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Biomedical subjects

R M Klein

Publications and source records attributed to R M Klein.

At least 19 recordsLinked to original sources

[The local lysis therapy of spontaneous renal artery dissection with arterial thrombosis].

A 33-year-old previously completely healthy man developed severe, at first colicky then persisting, pain in the left flank. The blood pressure was 190/110 mm Hg and he had pain over the left kidney on percussion. There was a mild leucocytosis (10,300/microliters), serum creatinine of 1.5 mg/dl and a rise in lactate dehydrogenase level to 395 U/l, while the urine was unremarkable. The pyelogram demonstrated on the left the upper calyceal system only and this very weakly. Colour Doppler ultrasound showed a massively reduced blood flow in the left renal vein while the artery was not visible. Digital subtraction angiography demonstrated eccentric narrowing of the left renal artery by an intravascular thrombus, providing the diagnosis of spontaneous renal artery dissection with thrombosis. Complete recanalization occurred after local thrombolysis with 500,000 IU urokinase over 7 hours, and subsequent administration of four times 40 mg tissue plasminogen activator over 4 hours. But the scintigram still demonstrated impaired renal function with decrease in clearance to 10% of total. The patient was still symptom-free on re-examination 16 months later, serum creatinine concentration was stable at 1.3 mg/dl and the blood pressure was normal.

Adult

Effects of green light on biological systems.

Green light (510-565 nm) constitutes a significant portion of the visible spectrum impinging on biological systems. It plays many different roles in the biochemistry, physiology and structure of plants and animals. In only a relatively small number of responses to green light is the photoreceptor known with certainty or even provisionally and in even fewer systems has the chain of events leading from perception to response been examined experimentally. This review provides a detailed view of those biological systems shown to respond to green light, an evaluation of possible photoreceptors and a review of the known and postulated mechanisms leading to the responses.

Animal Population Groups

Epidermal growth factor in the neonatal mouse salivary gland and kidney.

In the adult mouse, epidermal growth factor (EGF) is synthesized in granular convoluted tubule (intralobular) duct cells of the submandibular gland and in distal tubule cells of the kidney. The presence of EGF in developing tissues and maternal milk and the localization of EGF receptors in developing tissues suggest a role for EGF in developmental processes. The primary aims of the present study were to: (1) localize EGF and EGF-binding sites in the kidney and submandibular gland during neonatal development and (2) to determine the effect of exogenously administered EGF on cell proliferation in these two developing organs. In the present study, EGF was localized by immunocytochemistry in granular convoluted tubule cells of the submandibular gland initially on day 21 after birth and in distal tubule cells of the kidney on postnatal day 6. EGF binding in the kidney decreased after birth with some localization to the glomerulus. In submandibular glands of newborn and 10-day-old mice, EGF-binding sites were associated with both acinar and duct cells with peak binding at 10 days postnatally. Submandibular glands from 20-day-old mice demonstrated primarily ductal EGF-binding sites. Exogenously administered EGF induced a mitogenic response in acinar and interlobular duct cells of submandibular glands during the first week after birth. EGF treatment during this period had an inhibitory effect on 3H-thymidine incorporation into cellular compartments in the developing kidney. The identification of EGF-binding sites in the kidney and submandibular gland before the presence of EGF suggests that an EGF-like molecule such as transforming growth factor alpha (TGF-alpha) may be present as a potential ligand in these organs. In order to assess this possibility, developing kidneys and submandibular glands were stained with anti-TGF-alpha. These immunocytochemical studies localized TGF-alpha to the proximal tubule of the kidney and immature acinar cells of the newborn mouse. Our data strongly support an autocrine, juxtacrine or paracrine role for EGF and/or TGF-alpha in the regulation of cell proliferation and cytodifferentiation in the kidney and submandibular gland.

Animals

Developmental delay of lingual lipase expression after guanethidine-induced sympathectomy.

Rat lingual lipase increases during postnatal development. To evaluate the role of the sympathetic nervous system in the control of lingual lipase during development, suckling rats were chemically sympathectomized by chronic treatment with guanethidine. This treatment was found to be effective in suppressing the developmental increase of lingual lipase. The effect was age dependent and also related to the dose of guanethidine given (i.e., the higher the dose, the more effective the suppression is, up to 40 micrograms/g body wt). The effect of guanethidine on lingual lipase suppression was not a result of induced stress, since simultaneous treatment with RU-38486, a known glucocorticoid receptor antagonist, did not prevent the decrease in lingual lipase activity. Ephedrine, a known sympathomimetic agent, restored the lingual lipase to a near normal level in guanethidine-treated animals, confirming that guanethidine acts through the sympathetic nerves. Furthermore, histochemical studies showed that guanethidine-treatment resulted in the reduction or elimination of catecholaminergic fibers in the von Ebner's glands. The effect of guanethidine was found to be transient, in that the lingual lipase activity showed complete recovery upon withdrawal of the treatment for 1 week. Together, the results indicated that sympathetic nerves have an important regulatory role in lingual lipase in rat pups during development.

Age Factors

Sacrococcygeal dysgenesis association.

In the malformation analysis of 445 patients ascertained only for a sacrococcygeal malformation, a new phenotype, the sacrococcygeal dysgenesis association (SDA), was delineated in 34%. In addition, sirenomelia patients were found in 12%, the VATER association in 27%, and 27% could not be classified. Heterogeneity in the patients with sacrococcygeal malformations was identified by the differences found in their associated malformations. SDA patients have a relatively small average number (3.3) of anomalies per patient as compared with 9.3 in sirenomelia and 6.2 in VATER patients. SDA abnormalities occurred to a significant degree only in 6 of 20 designated malformation categories (vertebral, rib, pelvic, lower limb, central nervous system [CNS], renal) in contrast to 17 in VATER and 18 in sirenomelia patients. The SDA vertebral malformation pattern also differed from that of VATER/sirenomelia patients as did the high sacrococcygeal agenesis:dysgenesis ratio and low thoracolumbar vertebrae and/or rib hypersegmentations. Most significantly, SDA patients had a large number of CNS anomalies and CNS-related dysfunctions of the urinary and distal intestinal tracts but no anatomic urinary or intestinal tract malformations. This contrasted sharply with the markedly increased occurrences of anatomic abnormalities in these body regions of the sirenomelia and VATER patients. Demographic data such as patient survival, twinning and, particularly, the high (28%) incidence of maternal diabetes in the SDA further support its differentiation from VATER/sirenomelia patients.

Abnormalities, Multiple

Medial dislocation of the patella.

Medial dislocation of the patella is a previously unreported entity. This disorder can be disabling to the patient and may require a hospital visit for reduction. Three cases are presented in this article in which computed tomography demonstrated the dislocation. All three patients had undergone a lateral retinacular release to the involved knee for treatment of chronic knee pain or recurrent lateral patellar subluxation.

Adult

Intestinal neoplasm mimicking a Meckel's diverticulum on scintigraphic imaging.

A 33-year-old man presented with colicky, intermittent, midabdominal pain with nausea and vomiting. A Tc-99m pertechnetate abdominal scan was performed and revealed a focal area of increased uptake in the midabdomen associated with dilated proximal loops of small bowel. Surgery revealed a high-grade partial obstruction of the midportion of the jejunum secondary to an annular adenocarcinoma of the jejunum. This is the first known report of abnormal Tc-99m pertechnetate accumulation in an adenocarcinoma of the small bowel.

Adenocarcinoma

Deletion of 16q with prolonged survival and unusual radiographic manifestations.

Deletion of 16q is characterized by mental retardation, microcephaly, a characteristic combination of minor facial anomalies, and broad halluces. Various break points have been described. This patient's phenotype is typical of this syndrome, but in addition, unusual radiographic findings were present. This chromosome abnormality is compatible with survival into adulthood. Expression of this phenotype does not appear to be correlated with specific break points.

Abnormalities, Multiple

Defective epidermal growth factor gene expression in mice with polycystic kidney disease.

The C57BL/6J-cpk mouse has an inheritable form of polycystic kidney disease similar to the autosomal recessive disorder seen in humans. Between approximately 1 and 3 weeks of age, affected cpk mice develop numerous large cysts in the collecting tubule segment of kidney nephrons. The present study examined the ontogeny of renal and submandibular gland prepro-epidermal growth factor (preproEGF) gene expression in the cpk mouse using Northern blot hybridization and immunohistochemistry. There was a virtual absence of renal preproEGF gene expression in cystic kidneys over the 3-week postnatal period, during which time renal preproEGF mRNA and proEGF/EGF protein normally reach significant levels. PreproEGF mRNA was expressed in salivary glands of cystic mice; however, this mRNA could not be further elevated with testosterone suggesting that there are abnormalities in the regulation of the preproEGF gene in the submandibular gland, as well as in the kidney. Since renal preproEGF expression during the early postnatal period occurs when collecting duct cysts form, it is possible that a deficiency in renal proEGF or EGF contributes to the rapid development of collecting duct cysts and the concomitant renal failure in the C57BL/6J-cpk cystic mouse.

Animals

Atrial natriuretic peptide in heart and specific binding in organs from fetal and newborn rats.

To assess the possibility that atrial natriuretic peptide plays a role in salt and water balance during early mammalian development, we examined hearts from fetal and neonatal rates for the presence of this peptide and presumed target tissues for their ability to bind the hormone. Immunohistochemistry was used to localize and radioimmunoassay to quantify this peptide in heart. Immunoreactive atrial natriuretic peptide was visualized in the fetal heart on day 17.5 post-conception. It was distributed throughout the atrial appendages and free wall and, in ventricle, in the trabeculae carnae and chordae tendineae. The concentrations of immunoreactive atrial natriuretic peptide in atria of rats on day 19.5 post-conception were one-tenth of those in the adult. Levels of this peptide in fetal ventricle were low and virtually absent from the adult tissue. Specific binding of radiolabelled atrial natriuretic peptide measured by whole organ counting occurred in several organs from 19.5-day fetal and neonatal rats. A number of these tissues, including the kidney, ileum, adrenal, lung and liver, are targets for and/or bind the peptide in adult rats. Specific binding in these tissues was localized using autoradiography at anatomical sites similar to those in adult organs. Specific binding was also seen in fetal but not neonatal skin. In the kidney, binding was associated with immature as well as mature glomeruli. These findings support the proposition that atrial natriuretic peptide may function in the perinatal rat as it does in the adult and, in addition, may play a unique role during fetal life.

Adrenal Glands

The development of lacquer cracks in pathologic myopia.

We examined three patients with pathologic myopia who had mild visual symptoms and subretinal hemorrhages. None had subretinal neovascularization. In all three patients, lacquer crack lesions of the choroid appeared shortly after clearing of the subretinal hemorrhages. The lacquer cracks were always more extensive than the preceding hemorrhages. These findings support the theory that mechanical stretching and rupture of the Bruch's membrane-pigment epithelium-choriocapillaris complex is the cause of these lesions. Fluorescein angiography helped differentiate these subretinal hemorrhages from those caused by subretinal neovascularization.

Adult

Oral feeding of isolated lectins from red kidney bean stimulates rat small intestinal mucosal DNA synthesis and crypt cell division.

A lectin preparation containing enterokinase inhibitor purified or partially purified from red kidney bean (RKB) when fed to weanling rats was shown to cause small intestinal hyperplasia. To see if this hyperplastic effect on the rat small intestine was due to the mitogenic properties of the isolated lectin, male weanling rats were fed a chow containing 0.1% of the isolated lectin for six days. Age-matched control rats were fed regular chow. Both control and lectin-fed rats were sacrificed at one, two, three, four, and six days after the start of lectin feeding. The proximal small intestinal mucosa of rats fed lectin showed gradual increases in protein and DNA contents throughout the experimental period. Morphological studies showed marked increases in crypt depth from days 1 through 6 in these rats with essentially no change in mucosal thickness or villous height. DNA synthetic activity peaked at day 2, but was higher than control throughout the experimental period. Labeling index was 0.36 +/- 0.03 in duodenum of controls as compared to 0.45 +/- 0.02 in duodenum of weanling rats fed lectin for two days. These results demonstrate that RKB lectin stimulates overall DNA synthetic activity and increases crypt cell proliferation on the small intestine of weanling rats. The observed mucosal hyperplasia is probably due to increases in crypt cell population as shown by the increase in crypt depth.

Animals

Penetration of imipenem into human aqueous and vitreous humor.

Twenty-five patients about to undergo cataract surgery and ten patients about to undergo vitrectomy received a 1-g intravenous dose of imipenem before surgery. Specimens of aqueous or vitreous humor were then obtained and assayed for antibiotic content with a microbiologic disk agar technique. A mean peak aqueous humor level of 2.99 micrograms/ml was found at approximately two hours after administration, and a mean vitreous level of 2.53 micrograms/ml was found from two hours to three hours 15 minutes after administration. These concentrations were well above the minimum inhibitory concentration of imipenem for 90% (MIC90) of Staphylococcus epidermidis, S. aureus, and the Enterobacteriaceae commonly involved in bacterial endophthalmitis.

Aqueous Humor