Development of dark-field dynamic light scattering microscopy and its application: Tracking dynamics of particles in condensed slurries spreading on planar/nonplanar substrates.

HYPOTHESIS: While dynamics of particles in slurries is usually evaluated by dynamic light scattering measurements, this technique had only been applicable to particles in the bulk slurries. Because this limitation is mainly owing to strong reflection of light, the dynamics of particles in slurries spreading/drying on solid substrates is to be obtained by spatially separating the reflection light from scattering (signal) light. This may allow us to track the particles in practical samples such as cosmetics or inks spreading on solid surfaces. EXPERIMENT: We developed novel "dark-field dynamic light scattering microscopy". The system was evaluated with test samples of polystyrene beads dispersed in several viscosities of bulk glycerol aqueous solutions. This setup was then applied to slurries spreading/drying on planar and nonplanar substrates. FINDINGS: The results for planar surface indicate that origin of coffee-ring are the particles flowing into the edge of the droplet just before complete drying. On a skin-modelled nonplanar substrate, the slurry on bumps was found to maintain semi-dry condition longer than that at dents. This suggests that the dispersive medium was supplied to bumps from dents. This unique flow was explained as effective drying from the bumps increased surface tension at the bumps to pull up the liquid around.

Effects of rapid or slow body weight reduction on intramuscular protein degradation pathways during equivalent weight loss on rats.

The purpose of this study was to compare the effects of short-term fasting-induced rapid weight loss with those of slower but equivalent body weight loss induced by daily calorie restriction on muscle protein degradation pathways and muscle protein content. Male Fischer rats were subjected to either 30 % calorie restriction for 2 weeks to slowly decrease body weight (Slow) or 3-day fasting to rapidly decrease body weight by a comparable level of that of the Slow group (Rapid). The final body weights were about 15 % lower in both the Slow and Rapid groups than in the Con group (p<0.001). The total protein content and wet weight of fast-twitch plantaris muscle, but not slow-twitch soleus muscle, were significantly lower in the Rapid group compared with the control rats fed ad libitum. Substantial increases in the expression ratio of autophagosomal membrane proteins (LC3-II/-I ratio) and polyubiquitinated protein concentration, used as biomarkers of autophagy-lysosome and ubiquitin-proteasome activities, respectively, were observed in the plantaris muscle of the Rapid group. Moreover, the LC3-II/-I ratio and polyubiquitinated protein concentration were negatively correlated with the total protein content and wet weight of plantaris muscle. These results suggest that short-term fasting-induced rapid body weight loss activates autophagy-lysosome and ubiquitin-proteasome systems more strongly than calorie restriction-induced slower weight reduction, resulting in muscular atrophy in fast-twitch muscle.

Endocardial Invasion of Lung Cancer Undiagnosable before Autopsy.

A 59-year-old male patient presented with left chest discomfort on admission. His medical history included encephalitis in childhood and his smoking history was 20 cigarettes per day for 40 years. A physical examination showed an anemic and edematous face with weak respiratory sounds in the left lung. The patient had elevated calcium levels and decreased hemoglobin and potassium. His parathyroid hormone-related protein level was elevated. Thoracic radiography showed cardiomegaly and computed tomography revealed a left lung mass with invasion of the heart and pleural effusion. Magnetic resonance imaging showed endocardial invasion of the tumor mass. Gallium-68 imaging revealed positive accumulation in the region surrounding the heart. No diagnoses were possible upon frequent cytology of his sputum and pleural effusion. The patient died from congestive heart failure with anoxia 38 days after admission. An autopsy revealed tumoral mass occlusion in the left main bronchus and tumoral invasion of the left atrium, left ventricle, and aorta.

Spontaneous remission of epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly.

A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R). Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.

Immunohistochemical study of hyaluronate receptor (CD44) in alcoholic liver disease.

BACKGROUND: It has been suggested that the elevation of serum hyaluronate (HA) levels in liver diseases may be due to increased synthesis of HA by hepatic stellate cells or decreased degradation by sinusoidal endothelial cells. The increase in serum HA levels in patients with cirrhosis is thought to be a response to a reduction in HA receptors (CD44) in hepatic sinusoidal endothelial cells. To learn more about how alcohol affects the number and distribution of HA receptors of hepatic sinusoidal endothelial cells, we immunohistochemically studied CD44 levels in liver biopsy obtained from patients with alcoholic liver disease (ALD patients) and also from patients with nonalcoholic liver disease (non-ALD); ALD patients were evaluated when they were currently drinking and again after they became abstinent. Normal liver tissue obtained from three autopsy cases served as a control. METHODS: Liver biopsy specimens were obtained from 18 ALD patients and 12 non-ALD patients. In ALD patients, liver biopsy was performed twice within 3 days and 4 to 8 weeks after abstinence when serum levels of aspartate aminotransferase and alanine aminotransferase became normal. CD44 in liver specimens was stained with anti-CD44 antibody by streptavidine-biotin-peroxidase complex. The intensity of the staining of CD44 in liver tissue was determined by a computer-assisted imaging analyzer. We also measured serum levels of CD44 in both ALD and non-ALD patients. RESULTS: The intensity and the number of CD44 staining increased in both ALD and non-ALD patients compared with those in normal liver, which was negative. The staining intensity of CD44 in liver specimens obtained from patients with ALD who were active in alcohol consumption were significantly higher when compared with patients with ALD after abstinence. Serum levels of CD44 in patients with liver disease increased compared with those of healthy subjects. CONCLUSIONS: The results suggest that HA receptors may increase to degrade the increased HA in serum and/or liver.

Effects of a new orally active dopamine prodrug, docarpamine, on refractory ascites: a pilot study.

OBJECTIVE: Refractory ascites is a debilitating condition in patients with cirrhosis. Recently, docarpamine, an orally active dopamine prodrug, was reported to increase renal blood flow, glomerular filtration, and sodium excretion. This suggests docarpamine may be useful for the treatment of refractory ascites. METHODS: In this study, we investigated docarpamine metabolism in cirrhotic patients and its effect on refractory ascites. RESULTS: Blood samples were obtained from seven cirrhotic patients and six healthy subjects after administration of 750 mg docarpamine, and plasma levels of free dopamine were measured. In healthy subjects, maximum plasma concentration (Cmax), time taken to reach Cmax (Tmax), elimination half-life (T(1/2)), and area under the plasma concentration-time curve (AUC) of plasma free dopamine were 76.8 +/- 24.1 ng/ml, 1.3 +/- 0.2 h, 0.8 +/- 0.1 h, and 97.5 +/- 21.1 ng x h/ml, respectively. In patients with cirrhosis, Cmax (53.1 +/- 24.9 ng/ml), T(1/2) (0.8 +/- 0.1 h), and AUC (100.6 +/- 45.6 ng x h/ml) were no different from healthy subjects when comparing each parameter, whereas Tmax (2.7 +/- 0.2) was significantly longer than that of healthy subjects. We treated 10 cirrhotic patients with refractory ascites with docarpamine or placebo and the same dose of diuretics used before hospitalization. After 8 wk of docarpamine treatment, ascites disappeared completely in three of the five patients and decreased in the remainder. However, in five patients treated with placebo, ascites was not changed or increased. Side effects were not observed in any case. CONCLUSIONS: Docarpamine was found to metabolize in cirrhotic patients as well as in normal subjects and may be an effective treatment for refractory ascites.

Clinicopathological study of chronic hepatitis induced by alcohol with or without hepatitis G virus.

The concept of chronic hepatitis induced by alcohol (AL-CH) has not been widely accepted, because AL-CH may be due to non-A-E hepatitis virus in heavy drinkers. Recently, hepatitis G virus (HGV) was identified as a positive-strand RNA virus related to members of the Flaviviridae family. In this study, we determined serum HGV in patients with AL-CH and analyzed the clinicopathological changes after abstinence to evaluate whether AL-CH is caused by alcohol or not. Serum samples were obtained from 16 patients with AL-CH who had neither hepatitis B nor C virus. The diagnosis was confirmed histologically. In eight patients, liver biopsy was performed twice, within 3 days and 4 to 8 weeks after abstinence. The NS3 region of the HGV genome was detected using an reverse transcriptase-polymerase chain reaction method. Serum levels of AST, ALT and gamma-glutamyltranspeptidase were measured once a week sequentially after admission. Serum HGV-RNA was detected in only one patient with AL-CH (6.3%). In all patients, including one patient with HGV, serum levels of AST, ALT and gamma-glutamyltranspeptidase clearly decreased to normal levels after abstinence. Inflammatory activity in the periportal area of patients with actively drinking decreased or disappeared after abstinence for 4 to 8 weeks. These results suggest that HGV may not play an important role for development of AL-CH, and that AL-CH may be caused by alcohol itself, although a more larger number of patients with AL-CH are needed to obtain definitive conclusions.

Histochemical study of hyaluronate in alcoholic liver disease.

Recently, it has been reported that serum hyaluronate (hyaluronic acid; HA) concentrations increase in various liver diseases, especially in alcoholic liver disease (ALD), and serum HA concentration has been used as a marker for hepatic fibrosis. However, it is unknown whether hepatic HA contents in ALD increase by alcohol or not. In this study, we histochemically stained HA in liver biopsy specimens obtained from ALD patients while actively drinking and after abstinence to clarify the effects of alcohol on hepatic HA contents. Liver biopsy specimens were obtained from 13 patients with ALD and 10 patients with non-ALD. In ALD patients, liver biopsy was performed twice within 3 days, and 4 to 8 weeks after abstinence when serum levels of AST and ALT normalized. HA in biopsy specimens was stained histochemically with biotinylated HA binding protein. Staining intensity of HA in liver tissue was also determined by computer-assisted imaging analyzer. HA staining was clearly observed in sinusoidal wall and fibrous regions around the portal tract and central vein in liver diseases. HA staining intensities in patients actively drinking with ALD increased markedly, compared with those in patients with non-ALD, and these intensities decreased with abstinence. These results clearly suggest that hepatic HA contents in ALD may be increased by alcohol in addition to hepatic fibrosis, and, therefore, increased HA deposition in the liver may be reversible by abstinence of alcohol.

Characteristics of serum hyaluronate concentrations in patients with alcoholic liver disease.

It has been reported that serum hyaluronate [hyaluronic acid (HA)] concentrations are increased in liver diseases, especially in alcoholic liver disease (ALD). However, the characteristics of serum HA concentration in patients with ALD have not been studied. In this study, first, we measured serum HA concentrations in patients with different stages of both ALD and non-ALD to clarify the characteristics of serum HA concentration in patients with ALD. Second, we measured serum HA concentrations in patients with ALD sequentially after abstinence. We also measured serum HA concentrations in patients with chronic type C hepatitis before and after treatment with interferon. Finally, we analyzed the relationship between serum HA concentrations and the contents of type IV collagen and laminin in the livers of both ALD and non-ALD patients. Serum HA concentrations in liver disease were higher than the cut-off value, and increased significantly (p < 0.001) in parallel with the progression of hepatic fibrosis in both ALD and non-ALD patients. Serum HA concentrations in patients actively drinking with ALD were significantly higher (p < 0.001) than those in non-ALD. After 4 weeks of abstinence, these concentrations fell to the levels of non-ALD. Although serum ALT levels were decreased in 80% of patients treated with interferon, serum HA concentrations were not changed or increased. A significant correlation between serum HA concentrations and hepatic type IV collagen and laminin content was present in ALD, but not in non-ALD. These results clearly suggest that the increase of serum HA concentrations in ALD may be associated with not only hepatic fibrosis, but also alcohol drinking.

Serum markers for hepatic fibrosis in alcoholic liver disease: which is the best marker, type III procollagen, type IV collagen, laminin, tissue inhibitor of metalloproteinase, or prolyl hydroxylase?

Although various serum markers for the evaluation of hepatic fibrosis have been introduced, it remains unclear which is the best marker to evaluate the hepatic fibrosis observed in alcoholic liver disease (ALD). In this study, we measured serum concentrations of the immunoreactive beta-subunit of prolyl hydroxylase, procollagen type III peptide, the 7S domain (7S-IV) and triple-helix domain (TH-IV) of type IV collagen, laminin, and tissue inhibitor of metalloproteinase (TIMP) in patients with and without ALD (non-ALD), and controls to evaluate the best serum marker reflecting the characteristic histologic features of ALD. After Azan-Mallory and silver-impregnated reticulin staining, histologic specimens were examined; and the degree of hepatic fibrosis was classified as mild, moderate, or severe. Although serum concentrations of all markers, except for TIMP, in patients with each type and stage of liver disease were higher than cut-off values and these concentrations increases with the progression of liver disease, statistical analyses indicate that serum TH-IV concentration is the best marker to distinguish ALD from non-ALD. A good correlation was also found between the hepatic type IV collagen content and serum TH-IV, but not serum 7S-IV concentration. Moreover, after abstinence from alcohol, serum concentrations of TH-IV decreased more quickly than other serum markers. These results clearly suggest that, compared with other markers, serum concentration of TH-IV may more strongly reflect the histologic features of ALD. However, other serum markers, except for TIMP, may be useful in evaluating the degree of hepatic fibrosis.

Changes in laminin content in livers of patients with alcoholic liver disease.

An increase in serum laminin levels has been reported in patients with liver disease; however, the mechanisms for this increase have not yet been clarified. In the present study, the laminin content of liver biopsy specimens obtained from patients with alcoholic liver disease and non-alcoholic liver disease was determined with a one-step sandwich enzyme-immunoassay system, using monoclonal antibodies for human placental laminin. Hepatic laminin content was significantly higher in patients with liver disease than in normal controls. In alcoholic liver disease, the content in patients with mild fibrosis was lower than in patients with advanced types of alcoholic liver disease. In non-alcoholic liver disease, the hepatic laminin content tended to increase in parallel with the progression of fibrosis. The laminin content in alcoholic liver disease was significantly higher than in the corresponding type of non-alcoholic liver disease. The ratio of laminin to total collagen content was highest in alcoholic liver disease showing mild fibrosis and decreased in parallel with the progression of fibrosis. In contrast, the ratio was low in all types of nonalcoholic liver disease. The ratio in patients with alcoholic liver disease was significantly higher than these with the corresponding non-alcoholic liver disease. Hepatic laminin content increased in parallel with the increase in hepatic type IV collagen in alcoholic liver disease, and the correlation was statistically significant. However, similar correlation was not found in non-alcoholic liver disease. These results indicate that the response to laminin synthesis to alcoholic liver disease is strong in mild fibrosis and reached a plateau at a relatively early stage of fibrosis. The stimulation for laminin synthesis in non-alcoholic liver disease is different from that in alcoholic liver disease.

Detection of antigens related to hepatitis C virus RNA encoding the NS5 region in the livers of patients with chronic type C hepatitis.

Hepatitis C virus is a positive single-strand RNA virus distantly related to flaviviruses. Therefore RNA replicase, an RNA-dependent RNA polymerase, may be essential for the replication of hepatitis C virus, as well as other RNA viruses. In this study we synthesized the recombinant polypeptide (HCV-NS5 antigen) with a 576 bp cDNA encoding a part of the NS5 region of the HCV genome that has the Gly-Asp-Asp motif. The antibody against this polypeptide was obtained from rabbit serum. In Western-blot analysis with NS5 IgG HCV antibody, an 84-kD protein was clearly detected as a single band in the microsomal fraction but not in the nuclear and mitochondrial fractions or in the cytosol fraction. Immunohistochemically, HCV-NS5 antigen was clearly stained in the cytoplasm of hepatocytes but not in the nucleus or cell membrane. Moreover, as determined on immunoelectron microscopy, HCV-NS5 antigen was demonstrated with fine granular distribution along the endoplasmic reticulum but not in other organelles, including the nucleus and mitochondria. Immunoreaction in other cell types was negative. These results indicate that replication of HCV may occur only in hepatocytes and that HCV-NS5 may be produced in the endoplasmic reticulum of these cells. HCV-NS5 antigen was stained only in the livers of hepatitis C virus-positive patients but not in sections from patients with chronic type B hepatitis or alcoholic fibrosis. In chronic type C liver disease, the overall detection rate of HCV-NS5 antigen was 56% (33% in chronic persistent hepatitis, 52% in chronic active hepatitis and 86% in cirrhosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in type IV collagen content in livers of patients with alcoholic liver disease.

An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one-step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Type IV collagen and laminin contents of livers from patients with alcoholic liver disease.

Characteristic histological features of alcoholic liver disease (ALD) are pericellular and perivenular fibrosis. It has been emphasized from immunohistochemical studies that pericellular and perivenular fibrosis may be caused by the increase of type IV collagen (IV-C) and/or laminin (LM). However, quantitative changes of hepatic IV-C and LM contents in ALD are not well known. Recently, we have developed assay systems for IV-C and LM contents in liver biopsy specimens. In the present study, hepatic IV-C and LM contents in ALD and non-ALD patients were measured. Liver biopsy specimens were obtained from 36 patients with ALD, 24 patients with non-ALD and five patients without liver disease. IV-C and LM contents in liver biopsy specimens were measured using the one-step sandwich enzyme immunoassay system for human serum IV-C and LM levels. Total collagen (T-C) content was also measured by the method of Leon and Rojkind. Hepatic IV-C, LM and T-C contents were significantly higher in all types of liver disease than in controls, and tended to increase with the progression of fibrosis. Especially in ALD, both IV-C and LM contents increased from the early stage, and the values in each type of ALD were significantly higher than those in the corresponding type of non-ALD. The ratio of IV-C or LM to T-C was also significantly higher in ALD than in the corresponding non-ALD. The prominent increases of IV-C and LM at the early stage of fibrosis may be one of the characteristics of collagen metabolism in ALD.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on capillarization of the hepatic sinusoids in alcoholic liver disease.

It has been reported that basement membranes were found around the sinusoidal walls in cirrhotic livers, indicating the development of capillarization of the sinusoids. It has been also emphasized that capillarization of the sinusoids is more prominent in alcoholic liver disease (ALD). In the present study, factor VIII related antigen (VIII-Ag) and UEA-1 were identified immunohistochemically in order to analyze capillarization of the sinusoids in chronic liver diseases. Electron microscopic studies on the endothelial cells and sinusoids were also performed. Electron microscopic studies revealed that the number of fenestra in the endothelial cells decreased and basement membranes were clearly observed in the space of Disse from an early stage of ALD. However, these changes were not observed in the early stage of non-ALD. VIII-Ag or UEA-1 was not stainable in the sinusoidal cells of normal livers or at an early stage of non-ALD. However, in ALD, both VIII-Ag and UEA-1 were clearly demonstrated in the sinusoidal cells from the early stage of fibrosis. These results suggest that the sinusoidal endothelial cells may transform to vascular endothelial cells from an early stage of ALD. The alterations in the sinusoidal endothelium and the basement membrane formation in the Disse space indicate that capillarization of the sinusoid may occur. Capillarization of the sinusoid may cause a disturbance in exchanges of many bioactive substances between the sinusoidal blood and hepatocytes across the Disse space and may thereby contribute to the pathogenesis of ALD.

Changes in the markers related to collagen synthesis in the liver of chronically alcohol treated rats.

In order to clarify the roles of Ito cells in the development of alcoholic fibrosis, markers related to collagen synthesis in the liver were analyzed in chronically alcohol treated rats. The livers were obtained from rats fed a diet containing alcohol (alcohol group) and those fed a control diet (control group) for 4 weeks. Prolyl hydroxylase (PH) activity in the whole liver tissue did not differ in the alcohol and control groups. However, the activity in the isolated Ito cells was significantly higher in the alcohol group than in the control group. Immunoreactive PH beta-subunit contents in the liver and serum were significantly higher in the alcohol group than in the control group. Hydroxyproline contents in the liver did not differ in either groups. Immunohistochemically, type IV collagen and laminin were clearly stained along with the sinusoid in the livers of the alcohol group. However, the staining reactions were very weak in the control group. Staining reactions to types I and III collagen were very weak or almost absent in the livers of both groups. Desmin-positive cells, along with the sinusoid, increased significantly in the alcohol group, especially at the centrilobular area, suggesting that the number of Ito cell increase in the centrilobular areas of the alcohol treated rats. These results suggest that type IV collagen and laminin synthesis increase in the Ito cells of chronically alcohol treated rats, although clear evidence of hepatic fibrosis was not obtained. This increase may be related to capillarization of the sinusoids and finally to the development of perisinusoidal fibrosis in alcoholics.

[Pulsatile flow in an elastic circular tube. 1. The application of the finite Hankel transforms to the equations for the flow].

The finite Hankel transforms are applied to the linealized equations of motion for the pulsatile flow in an elastic circular tube. In this paper, the time dependency of the pressure is the known function which is represented by Fourier series expansion. The Fourier transforms are applied to the quantities of the axial components of the pressure and flow velocities, and the finite Hankel transforms are applied to the radial components of them. It is shown that the solutions of the flow velocities are adequate forms for computer calculation. Using the Fourier series coefficients given by the data of the pressure in time, we can calculate the flow pattern in the steady state.

Studies on aldehyde dehydrogenase type V-A isozymes in liver disease.

Aldehyde dehydrogenase (ALDH) V-A isozymes in saliva were detected in 96 patients with or without liver disease in order to clarify the relationships of the presence or absence of ALDH V-A isozymes to the metabolism of acetaldehyde (Ac-CHO) and alcoholic liver disease. The incidence of ALDH V-A deficiency was not different between the patients with alcoholic liver disease and those with non-alcoholic liver disease, nor between the patients with liver disease and without liver disease in no relation to alcohol misuse. Ac-CHO metabolism was not different between ALDH V-A deficient and non-deficient patients even in the ALDH I-deficient patients. These results indicated that ALDH V-A isozymes play virtually no role in the metabolism of Ac-CHO and its deficiency is not related to the development of alcoholic liver disease.

Increased patchy renal accumulation of 99mTc-methylene diphosphonate in a patient with severe loin pain after exercise.

Radionuclide imaging in a patient who had acute renal failure with severe loin pain and patchy renal vasoconstriction is described. The patient was studied 3h after the intravenous bolus injection of 25 mCi99mTc-methylene diphosphonate (99mTc-MDP). An intense patchy renal concentration of 99mTc-MDP was observed.