cDNA and deduced amino acid sequences of a male dominant P-450Md mRNA in rats.
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Biomedical subjects
Publications and source records attributed to M Miyata.
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We studied the expression and distribution of the polypeptide diazepam binding inhibitor (DBI) in rat peripheral organs by immunocytochemistry, radioimmunoassay, Northern blot analysis and binding assay. Variable amounts of the DBI peptide and DBI mRNA were found in all the tissues examined (liver, duodenum, testis, kidney, adrenal gland, heart, ovary, lung, skeletal muscle and spleen), with the highest level of expression in liver (220 pmol of DBI/mg protein) and the lowest in spleen (11 pmol of DBI/mg protein). A good correlation between DBI-like immunoreactivity (DBI-LI) and mRNA content was found in all tissues except the heart. The immunohistochemical analysis revealed discrete localization of DBI-LI in cell types with specialized functions: for example, the highest DBI-LI content was found in steroid-producing cells (glomerulosa and fasciculata cells of adrenal cortex, Leydig cells of testis); lower DBI-LI immunostaining was found in epithelial cells specialized for water and electrolyte transport (intestinal mucosa, distal convoluted tubules of kidney). Hepatic cells contained moderate immunoreactivity however the total content of DBI in liver is relatively high and is due to the diffuse presence of DBI in every hepatocyte. Cells with high expression of DBI have been shown to contain a high density of mitochondrial benzodiazepine (BZ) binding sites. This observation led us to perform a competitive binding assay between DBI and [3H]PK11195 (a ligand for the mitochondrial BZ binding sites) on mitochondrial membranes of adrenal cortical cells. In this experiment, DBI yielded an apparent competitive inhibition of the binding of PK11195 to the BZ binding sites. Our data support a possible role for DBI as endogenous regulator of intracellular metabolic functions, such as steroidogenesis, via the mitochondrial BZ receptors.
The follow-up results of surgical procedures for cancer of the pancreas at three affiliated hospitals during the past 15 years (1974-1989) were retrospectively analyzed to evaluate the merit of pancreatectomy in surgical treatment of advanced stages of this disease. Included were 4 cases of stage I, 14 cases of stage II, 19 cases of stage III, 43 cases of localized stage IV, and 35 cases of generalized stage IV. Pancreatectomy was performed in 67 cases; 100%, 92.9%, 89.5%, 67.4%, and 11.4% of the stage I, II, III, localized IV, and generalized IV cases, respectively. For the localized stage IV cases, in which the cancerous lesions were advanced but limited to the peripancreatic region, 29 pancreatectomies, 12 bypass operations, and 2 exploratory laparotomies were performed. This group included 17 curative and 12 noncurative pancreatectomies. The 50% survival periods were 257 days after curative pancreatectomy, 226 days after noncurative pancreatectomy, 120 days after bypass operation, and 33 days after exploratory laparotomy. The difference in overall survival rate between curative and noncurative pancreatectomies was not significant. The overall survival rates after both curative and noncurative pancreatectomies were significantly higher than the rate after bypass operation. The postoperative physical performance status after pancreatectomy was significantly better than after the palliative procedures. No significant difference in the status was found between patients after standard and extended pancreatectomies. There was no significant difference in the survival rates or the physical performance status between the pancreatectomy group and the palliative surgery group for the generalized stage IV cases, in which the cancerous lesions extended beyond the peripancreatic region. On the basis of these findings, it is concluded that pancreatectomy extends the postoperative survival period without impairment of the physical performance status in patients with advanced cancer of the pancreas. Even when the pancreatectomy proves to be a noncurative resection, this aggressive surgical approach may be of benefit to this group of patients. It should be noted, however, that pancreatectomy is not beneficial to patients whose lesions have already become generalized.
Phenotypic subpopulations of tumour-infiltrating lymphocytes (TIL) separated from human oesophageal cancer tissues were defined by quantitative two-colour analysis with flow-cytometry (FACScan), and their characteristics were investigated by comparison with peripheral blood lymphocytes (PBL) and intra-oesophageal lymphocytes from noncancerous tissue (IEL) as the controls. Fifteen patients (13 males and 2 females) with squamous cell carcinoma of the oesophagus were entered into the study. Lymphocytes were analyzed by FACScan and the frequencies of the subpopulations were determined using monoclonal antibodies for surface markers. Single colour analysis revealed a predominance of T cells among TIL and a significant reduction of natural killer (NK) cells compared with the controls. Two-colour analysis showed that CD4+ Leu8- (helper T cells) and CD8+ CD11b- (cytotoxic T cells) were significantly increased among TIL when compared with the controls. This significant increase of both helper and cytotoxic T cells, which are indispensable components of cellular immunity, strongly implies that TIL are performing a role in the expression of antigen-specific cellular immunity against the tumours. This is the first report of a phenotypic study of human oesophageal cancer that clearly indicates the significance of the TIL and suggests their potential for use as a source of adoptive immunotherapy.
We investigated what subpopulations of tumour-infiltrating lymphocytes (TIL) play a key role in in vivo function and what determines the degree of local host response represented by lymphocyte infiltration in human oesophageal cancer. We examined the increased subpopulation of TIL in "good responders" (GR) (patients with intensively TIL infiltrated tumours) when compared with "poor responders" (PR) (patients with weakly TIL infiltrated tumours). The frequency of each subpopulation was determined by quantitative flow-cytometric measurement on TIL separated from fresh tumours. Of TIL in GR, the frequency of CD3+ cells increased significantly (P less than 0.05) but the frequencies of CD16+, Leu7-, and CD16+ Leu7- cells were low and did not increase significantly compared with those in PR. With respect to T-cell subsets of TIL in GR, the frequency of CD8+ cells was significantly higher than that in PR (P less than 0.01), and CD4+/CD8+ ratio was lower than that in PR (P less than 0.025). On two-colour analyses, most of CD8+ cells (cytotoxic/suppressor T-cells: Tc/s) did not co-express CD11b and the frequency of CD8+ CD11b- cells (cytotoxic T-cell: Tc) increased significantly compared with that in PR. Clinicopathological and phenotypic analysis of peripheral blood lymphocytes revealed that there are no major differences in general immunocompetence between GR and PR. These results suggest that Tc/s, especially Tc, might play a key role in local host response. They also suggest that not only the general immune status of the host but also the identification of class I major histocompatibility complex antigens by the host at the tumour site may strongly affect the degree of host response in oesophageal cancer.
A vertical banded gastroplasty was performed in an adult female patient with Prader-Willi syndrome in an attempt to prevent the metabolic deterioration caused by polyphagia. After her operation, the patient felt satiated with the scheduled amount of food and one month later, her fasting blood sugar concentration (FBS) decreased from 521 to 125 mg/dl, and her urinary sugar excretion (US) from 257 to 9 g/day. Both glucose tolerance and insulin secretion were also improved. However, these parameters subsequently became worse after dietary control was lost since the surgical procedure alone was unable to continue to suppress the insatiable desire to eat food. Both her glucose tolerance and insulin secretion by the 31st postoperative month were better than before the surgery, but worse than at one month after the surgery. At the end of the surgery, but worse than at one month after the surgery. At the end of the 34th postoperative month, even under the temporary administration of 0.625 mg/day of glibenclamide, her FBS was 158 mg/dl and US, 38.1 g/day. Her body weight had also increased to over her preoperative value. Based on these results, we conclude that the effect of gastroplasty to prevent metabolic deterioration in our patient with Prader-Willi syndrome gradually diminishes.
A 36-year-old housewife complained of a tight feeling in the pharynx with increasing dysphagia, dyspnea, and mild fever. Chest roentgenogram was interpreted as a cystic mass in the middle mediastinum. Computed tomography showed a cystic mass compressing the carina and the esophagus. Ten days after onset, symptoms were suddenly relieved followed by a tarry stool. The chest mass shadow decreased. Esophagofiberscopy showed two fistulas communicating with a cyst that had two chambers. Thoracotomy performed 40 days after onset showed a true duplication of the esophagus with rupture into the esophagus. This is a rare case in which it was possible to observe the sequence of events of a ruptured intramural duplication cyst by means of chest roentgenography, computed tomography, esophagofiberscopy, and cystogram.
The patterns of end growth of individual cells of Schizosaccharomyces pombe, wild-type cells (strain 972 h-), cells exposed to 8 mM hydroxyurea, and cdc mutants (cdc11-123 and cdc2-33), were investigated by time-lapse photomicrography. It was reconfirmed that there are three patterns of end growth: cells growing at the old end, at the new end, and at both ends from the beginning of the cell cycle. Cells that initiated growth at the old (new) end increased their growth rate at the new (old) end and became constant in their growth rate at the old (new) end when cells had their growth rate higher than a critical value: 0.08, 0.09, 0.08, and 0.11 microns/min in wild-type cells, cells exposed to hydroxyurea, cdc11-123 cells, and cdc2-33 cells, respectively. The critical value is proportional to the doubling time in length.
Co-Cr alloy is used more frequently than Ni-Cr alloy as a non-precious alloy for cast plates in Japan. However, since the melting point of Co-Cr alloy is very high, about 1300 degrees C, and since it oxidizes easily, a vacuum-pressure casting machine capable of melting this alloy in a reducing atmosphere has recently been developed. Using this vacuum-pressure casting machine, the authors studied the effects on the castability of Co-Cr alloy due to the form of sprue attachment to the wax pattern. The results clarified that in the vacuum-pressure casting method, the form of sprue attachment to the wax pattern has a significant effect (p less than 0.01) on the castability of Co-Cr alloy.
Voiding parameters on the Uroflow Diagnostic Interpretation (UDI) were analysed in relation to the voided volume in 58 micturitions of 36 healthy adult females. The maximum flow rate (Qmax) and the mean flow rate during central 90% of the voided volume (QM90) increased linearly up to the voided volume of 400 ml. The voiding time (T100) took a value within a certain range independently of the voided volume from 100 to 400 ml and never exceeded 21 seconds in all micturitions. Voiding time for the central 90% of the voided volume (T90), time to Qmax (TQmax) and time from Qmax to 95% of the voided volume (Tdesc) were independent of the volume voided. The maximum rate of increase of flow rate (dQ/dT max) and the estimated bladder wall contraction velocity at 40 ml bladder contents (dL/dT 40) showed a tendency to increase depending on the volume voided. T100 showed a prolongation in 84.0% of 25 micturitions in 20 neurogenic bladder patients and in 66.7% of 27 in 21 chronic cystitis patients, always accompanied by a prolongation of T90. No other parameters were clearly different between healthy women and patients and/or between the two groups of patients. Voiding time is a useful parameter representing female micturition.
By continuous and simultaneous recording of nocturnal penile rigidity and circumferential expansion (tumescence), nocturnal penile rigidity and tumescence have been classified into 6 patterns: normal, dissociation, uncoupling, short episode, low amplitude and flat trace. The monitoring will be helpful to diagnose underlying disorders involving erectile impotence, if the pattern of nocturnal penile rigidity and tumescence are related with the disorders. This study analyzed the relationship between the pattern of nocturnal penile rigidity and tumescence and associated disorders in 105 patients with erectile impotence. Of 15 patients with central nervous system disorders, 9 (60%) had a pattern of short episode of rigidity. In 29 patients with cardiovascular disorders, the patterns of dissociation, low amplitude and flat trace were the main findings and observed in 41, 41, 35% of the group, respectively. No patients with diabetes mellitus showed normal pattern. Although the group of non insulin dependent diabetes mellitus (21 patients) had various patterns of rigidity and tumescence, the insulin dependent group (14 patients) mainly showed patterns of low amplitude (21%) and/or flat trace (71%). The continuous and simultaneous monitoring of penile rigidity and tumescence will be helpful, with an integral analysis of its pattern and other examinations, for accurate diagnosis of underlying disorders of organic impotence, besides for differentiation of organic impotence from psychogenic one.
Subarachnoid phenol block was applied to four traumatic spinal cord injury patients who had been suffering from urinary incontinence caused by detrusor hyperreflexia. Two were females with complete thoracic cord injury, the others were males with incomplete cervical cord injury. In all patients, detrusor hyperreflexia and urinary incontinence disappeared after 0.3-0.6 ml injection of 10% phenol glycerin. Vesicoureteral reflux observed in three ureters of two patients disappeared or improved. Two obtained sufficient bladder capacity for urine storage, while the others who had been treated by continuous urine drainage for a long time prior to the block could not obtain sufficient bladder compliance. The cause seemed to be organization of the bladder wall.
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The effect of epinephrine on the plasma gastrin level was investigated in three patients with Zollinger-Ellison syndrome (ZES) and in 14 normal subjects. Two ZES patients had undergone total gastrectomy, and the third had undergone subtotal gastrectomy before our study. A significant increase in plasma gastrin, from 23 +/- 5 pg/ml to 53 +/- 20 pg/ml, in response to intravenous epinephrine (40 ng/kg.min), was observed in the normal subjects. This response was completely abolished by beta-blockade. In the ZES patients, epinephrine (40 ng/kg.min) also resulted in an increase in the plasma concentration of gastrin. The basal and maximum concentrations of gastrin were 580 and 1680 pg/ml in patient 1, 145000 and 320000 pg/ml in patient 2, and 200 and 1800 pg/ml in patient 3, respectively. beta-Adrenergic blockade suppressed the epinephrine-stimulated gastrin release in these patients as well. Graded intravenous doses of epinephrine given to the ZES patients resulted in elevation of the plasma gastrin in a dose-dependent manner. Insulin hypoglycemia caused an increase in both plasma epinephrine and plasma gastrin in ZES patients and normal subjects. A significant correlation between plasma gastrin and epinephrine during insulin hypoglycemia was observed in both groups. Exercise, with use of a bicycle ergometer, resulted in an increase in plasma epinephrine. An increase in plasma gastrin with exercise was observed in the ZES patients, and this was also suppressed by beta-blockade. The results suggest that gastrinoma cells, like normal G cells, are equipped with beta-adrenergic receptors that regulate gastrin release.
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The portal and systemic hemodynamics in 23 patients with esophageal varices caused by portal hypertension were studied by the thermodilution method with a thermodilution catheter. The patients had a mean age of 48.2 years and underwent splenectomy and devascularization with (17 cases) or without cardiectomy (six cases). The initial portal venous blood flow in all 23 patients was 0.99 +/- 0.31 L/min/m2, and this decreased significantly after splenectomy to 0.67 +/- 0.29 L/min/m2 in proportion to the resected spleen weight. The initial portal venous pressure was 36.5 +/- 6.8 cm H2O, and this decreased after splenectomy to 29.1 +/- 5.7 cm H2O but returned to the initial level after the devascularization procedure. Thus the portal hypertensive status was preserved in spite of the reduction in portal venous blood flow. There was no difference in the pattern of portal hemodynamic change between the patients who underwent cardiectomy and those who did not. In conclusion, it is indicated that the portal hemodynamic change after the devascularization procedure was not caused by cardiectomy but by the lack of splenic blood flow to the portal vein after splenectomy.