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Biomedical subjects

D M Brown

Publications and source records attributed to D M Brown.

At least 307 records · Page 17Linked to original sources

Glomerular basement membrane thickness following islet transplantation in the diabetic rat.

Glomerular basement membrane (GBM) thickness was measured in diabetic rats prior to and following islet transplantation. Over the course of the experiment (from 7 to 13 months of diabetes) GBM thickness in diabetic animals exceeded that of littermate controls. After 7 months of diabetes a group of animals received successful intraportal transplants of neonatal pancreatic tissue. GBM thickness at 2 and 6 months following islet transplantation matched the thickness in nontransplanted diabetic rats and exceeded that in control animals. Failure to reverse GBM thickening in diabetic rats following islet transplantation may be due to very slow rates of GBM tunover in the rat. Previous work has demonstrated normalization of urinary albumin excretion after islet transplantation, suggesting that GBM thickening, per se, is not a significant factor causing albuminuria in rats with longstanding diabetes.

Animals↗

Enhancement of radioresponse of a mouse mammary carcinoma to combined treatments with hyperthermia and radiosensitizer misonidazole.

The regrowth delay of a transplanted syngeneic mouse mammary carcinoma designated MT2 was used to estimate the effects of three-fold combination treatments: X-irradiation; hyperthermia and radiosensitizer; and misonidazole (Ro-07-0582). The experiment entailed five groups of experimental mice: untreated control; X-rays alone; X-rays plus hyperthermia (42--43 degrees); X-rays plus misonidazole; and X-rays plus hyperthermia plus misonidazole. X-Ray treatments consisted of 4000 rads administered locally to the tumors in two equal fractions at a 48-hr interval. Misonidazole (0.67 mg per g body weight) was injected i.p. 30 min before exposure to X-irradiation. Hyperthermia was administered 10 min prior to and for 17 min during irradiation. The regrowth delay factor of 3.9 was obtained by administering combined treatments of the three agents (X-rays plus hyperthermia plus misonidazole). The enhancing effect on a syngeneic mouse mammary adenocarcinoma by the modality of treatment herein described lends support to the usefulness of combining X-rays with other agents in the treatment of neoplasms.

Adenocarcinoma↗

Feedback goniometers for hand rehabilitation.

Active range-of-motion exercises and related activities are an important means for applying progressive stress to induce remodeling of various tissues that restrict range of motion in the hand and wrist. Supplying joint angle feedback to patients as they exercise can help them more consistently to reach the flexion/extension goals set by the therapist. To accomplish this aim, feedback goniometers have been developed that are worn on the hand during exercise and therapeutic activities. These devices supply a threshold feedback signal when a predetermined joint angle is attained. Clinical trials indicate that many patients in a comprehensive hand rehabilitation program after injuries or corrective surgery will improve somewhat more in active range of motion if they use feedback goniometers while exercising. Plans are available for fabricating such devices from readily obtained tools and parts at a modest cost.

Electromyography↗

Mesangial uptake and processing of macromolecules in rats with diabetes mellitus.

The uptake and processing of colloidal carbon by the glomerular mesangium was studied in an attempt to determine whether abnormal mesangial function occurs in rats with longstanding streptozotocin-induced diabetes mellitus. The chronically diabetic rats were considerably smaller than their normal littermates receiving a similar dose of colloidal carbon based upon body weight. Thus, further control groups, animals weight-matched with the diabetic rats (younger rats) and littermates of the diabetic rats given the mean quantity of colloidal carbon administered to the diabetic rats, were included. Quantitative evaluation of renal tissues indicated that younger rats have more avid mesangial uptake of colloidal carbon from the circulation and more rapid processing of these macromolecules through the mesangium than the other groups studied. These quantitative studies did not demonstrate any marked impairment in diabetic rats in the over-all capacity of their mesangium to take up and process colloidal carbon when compared with the two groups of littermate nondiabetic animals. However, in those areas of the mesangium thickened by the diabetic process large aggregated of carbon accumulated and persisted over the 6-week period of the study. It appears, therefore, that those areas of the mesangium in diabetic rats with pathologic changes consequent to the diabetic state have significant functional impairment.

Animals↗

Collagen synthesis by human glomerular cells in culture.

Collagen synthesis was studied in three subcultured human glomerular cell types, by radiolabeled incorporation of [14C]proline and [3H]lysine. The epithelioid circular glomerular cells secrete a collagen with a single size of chain (possibly type IV) with a high ratio of hydroxyproline to proline, hydroxylysine to lysine, and 11--17% of hydroxyproline as the 3-isomer. The smooth muscle-like rhomboid glomerular cells secrete collagen with a chain pattern suggesting types III and I collagen, distinct from that found in the media of fibroblasts. Small ovoid glomerular cells are morphologically and biochemically intermediate between circular glomerular cells and rhomboid glomerular cells, and may represent an in vitro modification of either circular glomerular cells or rhomboid glomerular cells.

Basement Membrane↗

Base-specific reactions useful for DNA sequencing: methylene blue--sensitized photooxidation of guanine and osmium tetraoxide modification of thymine.

Exposure of DNA to methylene blue and visible or ultraviolet light causes guanine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at each guanine residue. Treatment of DNA with osmium tetraoxide in dilute pyridine leads to thymidine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at the modified thymidine residues. Both reactions can be used in conjunction with other base specific modifications described by Maxam and Gilbert (1) for the determination of the nucleotide sequence in DNA.

Base Sequence↗

Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays.

Cell-mediated and humoral immune responses of mutant diabetic db+/db+ mice were evaluated using in vivo and in vitro immunological assays. When compared to lean, nondiabetic db+/m+ or m+/m+ mice, db+/db+ mice demonstrated markedly altered in vivo immune responses characterized by a significantly diminished ability to reject allogeneic skin grafts, a markedly diminished capacity to generate cytotoxic cells after sensitization with allogeneic EL-4 lymphoma cells and a significantly enhanced plaque-forming cell response to sheep erythrocytes. In contrast, spleen cells from db+/db+ mice demonstrated only minimal alterations in in vitro responses to mitogens and allogeneic cells and no alteration in their capacity to generate an in vitro plaque-forming cell response. The spleens and thymuses of db+/db+ mice weighed significantly less than organs from db+/db+ mice. In addition, thymuses from db+/db+ mice demonstrated a marked deficiency in in vivo [125I]UdR uptake. These data suggest that the altered metabolic status of the diabetic host influences immune function in vivo possibly due to abnormal function of lymphocyte subpopulations.

Animals↗

Diabetic glomerulopathy following unilateral nephrectomy in the rat.

One month following induction of diabetes with streptozotocin, one half of diabetic and control rats underwent unilateral nephrectomy. Subsequently, all animals were studied with respect to renal function and glomerular alterations of diabetes. Blood pressure levels were similar in all animals. Diabetic and control animals with unilateral nephrectomy had similar but elevated serum creatinine levels and lower creatinine clearance values as compared with the intact rats. However, on a per kidney basis the creatinine clearance levels were higher in the animals with unilateral nephrectomy. At both three and six months following nephrectomy, markedly increased mesangial matrix thickening and mesangial deposition of IgG and C3 were observed in diabetic rats with unilateral nephrectomy as compared with intact diabetic animals. Nephrectomy had no detectable effects on glomerular morphology or immunohistochemistry of nondiabetic rats. Thus, unilateral nephrectomy in the rat increases, at as early as three months, the severity of diabetic glomerular lesions.

Animals↗

The immunohistopathology of glomerular antigens. III. Increased mesangial actomyosin in experimental diabetes in the rat.

Antisera to rat smooth muscle actomyosin (AMY) and myosin localize in the rat glomercular mesangium. The width of mesangial staining for AMY is increased in rats diabetic for four months (p less than 0.01) and seven months (p less than 0.0005) compared with age-matched controls. Mesangial AMY staining of unilaterally nephrectomized control animals was moderately increased after seven months, whereas unilaterally nephrectomized diabetic rats had prominently increased AMY mesangial width at four months, when they were compared with intact diabetic animals (p less than 0.05). Thus, a distinctive alteration that is found in human diabetic nephropathy also occurs in experimental (streptozotocin) diabetes in the rat. Further, this alteration appears to be accelerated by the changes in nephron hemodynamics resulting from unilateral nephrectomy. While the function of mesangial AMY is unknown, it may be related to intrarenal regulation of glomerular ultrafiltration, which appears to be altered in diabetic nephropathy in man.

Actomyosin↗

The effects of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat.

Rats with classic Goldblatt (two-kidney) hypertension had diabetes induced by streptozotocin. After four months of diabetes, glomeruli of the unclipped kidney of hypertensive diabetic rats had markedly increased diabetic changes, including mesangial matrix thickening and mesangial immunoglobulin (IgG and IgM) and complement (C3) localization, when compared with glomeruli of the contralateral-clipped kidneys. Further, glomeruli of the unclipped kidneys of hypertensive diabetic animals had more mesangial thickening and IgG and IgM staining than glomeruli of normotensive diabetic rats. Although glomeruli of clipped kidneys in hypertensive diabetic rats had less mesangial thickening than glomeruli of normotensive diabetic rats, this did not reach statistical significance. However, these glomeruli did have significantly less IgG, IgM, and C3 staining compared with glomeruli of normotensive diabetic animals. Mesangial thickness in glomeruli of clipped and unclipped nondiabetic hypertensive rats did not differ from that in normal animals. However, there was less mesangial IgG staining in clipped than in unclipped kidneys of nondiabetic hypertensive rats or in kidneys of normal animals. We have interpreted these results to imply that alterations in nephron hemodynamics combine with the diabetic state to influence the rate of development of diabetic glomerulopathy in rats.

Animals↗

Treatment of severe hypophosphatemia.

Aspects of phosphate biochemistry pertinent to therapy, the distribution of phosphorus in body compartments, therapeutic phosphorus preparations, prevention of hypophosphatemia, therapeutic guidelines, and side-effects of phosphorus therapy are reviewed. Severe hypophosphatemia (less than 0.32 mmol/litre or less than 1 mg/dl) can occur with normal or depleted body stores. Because a large amount of phosphorus may shift rapidly between the extracellular and intracellular or bone compartments, the size of a possible total body deficit cannot be estimated from the serum phosphorus level. Similar shifts may occur unpredictably during repair of hypophosphatemia. Therefore, correction of hypophosphatemia in any patient must be empiric and the response of serum levels to therapy should be followed closely. We discuss a method likely to correct hypophosphatemia while minimizing side-effects.

Chemical Phenomena↗

Social institutions and economic decision making.

Perpetuating the present U.S. health care system, which spends more and more to produce about the same output, is irrational. Incentives that affect insurers and insureds, physicians, hospitals, and government are a necessity if a viable voluntary health care system is to survive.

Costs and Cost Analysis↗

Electromyographic biofeedback in the reeducation of facial palsy.

Electromyographic biofeedback techniques have been successfully applied in various neuromuscular disorders. Data on the use of this technique in reeducation of facial paralysis after initial surgical correction are scarce. The authors have developed a treatment program consisting of EMG biofeedback with the use of the Basmajian-Emory myotrainer. Two case reports are presented which show successful results after a three month training period.

Adult↗

Bioconverter for upper extremity rehabilitation.

The bioconverter is a simple instrument which uses the output of the Basmajian-Emory myotrainer to activate electrical devices, such as radios, television, etc. It can be used to assist in training by providing an acceptable and/or pleasurable stimulus (such as a radio) as muscle activation improves. The myotrainer contains adjustable sensitivity circuits, and the bioconverter has a pre-set holding circuit of 2, 4, or 6 seconds duration. A case of a deaf and blind patient is presented where the bioconverter is used to activate other sensory (skin) stimuli rather than audio-visual ones. The bioconverter can also be used in relaxation training. In this mode of operation the controlled equipment is on when no EMG is present and is turned off when too high an EMG level exists.

Adult↗

Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VIII. Isolation and sequences of peptides from a tryptic hydrolysate of the maleylated protein.

The NAD-specific glutamate dehydrogenase of Neurospora crassa was S-carboxymethylated with [14C]iodoacetate, maleylated, and hydrolyzed with trypsin. The isolation and sequences of the resulting peptides are described. These peptides gave information on the structure of the protein that was previously unknown and gave many overlaps of previously isolated segments of the protein.

Amino Acid Sequence↗