 0.04). Levels of nicotinamide adenine dinucleotide (NAD) and the reduced compounds NADH and NADPH were comparable in patients and controls. Elevations of succinate dehydrogenase and citrate synthase activities and high NADP(+) levels suggest that alterations of mitochondrial functions may be associated with this disorder.
Endoscopical measurement of gastric mucosal blood flow seems to provide substantial advantages for noninvasive and repetitive scrutiny, especially in small animals. We employed a quartz probe 0.5 mm in diameter which was inserted into the gastric lumen through the forceps channel (0.8 mm in diameter) of the endoscope. Gastric mucosal blood flow determined with this probe in combination with laser Doppler velocimetry were sufficiently consistent and reproducible in the corpus as long as the tissue-to-probe distance was positioned in gentle contact with the gastric mucosa perpendicularly. Topical application of endothelin-1 produced a significant long-lasting decline in gastric mucosal blood flow, although laparotomy per se resulted in a slight decrease of the blood flow. Endoscopic measurement of gastric mucosal blood flow seems simple and reproducible with high potential for chronic studies.
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In order to obtain a good phonatory function after glottic reconstruction following vertical partial laryngectomy, the following basic conditions should be satisfied: (1) adequate glottic closure should occur during phonation; (2) the top of the bulge constructed on the affected side should be located at the level of the vocal cord in order to facilitate vocal cord vibration and to prevent false cord vibration; and (3) the surface of the bulge should be smooth. A technique for glottic reconstruction which appears to meet these conditions is described. The sternohyoid muscle is dissected at the level 5 cm below the vocal cord, and the upper portion is used as a single pedicled flap. The muscle flap is bent approximately 90 degrees at the level of the upper border of the cricoid cartilage and inserted into the intralaryngeal wound so as to make a large bulge. The muscle flap is covered by hypopharyngeal mucosa or a free graft of oral mucosa.
Contact granuloma of the vocal folds caused by physical trauma secondary to voice abuse has traditionally been treated by surgical removal. This mode of handling can be frequently disappointing since these lesions have a strong tendency to recur and may require additional operative procedures. This paper describes 17 patients in whom treatment of the primary problem was approached through voice therapy. Treatment consisted of a comprehensive history and voice evaluation, stress reduction, relaxation methods, auditory and kinesthetic feedback, pitch change and elimination of voice abuse. Patients were closely followed by the speech pathologist and laryngologist who worked together as a team. The results of voice therapy were evaluated by the laryngologist, the speech pathologist and the patient himself. As a result of voice therapy, the granuloma disappeared in 9 patients, was reduced in size in 4 and remained unchanged in 1. For the remaining three patients, posttherapeutic laryngoscopic findings were not available. The speech pathologist found voice and manner of phonation returned to normal in 4 patients, improved in 7 and remained unchanged in 6. Four patients felt that complete recovery had taken place, 10 felt that some improvement was noted, and 3 felt no change had taken place. Based on the assessments of all three evaluators, the success rate of treatment with voice therapy can be stated as 71% (12 of 17 cases) or 100% (eliminating 5 of 17 cases who terminated treatment very early).