Biomedical subjects
Publications and source records attributed to R M Klein.
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In this study cell proliferation in Peyer's Patches (PP) and the crypts of Lieberkuhn of the follicle-associated ileal epithelium was analyzed during the development of acute lethal graft-versus-host disease (GVHD) in adult rats. In addition, the effect of thymectomy on GVHD-induced lymphoproliferation was determined by analyzing the 3H-thymidine labeling index in neonatally thymectomized-control and thymectomized-GVHD rats. A significant increase in the 3H-thymidine-labeling index was found in interfollicular (days 2-7), dome (days 5-10), and follicular (days 5-12) regions of PP as well as in associated ileal crypts (days 5-12) of GVHD rats as compared with controls. Thymectomy altered the proliferative response in PP of GVHD rats in that incorporation of 3H-thymidine by follicular and interfollicular cells was significantly lower than in sham-thymectomized GVHD controls during the later stages of the disease. The results suggest a possible role for host thymus-dependent cells in stimulation of or participation in cell proliferation within follicular and interfollicular areas of PP.
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Angiotensin II has been previously implicated as a mediator of vasoconstriction during the development of hypoxic pulmonary hypertension. The effect of angiotensin-converting enzyme inhibition with teprotide (SQ 20881) on development of pulmonary hypertension was determined by measurement of the drug's ability to modify hypertension-induced protein synthetic changes in the rat pulmonary trunk. Rats were injected with either SQ 20881 (2 mg/kg body wt every 8 hr) or saline vehicle during exposure to chronic hypoxia at 0.5 atm for either 3 or 7 days. Comparisons were made of tissue weight, absolute protein content, and in vitro synthesis of collagen and noncollagen protein of the pulmonary trunks of SQ-treated hypoxic, SQ-treated normoxic, saline-treated hypoxic, and saline-treated normoxic rats. Treatment of hypoxic rats with SQ 20881 was found to significantly decrease right ventricular pressure, tissue weight, absolute protein content, and in vitro protein synthesis after 7 days compared to saline-treated hypoxic rats. Neither right ventricular hypertrophy nor the development of polycythemia was decreased by SQ 20881 treatment.
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The results of this study indicate that both cell proliferation and increased synthesis of extracellular matrix protein contribute to hypertrophy of the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension. As determined by autoradiography after 3H-thymidine injection, pulmonary hypertension results in increased labelling in all cell compartments of the pulmonary trunk wall, the most dramatic response occurring in the adventitia following 3 days' hypoxic exposure. Autoradiography also demonstrated differences in the degree of incorporation of 3H-proline into extracellular protein between hypoxic (3 and 21 days) and control rats. The major focus of 3H-proline incorporation shifted from the adventitia at 3 days to the tunica media at 21 days, although incorporation was significantly higher at 3 compared to 21 days in all wall compartments. The patterns of hyperplasia and matrix protein synthesis in the extrapulmonary arteries of the rat, as reported here, are distinctly different from those seen in many large elastic arteries during development of systemic hypertension. For example, the hyperplastic response of arterial vessels follows a similar temporal sequence in pulmonary and systemic hypertension. However, the adventitia is the region of the pulmonary trunk with highest cell proliferation in pulmonary hypertension while the media is most affected by systemic hypertension. The relevance of the changing patterns of cell proliferation and protein synthesis in the wall of the pulmonary trunk of chronically hypoxic rats to the structural and biochemical properties of this vessel during the early development of pulmonary hypertension is discussed.
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The present study was designed to determine the effects of denervation on glycoprotein synthesis in the predentinal matrix of the mouse incisor. The inferior alveolar nerve (IAN), superior cervical ganglion (SCG) or both (IAN + SCG) were unilaterally resected in adult mice with the contralateral side remaining intact as a control. Fourteen days after surgery and 4 h prior to killing, 0.2 mCi of 3H-fucose was injected intravenously and mandibles were processed for standard histological and autoradiographic techniques. Silver halide grains were counted over the predentin matrix for 2000 micrometers per tooth. The results showed that the IAN and SCG resection affected 3H-fucose incorporation into the predentinal matrix; however, the highest absolute mean grain counts occurred after IAN + SCG resection. SCG resection increased the amount of 3H-fucose incorporated into the predentinal matrix by 48%, that of IAN by 24% and that of IAN + SCG by 14% as compared to contralateral controls. These data indicate a regulatory role for the nervous system and a possible interaction of neural components in the control of glycoprotein synthesis by odontoblasts in the mouse incisor.
An 11-year-old boy was noted to have a multinodular tumor involving the peripheral iris and trabecular meshwork in his left eye. During the next 12 years, the lesion slowly enlarged and produced pigmentary dispersion in the anterior chamber and glaucomatous changes in the optic disc. Histopathologic examination of the tumor after its removal by iridocyclectomy revealed features consistent with the diagnosis of adenoma of the iris-pigment epithelium. A correlation between the clinical and histopathologic features is presented. Clinical features that can be helpful in differentiating an adenoma of the iris-pigment epithelium from a malignant melanoma are discussed.
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The purpose of this study was to determine the temporal alterations in protein synthesis and accumulation in the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension and to correlate these results with the pattern of development of polycythemia, right ventricular hypertrophy (RVH) and increased right ventricular pressure (RVP). In vitro synthesis of collagen and noncollagen protein was determined in the pulmonary trunks (PT) of rats exposed to chronic hypobaric hypoxia (0.5 atm/380 Torr) for 3, 7, 10, 14 or 21 days and in respective control groups of pair-fed normoxic rats. In vitro collagen synthesis was increased 1,150% (p less than 0.01) in PT from rats exposed to hypoxia for 3 days compared to PT from normoxic rats. When duration of hypoxic exposure increased, the percentage increase in collagen synthesis in PT from hypoxic vs. normoxic rats declined but remained significantly elevated (340%, p less than 0.005) after 21 days. Comparison of in vitro synthesis of noncollagen protein demonstrated a similar pattern of alteration with increasing hypoxic exposure. Synthesis of noncollagen protein was increased 750% in PT from hypoxic rats compared to normoxic controls at 7 days (p less than 0.0005) and decreased in parallel with collagen synthesis until 21 days when the difference in mean noncollagen protein synthesis was no longer statistically significant. In contrast, the accumulation of protein in vitro during hypoxic exposure, as determined from measurement of absolute protein and hydroxyproline content, demonstrated a pattern of continued increase with hypoxic exposure. Absolute protein content (microgram protein/vessel) was increased 330% in PT from hypoxic rats after 3 days compared to controls (p less than 0.005). By 21 days, mean absolute protein content of hypoxic PT was increased 500% compared to controls (p less than 0.0005). Absolute hydroxyproline content became significantly elevated in PT from hypoxic rats compared to controls after 7 days (123%, p less than 0.005 and the difference increased to 135% at 21 days (p less than 0.025). From comparison of these results with the pattern of changes in established indicators of pulmonary hypertension, herein reproduced, it is deduced that increased protein synthesis is a very early response of the pulmonary trunk to the stimulus of increased arterial blood pressure. Protein synthesis then declines while accumulation increases in a manner which suggests that the newly synthesized protein alters the response of the vessel to the continuing stimulus. It is proposed that increased accumulation of protein, particularly collagen, decreases the distension of the vessel wall caused by increased transmural pressure.
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The disappearance of the characteristic supranuclear vacuole and extensive apical canalicular system from enterocytes of the ileal villi occurs during the third postnatal week in rats. This phenomenon is associated with loss of permeability of these cells to macromolecules and is therefore termed closure. The present study was designed to analyze the influence of neonatal guanethidine (GTN)-induced sympathectomy on the morphology of the pre- and postclosure ileum of the rat. Light and electron microscopy of control and GTN-sympathectomized rats demonstrated the retention of immature, vacuolated cells on ileal villi as late as 23 days postnatally in GTN-treated rats. Villi from control rats contained only adultlike nonpermeable cells. Electron microscopy further demonstrated no structural differences in the apical canalicular system or storage vacuoles of the delayed cells in GTN rats when compared to the ileal epithelium from preclosure time periods (7 and 15 days) in both GTN-sympathectomized and control rats. Goblet cells were counted on Periodic-Acid-Schiff-stained sections of ileum from 7, 15, and 23-day GTN and control rats. The percentage of goblet cells in the total epithelial cell population of the villus was significantly higher in control versus GTN rats at all time periods. The percentage of goblet cells increased in both groups from day 7 to 15. However, closure in the control group (approximately day 18) was coincident with a steep increase in the percentage of ileal goblet cells which was not evident in the goblet-cell population of the GTN villus. This pattern of change in control versus GTN goblet-cell production was correlated with a similar pattern of variation in the number of crypt cell mitoses between the two groups over the same time period.
Although the rat salivary glands are deficient in acini at birth, acinar cells proliferate rapidly during the early post-natal period. The pattern of acinar cell proliferation was analysed in the parotid and submandibular glands of neonatal rats from day to birth until day 34. Mitotic and [3H]thymidine ([3H]TdR) labelling indices of the two glands show distinctly different patterns. Analysis of cell division in the rat parotid gland demonstrated a peak of mitotic index at 14 days (2.9 +/- 0.4%) and labelling index at 16 days (25.2 +/- 2.1%). Submandibular gland acinar cell proliferation reaches a zenith between 7-8 days; labelling index (14.2 +/- 1.1%) and mitotic index (2.3 +/- 0.3%). Cell proliferation decreases rapidly in both glands after reaching a peak in activity. Gland size increases more rapidly in both glands after gland which correlates with the earlier shift from cell proliferation to differentiation which occurs in this organ. Circadian rhythms of [3H]TdR incorporation were also investigated in this study. A circadian rhythm of [3H]TdR incorporation into DNA occurs at 15 days after birth with a peak at 06.00 hours in both glands and a trough occurring at 15.00 hours in parotid gland and 18.00 hours in the submandibular gland. Determination of specific activity of DNA (ct/min per microgram DNA) on days 8, 10, 12, 13, 14, 15, and 16 after birth at 06.00 and 15.00 hours indicated that a circadian rhythm in [3H]TdR incorporation into DNA began on day 14. The developmental switch from suckling to solid food may be an initiating factor in the sychronization of the circadian rhythm in cell proliferation.
The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate.
The effects of prolonged in vivo infusion of isoproterenol (400 micrograms/kg/hr) or norepinephrine (200 micrograms/kg/hr) from a minipump on the physiological reactivity and binding properties of cardiac beta and alpha-1 adrenoceptors were tested in rats. Infusion of either catecholamine significantly reduced the in vitro inotropic and chronotropic potency of isoproterenol in isolated left and right atria, respectively; desensitization was near maximal as early as after 2 hr of infusion. No significant change in the density of [3H]dihydroalprenolol-labeled beta receptors was evident at this time point in either atrial or ventricular tissue, although isoproterenol did decrease binding site density after 7 days of infusion. There was no change in the binding affinity or physiological blocking potency of dihydroalprenolol after isoproterenol infusion. The inotropic potency of phenylephrine in the presence of dihydroalprenolol was unaffected by infusion of either isoproterenol or norepinephrine and methoxamine failed to increase right atrial rate either in control or in isoproterenol-infused rats. There was also no change in the density and affinity of [3H]prazosin binding sites after isoproterenol infusion. These results indicate selective desensitization of cardiac beta receptors without changes in alpha-1 receptors by prolonged in vivo stimulation with catecholamines. This reaction pattern is different from the well documented effects of hypothyroidism, which include decreased sensitivity of cardiac beta and increased sensitivity of cardiac alpha-1 receptor-mediated responses in rats. Thus, the mechanisms responsible for altered receptor function in the two conditions appear to be different.
A scale for measuring activities of daily living (ADL) functioning is described and reviewed. Teh Klein-Bell ADL Scale has been empirically constructed to yield a score of independent functioning for research and clinical purposes. Interrater reliability is 92%, even without extensive training in the use of the scale. Validity was measured by correlating ADL scores at discharge with hours/weeks of assistance (physical, verbal cueing, and type) received 5 to 10 months postdischarge; correlation was -0.86 (p less than 0.01), indicating that persons with low ADL scores receive much assistance, and that the amount of assistance received decreases steadily as the ADL score increases. Further research applications are suggested.