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Biomedical subjects

K F Lee

Publications and source records attributed to K F Lee.

At least 73 records · Page 4Linked to original sources

Prolactin receptor expression in the developing human prostate and in hyperplastic, dysplastic, and neoplastic lesions.

In situ hybridization and immunohistochemistry were used to localize and compare the expression of the long form of the human prolactin receptor in fetal, prepubertal, and adult prostate. Results were then compared with hyperplastic, dysplastic, and neoplastic lesions. Both receptor message and protein were predominately localized in epithelial cells of the fetal, neonatal, prepubertal, and normal adult prostate. In hyperplastic lesions the expression of the receptor was unchanged with respect to normal epithelial cells. Irrespective of grade, markedly enhanced expression of the receptor was evident in dysplastic lesions. In lower Gleason grade carcinomas the intensity of receptor signal at the message and protein levels approximated that found in normal prostatic epithelium. However, in foci within higher grade cancers, receptor expression appeared diminished. Results from our study suggest that prolactin action plays a role in the development and maintenance of the human prostate and may also participate in early neoplastic transformation of the gland. Diminution of receptor expression in high grade neoplasms could reflect the emergence of a population of cells that are no longer responsive to the peptide hormone.

Aged↗

Rescue of the cardiac defect in ErbB2 mutant mice reveals essential roles of ErbB2 in peripheral nervous system development.

ErbB2 receptor tyrosine kinase plays a role in neuregulin signaling and is expressed in the developing nervous system. We genetically rescued the cardiac defect of erbB2 null mutant embryos, which otherwise died at E11. These rescued erbB2 mutant mice die at birth and display a severe loss of both motor and sensory neurons. Motor and sensory axons are severely defasciculated and aberrantly projected within their final target tissues. Schwann cells are completely absent in the peripheral nerves. Schwann cell precursors are present within the DRG and proliferate normally, but their ability to migrate is decreased. Acetylcholine receptors cluster within the central band of the mutant diaphragm muscle. However, these clusters are dispersed and morphologically different from those in control muscle. Our results reveal an important role for erbB2 during normal peripheral nervous system development.

Animals↗

Tumor vascular pattern and blood flow impedance in the differential diagnosis of leiomyoma and adenomyosis by color Doppler sonography.

PURPOSE: Our objective was to evaluate the differences between leiomyoma and adenomyosis by color Doppler sonography with new criteria. METHODS: A total of 78 patients with symptomatic uterine nodularities who were sonographically suspected to have leiomyoma or adenomyosis without other coexisting pathologic conditions was enrolled in the study. All patients underwent transvaginal color Doppler sonography (7.0-MHz vaginal probe) or transabdominal color Doppler sonography (5.0 MHz) during the early follicular phase. The morphology, tumor vascular pattern, and blood flow impedance of the uterine tumors were measured. All of the patients underwent surgery and the pathologic reports were used as references. RESULTS: The mean age was not statistically significant in patients with adenomyosis versus leiomyoma (P > 0.05). The morphologic criteria for adenomyosis and leiomyoma by sonography detected 79% of adenomyosis and 84% of leiomyoma. Adenomyosis had 87% randomly scattered vessels or intratumoral signals and 88% of leiomyomas showed peripheral scattered vessels or outer feeding vessels. Eighty-two percent of adenomyosis had a pulsitility index (PI) of arteries within or around uterine tumors > 1.17 and 84% of leiomyomas had a PI < or = 1.17. The reliability test of tumor vascular pattern and blood flow impedance were better than that of using morphological criteria alone. CONCLUSIONS: With the aid of color Doppler sonography, tumor vascular pattern and blood flow impedance of the arteries within or around uterine tumors could more accurately diagnose adenomyosis and leiomyoma in addition to the morphologic criteria on transvaginal sonography.

Adult↗

Phase II trial of neoadjuvant chemotherapy in early-stage small cell cervical cancer.

Clinical complete response (CR) to chemotherapy is not uncommon in small cell carcinoma. To understand its pathologic response, we conducted a phase II trial with neoadjuvant chemotherapy followed by hysterectomy in patients with small cell cervical cancer and reviewed all reported cases receiving neoadjuvant chemotherapy followed by hysterectomy through a MEDLINE search. From December 1993 to December 1997, the enrolled patients were treated with two to three courses of vincristine, adriamycin and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE) before hysterectomy. Another three courses of chemotherapy were added after surgery. A total of seven patients was enrolled. Clinical CR was observed in six patients, but microscopic residual tumor was present in all. Lymphatic permeation, scattered residual tumor clusters and residual superficial invasive adenocarcinoma over the cervix presented in five cases, and another had a metastatic pelvic node with no residual cervical tumor. Three of these seven patients have been alive with no evidence of disease for 16.2, 45.2 and 56.6 months, respectively. The other four died from disease 10.3-23.6 months after diagnosis. These findings indicate the discrepancy between clinical and pathologic responses in small cell cervical cancer after chemotherapy and emphasize the necessity of local treatment.

Adult↗

CRF type I receptor-deficient mice exhibit a pronounced pituitary-adrenal response to local inflammation.

Recent studies indicate that the regulation of adrenocorticotropin (ACTH) secretion by corticotropin-releasing factor (CRF) is mediated predominantly by the type I CRF receptor (CRF-R1). Indeed, CRF-R1-deficient (CRF-R1 -/-) mice show marked impairment of the pituitary-adrenal axis. However, the plasma ACTH concentrations of unstressed CRF-R1 -/- mice are similar to those in wild-type mice. We show here that arginine vasopressin (AVP) is a major ACTH secretagogue in CRF-R1 -/- mice in resting conditions, since administration of anti-AVP serum, but not anti-CRF serum, markedly reduced (by 60%) resting plasma ACTH concentrations in these mutants. We also investigated the pituitary-adrenal response to turpentine-induced local inflammation in CRF-R1 -/- mice. Administration of turpentine into the hind-limb of CRF-R1 -/- mice produced a slightly (15-25%) smaller swelling of the limb, but a 10 fold greater rise in plasma IL-6 levels, compared to CRF-R1 +/+ controls. Turpentine-induced local inflammation produced pronounced elevations in the plasma concentrations of both ACTH and corticosterone in both CRF-R1 -/- and wild-type mice, but ACTH secretion could be inhibited by anti-CRF and anti-AVP sera only in wild-type mice. These data indicate that resting ACTH secretion in CRF-R1 -/- mice is in part attributable to AVP-dependent mechanisms. Furthermore, while in normal mice the pituitary-adrenal response to local inflammation is mediated largely via CRF-dependent mechanisms, mice deficient in CRF-R1 are still able to mount a pituitary-adrenal response via mechanisms that do not depend critically on either CRF or AVP action.

Adrenocorticotropic Hormone↗

Gastric adenocarcinoma with tonsil and submaxillary gland metastases: case report.

Local invasion, hematogenous and lymphatic metastases are the major modes of spreading gastric cancer. The most common sites of metastases in patients with gastric cancer are liver, peritoneum, omentum, lungs and mesentery. Of the two pathological types of gastric cancer, intestinal-type gastric cancer showed preferential metastasis to the liver, whereas the diffuse-type showed a preference for peritoneal involvement and lymph node metastasis. However, metastases of gastric cancer to the head and neck regions are not common. The hematogenous route appears to account for a great majority of metastases to the head and neck regions. Malignant neoplasm metastases to major salivary glands or tonsils are not common. Several patients with cancers from the infraclavicular area have been reported with parotid gland or tonsil metastases. However, metastasis of gastric adenocarcinoma to the tonsils or submandibular glands is rare. We present a patient with recurrent gastric adenocarcinoma with both tonsil and submandibular gland metastases which is even rarer.

Adenocarcinoma↗

Successful surgical treatment of solitary adrenal metastases from non-small cell lung cancer: case report.

Lung cancer is one of the most common types of maligancies and has been one of the leading causes death due to cancer for a long time. Although surgery is the treatment of choice for patients with non-N2 localized disease, most of the lung cancer patients are found to have metastatic lesions at the same time as initial diagnosis. The median survival of patients with metastatic lung cancer is less than one year even when systemic chemotherapy is given. We present a patient with non-small cell lung cancer with no initial evidence of metastasis. He underwent curative resection of the primary tumor followed by local radiotherapy. Adrenal gland metastasis was found fours years after the first surgery. After surgical resection of this metastatic lesion, followed by adjuvant chemotherapy, this patient's survival was prolonged with no evidence of disease recurrence until now. The prolonged survival of this patient may be due to a slow rate of progression of the primary tumor.

Adrenal Gland Neoplasms↗

Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development.

Corticotropin releasing factor (CRF) is a major integrator of adaptive responses to stress. Two biochemically and pharmacologically distinct CRF receptor subtypes (CRFR1 and CRFR2) have been described. We have generated mice null for the CRFR1 gene to elucidate the specific developmental and physiological roles of CRF receptor mediated pathways. Behavioral analyses revealed that mice lacking CRFR1 displayed markedly reduced anxiety. Mutant mice also failed to exhibit the characteristic hormonal response to stress due to a disruption of the hypothalamic-pituitary-adrenal (HPA) axis. Homozygous mutant mice derived from crossing heterozygotes displayed low plasma corticosterone concentrations resulting from a marked agenesis of the zona fasciculata region of the adrenal gland. The offspring from homozygote crosses died within 48 hr after birth due to a pronounced lung dysplasia. The adrenal agenesis in mutant animals was attributed to insufficient adrenocorticotropic hormone (ACTH) production during the neonatal period and was rescued by ACTH replacement. These results suggest that CRFR1 plays an important role both in the development of a functional HPA axis and in mediating behavioral changes associated with anxiety.

Adaptation, Physiological↗

Delayed hemothorax after blunt thoracic trauma: an uncommon entity with significant morbidity.

OBJECTIVE: To describe the nature of delayed hemothorax occurring after blunt thoracic trauma and to identify the population at risk for this complication. METHODS: A retrospective review was conducted of 36 consecutive patients with hemothorax consequent to blunt trauma. Criteria for the definition of delayed hemothorax were established involving normal interval chest radiographs or computed tomographic scans during hospitalization. RESULTS: Twelve cases of delayed development of hemothorax were identified. Ninety-two percent of cases occurred in patients with multiple or displaced rib fractures. Presentation occurred from 18 hours to 6 days after injury. Eleven of the 12 cases were heralded by a prodrome of new pleuritic chest pain and dyspnea that occurred from 4 to 19 hours before treatment. CONCLUSION: Delayed hemothorax after blunt trauma is a unique entity occurring in patients with multiple or displaced rib fractures. Vigilance for the recognizable prodrome in the high-risk population should allow early remediation of this complication.

Aged↗

Pregnancy in a previous cesarean section scar: case report.

An ectopic pregnancy developing in a previous cesarean section scar is an extreme rarity among all ectopic pregnancies. Due to the difficulty of making an accurate diagnosis, this kind of ectopic pregnancy is the most dangerous and life-threatening type. A 30-year-old woman, who was gravida 4, para 3, was admitted to our emergency room with massive vaginal bleeding. She had undergone a cesarean section due to a breech birth 3 months prior to this admission. Ultrasound examination showed a pregnancy located in the low corpus uterus. The possibility of a spontaneous abortion in progress or a cervico-isthmic pregnancy were considered. Due to the massive vaginal bleeding and unstable vital signs of the patient, surgical intervention was decided upon to save the woman's life. We first performed dilatation and curettage. There was no gestational villi and severe vaginal bleeding was noted during this procedure. An emergent exploratory laparotomy was then performed, followed finally by a hysterectomy. Pathologic findings confirmed the diagnosis of a pregnancy in the previous cesarean section scar. Diagnosis, prevention, clinical evaluation and management of these conditions are discussed.

Adult↗

A factor IX-deficient mouse model for hemophilia B gene therapy.

We have generated a mouse where the clotting factor IX (FIX) gene has been disrupted by homologous recombination. The FIX nullizygous (-/-) mouse was devoid of factor IX antigen in plasma. Consistent with the bleeding disorder, the factor IX coagulant activities for wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice were 92%, 53%, and <5%, respectively, in activated partial thromboplastin time assays. Plasma factor IX activity in the deficient mice (-/-) was restored by introducing wild-type murine FIX gene via adenoviral vectors. Thus, these factor IX-deficient mice provide a useful animal model for gene therapy studies of hemophilia B.

Adenoviridae↗

Dental innervation and CGRP in adult p75-deficient mice.

Adult dental tissues have unusual neurotrophin biology. Pulpal fibroblasts express nerve growth factor (NGF) and the low-affinity p75 neurotrophin receptor, their sensory nerve fibers express p75 and trk A, and pulpal sympathetic fibers lack p75. Following tooth injury, there is increased pulpal NGF, sprouting of sensory nerve endings, and increased immunoreactivity for the sensory neuropeptide calcitonin gene-related peptide (CGRP). In the present study, we have analyzed tooth structure and innervation of pulp and periodontal ligament in young (6-8 weeks, 3 months) and older (5-12 months) adult mice carrying a null mutation in the p75 gene and compared the results with those of age-matched wild-type controls. Our hypotheses were that tooth structure would be abnormal and that pulpal innervation would be greatly reduced because it consists primarily of nociceptive fibers that have been found to be severely depleted in skin of p75(-/-) mice. Tissues were fixed, X-rayed for gross dental morphology, decalcified, and analyzed for immunoreactivity for CGRP and for a general nerve marker, protein gene product 9.5. Radiographs showed worn-down molar crowns in p75-deficient mice. Light microscopy confirmed the accelerated molar wear and showed intense CGRP immunoreactivity in pulp nerve endings of mutant mice, compared with a gradual decrease in CGRP intensity in controls during normal aging. The CGRP intensity in 5-12-month-old pairs of mice was threefold greater in the mutants (P < 0.03), and in younger mice the mutant always had more CGRP than its matched control. The innervation of molar ligament in all p75-deficient mice was similar to that of controls except there was nerve sprouting near bone loss in mutants. The incisors of mutant mice did not have unusual wear and their pulpal CGRP immunoreactivity remained normal, but their periodontal ligament had fewer thin branched nerve endings at all ages. Thus, most innervation of teeth and their supporting tissues developed normally, and the only neural changes in p75(-/-) mutant mice were the reduction of incisor ligament sensory receptors and increased molar CGRP. Sensory nerves in teeth gradually lose neuropeptide intensity during aging, but that did not happen in the mutant mice, suggesting that the accelerated molar wear stimulated persistent high levels of CGRP.

Animals↗

Turning of nerve growth cones induced by the activation of protein kinase C.

Pathfinding by growing nerve processes in the developing nervous system depends on the turning response of the growth cone to extracellular guidance cues. Embryonic spinal neurons were prepared from 1-day-old Xenopus embryos. After 4 h incubation, a repetitive pulse application was used to produce microscopic chemical gradients near the growth cone. A micropipette containing the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol 13-acetate (TPA) or phorbol 12,13-dibutyrate, produced a significant growth cone turning response. A micropipette containing adenosine 5'-triphosphate (ATP) also induced growth cone turning towards the pipette tip. H-7, a PKC inhibitor, inhibited the ATP-induced turning response of the growth cone. Our results suggest that the activation of PKC in developing motoneurons may induce the turning response of growth cones.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus.

BACKGROUND: Several studies had suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. METHODS: We prospectively studied the prevalence of NDRD among a Chinese NIDDM population. Renal biopsy specimens were evaluated with light-, immunohistological and electron-microscopy. The cohort consisted of 51 patients who had NIDDM and proteinuria > 1 g/24 h. RESULTS: Patients with both isolated diabetic nephropathy (DN, n = 34) and NDRD (n = 17) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and glycosylated haemoglobin levels, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had microscopic haematuria (P = 0.043) or non-nephrotic proteinuria (P = 0.004). IgA nephropathy accounted for 59% of the NDRD identified. CONCLUSIONS: In this study, microscopic haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients presenting with renal disease.

Diabetes Mellitus, Type 2↗

Restriction endonucleases in clinical isolates of Shigella spp.

Thirteen restriction endonuclease-containing strains were isolated from a collection of 186 clinical isolates of Shigella spp. Among these, eight and five isolates carried isoschizomers of EcoRII and NciI, respectively. The former restriction-modification (R-M) system was homologous to that of EcoRII and was located on plasmids with sizes of 46.6 or 55.6 kb. Isolates producing NciI isoschizomers contained a 5.7-kb non-transferable plasmid. Together with antimicrobial susceptibility tests and plasmid profile studies, it is concluded that these two R-M systems are not widely spread but confined to strains with similar antibiotic resistance and plasmid profile.

Anti-Bacterial Agents↗

Regulation of quantal transmitter secretion by ATP and protein kinases at developing neuromuscular synapses.

The effects of endogenously released ATP on the maturation of developing neuromuscular synapses were investigated in Xenopus nerve-muscle co-cultures. The potentiating action of ATP (1 mM) on spontaneous acetylcholine release was inhibited by P2-purinoceptor antagonists suramin (0.3 mM) and reactive blue 2 (RB-2, 3 microM) in day 1 cultures. Bath application of suramin (10 microM) or RB-2 in day 1 cultures and prolonged treatment for 2 days dramatically decreased the amplitude of both spontaneous synaptic currents (SSCs) and evoked synaptic currents (ESCs) in the same cultures on day 3. Chronic treatment with 8-cyclopentyltheophylline (4 microM) or 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM), P1-purinoceptor and glutamate receptor antagonists respectively, did not exert such an inhibitory effect. Chronic treatment with suramin or RB-2 for 2 days had no significant effect on the amplitude of either iontophoretic acetylcholine-induced whole-cell currents or single acetylcholine channel measurements in 3-day-old cultured myocytes. In addition, prolonged treatment for 2 days with various kinase inhibitors such as H-8 (10 microM), KN-62 (5 microM) and H-7 (10 microM) also decreased the amplitudes of both spontaneous and evoked synaptic currents in natural synapses, but not those of iontophoretic acetylcholine-induced currents. Furthermore, suramin and these protein kinase inhibitors also decreased the amplitude of spontaneous synaptic currents in manipulated synapses of 'vacated' nerve terminals. The results suggest that endogenously released ATP, acting in concert with various protein kinases, is involved in the maintenance and/or development of the quantum size of synaptic vesicles at embryonic neuromuscular synapses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex.

During neuronal migration to the developing cerebral cortex, neurons regulate radial glial cell function and radial glial cells, in turn, support neuronal cell migration and differentiation. To study how migrating neurons and radial glial cells influence each others' function in the developing cerebral cortex, we examined the role of glial growth factor (a soluble form of neuregulin), in neuron-radial glial interactions. Here, we show that GGF is expressed by migrating cortical neurons and promotes their migration along radial glial fibers. Concurrently, GGF also promotes the maintenance and elongation of radial glial cells, which are essential for guiding neuronal migration to the cortex. In the absence of GGF signaling via erbB2 receptors, radial glial development is abnormal. Furthermore, GGF's regulation of radial glial development is mediated in part by brain lipid-binding protein (BLBP), a neuronally induced, radial glial molecule, previously shown to be essential for the establishment and maintenance of radial glial fiber system. The ability of GGF to influence both neuronal migration and radial glial development in a mutually dependent manner suggests that it functions as a mediator of interactions between migrating neurons and radial glial cells in the developing cerebral cortex.

Animals↗