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Biomedical subjects

J H Stein

Publications and source records attributed to J H Stein.

At least 19 recordsLinked to original sources

Thrombus associated with mitral valve calcification. A possible mechanism for embolic stroke.

BACKGROUND: Several studies have demonstrated an association between mitral annular calcification and stroke; however, the pathophysiological explanation remains speculative. CASE DESCRIPTIONS: We describe two patients with cerebral embolism in whom mitral valve calcification was demonstrated by transthoracic echocardiography. In both patients, transesophageal echocardiography identified a mass that appeared to be thrombus on the calcified portion of the mitral apparatus. There was no evidence of a hypercoagulable state or endocarditis in either case. Repeated transesophageal echocardiography after anticoagulation demonstrated resolution of the masses in both patients. CONCLUSIONS: These cases support the hypothesis that thrombus formation may be a pathophysiological link between ischemic cerebral events and mitral annular calcification in some patients.

Aged

A unique left-to-right shunt characterized by multimodality cardiac imaging.

We describe the first reported patient with a persistent left superior vena cava that communicates directly with the left atrium as an isolated congenital defect. She developed mitral stenosis and physiologic conditions that favored left-to-right shunting--a modified Lutembacher's syndrome. Noninvasive cardiac imaging completely elucidated her cardiac anatomy and physiology.

Coronary Angiography

Acute renal failure. Lessons from pathophysiology.

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, SanFrancisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine.

Acute Kidney Injury

Grand cru versus generic: different approaches to altering the ratio of general internists to subspecialists.

In the last decade internal medicine has become a less popular career choice among medical school graduates. In addition, there has been an increase in the percentage of internal medicine residents choosing subspecialty training. The factors that have led to the change in the ratio of subspecialists to general internists are discussed, and a plan is proposed that would make the practice of general internal medicine more attractive and reduce the number of subspecialty training positions in the United States.

Education, Medical

Comparison of three commercially available antibodies for flow cytometric monitoring of P-glycoprotein expression in tumor cells.

Cellular drug resistance to natural products is often due to the presence of an efflux pump which reduces intracellular drug content and chemosensitivity. A 170 kD cell surface resident P-glycoprotein is believed to act as the efflux pump. In the present report, we have compared three commercially available antibodies C-219, JSB-1, and mdr(Ab-1) for use in flow cytometric detection of P-glycoprotein positive cells. Our data show that C219 gives uniformly good results in a variety of murine and human tumor cell lines for detection of P-glycoprotein positive cells. We have also compared data of C219 stained cells analyzed in parallel on a flow cytometer equipped with a small laser (15 mW) and a large laser (5 watt) cell sorter. Data obtained on these two instruments are comparable. A staining protocol and data on dual staining of cells for DNA content by propidium iodide and P-glycoprotein expression after FITC labeling are also presented.

ATP Binding Cassette Transporter, Subfamily B, Mem

Effect of Ringer infusion on ischemic acute renal failure: caution on interpreting the results of short-term studies.

The effect of a 4.5 mL/h Ringer infusion on the recovery from a unilateral 40-min renal artery occlusion was investigated in Sprague-Dawley rats. The inulin clearance measured in the experimental kidney 24 and 48 h after the insult in control animals that did not receive the Ringer infusion was 0.14 +/- 0.10 (mean +/- SE) and 0.11 +/- 0.05 mL/min, respectively. In animals that received 24 h of Ringer infusion begun at the time of the renal artery occlusion the inulin clearance was 0.81 +/- 0.07 mL/min, a value significantly higher than either of the control groups (p less than .05). If, however, the Ringer infusion was stopped at 24 h and the inulin clearance measured at 48 h, it had decreased significantly (0.27 +/- 0.09 mL/min) and was no longer greater than the control groups. Similarly, if the infusion was continued for 48 h there was no longer a significant difference between the inulin clearance (0.37 +/- 0.11), when compared with 48 h of no infusion (0.11 +/- 0.05). The histology of the different groups corresponded with the functional data. We conclude that 24 h of Ringer infusion leads to functional and histological protection when measured at 24 h; however, if measured at 48 h, protection is no longer evident. These studies suggest that caution should be exercised in extrapolating from the results of protective maneuvers in ischemic acute renal failure investigated by short-term studies.

Acute Kidney Injury

Alanine protects rabbit proximal tubules against anoxic injury in vitro.

Rabbit proximal tubules were incubated aerobically or subjected to anoxia for 30 min followed by 60 min of reoxygenation. The medium contained (in mM) 5 glucose, 10 butyrate, 4 lactate or alpha-ketoglutarate (alpha-KG), and 1 alanine. Anoxic tubules in this medium were severely injured and recovered poorly. If the incubation medium was supplemented with additional alanine (up to 2.5 or 5 mM), then anoxic injury was prevented almost completely. Tubules in high-alanine medium showed modest elevations of ATP during anoxia. Comparable elevations of ATP were induced in anoxic tubules incubated with 4 mM alpha-KG and 5 mM aspartate without alanine. These substrates are metabolized anaerobically in the mitochondria to yield ATP. Surprisingly, anoxic tubules with alpha-KG and aspartate showed severe injury despite elevated ATP. If 5 mM alanine was also present, then additional increments of ATP did not occur, but injury was prevented. Examination of glucose metabolism failed to provide evidence for stimulation of anaerobic fermentations by alanine. These results suggest that alanine-induced cytoprotection during anoxia occurs by mechanisms not related to ATP synthesis, and that elevated ATP in alanine-supplemented tubules may be a result and not the cause of protection. Cytoprotection by alanine was shown to last for less than or equal to 90 min of anoxia. Glycine, a structurally related amino acid, also protects anoxic proximal tubules (J. Clin. Invest. 80: 1446, 1987). The mechanisms that underlie the cytoprotective effects of alanine and glycine remain to be determined.

Adenosine Triphosphate

The natural history of diabetic nephropathy.

Diabetic nephropathy is now the most common cause of ESRD in the US, and no other complication of diabetes is associated with more deaths. In addition to its impact on morbidity and mortality, it extracts a tremendous cost from the health-care economy. Prevention and better treatment of diabetic renal disease should be a high priority for both the health-care system and society at large. Ultimately, diabetic nephropathy should be preventable, but that goal can be accomplished only by the coordinated efforts between investigators, who work to uncover pathophysiologic processes and design new treatments, and clinicians, who take those findings to the patient's bedside.

Diabetes Mellitus, Type 1

Incidence and results of arterial complications among 16,350 patients undergoing cardiac catheterization.

A total of 16,350 patients underwent cardiac catheterization from January 1981 to December 1987. The brachial artery was used in 10,500 patients (group I), and the femoral artery was used in 5850 patients (group II). Surgical intervention for complications was necessary in 60 (0.57%) of the group I patients and in 14 (0.23%) of the group II patients. Hand ischemia in group I and bleeding in group II were the most frequent indications for operation. Procedures performed were segmental resection, vein interposition, and long bypass in group I, and simple suture and angioplasty were performed in group II. Fifty-six patients of the total of 74 underwent early repair (within 48 hours), and 18 patients underwent delayed intervention. Only one (1.7%) of the 56 patients who had early repair had a complication. Five of the 18 patients (28%) with delayed intervention suffered significant complications. Cardiac catheterization by the brachial or femoral route has a low incidence of complications. Delayed intervention is associated with high morbidity despite adequate restoration of circulation. Although there were fewer complications in the femoral group, they were far more serious with respect to life- or limb-threatening events.

Adult

High avidity monoclonal antibody to imidazole ring-opened 7-methylguanine.

A hybridoma (K1A8) secreting a high affinity antibody to imidazole ring-opened 7-methylguanine (N5-methyl-N5-formyl-2,5,6-triamino-4-hydroxypyrimidine) was obtained from spleen cells of a mouse immunized with a conjugate of keyhole-limpet hemocyanin and imidazole ring-opened 7-methylguanylic acid (iro-7mGMP). The antibody recognizes the iro-7-methylguanine (iro-7mG) determinant in the BSA-iro-7mGMP conjugate, in chemically methylated, denatured DNA, and in the ring-opened 7-methylguanosine, 7-methyldeoxyguanosine and 7mGMP haptens. In the competitive ELISA of DNA-iro-7mG, 50% inhibition (I50) was observed at 4 fmol determinant per well (8 x 10(-11) M) using BSA-iro-7mGMP as the immobilized antigen. The lower limit of 7-methylguanine (7mG) detection in DNA is determined by the binding of unmodified DNA per se to the antibody. The intrinsic reaction of DNA with antibody is low; in the competitive ELISA I50 was obtained with 330 micrograms calf thymus DNA per 50 microliters well, equivalent to 4 nmol iro-7mG per mol nucleotide. The 7mG content of calf thymus DNA is 7 nmol per mol nucleotide (approximately 20 amol per micrograms DNA). The limit of detection of 7mG by competitive ELISA is quoted provisionally as 7 nmol iro-7mG per mol nucleotide, where 30% inhibition of antibody binding is obtained in the presence of 105 micrograms DNA per 50 microliters well. Nuclear DNAs of tissue culture cells treated with 0, 0.01 and 0.1 mM N-methyl-N'-nitro-N-nitrosoguanidine contained 0.18, 31 and 320 mumol, respectively, of 7-methylguanine adducts per mol of nucleotides. This report indicates that the K1A8 antibody will serve to quantify DNA alkylation in human populations exposed to low levels of methylating carcinogens.

Alkylating Agents

Oxidant stress following renal ischemia: changes in the glutathione redox ratio.

Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals