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Biomedical subjects

J H Carter

Publications and source records attributed to J H Carter.

At least 55 records · Page 3Linked to original sources

Immunohistochemical detection of RAS, JUN, FOS, and p53 oncoprotein expression in human colorectal adenomas and carcinomas.

BACKGROUND: Recent evidence suggests that progressive stages of colorectal tumorigenesis can be defined by a sequence of genetic events characterized by deletion and expression of certain genes and appearance of several oncoproteins. Although the significance of these events is not entirely clear, oncoprotein expression may be directly involved in the tumorigenic mechanism. EXPERIMENTAL DESIGN: We examined the expression of two nuclear oncoproteins, JUN and FOS (Abbreviations used in this paper are lower case letters for oncogenes and upper case letters for oncoproteins), that have not been previously associated with development of colorectal cancer. This study involved detecting p39 c-JUN and p55 c-FOS, as well as two oncoproteins previously known to be expressed during colorectal tumorigenesis, p21 RAS and the tumor suppressor protein, p53. Expression was detected with immunohistochemical methods on formalin-fixed, paraffin-embedded sections of normal human colons, tubular adenomas, tubulovillous adenomas, and adenocarcinomas. Either single oncoprotein expression or coexpression of four selected pairs; RAS/JUN, RAS/FOS, RAS/p53, or JUN/FOS were evaluated. RESULTS: We found that the expression of all four single oncoproteins and oncoprotein pairs were detected in very few normal colon specimens or tubular adenomas. However, all four oncoproteins and the four oncoprotein pairs were expressed significantly more often in adenocarcinomas. Oncogene expression in tubulovillous adenomas varied with lesion size. The number of lesions expressing any of the four oncoproteins or pairs was not significantly different than normal colon in small (< 1 cm diameter) tubulovillous adenomas. Significantly more large lesions (> 1 cm. diameter) expressed the single oncoproteins RAS, JUN, and FOS than normal colon. Of the four oncoprotein pairs, only RAS/JUN was significantly coexpressed in large tubulovillous adenomas. CONCLUSIONS: We conclude that independent expression of RAS, JUN, and FOS occurred significantly more often in large tubulovillous adenomas and adenocarcinomas while p53 expression occurred primarily in adenocarcinomas. Also, although all four oncoprotein pairs were expressed significantly more often in adenocarcinomas, only RAS/JUN was significantly coexpressed in the large tubulovillous adenomas. These results are comparable with the observed sequential activation of Ki-ras and p53 described by others and suggests that the expression of the nuclear oncogenes, JUN and/or FOS, are also important events in colorectal tumorigenesis.

Adenocarcinoma↗

Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon.

To determine how the response to levodopa is altered by long-term therapy, we examined the dose response to 2-hour infusions of levodopa in three groups of parkinsonian patients: those who were previously untreated, those who exhibited stable responses, and those who exhibited fluctuating responses to levodopa therapy, using tapping speed as an index of bradykinesia. The baseline tapping speed was greater in the patients with stable responses than in the untreated patients, probably representing a "long-duration response" to levodopa therapy. A "short-duration response," indicated by an increase in tapping speed lasting hours, was observed in most patients in all groups. The onset of the short-duration effect was more rapid and the incremental increase in tapping speed was twice as large in the patients with fluctuating responses compared with the untreated patients and patients with stable responses. The duration of the short-duration effect was greatest in the untreated group but did not differ between the groups with stable and fluctuating responses. Dyskinesia was not observed in any of the de novo patients but was observed in three of 12 patients with stable responses and eight of nine patients with fluctuating responses to levodopa therapy. Dyskinesia appeared before or with the antiparkinsonian effects in patients with stable responses, giving no indication of a higher threshold for dyskinesia in these patients compared with those with fluctuating responses. The plasma half-life clearance, volume of distribution, and maximum plasma concentrations of levodopa did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Quantitative image cytometry of hepatocytes expressing gamma-glutamyl transpeptidase and glutathione S-transferase in diethylnitrosamine-initiated rats treated with phenobarbital and/or phthalate esters.

Image cytometry was used to quantify the volume of liver expressing two histochemical markers associated with neoplasia, gamma-glutamyl transpeptidase (GGT) and the placental isozyme of glutathione S-transferase (GST-P). Rats were treated with diethylnitrosamine (DENA) followed by phenobarbital (PB), di(2-ethylhexyl)phthalate (DEHP), or di-n-octyl-phthalate (DOP) for 26 weeks. In one series, PB-treated rats were given 2.0%, 0.5%, or 0.1% DEHP in the feed. GGT expression was detected diffusely throughout the liver parenchyma in several treatment groups so that any enhanced expression in altered foci (AF) and nodules (N) was not apparent. GST-P was detected only in AF and N. GST-P may represent a second genetic alteration, as GST-P+ AF and N also expressed GGT but not the reverse. The peroxisome proliferator DEHP inhibited expression of GGT or GST-P in livers of either DENA-treated or DENA+PB-treated rats. With GST-P the reduction was correlated to a reduced number of AF and N. In contrast, DEHP's stereoisomer, DOP, was as effective as PB in promoting expression of both markers. We conclude that image cytometry of hepatocytes expressing GST-P can be used in the bioassay of the carcinogenic potential of chemicals that affect liver proliferation.

Animals↗

The effect of exercise on levodopa absorption.

We studied the effect of exercise using cycle ergometry on levodopa absorption in ten patients with Parkinson's disease. Oral levodopa was administered during exercise and at rest on separate days. Exercise delayed levodopa absorption in five patients, increased it in three, and did not influence it in two. We conclude that exercise can either increase or decrease levodopa absorption.

Absorption↗

Black health professional families: assessment of strengths and stability.

Despite pernicious racism, most black health professionals achieve professional success and most have stable marriages. A 19-item questionnaire was designed to assess this hypothesis following a lecture on the strengths and weaknesses of black health professional families to physicians, dentists, and their spouses (n = 38) at the 1990 annual meeting of the combined Old North State Medical and Dental Societies of North Carolina. Surprisingly, these families seemed eager to disclose feelings about themselves, their professions, and their marriages. Major preliminary findings were that these health professionals were more prone to indicate unhappiness than their spouses and less likely to see racism as an impediment to careers, and more willing to acknowledge that they would like to correct something in their lives.

Black or African American↗

Tics through Tourette's syndrome.

The concept of Tourette's syndrome as a bizarre and disabling disorder has changed with greater appreciation that this is a spectrum of symptoms and degrees of severity. A thorough understanding of the latest concepts regarding recognition and management is essential for the neuroscience nurse to play a meaningful role as counselor, educator and clinician in the care of these patients and families.

Antipsychotic Agents↗

Chronic mental illness and homelessness in black populations: prologue and prospects.

Psychiatry has shown little regard for the special health concerns of African Americans, who are disproportionately represented among America's homeless. Although psychiatric literature is replete with data on homeless mentally disordered citizens, only incidental references are made to African Americans to satisfy federally funded research guidelines mandating the inclusion of racial minorities. Additionally, psychiatry has hesitated to suggest corrective actions for this national scourge and has begun to raise questions about the efficacy of case management and demonstration projects.

Black or African American↗

Mutual support and mobilization preparedness: the method of an Army Reserve hospital.

Military literature fails to describe a successful methodology for developing and implementing active Army/active Army Reserve mutual medical support and mobilization planning. The author presents a method for addressing these critical issues that evolved over a period of 11 years between the 3274th Army Hospital (1000B), a Reserve unit in Durham, North Carolina and its CAPSTONE, Womack MEDDAC, Ft. Bragg, North Carolina. The principles utilized here are believed to be applicable to similar Table of Organization & Equipment Armed Forces Reserve Medical Units. Additional advantages of the method are that it enhances recruitment and retention, and maximizes the medical skills of Reserve medical personnel.

Cost-Benefit Analysis↗

Influence of fluctuations of plasma large neutral amino acids with normal diets on the clinical response to levodopa.

Plasma large neutral amino acids (LNAAs) compete with levodopa for entry into the brain. Fluctuations in plasma LNAA concentrations could therefore contribute to variability in clinical response to levodopa. The hourly plasma levodopa, plasma LNAAs and clinical response were investigated in 11 fluctuating Parkinsonian patients on a regular hospital diet. The fluctuations in plasma levodopa were 2 to 3 times greater than the fluctuations of plasma LNAAs. The correlation between clinical response and plasma levodopa was substantially improved in only one patient by considering plasma LNAAs and calculating relative levodopa flux into brain. Although plasma LNAAs significantly increased during the day, the patients' clinical status did not uniformly deteriorate and mean afternoon clinical scores correlated better with mean plasma levodopa and levodopa flux than with mean plasma LNAAs. Minimum effective concentrations of levodopa for clinical response did not correlate with 9 am LNAA concentrations. It is concluded that in most patients, the relatively small variation in plasma LNAAs in comparison with the large variations in plasma levodopa indicates that fluctuations in LNAA are not an important contributor to the fluctuating response to levodopa.

Adult↗

Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson's disease.

Reducing dietary protein improves the effectiveness of levodopa (LD) but the most effective distribution of a low-protein diet (0.8 g/kg) is unclear. We compared a 1.6 g/kg protein diet, a 0.8 g/kg diet with protein evenly distributed between meals, and a 0.8 g/kg diet with protein restricted to the evening meal in 5 parkinsonian patients with motor fluctuations. We monitored clinical response, plasma LD, and plasma large amino acids (LNAAs) hourly throughout the day. Mean "on" times were 51% (1.6 g/kg diet), 67% (0.8 g/kg evenly distributed), and 77% (0.8 g/kg restricted). Hourly averages of plasma LD did not differ between the diets. The mean plasma LNAAs were 732 nmol/ml (1.6 g/kg diet), 640 (0.8 g/kg distributed), and 542 (0.8 g/kg restricted), and the diurnal pattern reflected the distribution of protein intake. In conclusion, the amount and distribution of dietary protein affect clinical response to LD. These effects are not related to LD absorption but are explained by the variation in plasma LNAAs.

Aged↗

Impaired black physicians: a methodology for detection and rehabilitation.

The author contends that the great majority of black physicians lead happy and productive lives. Regrettably, black physicians must not only cope with stress related to marriage, finances, parenting, and other daily problems, but they must also cope with institutional racism. Consequently, some black physicians become impaired. This article discusses issues related to the problem of impairment in black physicians and suggests a methodology for detection and rehabilitation. It is the author's belief that future intervention should be culturally compatible and that black physicians themselves must bolster the effort to prevent impairment. At an empirical level, the author brings together the sparse amount of epidemiological and cultural data related to the subject.

Black or African American↗

Adrenal regulation of mammary tumorigenesis in female Sprague-Dawley rats: incidence, latency, and yield of mammary tumors.

Huggins and Morii (J. Exp. Med., 114: 741, 1961) reported that massive adrenal necrosis occurs in 79 and 100% of female Sprague-Dawley rats receiving 20 and 30 mg, respectively, of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Here, adrenal necrosis and regeneration were studied in 158 rats for up to 21 days post-DMBA by radioautography of the adrenals of animals given 50 microCi [3H]thymidine 30 min before sacrifice. Adrenal cell proliferation was markedly inhibited 21 days post-DMBA. Regenerated adrenals were more susceptible to this adrenocorticolytic effect. To investigate if alterations in adrenal function modify tumorigenesis, animals underwent adrenalectomies (ADX), hypophysectomies, ovariectomies, and pituitary transplants alone or in combination 6 days after receiving DMBA (20 mg/100 g intragastrically) at 50 days of age. To prevent adrenal necrosis, 24 animals were pretreated with metyrapone. Methylprednisolone acetate, 1 mg i.m., was given to 40 animals every 5 days beginning 6 days post-DMBA. There were 50 non-DMBA-treated intact and surgical controls. DMBA was necessary but not sufficient to induce mammary tumors. No tumors developed in controls or in 46 animals hypophysectomized 6 days after DMBA. Metyrapone reduced tumor incidence and yield. ADX after DMBA treatment increased the tumorigenic response and eliminated resistance to tumorigenesis in older rats. Only three tumors developed in DMBA-treated rats receiving methylprednisolone acetate. Mammary tumorigenesis was increased by pituitary transplant 6 days after DMBA to intact and ADX animals. Ovariectomy 6 days after DMBA was as effective as methylprednisolone acetate in preventing tumorigenesis; ADX did not overcome either inhibition. We conclude that adrenal hormones inhibit proliferation of initiated mammary cells.

9,10-Dimethyl-1,2-benzanthracene↗