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Biomedical subjects

K Miki

Publications and source records attributed to K Miki.

At least 361 records · Page 20Linked to original sources

Enzyme-linked immunosorbent assay of serum pepsinogen I.

A hybridoma monoclonal antibody against human pepsinogen I was used to develop an enzyme-linked immunosorbent assay for pepsinogen I in serum. In the two-step competitive procedure using antimouse immunoglobulin F(ab')2 fragment coupled to alkaline phosphatase, the measurable assay range was 8-256 micrograms/l. No cross-reactivity with rat pepsinogen 1, human pepsinogen II, gastrin I, bombesin, somatostatin and peptide YY was shown. However, there was slight cross-reactivity (0.09%) with porcine pepsinogen. The coefficients of variation within and between series were 7.6% and 13.0%. This enzyme-linked immunosorbent assay for serum pepsinogen I correlated positively with radioimmunoassay (r = 0.87, n = 92). The concentration range of serum pepsinogen I in 354 healthy controls was 15-100 micrograms/l with a lognormal distribution. Serum pepsinogen I levels were significantly higher in the subjects who developed active duodenal ulcer or active gastric ulcer, but significantly lower in those who had gastric cancer, than in control subjects.

Adult↗

A rare case of Maffucci's syndrome combined with tuberculum sellae enchondroma, pituitary adenoma and thyroid adenoma.

Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and haemangiomatosis, and there are only about 150 reported cases. This syndrome is often combined with other neoplasms. Our case was associated with goitre, enchondroma of the tuberculum sellae and pituitary adenoma; the latter brought about disturbance of vision. Including ours, four cases of Maffucci's syndrome associated with pituitary adenoma are found in the literature. In the case of Maffucci's syndrome, it is necessary to examine associated disease as well as associated pituitary adenoma and skull base enchondroma, similar to the correlation of von Recklinghausen's disease with acoustic neurinoma.

Adenoma↗

Serum pepsinogens as a screening test of extensive chronic gastritis.

The serum level of pepsinogen I (PG I) and pepsinogen II (PG II), and the PG I/PG II ratio were compared with the surface area of the fundic mucosa, as determined endoscopically by the Congo red staining method. Reduction in the area of the fundic mucosa due to gastritis was associated with stepwise reduction in the PG I levels and the PG I/PG II ratios. Reduction in the area of the fundic mucosa was also associated with decreases in the basal acid output, maximal acid output (MAO), the basal pepsin output and the stimulated pepsin output. The best sensitivity and specificity levels for the diagnosis of normal mucosa and severe gastritis were obtained with the PG I/PG II ratio and the MAO. A retrospective study of 58 patients with gastric cancer and 162 cancer-free patients showed that a PG I/PG II ratio identified 86.2% of all carcinomas and 87.5% of early carcinomas. Although this test gave a positive rate of 36% among the cancer-susceptible age group controls, its use would lower the cost of mass screening by targeting a smaller test population.

Chronic Disease↗

A new type of albumin with predominantly increased binding affinity for 3,3',5-triiodothyronine in a patient with Graves' disease.

A new type of serum albumin, that shows a markedly enhanced binding activity for 3,3', 5-triiodothyronine (T3), a somewhat increased activity for thyroxine (T4), and a normal activity for 3,3', 5-triiodothyronine (rT3) is described. This albumin was found in a patient with Graves' disease. After successful subtotal thyroidectomy, the existence of abnormal binding activity for T3 was suspected in this patient because of persistently increased total T3 concentrations in spite of elevated thyrotropin levels. Although free T3 and T4 concentrations measured by radioimmunoassay using commercial tracer analogue kits were markedly increased, those measured by equilibrium dialysis were within normal ranges. Electrophoretic studies revealed that these abnormalities were due to the markedly increased T3 binding activity by the serum albumin; that for T4 was also slightly increased. Scatchard plot analysis revealed that the association constant (Ka) for T3 of the patient's albumin was 5.1 X 10(6)/M (normal pooled albumin; 6.2 X 10(5)/M), and those for T4 and rT3 were 5.2 X 10(6)/M and 2.7 X 10(6)/M, respectively (normal pooled albumin; 2.1 X 10(6)/M for both T4 and rT3). The increased binding of albumin to T3 and T4 was markedly inhibited by barbitone, and 8-anilino-1-naphthalene-sulfonic acid. These characteristic features, and erroneously high values of free T3 and T4 concentrations measured by tracer analogue kits were similar to those seen in patients with familial dysalbuminemic hyperthyroxinemia, which have been previously reported. These findings strongly suggest that this albumin is a new variant in various dysalbuminemic syndromes, and the abnormal binding of iodothyronines moieties in these syndromes are not biochemically identical.

Adult↗

Efficacy of a multiple insulin injection regimen in teenagers with insulin-dependent diabetes. Carbohydrate and lipid oxidation measured by continuous indirect calorimetry.

Our study of insulin-dependent diabetic teenagers proved that a multiple insulin injection regimen (MIR) can be an acceptable and effective method of glycemic control. Further, the artificial beta cell can be used to determine insulin requirements for MIR. And finally, continuous indirect calorimetry can be used to assess metabolic control in diabetes.

Adolescent↗

Reversible interconversion between primitive endoderm- and parietal endoderm-like F9 cells demonstrated by mRNAs expression.

The differentiation of retinoic acid-treated F9 cells (primitive endoderm-like F9 cells) into parietal endoderm-like F9 cells induced by dibutyryl cAMP was studied as a culture model of the morphogenesis of early mouse embryo. For this purpose, 6 cDNA clones coding for mRNAs specifically expressed in parietal endoderm-like F9 cells were selected. Northern hybridization of RNA extracted from variously treated F9 cells to nick-translated plasmid DNA of these clones demonstrated the reversible expression of many mRNAs depending on the presence of dibutyryl cAMP in the culture medium. This result suggested that the differentiated state of parietal endoderm, which is formed from primitive endoderm at a position adjacent to the trophectoderm in mouse embryo, can be reversed if the local signal is removed. One of the selected clones, pLAM, hybridized to an mRNA of 6.3 kb and selected mRNA producing a laminin B subunit in an in vitro translation system. This clone has an inserted sequence of 3.1 kb. Among the restriction sites in this sequence, six were consistent with those in a 1.7 kb inserted sequence of pPE 49 and pPE 386, which were isolated by Barlow et al. as laminin B1 clones. An XbaI site found in both pPE 49 and pPE 386 was, however, not found at the corresponding position of pLAM. Dot hybridization of RNA with pLAM showed that expression of laminin B in F9 cells is stimulated more than 100-fold during differentiation of F9 stem cells into parietal endoderm-like F9 cells.

Animals↗

Genetic analysis of vaccinia virus Lister strain and its attenuated mutant LC16m8: production of intermediate variants by homologous recombination.

We prepared vaccinia virus variants by introducing part of the HindIII D fragment of the DNA of the parental Lister (LO) strain (temperature-resistant and forming large plaques and pocks) into the attenuated LC16m8 strain (temperature-sensitive and forming small plaques and pocks) by the use of a homologous recombination technique in vivo. Special attention was paid to the HindIII D fragment, since this fragment has an extra XhoI site in LC16m8 which is absent from LO. After HindIII D of LO was introduced as a calcium phosphate precipitate into rabbit kidney (RK13) cells which had been infected with LC16m8, five virus variants (LOTC-1 to LOTC-5) forming much larger plaques than LC16m8 were cloned. In LOTC-2, LOTC-4 and LOTC-5, the introduction of at least part of HindIII D of LO into the corresponding HindIII D region of the LC16m8 genome was apparent as judged by the disappearance of the XhoI site, whereas variants LOTC-1 and LOTC-3 retained the site. The biological characteristics of all the LOTC variants were similar to each other. Their plaque size and pock size were similar to those of LO, whereas they were rather akin to LC16m8 with regard to temperature sensitivity and neurovirulence. The present results strongly suggested that part of the HindIII D fragment was involved in determining biological characteristics affecting plaque size and pock size, but had little influence on temperature sensitivity and neurovirulence.

Animals↗

Complete and incomplete pyloric gland metaplasia of human gallbladder.

The features of pyloric gland metaplasia in the gallbladder epithelium were studied by histochemical staining for mucin and the immunoperoxidase method for pepsinogens (Pg) I and II. Pyloric gland metaplasia was found in 48 of 72 gallbladders removed surgically. All the pyloric gland metaplastic cells contained class III mucin demonstrated by paradoxical concanavalin A (Con A) staining. Pyloric gland metaplasia was classified into complete and incomplete types on the basis of the immunohistochemical reactivities of Pgs I and II: The complete type of pyloric gland metaplasia contained neutral mucins and weak Pg I and strong Pg II activities, like normal pyloric gland cells. Almost all specimens of the incomplete type of pyloric gland metaplasia contained acid mucins and were further classified into two types: an incomplete type 1, which had Pg II but no Pg I activity, and an incomplete type 2, which had no Pg I or II activity.

Epithelium↗

Control of arterial pressure in conscious, sinoaortic-denervated sheep in normoxia and hypoxia.

The contribution of the sinoaortic reflexes to the control of both the mean level and variability of arterial pressure (Pa) and heart rate (HR) was studied in five adult ewes after chronic section of the carotid sinus and aortic depressor nerves (SAD). SAD group responses were compared with a sham-operated group (n = 6). Pa was 15% lower in the SAD group due to a reduction of total peripheral resistance. The standard deviations and coefficients of variation for both Pa and HR obtained by continuous 16-h monitoring (10-s intervals) in the SAD sheep were not significantly different from those of the sham group. Arterial hypoxia (arterial PO2 = 40 mmHg for 96 h) had no significant influence on the mean values or variability for Pa and HR for either group, although both groups spent more time lying down. Ventilation was unchanged in the SAD group. Thus mean Pa is lower after removal of baroreceptor and chemoreceptor inputs, but the variabilities of both HR and Pa are unaltered during both normoxia and hypoxia in this sedentary species.

Animals↗

Thoracic duct lymph flow during head-out water immersion in conscious dogs.

Water immersion (WI) increases plasma volume in awake dogs. The contribution of lymph flow to this fluid shift was studied in six splenectomized conscious dogs with a side fistula of the thoracic duct. Lymph flow, hematocrit (Hct), and plasma (CP) and lymph (CL) protein concentration were measured during 60 min in air and 120 min of WI (37 degrees C). Lymph flow in air averaged 0.96 +/- 1.0 (SE) ml/min. Lymph flow tended to decrease immediately in WI and was maintained at a level averaging 0.66 ml/min. CP/CL did not change significantly, whereas Hct fell significantly by 1.51 +/- 0.2% (Hct units) at 40 min of WI. Urine flow increased significantly to a maximum value of 1.5 +/- 0.5 ml/min at 40-60 min of WI compared with a mean value in air of 0.3 +/- 0.1 ml/min. The Hct and urine flow responses indicate that fluid shifted into the intravascular space during WI. Since lymph flow tended to decrease, the fluid shift in WI occurs across the capillary wall and not via lymphatic channels.

Animals↗

Extracellular fluid and plasma volumes during water immersion in nephrectomized dogs.

Extracellular fluid volume (ECF, [125I]iothalamate space), blood volume (BV, 51Cr-labeled erythrocyte space), and hematocrit were measured continuously to study the kinetics of fluid movements between intracellular, interstitial, and plasma compartments during water immersion (WI) at 38 degrees C in seven splenectomized and acutely nephrectomized dogs. ECF and plasma volume (PV) increased linearly during WI by 10 +/- 2 ml/kg (4% of initial ECF volume, P less than 0.05) and 12 +/- 2 ml/kg (33% of initial PV, P less than 0.05), respectively, above the control level by 120 min of WI. We estimate that 83% of the fluid entering the intravascular compartment is derived from the intracellular space at 120 min of WI. The results of this study indicate that WI leads to a sustained fluid movement of intracellular fluid toward the intravascular compartment. The increase in interstitial hydrostatic pressure (wick method) by 28.5 mmHg from the control level at 5 min of WI in response to the external water pressure exceeds the increase in mean capillary pressure by 10-11 mmHg relative to the control level. We postulate that this negative hydrostatic pressure gradient across the capillary wall leads to an increase in PV during WI.

Animals↗

Role of cardiac nerves in response to head-out water immersion in conscious dogs.

The circulatory, renal, and hormonal responses during 100 min of thermoneutral (37 degrees C) head-out water immersion (WI) were investigated in conscious intact (INT) and cardiac-denervated (CD) dogs. In the INT group, both left and right atrial and aortic transmural distending pressures and left ventricular contractile performance (LV dP/dtmax) increased, and total peripheral resistance remained unchanged. Cardiac output (QCO) increased in association with an increase in heart rate and LV dP/dtmax. Urine flow (V), sodium excretion (UNaV), and osmolal clearance (Cosmol) all increased, whereas glomerular filtration rate, as indicated by creatinine clearance (CCr), remained constant. The diuresis and natriuresis occurred in the absence of any significant changes in plasma levels of antidiuretic hormone (ADH), aldosterone, or plasma renin activity. The CD animals showed a similar hemodynamic response except that the increase in QCO was now associated with an increase in stroke volume and no change in heart rate or LV dP/dtmax. Although the increase in V was similar in both magnitude and time course of the INT animals, there was no significant change in UNaV. Thus there is a striking change in the character of the response of the denervated group in that the natriuresis is abolished and, instead, a water diuresis occurred. Free water clearance increased, but no significant changes in Cosmol or CCr were observed. In addition plasma ADH levels significantly declined during WI in the CD group. These data indicate that cardiac receptors are important in determining the nature of the renal response to WI.

Animals↗

Regional circulatory responses to head-out water immersion in conscious dogs.

We determined the regional blood flow responses to head-out water immersion (WI) in intact (INT) and cardiac-denervated (CD) conscious dogs. Immersing dogs in thermoneutral water (37 degrees C) in the quadruped position for 100 min resulted in significant increases in cardiac output (Qco) above control values by 38.7% in the INT dogs and 39.2% in the CD dogs (P less than 0.01). Arterial pressure increased by 32 and 34.7% in the INT and CD groups, respectively, during WI, with no significant changes occurring in the calculated total peripheral resistance. Regional blood flow responses were measured with 15-microns radiolabeled microspheres. Flows in the INT and CD groups increased significantly to the heart (40, 38%), skin (93, 96%), fat (79, 83%), diaphragm (44, 48%), and intercostal muscles (58, 55%), whereas there were no changes in renal cortical blood flows during WI. Total brain blood flows did not change significantly on immersion; however, blood flows in both INT and CD animals were increased to the cerebellum (19, 22%), but a significant decrease in pituitary flow (52%) was observed only in the CD group during WI. Gastrointestinal tissue flows increased only during early WI in both INT (45%) and CD (47%) animals. However, blood flows to the skeletal muscles increased only during late WI in the INT (53%) and CD (47%) groups. There were no significant differences between the INT and CD groups. Rectal temperatures and systemic O2 consumption (VO2) were unchanged during WI in both groups of animals. These observations indicate that WI leads to a sustained elevation of Qco accompanied by selective increases in regional tissue perfusion that may be accounted for in some tissues by an increase in metabolic demand or by local heating responses and produces a time-dependent redistribution of blood flow away from the gastrointestinal tissues toward skeletal muscle tissues, which may be due to a partial uncoupling of the normal Q/VO2 relationship. This may be caused by thermal or central neurohumoral mechanisms. These regional circulatory responses are not dependent on the presence of the cardiac nerves.

Animals↗

Physiological responses of aged men to head-up tilt during heat exposure.

The effects of age on cardiovascular and thermoregulatory responses to passive tilting were investigated using six old (61-73 yr) and 10 young (21-39 yr) unacclimatized men. Experiments were carried out at 26 degrees C and after exposure to 40 degrees C and 40% relative humidity for 105 min. Continuous measurements of esophageal (Tes) and mean skin (Tsk) temperatures and heart rate (HR) were recorded. Other variables studied included blood pressure (BP), forearm blood flow (FBF), and cardiac output (CO), which were measured at 4- to 5-min intervals. Measurements were made in the supine position and after 70 degrees head-up tilt for 15 min. Cardioacceleration during the tilt test was greater in the young men than in the old. Other cardiovascular responses of the old men to orthostatism were qualitatively similar to that of the young except for FBF and forearm vascular conductance. The old men did not show significant changes in FBF during tilting, suggesting a deterioration in the sympathetic nervous reflex in the aged. However, other circulatory adaptations seemed to overcome this deficiency resulting in orthostatic tolerance similar to that of the young. During head-up tilt at 26 and 40 degrees C, Tes of both age groups increased. This may reflect a decrease in conductive heat transfer presumably due to diminished blood flow to the periphery.

Aged↗

Estimation of plasma volume from hematocrit and plasma oncotic pressure during volume expansion in dogs.

Changes in hematocrit and plasma oncotic pressure were measured continuously during and after isotonic volume expansion in splenectomized dogs in order to test the potential of these types of measurements to predict changes in plasma volume. A volume of Ringer's solution amounting to 15% of the initial blood volume was infused over 10 min. At the end of the infusion, 54% of infused fluid remained within the intravascular space and 9% of the infused volume was retained within the intravascular space at 50 min after the end of the infusion. Hematocrit and plasma oncotic pressure decreased by 2.4% and 2.4 mmHg, respectively, at the end of infusion and then variables returned to their control levels gradually. Changes in plasma volume were estimated indirectly from hematocrit and plasma oncotic pressure based on the dilution of the erythrocytes and the protein. Highly significant correlations were observed between the measured plasma volume (Y) and the plasma volume (X) calculated from hematocrit (Y = 0.95X + 0.22, r = 0.96) and the plasma oncotic pressure (Y = 0.86X + 0.46, r = 0.91). We therefore conclude that either hematocrit and plasma oncotic pressure measured continuously are reliable parameters for predicting the time course of the plasma volume change during an isotonic volume expansion of up to 15% of the initial blood volume.

Animals↗