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Biomedical subjects

D Cohn

Publications and source records attributed to D Cohn.

At least 55 records · Page 3Linked to original sources

Biodegradable PELA block copolymers: in vitro degradation and tissue reaction.

Degradation of, and tissue reaction elicited by a series of polyethylene oxide (PEO)/polylactic acid (PLA) PELA block copolymers were studied in vitro and in vivo. In particular, the effect of pH, temperature and enzymatic activity was addressed. The mass loss was faster, the more basic the media, while, expectedly, PELA copolymers degraded faster with the higher temperature. The addition of an enzyme (carboxylic ester hydrolase) had no effect. The degradation process strongly affected the mechanical properties of the materials under investigation, the elongation at break dropping drastically after two days of degradation. After seven days, only gross observation of the extensively degraded samples was possible. The in vivo studies compared the tissue reaction elicited by various PELA copolymers to that evoked by PLA. Evaluation of tissue reaction observed with a PELA sample after sterilization with gamma radiation showed acute inflammation with considerable dispersion of the material, 12 days after implantation. The granulomatous reaction observed with PELA copolymers after ethylene oxide sterilization was identical to the reaction observed with PLA.

Animals↗

Morphological study of biodegradable PEO/PLA block copolymers.

A series of PEO/PLA copolymers, covering a wide range of compositions and segmental lengths, was synthesized, and their morphology was investigated by means of DSC and IR studies. For matrices comprising PEO chains with molecular weights below 3400, no soft-segment crystallinity was detected. When long hard segments were present, essentially monophasic, semicrystalline polymers were obtained, with PLA blocks melting around 130 degrees C. Polymers containing longer soft segments (PEO 6000) exhibited a two-phase matrix, with both components being able to crystallize. The relative degree of crystallinity of PEO and PLA blocks was also determined. The thermal history of the sample strongly affected the morphology of the matrix, especially when both blocks were long enough to crystallize. To further explore these polymers, solvent cast films were prepared and their morphology assessed. Casting from acetone, which is an excellent solvent for PLA, resulted in hard blocks exhibiting lower degrees of crystallinity, while methanol had a similar effect on PEO soft segments.

Biocompatible Materials↗

The effects of daily cyclophosphamide administration on the development and extent of primary experimental interstitial nephritis in rats.

We examined the effects of daily cyclophosphamide administration on the development and extent of tubulointerstitial nephritis produced in rats injected with tubular basement membranes in adjuvant. 15 mg/kg/day of cyclophosphamide completely blocked the development of interstitial lesions, while 2 mg/kg/day enhanced the degree of interstitial injury. When cyclophosphamide in the higher dose was started early in disease, 12 days after immunization, protection from progression was also observed as well as significant reductive improvement. If cyclophosphamide was administered late in disease, 21 days after immunization, no further progression was demonstrable, but substantial injury remained. In the latter two experiments, the beneficial effects of cyclophosphamide could not be explained by a reduction in anti-tubular basement membrane antibodies bound to the kidney. In groups of immunized rats that were tested, however, cyclophosphamide was able to non-specifically impair the delayed-type hypersensitivity response to tubular antigen and PPD. We conclude, therefore, that cyclophosphamide, in high but not low dosage, if given before damage is extensive and prolonged, may successfully inhibit the cellular immune response producing primary interstitial nephritis.

Animals↗

Demodectic oviposition in the eyelid.

The normally torpid existence of demodectic mites of the eyelid changes with the onset of oviposition. There occurs a burst of activity characterized by flexion, extension and rotation.

Animals↗

Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats.

The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (alpha TBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity; NP = 3.1 +/- 0.2 vs. LP = 1.1 +/- 0.3; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.34 +/- 0.02 vs. LP = 0.82 +/- 0.03). Titers of alpha TBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established alpha TBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0 +/- 0.2; creatinine = 1.78 +/- 0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2 +/- 0.3 vs. LP = 1.4 +/- 0.2; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.92 +/- 0.05 vs. LP = 0.97 +/- 0.02). Again, the titers of alpha TBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.

Animals↗

Clinical, biochemical, serological, histological and ultrastructural features of liver disease in drug abusers.

Heroin abusers are frequently found to have abnormal liver function tests and hepatic histology. Hepatitis viruses A, B, and NANB, other drugs or drug contaminants and excessive alcohol consumption are factors thought to contribute. One hundred and sixteen heroin abusers attending a London treatment centre were studied. Sixty two (53%) had a raised aspartate transaminase. This was not explained by current infection with hepatitis A and B, cytomegalo or Epstein-Barr viruses, excessive alcohol consumption (greater than 80 g/day) or concomitant drug taking. Abnormal liver function tests were as frequent in those with markers of current or past HBV infection as those without and there was evidence that both HBV infection and the cause of the abnormal liver function tests were acquired in the first few years of intravenous drug abuse. Liver biopsies from eight patients showed chronic hepatitis with a mild lobular and portal inflammatory infiltrate, fatty change and prominent sinusoidal cells. Electron microscopy showed cytoplasmic trilaminar tubular structures and dense fused membranes in dilated endoplasmic reticulum. These clinical, biochemical, serological, and histological features would suggest a major role for NANB virus infection in the aetiology of hepatitis in heroin abusers.

Adult↗

Experimental infection of Tamarins with human non-A, non-B hepatitis virus.

Non-A, non-B (NANB) viral hepatitis was successfully transmitted to two colony-born Tamarins following inoculation with antihaemophilic factor VIII concentrate or the "H" inoculum. Both animals showed histological and ultrastructural evidence of viral hepatitis, with raised alanine aminotransferase (ALT) levels from the second week after inoculation through to the end of follow-up, 5 months later.

Alanine Transaminase↗

Factors affecting the frequency of occurrence of spironolactone bodies in aldosteronomas and non-tumorous cortex.

Histological sections taken from aldosterone-producing-adenomas and from non-tumorous adrenal cortex of 18 patients treated for primary aldosteronism by unilateral adrenalectomy were examined for spironolactone inclusion bodies. Typical inclusions were found in 10 of the 13 patients who received spironolactone up to within 24 h of surgery. They were present in the tumours of 7 patients, and their frequency correlated positively with the percentage of glomerulosa type cells in the tumours. In tumours containing 50% or more glomerulosa-type cells, their frequency correlated negatively with duration of treatment. They were present in the non-tumorous cortex of 4 of these 7 patients, and in the cortex of 3 others whose tumours did not contain them. In the cortex, they were found only in glomerulosa cells, and their presence appeared unrelated to dosage or duration of treatment. No spironolactone inclusion bodies were seen in either the tumour of the non-tumorous cortex of 3 patients who had discontinued spironolactone 19 to 97 d before surgery, or of 2 patients who had never received spironolactone.

Adenoma↗

Bacterial bioluminescence: isolation and expression of the luciferase genes from Vibrio harveyi.

Genes for the luciferase enzyme of Vibrio harveyi were isolated in Escherichia coli by a general method in which nonluminous, transposon insertion mutants were used. Conditions necessary for light production in E. coli were examined. Stimulation of transcription of the genes for luciferase (lux A and lux B) was required for efficient synethesis of luciferase. To enhance transcription bacteriophage promoter elements were coupled to the cloned lux gene fragments.

Escherichia coli↗

Co-evolution of luminous bacteria and their eukaryotic hosts.

Several species of three genera of luminous bacteria from marine and soil environments are known to form specific symbioses with fish, squid, urochordates, and nematodes. These bacteria contain a unique and easily detectable enzyme, bacterial luciferase, which allows the detection of the bacteria even when they cannot be cultured from animal tissue. The bacteria-animal associations vary; they range from transient, nonspecific gut symbionts in many fishes to highly specific, nonculturable, intracellular symbionts in pyrosomes. The study of these microbe-animal symbioses may allow understanding of the alterations that occur in the partners during the establishment of intracellular organelles. These studies are incomplete, in particular the level of partner integration, the nature of the metabolic exchange, the mechanism of transmission of symbionts to offspring, and the identification of the cellular inclusions as modified bacteria are not always known. However, the outline of what is likely to be a continuous evolutionary sequence of luminous bacterial symbionts with their various animal hosts is becoming clear. As more of these symbioses are studied, we anticipate that new systems will be found that represent states between those described here, and that the luminous bacteria will provide a living model for the gradual evolution from free-living microbes in intracellular organelles.

Bacteria↗

Electroencephalographic changes in acute water intoxication.

In this case report the electroencephalograph remained abnormal even when the sodium had returned to normal. Although it was not possible to monitor intracranial pressure in this patient, it is the presumption that the cerebral oedema was the cause of both the seizures and the electroencephalographic abnormalities.

Adult↗

Serum 3'-monoiodothyronine levels in normal subjects and in patients with thyroid and non-thyroid disease.

Serum 3'monoiodothyronine (3'-T1) levels were estimated by means of a specific radioimmunoassay (RIA) preceded by an ethanol extraction. The recovery of 3'T1 was in mean (+/-SEM) 110 +/- 9%, and the lower detection limit was 23 pmol/l. Serum levels of 3'T1 in 34 euthyroid healthy subjects were (median (range)) 55 pmol/l (less than 23 - 168 pmol/l), in 13 hyperthyroid patients 133 pmol/l (70 - 265 pmol/l) (P less than 0.01) and in 13 hypothyroid patients less than 23 pmol/l (less than 23 - 68 pmol/l) (P less than 0.01). In 11 patients with chronic renal failure serum 3'-T1 levels were highly increased 285 pmol/l (115 - 1538 pmol/l) (P less than 0.01) and correlated inversely to creatinine clearance (R = -0.68, P less than 0.05). In patients with liver cirrhosis serum 3'-T1 levels were unaffected, whereas in 19 patients with endogenous depression studied before and after recovery from the depression serum levels decreased from 70 pmol/l (less than 23 - 248 pmol/l) to 30 pmol/l (less than 23 - 95 pmol/l) (P less than 0.01). Administration of propranolol 40 mg b.i.d. for 2 weeks did not affect serum 3'-T1 levels. The study shows that 3'-T1 is present in serum from euthyroid man and varies with thyroid function. Further, it is suggested that 3'-T1 in contrast to other iodothyronines primarily is eliminated by the kidneys.

Adult↗